Category Archives: J-O

Models of Frontal Lobe Functioning

Norman & Shallice’s Framework:

2 basic “control” mechanisms that determine how we monitor our activities

  • The automatic contention scheduler (ACS)- automatic & direct priming of stored knowledge by stimuli in environment or conceptual thought
  • Supervisory attention system (SAS): conscious awareness of what we know that set the priorities for action. SAS can override ACS.
    • In frontal lobe dysfunction, the SAS goes down

Goldman-Rakic and Primate Working Memory

  • Based on electrophysiological studies of monkeys
  • Developed concept of working memory by noting that prefrontal cortical neurons fired only during delay between presentation of stimulus to remember and stimulus to recall. The prefrontal cortical cells were also specifically linked to where in space the stimulus was seen.

Fuster’s Temporal Processing Model

  • The prefrontal cortex is principally involved with representing the “temporal structure of behavior” i.e., the coding of place within a sequence of actions or perceptual observations.
  • Action sequences tend to be goal related (i.e., conceptually driven).
  • To encode temporal aspects of behaviors, the prefrontal cortex must be involved in the formation of “cross-temoral contingencies” i.e., ties between events that are related to other, not only in time, but because they have a common goal.
  • These temporal operations are unique to the prefrontal cortex according to Fuster

Stuss & Benson’s Behavioral/Anatomical Theory

They divide the functions of the frontal lobes into two groups

  • The first group is concerned with sequencing behaviors, forming mental sets, and integrating various behaviors.
    • Associated with dorsolateral prefrontal cortex activation
  • The second is concerned with more primitive processes such as drive, motivation, and will.
    • Associated with ventromedial prefrontal cortex activation
    • Lately, Stuss and colleagues have distinguished a large set of top-down attentional processes subserved by the frontal cortex.

Luria’s view: Problem solving & the frontal lobe

  • Luria’s approach was qualitative and relied on the analysis of verbal protocols of pts. trying to solve multistep problems
  • Impaired programming and regulation of behavior were the principle deficits, resulting in impulsivity and difficulty switching problems solving strategies.
  • FL Pts. can access fragmentary operations but cannot combine them into an overall schema
  • Luria believed that focal lesions could dissocicate types of problem-solving failures.

Damasio’s Somatic Marker Theraory

  • Pts. with inappropriate social behavior as a result of frontal lobe lesions fail to behave appropriately due to a “defect in the activation of somatic markers”
  • This somatic signal binds to social behaviors and modulates social decisions
  • Based on observation that pts with ventromedial frontal lesions have diminished GSRs (i.e., diminished somatic marker) during tasks which normals find arousing.

Mild Cognitive Impairment

What is MCI?

  • A clinical condition considered a transition phase between normal aging and dementia.
    • MCI was initially seen as a transition phase between normal aging and Alzheimer’s dementia – however, now recognized that other underlying conditions with different aetiologies may result in mild cognitive impairment that has increased risk of progressing to “dementia.”
  • Peterson et al (1999, 2001) coined term to describe individuals with memory complaints who have objective evidence of memory impairment but whose functioning does not meet currently accepted criteria for clinically probable dementia.
    • subjective memory complaints and objective evidence of mild memory impairment (at a level less than 1.5 standard deviations than health age-matched “normal” peers)
    • normal intellectual functioning
    • normal activities of daily living, and,
    • do not meet currently accepted criteria for clinically probable dementia.
  • Terms used in the past to describe such problems: Malignant Senescent Forgetfulness, Age-Associated Memory Impairment, Late-Life Forgetfulness, Age-Associated Cognitive Decline, Age-Related Cognitive Decline, Mild Cognitive Decline, Mild Neurocognitive Disorder.
  • The use of various terms and inclusion criteria make it difficult to compare studies in the past – there is a need for agreement in definition in order to research 1) estimates of incidence and prevalence, 2) conversion rates to dementia, 3) aetiology, 4) prognosis

Types of MCI

  • Peterson, Doody et al (2001)identified subclassifications of MCI with the primary clinical distinction being the presence or absence of prominent memory impairment
    • Amnestic MCI – probably reflects prodromal phase of dementia
      • Memory complaints, preferably corroborated by informant
      • Impaired memory function on formal testing for age and education level
      • Preserved general cognitive function
      • Intact activities of daily living
      • No evidence of dementia
    • Non-amnestic MCI
      • Mild impairments in one or several domains, including but not limited to language, visual spatial construction, attention, and/or executive functions

Differential Diagnosis

  • Must differentiate from normal aging AND dementia (cognitive impairments and interference with ADLs are more extensive)

Assessment of MCI

  • Some research (XU et al, 2002) suggests combination of Mini-Mental State Exam and Cognitive Capacity Screening Exam showed high sensitivity and specificity for identifying those with MCI who later converted to AD.
  • Neuropsychological assessment should:
    • Take into account patient-related factors such as physical illness, and, psychological and psychiatric comorbidities
      • Anxiety disorders
      • Mood disorders
      • Alcohol and/or other drug abuse
    • Key neuropsychological measures cover (ideally in verbal and nonverbal modalities)
      • Immediate retention of new information
      • Rate and pattern of learning
      • Efficiency of retrieval of recent and remote memory
      • Susceptibility to pro- and retroactive interference
  • Some studies have shown that MCI subjects had markedly lower scores than normals on smell identification tests – may want to include smell assessment in battery but realize that it may be sensitive but not specific
  • Must be aware of and account for sensory impairments on test results

Neuroimaging/ Neuropathology

  • Some evidence of hippocampal atrophy in patient with Amnestic MCI, which was predictive of conversion to AD
  • In individuals with documented MCI prior to death, there was evidence of neurofibrillary tangles and amyloid plaques

Prevalence of MCI

  • Ranges from 3-34% depending on definition and type of sample (community vs. clinical)
  • In general, prevalence of MCI is greater than that of dementia (MCI may be up to 4 times more prevalent than AD when based on community assessment of non-institutionalized individuals)

Progression to AD

  • Amnestic MCI progresses to dementia at a rate of 10-15%
  • Predictors of progression: hippocampal atrophy, genetic susceptibility
  • Remember that there is great heterogeneity in individuals with MCI and not all will progress to AD. Some may progress to other forms of dementia, others show stable cognitive abilities, while still others may show improvement
  • Current research looking at whether medications can alter progression to AD in individuals identified with MCI

Normal Aging (Notes from Lezak’s book)

  • Brain Changes:
    • Rapid shrinkage of brain volume after age 55 in normal adults
    • Cortical atrophy first evident in 40s (widened sulci, narrowed gyri, decrease in cortical mantle)
    • Ventricular dilation
    • Reduced volume in subcortical areas (more in basal ganglia and anterior diencephalons than thalamus)
    • Atrophy due to neuronal loss (or shrinkage in cell size), which is most pronounced in hippocampus and anterior dorsal frontal lobe and least evident in occipital lobes
    • Cerebral blood flow studies show progressive decline is greatest in prefrontal and inferior temporal cortex and least evident in occipital areas
  • Overall Cognition:
    • methodological differences between studies have produced contradictory results
    • “crystallized” knowledge shows gains into 70sand 80s while “fluid” intelligence show slow decline in middle years and more rapid decline following 50s or 60s
    • some suggest that slowing (psychomotor and cognitive), executive dysfunction or visuospatial deficits may account for much of the performance decline seen with increased age.
    • No change in cerebral asymmetry of laterality of functions with age.
  • Sensory and Motor Changes:
    • Senses decline in sensitivity and acuity
      • visual and auditory losses first evident in 40s and 50s but rapid decline seen after 60s. Into 70s and 80s, only a minority (~10-30%) have normal vision or hearing.
      • Also see decline in olfaction after 40s.
    • Response times increase and fine motor abilities decline:
      • Reaction time begins to gradually decline in 30s and continues at a steady rate
      • Mental processing slows dramatically in 60s
      • Slowing limits performance on timed tests (WAIS Performance subtests)
      • Diminished motor strength appears in 40s with accelerated losses thereafter.
  • Attentional Changes:
    • simple span measures remain intact until 80s
    • however, older people have more difficulty with divided attention (e.g., choice reaction time tests) and there are declines in sustained and selective attention.
  • Memory Changes:
    • short-term retention on simple span measures is most resistant to age-related declines
    • older people have more difficulty than younger in tests of supraspan (i.e., amount of material exceeds normal storage capacity)
    • performance on working memory tasks declines with age
    • learning efficiency diminishes with age and losses are most evident on spontaneous recall (rather than recognition)
    • visual recall (tested by recall or recognition formats) declines more quickly than verbal memory and shows sharper declines in later years.
    • Auditory and tactile memory show rapid decline between 40 and 60
    • Accuracy of source memory decreases with age
    • Verbal memory performance least compromised with normal aging.
  • Verbal Abilities:
    • most verbal abilities do not decline with age (i.e., vocabulary and verbal reasoning are stable over time).
    • Difficulty with verbal retrieval (i.e., poor access to verbal memory) is common complaint among elderly and is evident on formal testing (i.e., decreased verbal fluency, requires more cues on BNT to aid word retrieval).
  • Visuospatial Functions / Praxis:
    • visuoperceptual judgement declines steadily from 65 on into the 90s
    • general difficulties with visuoperceptual organization seen in people ages 70 to 90 years.
    • Spatial orientation is also sensitive to aging
    • No real change in praxis, although older people more likely to use body part as object
    • Decreased performance on WAIS BD and OA is due more to speed than visual abilities
  • Reasoning, Concept Formation, Mental Flexibility:
    • reasoning about familiar material shows no age-related decline, however, there is a decline in reasoning in novel or complex situations
    • decline in concept formation and abstraction; older people tend to be more concrete (especially after the age of 70)
    • mental inflexibility seen in difficulty adapting to new situations, solving new problems and changing mental set
  • Heath and Cognitive Aging
    • older people more lively to have health problems that are known to affect cognition (i.e., diabetes, hypertension,…)
    • regular exercise may slow rate of cognitive decline or even reverse it

Memory and Learning II


  • Hippocampi – specifically involved in registration and storage of new memories. Bilateral removal of hippocampus leads to severe anterograde amnesia similar to that seen in Korsakoff’s (but they do not have the other cognitive deficits associated w/Korsakoff’s- believed to be due to diffuse cortical atrophy). Common cause: inflammation, anoxia, temporal lobectomy, stroke (supplied by PCA)
    • Right hippocampal removal is associated w/ deficits in spatial learning and memory
    • Left hippocampal removal associated w/recall of verbal material
  • Amygdala – believed to be involved in associating a stimulus with a reward (necessary for learning)
  • Diencephalon (particularly the mammilary bodies) – the precise role is unclear, but the mammilary bodies consist of nerve fibers which connect the hypothalamus and the thalamus.
    • Bilateral damage results in global anterograde amnesia
      • Patients w/Korsakoff’s have been shown to have hemorrhagic lesions in the region around the diencephalon. (amnesia has also been shown in patients following trauma, stroke or tumors in this area)
  • Basal forebrain (nucleus accumbens, septal nuclei, anterior hypothalamus, nucleus basalis of Meynert, prefrontal cortex) – the nucleus basalis of Meynert is found in this area and also sends fibers to various regions including the hippocampus and cerebral cortex. It is a major source for Ach and is considered important for normal memory fxns.
    • Functions are disrupted with ACoA strokes and Alzheimer’s disease. Common cause of damage producing memory deficit: AD
  • Thalamus (dorsomedial nuclei and anterior nuclei) – associate with encoding and integration of new information. Common cause of damage: stroke
  • Cerebral cortex – e.g., in patients w/Korsakoff’s damage is not restricted to the brain regions typically associated w/short-term memory. Rather, the damage is widespread and thought to involve large regions of the cerebral cortex as well (patients w/Korsakoff’s tend to show cortical atrophy – seen as enlarged ventricles and widening of the sulci).
    • Specific cortical damage is seen in:
      • Prefrontal cortex – associated w/ emotional apathy and perseveration; also, attention, organization (e.g., self-generated encoding strategies), and time-tagging. Common cause of damage producing memory deficit: strokes, TBI
      • Bilateral temporal cortical atrophy- difficulty forming visual associations
      • Temporal cortex – lesions of anterior temporal lobe (which spare the hippocampus) result in a variety of impairments (but not global amnesia as seen in H.M.) (hemispheric specialization is same as seen in hippocampus lateralization) – damage is similar to unilateral removal of hippocampus. Lateral regions associated with immediate and short-term recall. Ultimately the “temporal lobe” (which includes anterior temporal neocortex, amygdala, hippocampus, entorhinal cortex) is responsible for amnesia, plus the affective component of memory
  • Temporal Lobe Functions:
  1. auditory sensation and auditory/visual perception
  2. long-term storage of sensory input
  3. affective tone to sensory input
  • Symptoms of Lesions:
  1. impaired auditory sensation & perception
  2. decreased selective attention of auditory & visual input
  3. decreased visual perception
  4. decreased organization and categorization of verbal material
  5. decreased language comprehension
  6. decreased LTM
  7. personality and affective behavioral changes
  8. sexual behavior
  • Neurotransmitters – both the cholinergic system (Ach) and the catecholamines (DA, NE, and epinephrine) have been associated w/memory
    • Ach has a major source in the nucleus basalis of Meynert which communicates directly w/the hippocampus and the cerebral cortex; deficiencies in Ach have been associated with Alz. disease. Korsakoff’s patients also have a reduction of Ach and cell loss in the basal forebrain (particularly the nucleus basalis of Meynert)** catecholamines – damage in Korsakoff’s patients frequently involve the origin of the NE pathway; deficits have been associated w/reduced activity of DA and NE.


  • Bilateral Hippocampal Damage – results in a total lack of recall for day-to-day events; i.e., anterograde amnesia. It can also lead to partial retrograde amnesia, but overall, early memories are usually intact. There is no deterioration in intellect or personality
  • Day to day fxning and basic reasoning skills may appear normal until signs of memory impairment are noticed
  • These patients can retain a 3-figure number or a pair of unrelated words for several minutes if they are not distracted during the interval – but they will forget as soon as they are distracted
  • When smaller portions of the hippocampus is damaged (leaving some of it intact) memory impairments are not as severe; thus there appears to be a positive relationship b/t the extent of damage to the anterior hippocampal complex and the degree of memory impairment.
  • Damage to mammillary bodies – have also been related to amnestic states (in Korsakoff’s syndrome). Thus, there appears to be two interrelated structures, which can lead to amnesia if damaged.


The role of frontal lobes in memory has been a controversial issue

  • some believe that memory functions per se are not impaired, but any memory difficulties are secondary to on-line processes (e.g., encoding, attention, and disinhibition)
  • others think frontal lobes are involved in (1) conditioned associative learning and (2) memory for temporal order
  • damage can result in impairments of STM for tasks w/c require temporal memory for stimuli (e.g., delayed matching to stimuli)

Cognitive Results (Fluency and Problems Solving)

Initiation and Perseveration Index – From Mattis’ Dementia Rating Scale This score reflects difficulties in organizing and searching information in semantic memory (similar to word fluency)

  • frontal patients impaired on Initiation and Perseveration Index of Dementia Rating Scale – if damage to left or bilateral damage (right frontal lobes unimpaired; but right frontal lobes have been implicated in nonverbal fluency tests)
  • amnesics impaired on Memory Scale of DRS
  • Korsakoff’s impaired on both (i.e., they have cognitive deficits and memory impairments) – thus they have frontal and diencephalic damage (confirmed by a radiological study)

Short-term Memory (e.g., Digit Span)

  • frontal patients – impaired
  • “amnesic patients” – intact

New Learning Ability

People with just frontal impairment typically do not display significant impairment in learning, i.e. no anterograde amnesia

Semantic Encoding and Release from Proactive Interference Theory – that one aspect of frontal lobe dysfunction is a failure to encode information semantically (developed due to responses on a test of “the release from proactive interference.”

  • release from proactive interference – subjects are presented 3 words and then asked to recall them following a 15 – 20 second distraction task. Trials 1 – 4: words from same semantic category are presented. (normals show a decline in performance across the four trials due to proactive interference). Trial 5, words are from a different category (normals perform as well as they did on trial 1)
  • Korsakoff patients – do not show this release (do poor on trial 5) presumably due to inadequate encoding in a semantic manner (so don’t benefit from a shift in semantic categories); attributed to frontal lobe damage (possibly secondary to degeneration of connections from the dorsomedial nucleus)
  • frontal patients – performance similar to normals. Thus does not support the theory, rather it suggests that both amnesia and frontal lobe dysfxn is necessary for the deficits seen in Korsakoff patients

Metamemory Metamemory is defined as knowledge about one’s own memory capabilities and knowledge about strategies that can aid memory by helping to plan, monitor and organize appropriate memory strategies.

  • components of metamemory – (include some fxns of frontal lobes) – planning, monitoring and organizing motor and cognitive fxns. Some believe that it is instead directly related to memory ability. e.g., the feeling of knowing (the subjective belief that the patient will know if they recognize an answer)
    • Korsakoff and frontal patients had deficits in feeling-of-knowing accuracy – BUT amnestics did not
    • thus amnestic patients can accurately express knowledge about what they do and do not know, despite having severe impairment in the ability to learn new information; and it is not a fxn of memory per se
    • the deficits seen in Korsakoff and frontal patients were not identical. For example, frontal patients did not have problems when performance was assessed after a short (5 minute) delay. Perhaps Korsakoff’s is worse b/c of deficits in memory and metamemory deficits.
  • thus, frontal lobes are critically involved in manipulation and organization of information (including information already in storage), despite not being critically involved in establishing new information in memory

Memory for the Temporal Order of Events

  • frontal patients – are impaired on recency memory (i.e., which item was presented most recently), but are not impaired on tests of item recognition memory — thus temporal order can be impaired even if their memory for the items is good
  • Korsakoff patients – are even more impaired on recency memory

Disorders of Source Memory

Source Memory refers to the process of remembering where the information was learned (contextual memory)

  • frontal patients – source memory was significantly impaired despite good recall for the facts themselves (suggests that frontal lobes contribute specifically to contextual memory)
  • amnestics can also be severely impaired in this (but not necessarily a requirement)
  • can also occur with normal aging; re: neuronal cell loss associated with aging occurs prominently in the frontal lobes, therefore source memory in normal aging may also be related to subtle frontal lobe dysfunction

Prospective Memory

  • Prospective memory refers to the strategies by which one remembers to perform and monitor future actions; could also include strategies involved in planning, monitoring and organizing memory, not just actions.
  • Theory – So, includes self-initiated searches and retrieval of information in memory. Re: in many ways memory searches are like problem solving tasks that require fluency, initiation and flexible thinking. Furthermore, impairment in inhibitory control could also reduce ability to discriminate b/t appropriate and useful strategies from inappropriate ones. This deficit would particularly impair free recall and temporal order tasks
  • Therefore, as expected frontal patients have difficult with this
  • Re: a deficit in prospective memory does not necessarily imply a deficit in declarative memory, and vice versa (e.g., amnesics do well on many tests of prospective memory)

Summary: The Memory and Cognitive Disorders in Frontal Patients

  • Memory Disorders
    • short-term memory (e.g., digit span)
    • free recall
    • metamemory
    • memory for temporal order
    • source memory
    • prospective memory
    • new learning not significantly impaired except on sensitive tests of free recall
  • Cognitive Disorders (Dysexecutive dysfunction)
    • planning
    • problem solving
    • initiation
    • perseveration
    • fluency
    • disinhibition

Notes from Kolb & Wishaw: Frontal patients show the following deficits:

  • failure to show release from proactive interference
  • errors of sequence when completing actions; poor memory for serial order
  • errors of intrusion and omission when asked to copy a series of facial movements
  • difficulty w/short-term memory


Theory: The hippocampal system interacts with perceptual pathways to transform sensory stimuli into memories

  1. Info is initially processed through the sensory cortex.
  2. From there, there are 2 distinct memory circuits involved in visual recognition:
    1. Hippocampus – specializes in memory for spatial location
    2. Amygdala – concerned with emotional significance of the material; is also responsible for combining memories obtained through different sensory modalities
      1. These systems work in a circuit (NOT totally independent) shown by the fact that cutting the connections between the two structures produced the same memory impairments seen when the structures themselves were damaged
        1. If either hippocampus or amygdala is destroyed, memories can still be stored because of parallel systems
  3. Diencephalon
  4. Prefrontal Cortex
    1. Hippocampus, amygdala, diencephalon (mammillary bodies), and prefrontal cortex all have connections with basal forebrain which is a cholinergic source
    2. Ach is hypothesized to be involved with the permanent structural (at the cellular level) changes that are responsible for long term storage
  5. Basal forebrain, via Ach, feeds back to the sensory cortex to complete the loop
  6. When same stimulus is again received by the sensory cortex, the “memory” is activated

Procedural Memory (i.e., “habits”)

  • Considered a separate system of learning, independent of the limbic system
  • it is noncognitive; NOT founded on knowledge or on memories, but on automatic conxns b/t a stimulus and a response
  • neural substrate – striatum (in the forebrain) – w/c receives extensive conxns from sensory systems and sends fibers to cerebral structures that communicate to the premotor cortex
    • The actual structural change responsible for LTM is described as, initially, a cell assembly that reverberates (STM). Structural changes and consolidation are a result of reverberation, which are then responsible for LTM.
  • damage to striatum has been show to impair habit formation

Criticisms of Mishkin’s Theory:

  • Does not address retrograde amnesia
  • Work was based on a very few simple experiments (i.e., delayed nonmatching to sample with monkeys)
  • Later work by Squire and Zola-Morgan suggest that it is the entorhinal cortex that is actually necessary for LTM, not the amygdala or hippocampus

Diencephalon (thalamus and hypothalamus)

  • damage can occur from Korsakoff’s syndrome, strokes, injuries, infections and tumors.
  • receive fibers running from the hippocampus and the amygdala (so directly connected to the memory systems)

The Amygdala

  • has connections with all sensory systems and communicates with the thalamus
  • also, the same parts of the amygdala on w/c sensory inputs converge to send fibers into the hypothalamus (the source of emotional responses) – thus, the amygdala links sensory experiences and emotions
    • animals w/ damage to amygdala lose fear of humans and even aversion to sensations such as pinching; they also have trouble remembering the positive associations of a familiar stimulus
  • memories are not sensory specific (e.g., sound of a voice will summon a memory of the person’s face; or a smell of a food will summon memories of its appearance, texture and taste); the amygdala mediates the association of memories formed through different senses


Memory is not unitary, but depends on the operation of potentially independent, but typically interactive, components; he argues that memory (like perception) consists of the operation of modules and central systems.


Each component aligns with different types of memory tests

  1. Nonfrontal neocortical component – made up of various perceptual and “semantic” modules; w/c mediate performance on item-specific, implicit tests of memory
  2. Basal-ganglia component – mediates performance on sensorimotor procedural tests of memory
  3. Medial-temporal/hippocampal component – mediates encoding, storage, and retrieval on explicit episodic memory tests (that are associative/cue dependent)
  4. Central-system frontal-lobe component – “works” with memory and mediates performance on strategic explicit and rule-based explicit tests

MODULES share several features:

  • Domain specificity (so damage to a specific area leads to impairment in purported domain)
  • information encapsulation – processes subserved by one module are not affected by deficits in other areas.
    • these two aspects support the criteria for “double dissociation”; i.e., each module is unique for a particular task
  • shallow output – output from a module is specific to the domain it covers; it has no meaning beyond the value assigned to it by the module. e.g., patients with associative agnosia can process faces visually but they cannot assign any meaning to the visual information computed

Thus, a module is essentially a stupid, closed computational device that delivers its shallow output to the interpretive central systems where meaning and relevance are assigned

CENTRAL SYSTEMS – unlike modules in that they:

  • integrate information from superficially dissimilar domains
  • are open to top-down influence
  • output is deep or meaningful
  • interlevel representations may be available to consciousness


According to Moscovitch, there are 2 classes of memory:

  • explicit (associative and strategic types)
  • implicit (procedural and item-specific types)
  1. Associative tests – test in which the cue is sufficient for retrieval (e.g., have you read the bible)?
  2. Strategic Tests – the cue does not automatically elicit the target memory, but only provides the starting point of a memory search (e.g., what did you do 2 weekends ago?)
  3. Procedural Tests – assess learning and retention of sensory-motor skills, procedures or rules.
  4. Item-specific tests – assess memory for a particular item, such as a certain word, face or object, by looking at the accuracy or speed of identification of the item when it is repeated


  • sensorimotor skills – should be retained in normal amnesic and demented patients with intact sensorimotor structures, but will be impaired if they have degenerative disorders associated with damage to the basal ganglia – part of extrapyramidal motor system (e.g., Huntington’s or Parkinson’s patients). But these same patients would perform normally on perceptual, item-specific implicit tests


Registration/recording (in this model) refers to the neocortical process involved in the forming of perceptual records or engrams necessary for implicit tests. (Thus, this differs from consolidation w/c involves long-term memory traces)

Perceptual Input Modules and Perceptual Repetition Priming (a module)

  • consistent with properties of modules discussed above, perceptual input modules restrict their information to a specific domain, are not affected by higher-order semantic information and the information is restricted to presemantic structural descriptions. (e.g., face-recognition system)
  • anatomical localization – posterior neocortex are sources for mediation of repetition-priming effects (there is both negative and evidence implicating these structures)
    • negative evidence – repetition-priming effects are well-preserved in amnestics (w/damage to medial temporal lobes/limbic structures)
    • positive evidence – domain specific agnosias and PET scans in normal people have supported this premise
  • exception: damage to the critical region for face recognition leads to impairments on both explicit and implicit tests of knowledge (they show no repetition-priming effects for faces). On the other hand, some patients (whose damage spares the crucial region) can respond differently to familiar and unfamiliar faces on implicit tests and show normal repetition-priming effects

Conceptual Repetition Effects and Semantic Records (a central system)

  • tasks differ from perceptual tests, b/c the target is not repeated at test (even in degraded form), rather it is elicited by semantic cues (e.g., a related word or a question).
  • influenced by semantic variables (so unlikely to be mediated by presemantic input modules) and are likely mediated by central systems which interpret the shallow output of perceptual modules and store a semantic record of their activity or representations
  • b/c they are mediated by interpretive central-system structures, conceptual, repetition-priming effects are reduced or absent in Alz. patients (despite intact perceptual priming). This pattern has also been seen in patients w/unilateral temporal lobectomies (BUT – damage to hippocampus leaves this process intact – so must be due to the cortex itself, not underlying subcortical structures)

The Hippocampal Component (a module for episodic, associative memory)

  • this component consists of a number of structures in the medial temporal lobes and diencephalon that form a circuit. These include (in addition to the hippocampus):
    • parahippocampal gyrus
    • entorhinal and perirhinal cortices
    • mammilary bodies
    • dorsomedial nucleus of the thalamus
    • cingulate cortex
    • fornix
    • amnesia is associated with bilateral damage to any one of these (except the fornix and cingulate where the evidence is unclear)
  • the domain of this module is consciously apprehended information (if an event does not receive full conscious attention, it is not processed by the hippocampal component)
  • b/c we don’t always know in advance what is worth committing to memory, the hippocampus is capable of encoding and storing information automatically as part of the process of consciously observing stimuli
  • the central idea of levels of processing theory (Craik & Lockhart) – that remembering is a natural by-product of cognition – follows directly from this view that the hippocampal component is modular. Thus what determines what will be remembered is not the intention to remember, but the extent to which events are attended and information is processed to a deep level and properly organized Paying close attention to the target and encoding it semantically makes it distinctive and makes its memory traces more easily retrievable.
  • the benefit of an automatic hippocampal component is that it does not draw cognitive resources away from other activities
  • disad of being modular – output is shallow; it is not interpreted properly in relation to other memories (i.e. spatial and temporal context or organizational memories – probably mediated by the frontal lobes)
  • this theory suggests, therefore, that a component of conscious recollection is no more intelligent or under voluntary control than perception.
  • damage to right hippocampal region (only) – associated with spatial memory loss
  • damage to left hippocampal region (only) – associated with loss of memory for verbal material

The Frontal Lobes (central systems and strategic explicit tests)

  • frontal lobes are necessary to convert remembering from a stupid reflexive act triggered by a cue (hippocampal module) to an intelligent, reflective, goal-directed activity under voluntary control
  • memory disorders of frontal lobes are not related to deficits in storage and retention (the hippocampal fxns), but with impaired organizational and strategic processes
  • deficits lead to problems with strategic explicit (and maybe some implicit) tasks. The tests are performed poorly not b/c the target event is forgotten, but b/c organization at encoding and strategic search and monitoring at retrieval id deficient


Evidence for double dissociation between medial temporal and frontal lobes (Winocur, Moscovitch, Stuss)

  • Not all aspects of memory fxn decline at the same rate during the aging process. This paper shows a fxnl double dissociation in old people b/t performance on implicit and explicit tests and performance on tests sensitive to different brain regions
  • explicit memories (which rely on recall or recognition techniques) – do not show a strong age difference (re: damage to hippocampus causes this kind of impairment)
  • implicit (or indirect) memory – is also generally preserved in the elderly, but there are some notable exceptions (e.g., word completion tasks after priming – as this paper shows)
  • implicit memory tests – measures performance that does not involve conscious awareness of any part of the prior experience (e.g., tests of general knowledge, skill learning and repetition priming in w/c exposure to a word biases subsequent identification in a word completion test)

Word Completion Tasks:

  • word-fragment completion – presents the complete word and then at test the subject is given a sample of the word’s letters (e.g., soldier; _o_ _i_ r)

– does not typically show an age difference

  • word-stem completion – still presented word at study period, but then at testing the first 3 letters of the word are presented (e.g., sol_ _ _ _)

– has been shown that elderly have less priming effects than younger subjects

  • since these two tests show different results in the elderly, it is believed that each task is mediated by different neural structures; that’s what this paper shows


  • age differences occur in word-stem completion but not in word-fragment completion tasks and the weakness in word-stem completion is correlated with tests of frontal lobe fxn
  • the dissociation of implicit memory tasks and explicit memory is not a new finding (previously seen in amnesics, and normals), but the finding that this correlates with frontal fxning is new; since frontal fxning was not involved in word-fragment completion, it suggests that 2 different processes underlie the 2 types of priming
  • therefore, they suggest that automatic and strategic processes can both contribute to conscious recollection and implicit memory
    • traditional belief is that automatic processes are associated with implicit memory and strategic processes with conscious recollection
    • if the cues on the implicit tests are inadequate and strategic search processes are necessary then the frontal lobes will b/c involved (and take over the automatic process led by the medial temporal lobes)
    • so, they suggests that word-completion tasks involve some strategic process (and, therefore, the frontal lobes), but that word-fragment tests do not because unlike initial stem letters, letters drawn randomly from the word are poor cues for locating words in the lexicon (believed to be mediated by posterior cortex)
  • this study also confirms previous studies that institutionalization exacerbates the process of cognitive decline associated with aging
  • the double dissociation of decline in different memory systems in the aging suggests that declines in performance with age can’t be attributed to a uniform effect across all fxns, nor to a selective effect on those most vulnerable in old age
    • in sum: age differences in word stem completion can be attributed to frontal lobes, but not medial temporal dysfxn, whereas the reverse is true of explicit tests of memory

Memory and Learning I

Learning and Memory

Learning and memory are not interchangeable terms; instead, they are complementary concepts. Memory is the behavioral change caused by an experience, and “learning” is how this happens. Learning is the process by which new information is acquired; memory is the process by which that knowledge is retained.


Learning can be divided into different processes that involve different modalities using different neuropsychological systems or neuroanatomical substrates: 1) Explicit learning and memory is the conscious acquisition of knowledge about people, places and things. It occurs in largely in diencephalic structures. 2) Implicit learning is the non conscious learning involving stimulus-response associations, such as classical and instrumental conditioning, motor learning and habit formation. It does not depend on the temporal lobe, but mainly engages brain circuits involving the basal ganglia, prefrontal cortex and amygdale.

Some basic forms of learning

  • Perceptual learning accomplished by changes in the sensory association cortex.
  • Stimulus-response learning involves establishing connections between circuits involved in perception and those involved in movement.
  • Motor learning a component of stimulus-response learning. Cannot happen without sensory assistance.
    • Perceptual learning is the establishment of changes within the sensory systems,
    • stimulus-response learning is the establishment of connections between sensory and motor systems,
    • motor learning is the establishment of changes within the motor systems.
  • Relational learning involves learning the relations among individual stimuli. Episodic and observational learning are forms of relational learning.

Learning and Synaptic Plasticity

The Hebb Rule (1949): if a synapse repeatedly becomes active at about the same time the post-synaptic neuron fires, changes will take place in the structure or chemistry of the synapse that will strengthen it.

Hebb’s Theory

  • Short-term memory (STM) is an active process of limited duration, while long-term memory (LTM) involves an actual structural change in the nervous system
  • Each psychologically important event is the flow of activity in a given neuronal loop
  • The synapses in a particular path become functionally connected to form a cell assembly (a system that is initially organized by a particular sensory event but is capable of continuing its activity after the stimulus has ceased)
  • Cell assembly must be repeatedly activated – after initial sensory input, assembly reverberates
  • Structural changes: STM is reverberation, LTM is lasting structural change
  • Consolidation: 15 min-1 hour in which assembly is undisturbed and undergoes structural changes
  • Any assembly can be excited by others

Lomo (1966) discovered that intense electrical stimulation of axons leading from the entorhinal cortex to the dentate gyrus caused a long-term increase in the magnitude of excitatory post-synaptic potential in the post-synaptic cells (long-term potentiation; LTP). LTP occurs when the postsynaptic cell is depolarized at the same time it is being stimulated – NMDA receptors only open when glutamate is in the cleft an the postsynaptic membrane is depolarized simultaneously

Additionally, when weak and strong synapses to a single neuron are stimulated at approximately the same time, the weak synapses become strengthened (associative long-term potentiation; ALTP).

LTP and ALTP require two things:

  • Activation of synapses
  • Depolarization of the post-synaptic neurons
  • Many experiments have demonstrated that LTP in hippocampal slices follows the Hebb rule. Additionally, LTP has been demonstrated in numerous other brain regions, including the prefrontal cortex, piriform cortex, entorhinal cortex, motor cortex, visual cortex, thalamus, and amygdala. NMDA (a specialized glutamic receptor that controls a calcium channel), is involved in LTP in most cortices.
  • Post-synaptic and pre-synaptic changes are two of several mechanisms that account for the increases in synaptic strength during LTP.
  • Several studies have shown that NMDA-mediated LTP increases the number of post-synaptic AMPA receptors (specialized glutamic receptor that controls a sodium channel).
    • This increase makes the post-synaptic membrane of the dendritic spine more sensitive to the release of glutamate by the pre-synaptic terminal button, thereby strengthening the synapse.
    • The LTP produced by the activation of NMDA receptors is initiated post-synaptically by the entry of calcium ions, but the entry of calcium activates special calcium-dependent enzymes known as protein kinases.
  • Pre-synaptic changes also occur by means of nitric oxide (NO) synthase, which is theorized to be a retrograde messenger involved in long-term potentiation.

Summary: entry of calcium ions through channels controlled by NMDA receptors activates at least two calcium-dependent protein kinases. These enzymes may activate processes that produce post-synaptic changes that cause the insertion of AMPA receptors into the post-synaptic membrane. Additionally, the entry of calcium activates a calcium-dependent NO synthase, and the newly produced NO then presumably diffuses out of the dendritic spine, back to the terminal button, where it induces pre-synaptic changes.

Location of Synaptic Change

If morphological change in neurons is the basis of memory, which neurons are modified by experience? Three issues address this question…

  1. A sensory experience cannot change every neuron in the relevant system. It is logical to assume that experiences will more likely affect higher level sensory areas than lower level sensory areas.
  2. Sensory experiences change sensory systems, allowing us to remember ideas or thoughts. However, the mechanism by which we remember is probably located elsewhere.
  3. Experiences result in widespread changes in synapses, but how we “find” a specific memory is probably related to the cortical and subcortical storing of memories and to the notion that memory is a multiple component system.


Memory is a process that results in a relatively permanent change in behavior. Events are not stored in toto; only certain critical elements are stored from which the event is reconstructed. The more cues or elements provided contextually, the more exactly the event can be reconstructed and “remembered.”


NP study of memory dates back to about 1915, when Lashley looked to identify the neural locations for learned habits. After years of study, dissection and neurosurgical experiments, he concluded: “it is not possible to demonstrate the localization of a memory trace anywhere in the nervous system. Limited regions may be essential for learning or retention of a particular activity, but … the engram is represented throughout the region.”

In 1953, a neurosurgeon, William Scoville (and his colleague Brenda Milner) made one of the most influential discoveries when he removed H.M.’s bilateral hippocampi (medial temporal lobes), rendering him unable to remember any events following the surgery. This surgery did not remove previous memories but interfered with the formation or retrieval of new memory. Subsequently, the study of memory shifted from trying to find its location in the brain to looking at how memory is formed and stored.

DEFINITIONS (simplified)

Sensory Memory – lasts only seconds

  • Echoic memory – auditory immediate memory
  • Iconic/eidetic imagery – visual immediate memory

Short-Term Memory – refers to the capacity for holding a small amount of information in mind in an active, readily available state for a short period of time. In some theories of memory, thought to be a separate system from long-term memory.

Long-Term Memory – corresponds best to the layperson’s conception of memory.

Consolidation – The process by which “new memories” (which are initially ‘labile’ and sensitive to disruption) undergo a series of processes (e.g., glutamate release, protein synthesis, neural growth and rearrangement) that render the memory representations progressively more stable.

Encoding – active organization or manipulation of incoming stimuli, such as visual imagery, mnemonics, rehearsal and repetition.

Retrieval – ability to access previously stored information; “tip of the tongue phenomenon,” state-dependent learning and memory

Forgetting – passive decay and interference;

  • Proactive interference – previously learned information interferes with current learning
  • Retroactive interference – recently learned information interferes with ability to remember previously learned information.

Amnesia – partial or total loss of memory abilities.

Retrograde amnesia (RA) – difficulty recalling events prior to amnesia onset; seen with diencephalic lesions (i.e., mammillary bodies, thalamic nuclei, and interconnecting pathways)

Anterograde amnesia (AA) – inability to recall events subsequent to amnesia onset; seen with hippocampal damage (bilateral + amygdala). Immediate recall does not require temporal lobe.

Ribot’s Law – oldest memories are the most resistant to amnesia

Priming – unconscious facilitation of performance due to prior exposure to stimuli. Works in normals and amnesics. Involved in error-free learning.

Metamemory – frontal process; “feeling of knowing”

Recent Memory – memory stored within last hours-months

Remote Memory (aka tertiary memory) – memory from earliest years of one’s life

Episodic memory – autobiographical form of memory for contextually specific events tied to time and place

Semantic memory – generalized world knowledge not tied to time or circumstance, linguistic skill, and vocabulary


  • Explicit (declarative) memory – available to awareness; conscious/intentional recollection process; information that can be stated explicitly (or declared), that can be brought to mind as an image or proposition in the absence of ongoing perceptual support, and/or of which one is consciously aware. Comprises both episodic & semantic material. This is what patients complain about, and it is not very amenable to treatment. Involves hippocampus and surrounding structures, and amygdala.
  • Aspects of Declarative Memory
  1. Retrieval – “remembering”
    1. Recall – active, complex, search process
    2. Recognition – always easier; stimulus triggers
  2. Material-specific – may forget only verbal or nonverbal, etc.
  3. Episodic (event) – one’s own experiences; unique and localizable in time and space. vs. Semantic – what is learned as knowledge; “timeless/spaceless”
  4. Automatic – passive learning (e.g., digits forward) vs. Effortful – learning with active, effortful processing (e.g. digits backwards)
  5. Source (contextual) – knowledge of where or when something was learned; may be a form of incidental memory
  6. Prospective – involves the “what” knowledge of declarative, and executive function; ability to remember to do something at a particular time
  • Implicit (Nondeclarative/Procedural) memory – reflects a constellation of abilities, such as the acquisition of motor or cognitive skills, classical conditioning, habituation, and priming. “Habit” memory. Learning without conscious awareness (see Squire, 1986, 1987). Relatively spared even in severe amnesics, except in PD and basal ganglia pathology. Can use this to chain habits.
  • Aspects of Procedural Memory
    • Falls under Implicit Memory – knowledge that is expressed in performance without subject’s awareness they possess it
    • Corpus striatum is key component; implicit memory usually unimpaired even in dense amnesia; not available to conscious awareness;
    • “Habit system” (e.g., walk, talk, dress, eat, etc.)
    • 3 categories: learning of these skills/procedures does not take conscious effort
      • Skill Memory – motor and cognitive skill learning and perceptual; “how to” learning
      • Priming – form of cued recall; prior exposure facilitates response without awareness
      • Classical Conditioning


Cermak (1984) – suggested that the episodic/semantic distinction helped explain temporally graded RA, whereby biographical material becomes progressively more semantic as it ages because it is retold and elaborated. This resembles the consolidation theory of memory, but implies that cognitive not automatic physiological processes result in the storage of memories.

  • Notably, recent evidence (Cermak; Butters; Zola-Morgan) suggests that many amnesic patients suffer impairments of semantic and episodic memory; thus, amnesia is probably not accurately described as an exclusively episodic deficit. Also, episodic and semantic memories are neither easily dissociable nor universally agreed upon.
  • Information-Processing Model Information processing model has several stages.
  1. Attention – alertness/arousal [brainstem, subcortical], focusing (preparedness), sustained (vigilance); more or less vulnerable to interference (distractibility) [thalamus or frontal], divided (allocate resources)
    1. working memory – hold info. in temporary storage and manipulate
  2. Encoding – In this process, information is received or registered through one or more of the senses and modified for entry into the memory system. The level of analysis/modification affects the likelihood of recall (e.g., deep –> semantic; shallow –> phonological) [language or visual processing systems; frontal; diencephalic structures – dorsomedial nucleus]
  3. Storage – transfer of transient memory to form or location for permanent storage/access [hippocampus/mesial temporal lobe]; facilitated by:
  4. Consolidation – construct; integrate new memories into cognitive/linguistic schema
  5. Retrieval – search/activate memory traces; monitor for accuracy and appropriateness
  • Baddeley’s (2000) Working Memory Model (Model of Short Term Memory)
    • Composed of three main components—the central executive which acts as supervisory system and controls the flow of information from and to its slave systems: the phonological loop and the visuo-spatial sketchpad. The slave systems are short-term storage systems dedicated to a content domain (verbal and visuo-spatial, respectively). In 2000 Baddeley added a third slave system to his model; the episodic buffer.
      • All are considered Fluid Systems that link to long-term memory, entailed in Visual Semantics, Episodic Long-Term Memory, and Language, which are considered crystallized systems.
  • Atkinson and Shiffrin’s 3-Stage Model of Declarative Memory
  1. Registration/Sensory Memory (milliseconds)
    1. Holds info for 1-2 seconds (in sensory store); not just memory or perception
    2. First traces: visual image (iconic memory) or auditory replay (echoic memory)
    3. Further processing depends on affect, set, & attention-focusing components
  2. Stage 2 — Short Term Memory
    1. Immediate Memory (1st stage of STM; 30 sec. to several minutes)
      1. Limited capacity store (+/- 7 bits of information)
      2. Then transfer to more permanent storage
      3. Info is maintained in reverberating neural circuits (two outcomes: more stable biochemical organization = LTM; dissipates = no memory)
    2. Rehearsal (hours) (Repetitive mental process that serves to lengthen duration of a memory trace that increases likelihood of permanent storage
    3. Longer Impermanent Memories (1 hour – 1or 2 day) This may just be brand-new LTM, and therefore vulnerable to interference
  3. Long-Term Memory (LTM, aka secondary memory)
  • General concepts in this model
    • LTM is the ability to store information
    • Concept of amnesia – intact STM capacity, impaired LTM
    • consolidation – process of storing information as LTM; what is “learned” is consolidated
    • incidental learning – requires no directed effort
    • LTM is organized based on meaning, STM is organized based on sensory properties
    • LTM occurs at a cellular level – alterations in neuron, synapse, elaboration of dendrite, pruning with disuse (i.e., no single storage site)


Note: Chapter 21 on Amnesic Syndromes in Clinical Neuropsychology: A Pocket Handbook for Assessment provides several nice tables that address neuroanatomic distinctions in, neurological illnesses associated with, and evaluation of amnesia. Also, Chapter 15 on Amnesic Disorders in Clinical Neuropsychology and Chapters 35 and 36 in Behavioral Neurology and Neuropsychology are excellent…

• Disorders may be transient (e.g., EtOH, toxic, TIA, seizure, ECT), in which memory disturbance is temporary but memories never regained, or permanent (e.g., TBI, attention deficit, Korsakoff’s, hypoxia, bilateral t-lobe damage)

Functional Amnesia

  • AA does not usually occur
  • RA is extensive and frequently includes loss of personal identity and can be limited to autobiographical memory.

Organic Amnesia

  • AA is severe without loss of personal identity (just the opposite in functional amnesia)
  • RA (plus public event and autobiographical memory) is usually temporally graded
  • Causes include temporal lobe surgery, chronic alcohol abuse, brain injuries, anoxia or ischemia, encephalitis, epilepsy, tumor, or cerebrovascular accident (stroke). Significant problems with new learning occur after bilateral temporal damage.

Transient Global Amnesia

  • Profound AA problems and variable profiles of RA, perhaps because of retrieval problems
  • Associated with decreased perfusion to the medial temporal or diencephalic regions
  • No clear etiology, but believed to be transient disturbance in the medial temporal lobe and/or diencephalon
  • Does correlate with migranes, but migraine and transient global amnesia do not share the same etiology
  • Onset is often abrupt, and may follow emotional or physical strains
  • Occurs after ECT; AA can be quite severe (esp. bilateral ECT). Recovery of new learning capacity occurs within several months after ECT, but some patients demonstrate residual deficits
  • People whose transient global amnesia is not secondary to ECT generally regain ability to form new memories, although they will not recall events that occur during the amnestic period

Medial Temporal Lobe Amnesia

  • Historically, described as having preserved insight, increased rates of forgetting, limited RA, and lack of confabulation.
  • Recent studies have underscored an association between severity of RA and extent of hippocampal (and adjacent cortices) pathology.
  • Causes include anoxia, limbic encephalitis, stroke, and probable Alzheimer’s disease. H. M. is the primary example.

Diencephalic Amnesia

  • Deficits in the initial processing stages of memory
  • Confabulation
  • Sensitivity to proactive interference
  • Lack of insight into the memory disturbance
  • Rate of forgetting may be normal. Remote memory is variably affected (some – minimal; others – severe problems in retrieval for events immediately predating the onset of amnesia.
  • Causes – infarctions of thalamic arteries, trauma, diencephalic tumors, and Korsakoff’s syndrome. Patients with thalamic amnesias demonstrate frontal pathology, which may also contribute to confabulation and lack of insight.

Frontally-related Amnesia

  • Attentional deficits adversely affect encoding and retrieval (therefore, some demonstrate RA).
  • Retrieval may be normal, suggesting that consolidation is relatively intact.
  • Unawareness of memory problems and tendency to confabulate are common.
  • Also includes proactive interference, poor contextual memory, and poor semantic categorization. [see Baddeley’s (2000) working memory model]


Memory problems can occur in a number of neurological (and psychiatric) conditions. Such conditions include:

  • Anoxic/hypoxic encephalopathy
  • Anterior communicating artery aneurysm/stroke
  • Herpes simplex encephalopathy
  • Posterior cerebral artery stroke
  • Surgical intervention
  • Wernicke-Korsakoff Syndrome

Anoxic / Hypoxic encephalopathy

This condition may occur following any disruption in oxygen satruation to the brain. Typically, five minutes or more without oxygen can permanently damage the brain. The medial temporal lobes are particularly sensitive to oxygen depletion. New learning is often impaired, while remote memory remains intact.

  • Frontal watershed cortex and basal ganglia structures often involved.
    • May result in perceptual, motor and executive deficits
  • Deficit in memory often one of retrieval rather than encoding.
    • These folks benefit from cues and recognition formats.

Anterior Communicating Artery Aneurysm

Persons with ACoA aneurysm may experience the following:

  • Amnesia
    • most likely secondary to basal forebrain damage
    • disorientation
    • confabulation common due to frontal systems involvement
    • attentionally based memory problems, again due to frontsl systems involvement
  • Apathy

Herpes Simplex Encephalitis

Herpes is most common cause of nonepidemic, sporadic viral encephalitis in the US.

  • Diagnosed by ID of virus in CSF or brain tissue through biopsy
  • Brain involvement diffuse
    • petechial hemorrhages and necrosis throughout medial temporal and inferior frontal lobes
      • may include hippocampus, parahippocampus,insula, basal forebrain, mammillary bodies, fornix.
  • Persons with HSE initially show confusion, aphasia, agnosia and impaired memory
    • may resolve over time to memory and learning problem, dependent on location of lesions.
  • Typical pattern of memory problems includes both verbal and nonverbal material, with severe retrograde amnesia

Posterior Cerebral Artery Stroke

Memory problems occur secondary to bilateral posterior cerebral artery stroke

  • Posterior cerebral artery irrigates medial temporal lobes and posterior occipital lobe
  • Material specific memory loss depending on laterality of lesion
    • Memory problems also noted on unilateral left PCA stroke but not well studied to this point
  • Other cognitive deficits may also be seen, including visual deficits, hemianopic alexia, color agnosia and object agnosia
    • more likely if lesion extends to occipitotemporal cortices

Surgical intervention

After Scoville’s surgical removal of HM’s bilateral thalami, many, many studies evolved on the nature of the memory impairment that HM experienced. Following this knowledge, surgical intervention for intractable seizures continues, but is usually restricted to unilateral ablation.

  • Surgery usually done after careful neuropsychological and neurological work-up
    • Typically includes intracarotid amobarbital studies to minimize or avoid new learning problems

Wernicke-Korsakoff’s Syndrome

Wernicke’s encephalopathy is an acute medical condition, often called Wernicke-Korsakoff’s Syndrome. It is usually the result of chronic alcohol abuse and thiamine deficiency. It is recognized by a classic triad of gait ataxia, oculomotor problems (nystagmus) and confusion, often exhibited in incoherent speech and disorientation. Treatment with thiamine usually leads to clearing of the ataxia and disorientation/acute confusion, but there may be persistent memory problems/amnesia, personality changes and other cognitive problems. There may be several mechanism of the memory problems, including nutritional deficits.

The residual memory problems are called Korsakoff’s syndrome. This is an example of diencephalic amnesia. Major symptoms include:

  • Anterograde amnesia – will have no recollection of what happened even 1/2 hour ago; involves intentional, episodic, or declarative memory
  • Retrograde amnesia – extensive impairment of remote memory which covers most of their adult life
  • Confabulation – rather than admit memory loss; often based on past experiences and are therefore often plausible
  • Meager content in conversation – little to say in spontaneous conversation
  • Visual-spatial deficits
  • Sensory processing deficits
  • Lack of insight into their deficit
  • Apathy – lose interest in things quickly and generally appear indifferent to change; tend to lack the impulse to initiate activity
  • Intact: incidental, semantic, or procedural memory.
  • In addition, people with Korsakoff’s syndrome may tend to be:
    • disoriented to time and space
    • often sit doing nothing even when they talk about wanting to do something
    • emotionally flat; if sad worrisome or even happy issues are brought to their attention they will display somewhat appropriate response but the arousal is only transitory

Neuropathology of Korsakoff’s

  • Bilateral damage along the diencephalon midline, esp. dorsomedial thalamic nuclei and mammilary bodies
  • Highlights importance of the medial thalamus for memory function, including the dorsomedial nucleus, anterior nucleus, and connections and structures within the internal medullary lamina.
  • Generalized cerebral atrophy
  • Believed to have a diencephalic lesion and frontal lobe deterioration (shown in CT scans and by test performance)

Differences b/t Temporal Lobe Amnesia and Korsakoff’s

  1. TL amnesics show normal release from proactive interference; diencephalic amnesias do not
  2. Korsakoff’s patients have extensive loss of remote memory; TL amnesics do not
  3. Moscovitch has suggested that Korsakoff’s patients also have frontal lesions (based on CT scans showing frontal atrophy)


More information can be found on the page called Neuroanatomy of Memory



  • bilateral ECT usually induces memory changes and effect on memory can be cumulative
  • effects seem to be reversible w/a return to pretreatment levels w/in 6 – 7 months
  • subtle defects may persist, usually in autobiographical info

Limbic System

Limbic System: Homeostasis, Olfaction, Memory, and Emotion

Anatomical and Clinical Review

  • Limbic system includes cortical and subcortical structures which are located mainly in medial and ventral regions of the cerebral hemispheres

Simplification of Limbic Functions and Corresponding Key Structures

Limbic Functions Key Structures
Homeostasis, autonomis and neuroendocrine control Hypothalamus
Olfaction Olfactory Cortex
Memory Hippocamplal Formation
Emotions and Drives Amygdala
  • mnemonic: HOME (Homeostasis, Olfaction, Memory, Emotion)

Main Components of the Limbic System

  • Limbic Cortex
    • Parahippocampal gyrus
    • Cingulate gyrus
    • Medial orbitofrontal cortex
    • Temporal pole
    • Anterior insula
  • Hippocampal Formation
    • Dentate Gyrus
    • Hippocampus
    • Subiculum
  • Amygdala
  • Diencephalon
  • Basal Ganglia
  • Basal Forebrain
  • Septal Nuclei (includes the nucleus accumbens)
  • Brainstem
  • Olfactory Cortex

Overview of Limbic Structures

  • Limbic cortex
    • forms a ring like limbic lobe around the edge of the cortical mantle, which surrounds the corpus callosum and upper brainstem-diencephalic junction
    • The limbic cortices share immunological markers. The herpes simplex virus has a tropism for limbic cortex and can cause severe encephalitis involving predominately limbic cortex or limbic association cortex
  • Amygdala
    • serves important functions in emotional, autonomic, and neuroendocrine circuits of limbic system
  • Diencephalic structures
    • participate in all functions of the limbic system
  • Basal Ganglia
    • ventral portions process limbic information
  • Basal Forebrain and Septal Region
    • contains cholinergic neurons that project to the hippocampus and cortex
    • nucleus basalis of Meynert (inside the substantia innominata) contains cholinergic neurons and is a major site of degeneration in Alzheimer’s Dementia
  • Hippocampal Formation
    • the medial and dorsal continuation of the parahippocampal gyrus
    • forms the floor of the temporal horn of the lateral ventricle
    • one of several C-shaped structures in the limbic system
    • unlike the 6-layered neocortex, the hippocampal formation has only 3 layers and is called archicortex
      • about 95% of the cortex in humans is 6 layered neocortex (also called isocortex meaning “same cortex)
      • more phylogenetically ancient forms of cortex, which do not have 6 distinct layers, are referred to as allocortex (i.e., “other cortex”)
  • Olfactory System
    • bipolar olfactory receptor neurons in the olfactory mucosa are activated by odor and send unmeylinated axons in the olfactory nerves to the olfactory bulb
    • without any relay in the thalamus, stimuli are sent directly to the ipsilateral and contralateral olfactory bulbs
    • Information then relayed in part to the orbital cortex, anterior entorhinal cortex (involved in memory) and amygdala, but not directly to the hippocampus

The Rhinencephalon – “nose brain” – term formally used from many limbic structures, but which is now more appropriately used only for the structures involved directly in olfaction

  • Hippocampal Formation and Other Memory Related Structures
    • Critical regions involved in memory formation, consolidation and retrieval:
      • Medial temporal lobe memory areas – including hippocampal formation and adjacent cortex of the parahippocampal gyrus
        • Hippocampal formation – has an elaborate curving S shape on coronal sections, which inspired the term hippocampus (meaning sea horse). Consists of 3 components (although sometimes “hippocampus” is used to refer to all 3 components): Dentate gyrus, Hippocampus, Subiculum
        • Parahippocampal gyrus – includes several cortical areas with connections to the hippocampal formation, the most important of which is the entorhinal cortex (Brodman’s area 28), which is the major input and output relay between association cortex and the hippocampal formation
      • Medial diencephalic memory areas – including the thalamic mediodorsal nucleus, anterior nucleus of the thalamus, internal medullary lamina, mammillary bodies, and other diencephalic nuclei lining the 3rd ventricle
      • White matter network connections – are also essential for normal memory function as these 2 regions are interconnected with one another and with widespread regions of cortex
      • Basal forebrain – may also play a role in memory through its widespread cholinergic projections but effects of lesions may be explained by damage to nearby white matter fibers….
  • Long-Term Potentiation
    • Long-term potentiation – a form of synaptic plasticity found in the hippocampal formation in which high frequency activity causes a long-lasting increase in synaptic strength between the involved neurons
      • It is believed that this property allows these synapse to perform an associative function, similar to the learning rule proposed by the psychologist Donald Hebb
      • Hebb Rule – “when an axon of cell A excites cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells so that A’s efficiency as one of the cells firing B is increased”—i.e., neurons that fire together wire together.
      • LTP has also been demonstrated at synapses in other areas of the nervous system. Also, many other forms of excitatory and inhibitory, short-term and long-term synaptic modulation have been described

Input and Output Connections of the Medial Temporal Lobe Memory System

  • History note: James Papez first described a circuit involving several of the following input and output structures (the Papez circuit) which led to the development of the concept of the limbic system in the 1950’s.
  • Main input to hippocampal formation: entorhinal cortex
    • Information travels from the association cortex in the 4 lobes to the entorhinal cortex in order to provide input to hippocampal formation
    • These inputs are thought to contain higher order information from multiple sensorimotor modalities which are processed further by temporal structures for memory storage
  • The memory storage process – is believed to occur NOT in the medial temporal structures, but in the association and primary cortices that allow a particular memory to be reactivated
  • Main output pathways occur via the subiculum:
  • projection from the subiculum
    • entorhinal cortex
    • back to the multimodal association cortex
    • subiculum
    • fornix (“arch”—follows curve of corpus callosum & lateral ventricles)
    • mammillary nuclei, diencephalon (directly from fornix and via mammilothalamic tract) &
    • septal nuclei
  • Hippocampal commissure – allows inputs to reach the hippocampus from the contralateral hippocampus

Memory Disorders

Patient HM

  • 27 y.o. male in 1953 underwent a bilateral resection of the medial temporal lobes including the hippocampal formation and parahippocampal gyri to control his medically refractory seizures
  • seizures improved, but he had severe anterograde memory problems
    • unable to learn new facts or recall new experiences
    • could recite 3-4 words back immediately, but no recall after 5 minutes even with cues – did not even remember the list had been given to him in the first place
  • Personality and IQ testing were normal
  • memory of remote events from childhood up to several years prior to the surgery was intact – no recollections from that point on (reflecting some degree of retrograde amnesia—see below)
  • procedural memories intact (e.g., mirror writing)
  • In part because of H.M., bilateral medial temporal lobe resection has been replaced with unilateral resection

Lessons Learned from H.M. – Classification of Memory and Memory Disorders

  • Declarative vs. nondeclarative memory
    • Declarative or explicit memory involves conscious recollection of facts and events
    • Nondeclarative or implicit memory involves nonconscious learning of skills, habits, and other acquired behaviors (e.g., priming, classical conditioning)
    • HM lost declarative memory but his nondeclarative memory remained intact
  • Amnesia – typically refers to loss of declarative memory which is related to bilateral medial temporal lobe or bilateral medial diencephalic lesions.
    • Unilateral lesions do not usually produce severe memory loss, although unilateral lesions of the dominant hemisphere can cause deficits in verbal memory
    • Specific/localized lesions rarely cause selective loss of nondeclarative memory
      • Learning of skills involves plasticity in several areas, including basal ganglia, cerebellum, and motor cortex.
      • Caudate nucleus appears important in habit learning – note that caudate pathology also linked to OCD.
      • Cerebellum appears to be involved in classical conditioning; amygdala involved in conditioned fear.
  • Temporal aspects of memory and memory loss
    • Different anatomical regions of the brain are important for storing memories at different times
      • Memories stored for <1 sec. (“attention” or “registration”) – involve the brainstem-diencephalic activating systems; frontal-parietal association networks and heteromodal cortices
      • Seconds – Minutes (working memory) – dorsolateral PFC; specific unimodal and heteromodal cortices
      • Minutes to years (“consolidation”) – medial temporal & diencephalic structures; specific unimodal and heteromodal cortices
      • Years – specific unimodal and heteromodal cortices
    • Immediate recall, attention, working memory do not depend on medial temporal or diencephalic systems
    • Medial temporal and diencephalic structures appear to mediate the process by which declarative memories are consolidated in the neocortex. Ultimately, declarative memories can be recalled through activity of the specific regions of neocortex without requiring medial temporal/diencephalic involvement
  • Anterograde amnesia – deficit in forming new memories
  • Retrograde amnesia – loss of memories from a period of time before the brain injury
    • The phenomenon of retrograde amnesia suggests that recent memories for a period of up to several years are dependent upon normal functioning of the medial temporal and diencephalic structures while more remote memories are not
    • Ribot’s law – vulnerability of memory loss is inversely related to age of memory
    • HM’s pattern of combined retrograde and anterograde amnesia is typical of lesions of the medial temporal lobe or diencephalic memory systems (although it can also be seen in concussion or other diffuse disorders)

Differential Diagnosis of Memory Loss

  • Memory loss caused by cerebral contusions – often involve the anteromedial temporal lobes and basal orbitofrontal cortex, thereby resulting in permanent deficits in memory
  • Concussion – associated with reversible memory loss, except for the hours around the time of the injury
  • Infarcts/ischemia – can cause memory loss, especially when bilateral medial temporal or diencephalic structures are affected (medial temporal lobes are supplied by distal branches of the PCA – thus arterial lesions at the top of the basilar artery are well positioned to cause bilateral medial temporal or diencephalic infarcts)
  • Anoxia – hippocampus is particularly vulnerable to anoxic injury
  • Rupture of ACA aneurysm – can damage basal forebrain – causing memory loss and other deficits seen in frontal lobes. Unclear in these patients if memory loss is due to damage to basal forebrain, medial diencephalon, frontal lobes, or a combination of these
  • Wernicke-Korsakoff Syndrome – caused by thiamin deficiency; bilateral necrosis of mammillary bodies and a variety of medial diencephalic and other periventricular nuclei
    • Acutely, will present with a triad of : ataxia, eye movement abnormalities (horizontal gaze paresis, nystagmus, opthalmoplegia) and confusional state (mnemonic: “ace”)
    • Severe cases can result in coma or death
    • Survivors left with anterograde and retrograde amnesia thought to be due to bilateral diencephalic lesions
    • Usually have other neuropsych deficits suggestive of frontal lobe dysfunction such as impaired judgment, initiative, impulse control and sequencing
    • In contrast to patients with pure medial diencephalic/temporal lesions these patients often lack awareness of memory deficits and tend to confabulate (presumed to be related to additional frontal dysfunction)
  • Complex partial and generalized tonic-clonic seizures – often associated with loss of memory for events during seizure and post ictal period; memory between seizures may be normal unless seizures are severe or there is some hippocampal sclerosis
  • ECT – during treatment period patients develop retrograde and anterograde amnesia similar to that seen in patients with bilateral temporal/diencephalic lesions. Amnesia gradually resolves after treatment; but residual memory loss around treatment period generally remains (both anterograde and retrograde)
  • Transient Global Amnesia – abrupt development of retrograde and anterograde amnesia with no obvious cause and no other deficits.
    • Episodes often occur with physical exertion or emotional stress. Amnesia typically lasts about 4 – 12 hours after which patient fully recovers except for permanent memory loss for a few hour before and after onset.
    • In about 85%, no recurrence.
    • Cause unknown.
      • EEG does not show epileptic activity during episode.
      • History of migraine is common, thus, a migraine-like mechanism has been proposed
      • Functional imaging studies show decreased blood flow or decreased glucose metabolism in medial temporal lobes and other areas during episodes.
      • Kaufman proposes that transient global amnesia due to TIAs in posterior circulatory system
  • Alzheimer’s – memory loss for recent events prominent, which may occur due to preferential affect on bilateral hippocampal, temporal, and forebrain structures.
  • psychogenic amnesia – can occur in dissociation, repression, conversion, malingering
    • Typically have memory loss for events of emotional significance rather than a pattern of retrograde and anterograde amnesia surrounding incident
  • Infantile amnesia – inability for adults to recall events from the first 1-3 years of life; actual cause unknown, but believed to be due to result of ongoing central nervous system maturational processes like myelination
  • Benign senescent forgetfulness – “normal” decline in memory function that occurs gradually with age

The Amygdala: Emotions, Drives, and Other Functions

  • As discussed above, plays a pivotal role in the emotions and drives. However, also is an active participant in all four major limbic functions due to its connections to other structures in the limbic system
  • Amygdala is important for attaching emotional significance to stimuli perceived by the association cortex
  • When both amygdalas have been ablated, behavior tends to be placid
  • Kluver-Bucy syndrome – nonaggressive behavior, together with other “behavioral changes” (hyperorality, hypersexuality) occur in monkeys with bilateral lesions of the amygdala and adjacent temporal structures
  • Seizures involving the amygdala cause powerful emotions of fear and panic
  • While amygdala is involved in states of fear, anxiety and aggression, activity in the septal area appears to be important in pleasurable states
  • Reciprocal connections between the amygdala and hypothalamic and brain systems allow for autonomic control of heart rate, sweating, and other changes commonly seen with strong emotions
  • Although the amygdala appears to play an important role in attaching emotional significant to memories, does not appear to be related to development of other memory functions

Seizures and Epilepsy

*General seizure information was consolidated into Seizure notes, except for the following sections:

Clinical Manifestations of Partial Seizures in Different Brain Regions

  • Temporal Lobe:
    • Medial Temporal Lobe:
      • Indescribable sensation
      • Rising epigastrium (“butterflies” in the stomach)
      • Nausea
      • Déjà vu
      • Fear, panic
      • Unpleasant odor
      • Autonomic phenomena – tachycardia, pupillary dilation, piloerection, belching, palor, flushing
      • Bland staring with unresponsiveness
      • Lip-smacking, chewing, swallowing
      • Gestural automatisms
    • Lateral Temporal Lobe:
      • Vertigo
      • Inability to hear
      • Simple auditory hallucinations (buzzing, roaring engines)
      • Elaborate auditory hallucinations (voices, music)
      • Receptive or expressive aphasia
  • Frontal Lobe:
    • Nocturnal exacerbation common
    • Elaborate motor automatisms w/o loss of consciousness or postictal deficits are often misdiagnosed as psychogenic episodes
      • Dorsolateral Convexity
        • Contralateral tonic or clonic activity
        • Strong version (turning) of eyes, head, and body away from side of seizure
        • Aphasia (if dominant hemisphere affected)
      • Supplementary Motor Area
        • Fencing posture with extension of contralateral upper extremity
        • Other tonic postures
        • Speech arrest
        • Unusual sounds
      • Orbitofrontal & Cingulate
        • Elaborate motor automatisms
        • Unusual sounds
        • Autonomic changes
        • Olfactory hallucinations (orbitofrontal)
        • Incontinence (cingulate)
  • Parietal Lobe
    • Vertigo
    • Contralateral numbness, tingling, burning sensations
    • Sensations of movement or need to move
    • Aphasia
    • Contralateral hemineglect
    • Eyes and head may deviate toward or away from side of seizure
  • Occipital Lobe
    • Sparkles, flashes, pulsating colored lights
    • Scotoma or hemianopia in contralateral visual field
    • Visual hallucinations
    • Eye blinking

Interesting facts about the “Wada” test

  • As you already know…sodium amytal is injected directly into each common corotid artery, causing transient inhibition of injected hemisphere for upto 10 minutes
    • Testing memory:
      • In patients with normal bilateral medial temporal memory function, injection of one hemisphere will not eliminate memory, since the other hemisphere can compensate
      • When a medial temporal lobe is not functioning properly (e.g., due to sclerosis) injection of the contralateral hemisphere causes severe memory difficulties. Preserved memory with injection of the ipsilateral hemisphere is reassuring, as it suggests the contralateral hemisphere will be able to support memory function after resection of ipsilateral medial temporal structures
      • Interestingly, amytal is injected into the carotid artery, which (as you no doubt remember…) serves the ACA and MCA. BUT the medial temporal lobes are perfused by the PCA. So….not entirely clear why the Wada test should inhibit medial temporal function. It is believed that it may be because the large ACA/MCA perfusion inhibits most of the hemispheric cortex, white matter, and corpus callosum, thereby indirectly inhibit the medial temporal lobe – by cutting off its major sources of input

Anatomical and Neuropharmacological Basis of Psychiatric Disorders

  • Schizophrenia
    • Abnormalities of the limbic system, frontal lobes, and basal ganglia have been implicated
    • Both pathologic studies and MRI’s have demonstrated bilateral decreases in volume of limbic system
    • PET has shown decreased activation of dorsolateral prefrontal cortex
    • Dopamine abnormalities have also been implicated
  • Obsessive-Compulsive Disorder
    • The improvement of symptoms with serotonin-enhancing meds suggests a role for this transmitter
    • Imaging studies have shown abnormally increased activity in the basal ganglia (especially the head of the caudate) as well as the anterior cingulate gyrus and orbitofrontal cortex – these changes improve with pharmacological or behavioral treatment
    • Given the apparent involvement of the caudate, cingulate gyrus, and orbitofrontal cortex – some have compared it to a hyperkinetic movement disorder, but with unwanted thoughts or compulsions instead of movements
      • Indeed, there may be some overlap, since OCD is present in about 50% of Tourette’s syndrome, and can also occur in Huntington’s disease, Sydenham’s chorea, and other basal ganglia disorders
  • Anxiety
    • Anxiety disorders are thought to be associated with an increase in noradrenergic and sertonergic transmitter systems
    • GABA may also be implicated since symptoms can be controlled with benzodiazepines
    • Amygdala may also be involved with panic disorders
  • Depression and Mania
    • Structural and functional neuroimaging studies of depression have been contradictory, but there is some evidence of a global decrease in cerebral cortex activity – with a more prominent decrease in the frontal lobes
    • Neuroendocrine changes occur in depression as well – e.g., an increased release of cortisol in about 40% of patients

Learning Disabilities

Learning Disabilities

  • First observations and studies focused on reading disorders, as early as 100 years ago.
    • No diagnostic category of “LD” until 1960’s.
    • Original label was minimal brain damage/dysfunction.
    • Ongoing etiological debate: biological nature of disorder vs. failure of educational system (nature vs. nurture).
  • 1987 definition (is there a more recent one?):
    • a generic term that refers to a heterogeneous group of disorders manifested by significant difficulties in the acquisition and use of listening, speaking, reading, writing, reasoning or mathematical abilities, or of social skills.
    • These disorders are intrinsic to the individual and presumed to be due to central nervous system dysfunction.
    • Even though a LD may occur concomitantly with other handicapping condition (e.g., sensory impairment, mental retardation, social and emotional disturbance) with socioenvironmental influences (e.g., cultural differences, insufficient or inappropriate instruction, psychogenic factors) and especially with attention deficit disorder, all of which may cause learning problems, a LD is not the direct result of those conditions or influences.
    • LD is based on a discrepancy between “ought” (e.g., IQ score) and “is” (e.g., academic performance score). MUCH controversy exists over cut-offs.
  • No single etiology; may be due to genetic influences, congenital factors, prenatal injury, perinatal distress, early brain injury; range from no observable evidence to some objective evidence to frank CT evidence
    • Duffy’s BEAM studies showed bilateral abnormalities, mostly in frontal regions, patients with dyslexia
    • Hynd and Semrud-Clikeman have also shown morphological markers of ADHD and dyslexia on imaging studies
    • Geschwind noted a higher incidence of autoimmune disorders (e.g., SLE) in family members of LD individuals, LD is more common in males, and higher proportion of left-handed individual in LD population. Therefore, hypothesized that that LD may be linked to hormonal (testosterone) influences on the brain in utero, which serve to delay the development of the left hemisphere, leading to dyslexia and other language processing disorders and to the change to left-handedness. Higher autoimmune d/o frequency reflects concomitant influence of testosterone on development of immune system. Galaburda has followed up.


  • Brain functions are modular
    • which means that brain systems are specialized for processing specific kinds of information and that these modules are autonomous in function and neural representation
  • These modules are differentially vulnerable
    • if all brain systems were equally vulnerable we should find equal numbers of developmental disorders for each brain system – but we don’t. Some areas are more vulnerable than others
  • Exception – executive functions aren’t completely distinct from other modules; they can affect how well modules function, partly because they control attention
  • Symptoms are divided into 4 categories:
    • Primary – core symptoms, universal, specific and persistent
    • Correlated – same etiology/affect different brain systems (e.g., autism and mental retardation – many have MR, but it is not universal or specific to the disorder)
    • Secondary – consequences of primary or correlated symptoms
    • Artifactual – appear associated/not causally related


Domain Location Disorder
Phonological Processing Left perisylvian region Dyslexia
Executive Functions Prefrontal Region ADD
Spatial Reasoning Posterior Right Hemisphere Math/Handwriting
Social Cognition Limbic, Orbital, Right hemisphere Autism spectrum
Long-term Memory Hippocampus, Amygdala Memory disorder / Amnesia

According to Pennington, these domains account for nearly all the learning disorders.

    • The perisylvian region includes Wernicke’s area in the posterior left temporal lobe and Broca’s area in the premotor portion of the frontal lobe.
    • This is modality specific, so blind children can still develop spatial cognition.
    • Functions in this domain include
      • object localization;
      • spatial or visual memory;
      • attention to extrapersonal space;
      • mental rotations;
      • spatial construction
    • There are several brain regions which subserve this funtion
      • generation of visual information has a left posterior localization
      • transfer of info. to long-term memory involves the limbic system especially in the rt. hem.
      • Although verbal knowledge shows continuing increases into the later decades of life, spatial reasoning peaks in adolescence and then slowly declines thereafter.
      • dyslexia – traditional beliefs feel it represents some kind of visual or spatial problem, but recent research has strongly shown that most dyslexics have impaired phonological processing skills
    • Developmentally – traditionally seen as occurring quite late in normal brain development, but studies have shown there are some important changes which occur during the second half of the 1st year.
    • Development seems to roughly correspond to the Piagetian stages of cognitive development.
    • Thus the WCST will be harder for preschoolers and early elementary children because “number” is much less salient a dimension than form or color.
    • Pathologies which can involve executive functioning:
      • ADHD
      • Schizophrenia
      • Tourette’s syndrome; since children can delay tics they are sometimes viewed as a failure of inhibition. Some evidence suggests basal ganglia involvement (w/c has strong connections w/frontal lobe)
      • Autism
      • Early treated PKU – children will have normal IQ’s but a higher rate of learning and cognitive problems than controls (especially on measures of executive fxning)


  • Treats LD as a disorder of information processing (so does Denckla, Weintraub, et. al.)
  • This system can also account for ADHD, conduct disorder, savant, special talents, etc.
  • LD results from dysfunction in one of three possible neural systems:
    • Phylogenetically lower to higher centers
    • Posterior cortex to anterior cortex
    • Right-left dysfunction
    • Verbal Processing Disorder
      • Disruption of language skills in auditory or visual modality
      • Includes developmental dysphasia, dyslexia, dysgraphia, spelling disorders, and some types of dyscalculia
      • Associated with dysfunction or frank damage to language networks in left hemisphere
  • Nonverbal Processing Disorder
    • Disruption of ability to perceive or produce nonverbal information
    • Most notable in development of social-interpersonal skills
    • Well-developed language skills, but with poor mathematical abilities, nonverbal and visuospatial functions, and attention. May also have affective disorders.
    • Reflective of dysfunction in neurocognitive networks in right hemisphere
  • Attention Deficits Disorder (with or without hyperactivity)
    • Disruption of arousal-attention-concentration
    • May or may not have associated LD, or may do well or poorly across board
    • Associated with dysfunction in right hemisphere and/or bifrontal dysfunction and/or reticular activating system (i.e., neurocognitive network for attention)
  • Insight/Judgment/Comportment Disorder
    • Disruption of insight, judgment, comportment (“conduct disorder”)
    • Can’t learn rules of socially acceptable behavior and decision-making strategies
    • Stimulus-bound, concrete
    • May reflect deficient development of frontal networks


  • Autism vs. Asperger’s
    • in Autism VIQ is relatively depressed, whereas the opposite is true for Asperger’s (in this respect Asperger’s is more like a NVLD)
    • Basic Defining Characteristics – developmental disorders in w/c the main symptom is a severe deficit in social contact w/c emerges early in life and persists into adulthood (2/3 of autistic samples are MR, but most Asperger’s have nonretarded IQ’s)
    • Sex ratio for Autism is approximately 3:1 (males:females)
    • Often impaired on executive fxn tasks (e.g., WCST)
    • Etiology – possibly heritable; it is specifically associated w/fragile X syndrome, and untreated PKU; but environmental factors have also been implicated
    • Brain mechanisms – the neurological basis still unknown partly b/c of the debate over which deficit is the “core symptom”. Current evidence suggests that a dysfxn in the limbic systems and frontal lobes reduce appropriate social fxning and cause the primary symptom.
      • Studies have shown these children have enlarged ventricles (suggesting cortical atrophy)
      • Atrophy of the cerebellum
      • Theory of mind – is believed to be disrupted in autistic children. That is they have difficulty predicting other people’s beliefs or feelings
      • Treatment – re: that stimulant medication is contraindicated in some cases of autism as stimulant medications may worsen some autistic symptoms (such as stereotypies) in some patients


  • Basic definition – an unexpected difficulty in learning to read and spell (i.e., no obvious reasons for difficulty such as inadequate schooling, sensory handicap, ABI, or low FSIQ)
  • Reading involves:
    • visual perceptual processes
    • word recognition
    • comprehension
  • Dyslexia involves the word recognition component due to deficit in the use of phonological codes to recognize words.
  • Kinds of Reading Errors:
    • Dysfluency – slow and halting reading due to decreased automatic decoding skills
    • Errors on fxn words – i.e., substitutions on “little” words such as articles and propositions (e.g., interchange a and the and misread propositions)
    • Visual words (whole word guesses) – e.g., reading “car” for “cat”
    • Lexicalization errors when reading nonwords – misreading nonword as real word (e.g., “boy” for “bim”)
  • Kinds of Dyslexia
    • Surface dyslexia – read by well established phonological rules, short words easier than long, difficulty with semantic access; trouble with nonwords, and with visual aspects of word recognition; good phonological skills, but comprehension is seriously affected
      • I.e., normal language skills but poor visual-perceptual abilities; may have features of Gerstmann’s syndrome
    • Deep dyslexia – read familiar words well (esp. nouns), but make many semantic paralexias in oral reading (see “mutton”, say “sheep”); rely on imageability, concreteness, and word frequency
      • I.e., superior perceptual skills but marked language disabilities
  • Kinds of Spelling Errors
    • Phonetically inaccurate errors (e.g., errors in consonants are added, omitted, or substituted)
    • “Reversal errors” e.g., spelling “bog” for “dog” – much rarer than used to be thought (used to believe these were “trademark” signs)
  • Both genetic and environmental factors can cause dyslexia
  • Common characteristics: difficulty learning letter names, generally good at math and spatial tasks, deficit persists into adulthood
  • May be associated with slow reading or writing speed, letter and number reversals, problems memorizing basic math facts and unusual reading and spelling errors
  • Higher rate of spoken language problems (e.g., early articulation disorders, problems finding names or remembering sequences (e.g., phone numbers, or months of the year)
  • Also associated with difficulty following directions, reduced speech or difficulty expressing themselves and problems with peer relations; language problems interfere with their ability to express their feelings so may be more likely to act out or withdraw into themselves
  • Deficit is due to difficulties in phonological coding – since dyslexics have difficulty sounding out words, reading is much slower and less automatic w/c detracts considerably from comprehension
    • Brain mechanisms – a developmental anomaly of the left hemisphere (re: literature re: symmetry of planum temporale (superior posterior portion of the temporal lobe/Wernicke’s area on left hem.) also seen when measuring the whole temporal lobe)
      • There is another neuroanatomical theory of dyslexia (w/less empirical support) that suggests that there is a deficit in the corpus callosum, so info. is transferred less efficiently b/t the two hemispheres
    • Developmental course – may have mild speech delay, articulation difficulties, problems learning letter names or color names, and problem remembering phone numbers/verbal sequences as early as preschool. Children do not typically “catch up”, but remain slower than their peers (incl. adulthood). Most are capable of going to college, but on average complete fewer years of formal education.
      • Some can learn to compensate for their difficulties so they are no longer diagnosable in adulthood (seen more often in females) – but they still report some dyslexic difficulties
    • History – high familial risk; should be evident by 1st or 2nd grade (may even be noticeable by kindergarten due to difficulty learning the alphabet)
    • Treatment – drilling in phonics-based approach to reading; whole word approaches do not help dyslexics; older dyslexics may need help with reading comprehension strategies and study skills; spelling is difficult to remediate, often better to use compensatory devices
      • also benefit from extra time on written exams, by not downgrading spelling errors.


Problems with math, handwriting, and social cognition (all believed to be rt. hemisphere fxns)

  • Math deficits – fundamental conceptual problems in understanding mathematics (w/c may be secondary to deficits in spatial cognition); difficulties with visuo-spatial problems makes it hard for kids to understand complex visual-spatial concepts
  • Dyslexia and “rt. hem LD’s” – re: there is a frequent co-occurrence of math and handwriting problems with dyslexia, but their symptoms generally differ from those seen in children with only math and/or handwriting deficits
    • Handwriting deficits linked to linguistic or motor sequencing problems, not spatial processing
    • Presenting symptoms – initial presentation may suggest an emotional or motivational problem (e.g., not turning in homework, power struggle); may be late in acquiring a good grip of the pencil (may still hold it awkwardly), may be less adept on the jungle gym; eye-hand coordination tends to be weak and difficulty finding their way in new places.
    • Etiology – some genetic syndromes w/c produces these symptoms (e.g., Turner syndrome and fragile X in females (most males with fragile X are MR so do not exhibit the LD’s); Rourke feels there is quite an overlap between NVLD and Asperger’s, but considers Autism to be a separate entity due to its greater language pathology)


  • ADD – developmentally inappropriate levels of inattention, impulsivity, and, often, overactivity
  • Associated neurochemical defect may involve dopaminergic system or noradrenergic system
  • Epidemiological surveys suggest as many as 49% of boys and 27% of girls are described as inattentive by their teachers (i.e., relatively common in normal children)
    • Serious deficits occur in 3-10% of school-age children (i.e., most prevalent of all childhood neuropsychological disorders) – most diagnosed ADD
    • Attention deficits also common in, e.g., autism, PDD, depression, conduct disorder, LD, as well as CHI, leukemia (plus tx for), epilepsy (and tx for), anoxia/hypoxia, tic disorders (up to 70% of Tourette’s), lead/toxin poisoning, exposure to biological hazards during perinatal period


  • History, including
    • prenatal/perinatal stress factors
    • early development and milestones,
    • medical history (child and family)
    • neurological hx
    • psychiatric hx,
    • psychosocial factors,
    • family h/o learning, neurological, medical, or psychiatric problems
    • Exclude possibility that “LD” is due to sensorimotor deficits, primary psychiatric illness, social or educational deprivation, or MR
    • Determine profile of strengths and weaknesses, and describe each deficit as primary or secondary
    • Qualitative description of disability and its limits – critical for recommendations
    • Recommendations for tx
      • meds
      • therapy (group, individual, family)
      • instructional strategies (improve deficit or compensate for it)
  • After neuropsych assmt (above), continue with neurological exam, diagnostic educational assmt, and psychosocial assmt


Lichtheim’s Model of Language Localization


Key to Symbols in the Diagram

A The area containing “sensory memory images for the sounds of words” Wernicke proposed these images were stored in the posterior portion of the first (superior) temporal gyrus in the left hemisphere. Damage in this area results in “sensory aphasia” or “Wernicke’s aphasia.” Auditory comprehension is impaired – patients hear the words, but the meaning of the words is lost

a Central projection pathway for auditory information (i.e. pathways between acoustic nerves and “A”). Damage results in “subcortical sensory aphasia” or “pure word deafness” (patients report can no longer hear the words….sounds like a foreign language)

M Area containing “motor memory images for the control of speech articulation”, i.e. Broca’s area – posterior portion of the third (inferior) frontal gyrus. Damage leads to “motor aphasia” or “Broca’s aphasia.”

m The central motor output pathway for speech articulatory muscles. Damage results in “subcortical motor aphasia”, with impaired speech expression but not written expression

B A diffuse set of associations between memory images (in A and M, as well as other areas) involving the memory images and the interconnecting fiber pathways. Therefore “B” involves a large part of both sides of the brain.

O The optic area containing visual memory images

E The area containing motor memory images for control of the hand musculature


(any disruption of the indicated pathway impairs the ability) Auditory Comprehension a – A – B

Voluntary Speech b – M – m

Repetition a – A – M – m

Voluntary Writing B – M – A – E

Reading Comprehension O – A – B

Reading Aloud O – A – M – m

Copying Writing O – E

APHASIAS (area or pathway lesioned)

Broca’s M

Wernicke’s A

Conduction M – A

Transcortical Motor B – M

Subcortical Motor M – m

Subcortical Sensory a – A


Anomia Lichtheim said this results from any disturbance in B, M, A, B Circuit, and may be first symptom

Localization of Language

Little tidbits of knowledge you may not already know….

  • The speech zones (i.e., Broca’s area, Wernicke’s area, sensory/motor areas of face and supplementary speech areas) are located in both hemispheres
  • Penfield & Roberts – stimulation of speech zones results in positive effects (e.g., vocalizations, but not speech… “oooo”) and negative effects (inability to vocalize or use words appropriately)
    • However, their data (and others) do not support strict localization model – stimulation outside of speech zones can disrupt speech while stimulation of speech zones affects more than just speech
    • Damage to Broca’s area does not lead to as severe aphasia as does damage to posterior speech zones

Subcortical components of Language

  • Thalamus (pulvinar and lateral posterior, lateral central complex) plays a large role in language; stimulation of this zones leads to speech arrests, naming problems, perseveration and protracted speech

Right Hemisphere Contribution to Language

Has a major role in prosody, attitudinal, emotional and gestural aspects of language and behavior

  • Little or no speech but good auditory comprehension
  • Good reading/not writing; good semantic/poor syntactic
  • RH lesions or removal result in:
    • changes in vocabulary selection, responses to complex statements
    • poor understanding of metaphors
    • right orbital removal leads to decreased fluency
    • reduction in understanding and use of prosody
  • prosody – the melody, pauses, intonation, stresses, and accents applied to the articulatory line.
  • Gestural activity – lesions of the right frontal operculum can cause a complete loss of spontaneous gesture without a disturbance of praxis (aphasic patients, in contrast, generally have preserved gestural activity)



The loss or impairment of language caused by brain damage; an acquired disorder, not a developmental retardation; can include multiple types of language including:

  • Not primary sensory, thought, or memory disorder
  • gestural, prosodic, semantic, syntactic and pragmatics
  • most discussions of aphasia center on semantics and syntactics
  • aphasics have normal turn-taking, head movements, eye movements – psychotic patients do not
  • lesions in L temporal regions and outside of Broca and Wernicke’s areas produce word retrieval/naming problems for nouns, but may leave verbs intact
  • general rule – in aphasia, the disturbance of language function is manifested by either incorrect grammar or incorrect choice of words
  • mutism – most frequently misdiagnosed disorder as aphasia
  • crossed aphasia – the occurrence of aphasia in a right-handed patient following right-hemispheric damage.
    • Relatively rare
    • High percentage of cases based on tumor or trauma, suggesting that many cases may actually represent bilateral damage

General info re: Aphasia

  • Children with acquired aphasia, even those with posterior lesions, almost invariably produce a nonfluent verbal output
  • Certain features, particularly dysarthria, phrase length, and agrammatism will only be present in those with anterior lesions
  • In acute stage, patients with posterior lesions may have nonfluent output for several days
  • Aphasia resulting from anterior lesions without hemiparesis or with transient paralysis have an excellent prognosis for recovery
  • Some degree of naming disturbance is present in almost every aphasic patient
  • Apraxia is often associated with aphasia as well


  • Spontaneous recovery is generally better for comprehension defects than for output problems
  • Aphasic syndromes caused by smaller lesions (e.g., conduction aphasia) characteristically show a better overall improvement
  • While early treatment is recommended, evidence suggests that treatment begun late can also be successful

Language Deficits can occur in basic skill areas

(Goodglass Kaplan)

  1. Auditory Comprehension
  2. Visual Comprehension – e.g., alexia; a disturbance of reading is commonly associated with impaired comprehension of auditory material, they can occur independently too
  3. Articulation – may be due to 3 different causes:
    1. dysarthria – defect in mechanisms of speech (larynx, pharynx and tongue)
    2. deficit in motor system w/c prevents desired sound from being pronounced properly
    3. defect in choosing the desired sound
  4. Paraphasia- the production of unintended syllables, words or phrases during the effort to speak. Differs from difficulties in articulation, b/c the sounds are correctly pronounced by they are the wrong sounds and either distort the intended words (e.g., pike instead of pipe) or produce completely unintended words (e.g., my mother instead of my wife)
  5. Loss of grammar and syntax
  6. Repetition – may result from deficits in comprehension or articulation or from a selective dissociation b/t the two centers involved in this task (in this latter type, repetition may be the only deficit seen)
  7. Verbal Fluency – ability to produce words in uninterrupted strings. Low verbal fluency may be due to word-finding difficulties or frontal lesions
  8. Writing – may be disturbed by:
    1. deficits in movement in limb to produce letters (but not considered a language impairment)
    2. an inability to recall the form of letters – agraphia
  9. many of the deficits observed in language may also occur in written language (e.g., paragraphia – writing the incorrect word)
  10. Prosody – tone or accent of language
  • fluent aphasias – fluent speech but difficulties either in auditory verbal comprehension and/or the repetition of words, phrases or sentences spoken by others
  • nonfluent aphasias – difficulties in articulating but relatively good auditory verbal comp.
  • “pure aphasias” – selective impairments of reading (alexia w/o agraphia), writing (agraphia) or recognition of words (word deafness).

Assessments of Aphasia

  • look at the way patient relates to you
  • auditory and verbal comprehension
  • cadence, inflections, prosody
  • oral and written expression
  • tests of repetition, reading, naming and fluency
  • conversational speech
  • word string length

Differential Diagnosis

  • Aphemia – (coined by Broca) disturbance of motor verbal output alone; occurs when pathology affects the left medial frontal cortex, the supplementary motor area, and/or the cingulate gyrus
    • Mutism or severely sparse verbal output with normal language characteristics is noted originally, usually accompanied by akinesia or paresis of the contralateral lower extremity and proximal upper extremity
  • lesions of the subcortical structures) or subcortical white matter in the dominant hemisphere can produce aphasia that can be mistaken for a cortical lesion

Rehabilitation of Aphasia

  • Limited evidence to support efficacy of aphasia therapy, though some patients clearly benefit
  • considerable spontaneous recovery usually occurs during 1st month post onset and continuing for several months
  • recovery of fxn is rarely complete

Broca’s Aphasia

damage to the 3rd frontal convolution/frontal operculum of left frontal lobe (Brodman’s areas 44 & 45) often involves subcortical involvement (e.g., white matter, basal ganglia), can also affect areas 6 and 47 fxn of Broca’s area – specialized for producing motor programs for speech (the “motor image of the word.”

Frequent etiology – CVA of dominant (left) MCA (superior division)


  • nonfluent output; loss of melody
  • person speaks in a very slow, deliberate manner w/very simple grammatical structure and limited prosody
  • limited use of verbs, adjectives, adverbs, and articles – only key words are used


  • agramaticism, content but limited function words


  • poor, but can be superior to spontaneous speech

naming/word finding

  • can have poor naming (aided by cueing, either contextual or phonetic)


  • intact, except for syntactically dependent structures

reading comprehension

  • generally intact, although trouble comprehending function words

reading aloud/writing

  • slow, effortful, agrammatic quality simlar to deficits in spoken language

associated symptoms

  • may have right hemiplegia (which can affect written output) and/or ideomotor apraxia affecting the “good” side; dysarthria

psychological presentation

  • frustrated and aware of deficits

Big vs. Little

• “Big Broca’s” is caused by large lesions (usually left MCA superior division infarct) and starts with global aphasia improving to Broca’s aphasia • “Little Broca’s” is caused by smaller, more localized lesions and starts with Broca’s aphasia and improves to naming difficulties and mildly decreased fluency

Wernicke’s Aphasia

damage to the 1st temporal gyrus (Heschel’s gyrus); the auditory association cortex (area 40) (can also involve areas 22, 37, and 21)

fxn of Wernicke’s area – center of language comprehension most common etiology – infarct in left MCA (inferior division)


  • fluent verbal output, normal rate, articulation, melody and inflection; but contaminated w/paraphasias and neologisms (new words, whose meaning may only be known to the patient; word salad)
  • paraphasias can be both semantic e.g., “ink” for “pen”, and phonemic e.g., “pish” for “fish”

syntax – normal syntax but empty speech


  • disturbed; anomia is common and prompting is rarely helpful


  • poor


  • inability to comprehend words or to arrange sounds into coherent speech


  • impairment in writing b/c they cannot categorize the sounds so cannot transcribe sounds into correct graphemes


  • poor like speech, but reading may not be equal to spoken language

associated symptoms

  • some patients have a contralateral, superior quadrantanopsia; apraxia (difficult to elicit due to impaired comprehension) may also have anosognosia.

psychological presentation

  • may be anxious because of changes in communication, agitated or may demonstrate a total lack of concern
  • Luria proposed there are 3 characteristics of this disorder:
  1. the inability to isolate the significant phonemic characteristics and to classify sounds into known phonemic systems
  2. defect in speech due to confusion of phonetic characteristics; word salad
  3. impairment in writing b/c cannot discern phonemic characteristics, and therefore graphemes (letter representation of phonemes) to form the word

Transcortical Motor Aphasia

can repeat and understand words and name objects, but cannot speak spontaneously or unable to comprehend words although they can still repeat them

general characteristics

  • like Broca’s aphasia (i.e., impaired fluency with normal comprehension) but repetition is spared

location of lesion

  • believed to be due to loss of the secondary sensory cortex (association cortex) – border zone of parietal lobe

most common etiology

  • watershed infarct of MCA-ACA branch that destroys the frontal lobe areas connected to Broca’s areas without afecting connections b/t Broca’s and Wernicke’s areas

Mixed Transcortica

  • analogous except able to repeat
  • Doesn’t speak unless spoken to
  • Echos
  • No conversational speech

Transcortical Sensory Aphasia


  • border zones, temporal/parietal lobes
  • Like Wernicke’s (i.e., impaired comprehension but normal fluency) but repetition is spared


intact, but paraphasias sometimes present


  • good, but empty content


  • good (unlike Wernicke’s)


  • impaired


  • good


  • poor comprehension


  • poor

Associated symptoms

  • echolalic, sometimes agitated

Most common etiology

  • watershed infarct of MCA-PCA that destroys parietal and/or temporal connections to Wernicke’s w/o afecting conections between Broca’s and Wernicke’s areas

Mixed Transcortical Aphasia

isolation of the speech area Like global aphasia (i.e., impaired fluency AND comprehension) but repetition is spared

– most common cause is combined watershed infarcts of MCA-ACA and MCA-PCA branches but also can be due to subcortical lesion


  • does not speak unless spoken to; echolalic

word finding

  • poor


  • Relatively preserved


  • poor


  • poor


  • Anterior & posterior border zones, generally due to hypoxia, head trauma or acute carotid occlusion

most common etiology

  • watershed infarcts of MCA-ACA an MCA-PCA branches, but also can be due to subcortical lesions

Conduction Aphasia

best characterized by paraphasias


  • intact, but paraphasic output (literal paraphasias)


  • impaired


  • somewhat impaired due to phonemic paraphasias


  • intact


  • aloud impaired, but reading for comprehension intact


  • impaired, but less than speech

associated symptoms

  • bilateral apraxia to command or imitation; sometimes hemiparesis or sensory loss
  • different from Wernicke’s b/c comprehension is clearly better; different from Broca’s b/c of fluent speech
  • location of lesion – the arcuate fasciculus (white matter) w/c connects Broca’s area and Wernicke’s area **but there has never been any proof that cutting these connections actually cause this symptom and there is debate as to whether this symptom really occurs in isolation
  • often confused with Wernicke’s aphasia but comprehension is intact

Anomic Aphasia

can comprehend speech, produce meaningful speech and can repeat speech but have difficulty finding the names of objects


  • intact


  • intact


  • intact


  • usually good (except for word-finding problems in writing)
  • often find this upon recovery from other aphasias


  • most likely the angular gyrus but nearly all aphasics have naming difficulties

Global Aphasia


  • all aspects of language are involved
  • severe, non-fluent output, severe disruption in comprehension, little or no ability to repeat


  • also disturbed


  • degree of impairment and localization may vary considerably, usually w/damage to the middle cerebral artery
  • a very large lesion affecting left frontal/parietal/temporal areas

associated symptoms

  • Right hemiparesis, hemisensory loss; hemianopsia

most common etiology

  • large left MCA infarcts affecting both superior and inferior divisions and with large subcortical lesions (can also be seen in initial stages of large left MCA superior infarcts that eventually improve to Broca’s aphasia)

Subcortical Aphasia

frequently a transient condition considerable variation in the clinical picture – depends on structures involved

  • acute onset – usually mutism or hypophonic voicing and hemiparesis and/or hemisensory loss
  • improves to paraphasic output, nonaphasic state or residual aphasia


  • mutism, hypophonic, poor articulation


  • better than speech due to fewer paraphasias and no dysarthria


  • variable, but often relatively good

location of lesion

  • associated w/damage to basal ganglia (caudate and putamen) and thalamus as well as in the SMA

associated symptoms

  • some patients show spastic dysarthria (high pitched, slow and effortful speech) – others produce hyper or hypokinetic speech (i.e., rapid or slowed speech with slurred articulation)

Subcortical Type I

Anterior superior extension


  • short phrases, impaired articulation


  • poor for low frequency phrases


  • intact for semantic comprehension, but poor for syntactic comprehension


  • poor

associated symptoms

  • right hemiplegia

Subcortical Type II

Posterior extension


  • intact, but with paraphasias


  • poor


  • poor, but better than Wernicke’s

naming/word finding

  • impaired letters, but better than objects


  • poor

associated symptoms

  • right hemiplegia

Subcortical Type III

Posterior and anterior extension

  • global aphasia

Pure Word Deafness

apperceptive auditory agnosia does not understand language and can’t repeat


  • intact


  • Impaired


  • impaired
  • may complain that speech is muffled or foreign
  • slowing of presentation may sometimes improve comprehension
  • good hearing and identification of non-verbal sounds

reading , writing and speaking

  • usually intact

paralinguistic features

  • may be preserved (e.g., able to tell who is speaking, identification of certain languages by their accent or language features, emotional expression of speech)

location of lesion

  • bilateral (some unilateral) symmetrical cortical-subcortical lesions of superior temporal gyri (with some sparing of Heschel’s gyrus on the left); bilateral discnxn of Wernicke’s area from auditory input