Category Archives: D-I



  • Definition
    • An abnormal increase in the amount of cerebrospinal fluid within the cranial cavity that is accompanied by expansion of the cerebral ventricles and (in infants)enlargement of the skull
    • Can result either from increased production or decreased absorption of CSF, or from blockage of one of the normal outflow pathways of the ventricular system
    • Anatomy of the ventricles
      • Two lateral ventricles (connects to 3rd by foramen of Monro)
      • 3rd ventricle (connects to 4th by Aqueduct of Sylvius)
      • 4th ventricle
    • Most common forms occur in infants
      • Because cranial sutures are not yet fused, head size increases progressively
      • Thus, periodic measurement of the skull’s circumference to detect enlargement is important in neonatal and infant care
  • Obstructive
    • Obstruction of CSF drainage from the lateral and third ventricles
    • Most cases of hydrocephalus, resulting from congenital stenosis of the aqueduct of Sylvius (aka, Cerebral aqueduct)
    • Commonly seen with brainstem tumor or a posterior fossa tumor encroaching on the fourth ventricle and obstructing the lateral aperture of Luschka or the median aperture of Magendie
    • In adults, it is also associated with brain tumors that impinge on the ventricular structures
  • Communicating
    • There is an interference with the normal rate of absorption
    • This may be seen after intraventricular hemorrhage in premature infants (or in adults due to stroke or infection)
      • The presence of blood breakdown products in the CSF interferes with the normal rate of absorption
  • Advanced Infantile Hydrocephalus
    • Scalp veins are distended because venous drainage from the scalp is impaired as a result of elevated intracranial pressure
    • We see a downward deviation of the eyes, referred to as “sunset eyes”
      • Probably results from pressure transmitted to the midbrain by the dilatation of the posterior part of the 3rd ventricles
      • Paralysis of upward gaze is resultant, called Parinaud’s syndrome
    • Affected infants appear emaciated, characterizing the poor feeding and recurrent vomiting that accompanies elevated intracranial pressure
  • Normal Pressure Hydrocephalus (NPH)
    • This adult/geriatric syndrome is not associated with an obvious increase in intracranial pressure
    • Initial symptoms are progressive dementia, gait disorders, and urinary incontinence (3 Ws: wet, wacky, and wobbly)
    • The CT scan shows ventricular dilatation, which must be differentiated from ventricular dilatation secondary to brain atrophy
    • Makes up approximately 6% of dementia cases (according to some studies)
    • Reversible dementia with surgery, but less so if the dementia is the most striking feature or has been present for more than two years
      • If the gait abnormality began before or at the same time as dementia, then there is a better chance for successful surgery
      • Alcohol abuse is a poor prognostic indicator
      • Aphasia is a poor prognostic indicator for surgical success
      • Only about 50% of those responding to shunt surgery improve cognitively by the criteria of a significant increase in the test scores in two or more neuropsychological areas (and no decline in another area)
    • 30% of patients experience either major or minor shunt complications
  • Shunting
    • A significant number of patients with communicating or obstructive hydrocephalus require shunting
    • For communicating hydrocephalus, the shunt can originate anywhere in the subarachnoid space or ventricular system
    • For obstructive hydrocephalus, the origin of the shunt depends on the location of the obstructing lesion
    • Most shunting operations involve placing a tube or ventricular catheter in the anterior horn of the lateral ventricle
    • The catheter is connected via a subcutaneous tube to either the right atrium of the heart or to the peritoneal cavity

Huntington’s Disease

Brief Overview of Huntington’s Disease

  • 30,000 affected in US; 200,000 at risk
  • Affects striatum/basal ganglia (esp. caudate nucleus)
  • Triad of clinical symptoms:
    • motor (unsteady gait, involuntary movements; slurred speech; difficulty in swallowing; intoxicated appearance)
    • cognitive and behavioral (personality changes, depression, mood swings,impaired judgment)
    • diagnosis relies on emergence of chorea (traditional);
    • progressively disabling, adult-onset, lethal
      • usual onset is 30-50, but can be from 2-80
      • average age of onset is 38
      • average length of life from diagnosis to death is 19 years
      • no effective treatment to delay onset or slow decline is currently available

Neuropsychological manifestations: subcortical dementia

  • decreased attention,
  • impaired executive functioning,
  • memory retrieval deficits
    • Neuropsychiatric manifestations common (affective disorders) – 50% of all patients
    • depending on study, motor, cognitive, or behavioral symptoms may appear first; also, some of the early features might be related to “being at risk” rather than carrying the gene
    • Diagnosis made by DNA marker of CAG repetitions:
      • CAG trinucleotide repeats <36 – no HD, 36-39 – questionable, >39 – HD;
      • repeat length accounts for half of the variance in determining age of onset (more repetitions = earlier onset)
    • this is also affected by how onset is defined (mood, personality or chorea, e.g.)
    • Also, the repetition length can change during transmission (e.g. from parent to child); it usually lengthens with a particular tendency to lengthen when passed from father to child
    • gene (huntingtin) found in 1993; HAP-1 (protein that works with huntingtin) found in 1995
  • Huntington Study Group (international coalition) formed in 1993 – coordinates research efforts – developed the UHDRS (motor, cognitive, behavioral, functional measurement of disease)
    • UHDRS battery uses Stroop, Symbol Digit, and Verbal Fluency – sensitive to basal ganglia dysfunction (study showed all declined in at-risk who eventually developed HD, not so in at-risk without gene)
    • Possible environmental modifiers: enriched environment; no other studies have produced convincing results

Recent Findings/Developments

  • First, HDSA is VERY active, has designated “Centers of Excellence” (U of R is one), and created “Coalition for the Cure” (1997) – 14 top labs in North America and Europe – will award 2 million in 2000/2001; ave. 2-yr award of 200,000 per investigator
  • NINDS and HDSA formed a partnership – “Screening FDA Approved Drugs for Neurodegenerative Disease” pilot project – joint sponsorship between goverment and voluntary health agency – will help speed research from lab to clinical trials – govt will supplement HDSA funding
  • 3/01 – report in Science detailing how gene attacks and kills cells – mutant huntingtin “hijacks” a key molecule termed CBP, which is necessary for activating genes necessary for neuronal survival. Without CBP, a pathway crucial for cell survival can’t get turned on. The molecular “hijack” makes direct use of the expanded polyglutamine stretch in huntingtin. Therefore, this mechanism can provide an elegant explanation for the pathology of the whole family of diseases – currently about 8 – caused by expanded glutamine stretches in different disease proteins.
  • Currently awaiting results on clinical trials involving Co-enzyme Q10, remacemide, and creatine
  • Human fetal nerve cell implants have had mixed findings – when they take, they appear to offer improvement; not yet an accepted treatment (goal would be to use human stem cells); genes do not appear to invade the transplants; small n
  • Reversible mouse model of HD created in 2000 – inserted a genetic switch that allows regulation of the protein (i.e., on or off) – found that a continuous influx of the mutant protein is required to maintain inclusions and symptoms; therefore, treatment might be aimed at preventing protein from being made or increase the removal of the protein – however, maybe huntingtin is crucial for normal brain functioning (i.e., turn off completely disrupts this function); don’t yet know what huntingtin (the gene) does in normal brain
  • Minocycline (antibiotic) found to delay mortality in HD mice (also, delays ALS and reduces size of injury post-CVA); implications for role of oxidants and stress in HD

Ongoing Studies

  • Broadly accepted criteria for clinical diagnosis/onset are lacking – MUST HAVE THIS prior to initiation of clinical tx trial
  • Neuroprotective interventions being studied aren’t implemented until manifest disease – this is rather late in the game for neuronal degeneration
  • We know lots about manifest HD and the gene defect, little about signs, symtoms, experiences, and attitudes of at-risk persons

Neurobiological PREDICTors of HD

  • Study name is PREDICT HD
    • Status: reviewed favorably and awaiting formal notice of funding; enrollment to begin this summer or fall
    • Goal: examine nature and pattern of progression of behavioral neurobiological changes that occur in the period leading up to the diagnosis of HD and to investigate the relations between the progressive prodromal changes, the degree of CAG expansion, and age of onset. (all are critical to design/implementation of future clinical trials)
    • Subjects: (1) 425 CAG expansion >40 (2) 75 At-risk No expansion; 30-55 y/o
    • Design: yearly evals X7 (UHDRS, criteria for disease onset, MRI, neurobehavior/cognition)
    • Inclusion: CAG known via predictive testing and >39; 30-55 y/o, involved sig other
    • Exclusion: any abnormal mvmt d/o, psych illness, EtOH/drug problem 1 yr pre, h/o LD/MR, h/o CNS dz/event, h/o antipsychotics, use of phenothiazine-derivative antiemetics, pacemaker/metallic implants
    • Primary Measures: Disease Onset, MRI (basal ganglia volume), Cognition
    • Secondary Measures: UHDRS, Neurobehavioral Rating Scales (BDI, FLOPS, Neuropsychiatric Inventory, Awareness Interview), CAG repeat length
  • PHAROS (Prospective Huntington At Risk Observational Study):
    • we know nothing about the 97% who have not undergone testing
    • PHAROS is a multi-site, double-concealed observational study
    • Status: reviewed, not funded, revised, resubmitted 3/1/01. In interim, funded by the HDSA to enroll. So far, 450 Ss at 25 sites (beginning 7/99). 19 at U of R (Peter is site PI) – half have returned for a second study visit. Expect completed enrollment of 1000 by 11/01; data analyses completed by 11/06; expect 400 to be HD+
    • Goal: Overall: observational study to find way to reliably measure onset of HD in untreated gene carriers so that therapies (when developed) can be tested. Have to determine when to begin therapy. Also, need to examine ethical issues and feasibility of conducting research in at-risk persons. Specifically:
      • define objective criteria for an early phenotype of HD
      • understand genetic and environmental variables that may influence the onset of the early phenotype of HD
      • clinical research methodology pertaining to the design and conduct of controlled therapeutic trials aimed at postponing onset of the early phenotype of HD
      • counseling and caring for adults at risk for HD
      • care and research of other adult-onset genetic diseases
      • Subjects: 30-55 y/o, 50:50 risk, never tested, can give consent (will enroll people with obvious signs who ‘don’t want to know’, but won’t analyze their data)
    • Design: undergo UHDRS every 9mos
    • Exclusion: dx with manifest HD; neuroleptics within past 6 months; phenothiazine-derivative antiemetics; psychosis or severe depression at screening
    • Primary Outcome Measures: early, HD gene-specific clinical precursors predictive of manifest HD; inter-rater agreement of manifest HD; association of CAG with onset of clinical precursors predictive of manifest HD; relationship between onset of clinical precursors with potential environmental modifiers; characterization of Ss personal beliefs and attitudes re: HD; feasibility of conducting long-term longitudinal research in adults at risk; feasibility of maintaining confidentiality of genetic risk status and genotype and characterization of potential consequences of disclosure of this information; willingness of research participants to consent to future use of DNA samples
    • Predictors: Motor (chorea, dystonia, oculomotor, rapid alternating movements), Cognitive (Stroop, Symbol Digit); will also look at environmental modifiers (diet, caffeine, medications, nutritional supplements, head injury, alcohol, tobacco use, hormone replacement tx)
      • in essence, looking for the other half of the variance in predicting age of onset
      • will gain info re: perceptions of risk, attitudes towards genetic testing, psych well-being, and clinical outcomes of the ‘other’ 97% who elect NOT to know gene status
      • will create a DNA bank for future research

PHAROS vs. PREDICT-HD: The Pharos Advantages

  • PHAROS will allow detection, in a double-concealed fashion, of subtle clinical signs that are specific for HD gene-carrier status and will have immediate application as potential therapeutic outcome measures
  • will also allow for the prospective assessment of the attitudes and beliefs of individuals who wish to remain unaware of their HD gene status.

Genetic Testing

  • despite gene test since 1993, only 3% of persons at-risk have elected testing
  • women seek testing more than men (2.5:1)
    • Current status: presymptomatic, prenatal, confirmation
    • Protocol:
      • initial phone contact,
      • 3 pretest evals (genetic counseling, neurological eval, psych eval)
      • disclosure session
      • post-test counseling
        • should take a good month
        • should identify a support person
        • identify a local counselor for follow-up
  • Pre-testing considerations: is testing necessary, opportunity to defer, informed decision
  • Reasons for declining to pursue:
    • child’s risk status may be revealed
    • lack of cure/tx, health insurance
    • no plans for more children
    • financial costs
    • inability to undo knowledge
    • could lose job/ insurance
    • inability to cope
    • lack of support
    • concerns re: privacy invasion
  • Reasons to deny
    • symptomatic
    • under 18
    • psychiatric instability
    • requesting testing for adoption purposes
  • Reasons to postpone
    • past psychiatric instability
    • poorly thought out reasons for pursuing
    • unstable living situation
    • unwillingness to involve a companion
    • lack of understanding (of disease, of risks, etc)
    • inability to give informed consent
    • recent diagnosis in family member
  • Consequences of HD+:
    • initial difficult adjustment period (many)
    • prolonged emotional distress (few)
    • few regret decision,
    • depression/anxiety common
    • no increase in suicide
    • increase in psychosocial problems (overall, past hx is best predictor)
    • individuals become more present-centered
  • Consequences of HD-: (60% of those tested)
    • most will have improved psych functioning
    • up to 10% may have adverse psych consequence
      • result contradicts expectation
      • consequences of past decisions (e.g., sterilization, finances)
      • survivor guilt
      • contradicts family members’ beliefs
      • psych dysfxn in spouse/sig other – these consequences happen later (2mos-2yrs)
  • Psych effects of prenatal testing: low demand; may disclose parents’ gene status; should definitely have parent tested first (prior to conception)
  • Ethical issues: unauthorized labs/no proper screening/follow-up; advice re: CAG length despite no compelling evidence, privacy/confidentiality (insurance), no tx available, pregnancy termination/voluntary sterilization, knowledge of unsolicited information (e.g., paternity issues), identical twin



  • Human immunodeficiency virus (HIV) infection is an infection by one of two viruses that progressively destroys white blood cells called lymphocytes, causing acquired immunodeficiency syndrome (AIDS) and other diseases that result from the impaired immunity


  • HIV-1
    • Most common in the Western Hemisphere, Europe, Asia, and in Central, South, and East Africa
  • HIV-2
    • Most common in West Africa, although HIV-1 also exists


  • A type of virus that stores genetic information as RNA rather than as DNA
  • When the virus enters a targeted host cell, it releases its RNA and an enzyme (reverse transcriptase), and then makes DNA using the viral RNA as a pattern
  • The viral DNA then is incorporated into the host cell DNA
  • Each time a host cell divides, it also makes a new copy of the integrated viral DNA along with its own genes
  • The viral DNA can take over the functions of the cell (become activated), causing the cell to produce new virus particles
  • These new viruses are released from the infected cell to invade other cells


  • In the early 1980s, epidemiologists (people who study the factors that affect the frequency and distribution of diseases) recognized a sudden increase in two conditions among American homosexual men
    • One was Kaposi’s sarcoma, a rare cancer
    • The other was pneumocystis pneumonia, a form of pneumonia that occurs only in people with a compromised immune system
    • The failure of the immune system that allowed the growth of rare cancers and the development of rare infections came to be known as AIDS
      • Immune system failure was found also in injecting drug users, hemophiliacs, and recipients of blood transfusions as well as in bisexual men
      • Some time later, the syndrome began to occur in heterosexuals who weren’t drug users, hemophiliacs, or recipients of blood transfusions


  • Gradual decline of the body’s immune system, primarily through the disabling of CD4+ cells
  • In order to establish infection in a person, the virus must enter cells such as lymphocytes, a type of white blood cell
  • The genetic material of the virus is incorporated into the DNA of an infected cell
  • The virus reproduces itself inside the cell, eventually destroying the cell and releasing new virus particles.
  • The new virus particles then infect other lymphocytes and can destroy them as well
  • Because HIV infection destroys helper T lymphocytes, it weakens the body’s system for protecting itself from infection and cancer
  • People infected with HIV lose helper T lymphocytes (CD4+ cells) in three phases over months or years
    • A healthy person has a CD4+ lymphocyte count of roughly 800 to 1,300 cells per microliter of blood
    • In the first few months after HIV infection, this count may decrease by 40 to 50 percent
    • After about 6 months, the number of virus particles in the blood reaches a steady level, which varies from person to person
      • Many years may pass during which the HIV-infected person has a slowly declining, below-normal count of CD4+ lymphocytes
    • In the 1 to 2 years before recognizable AIDS develops, the count of CD4+ lymphocytes usually drops more rapidly
      • The person’s vulnerability to infection increases as the CD4+ lymphocyte count falls below 200 cells per microliter of blood
  • HIV infection also disrupts the function of B lymphocytes, the part of the immune system that produces antibodies, often causing them to produce excess antibodies
    • These antibodies are directed mainly against HIV itself and those infections with which the person had previous contact
    • But the antibodies are not very helpful against many of the opportunistic infections of AIDS
    • At the same time, destruction of CD4+ lymphocytes by the virus reduces the immune system’s ability to recognize new invaders and target them for attack


  • 34.3 million worldwide are infected with HIV (according to United Nations Programme on HIV/AIDS & World Health Organization, 2000)
  • Since its beginning, almost 19 million have died from AIDS
  • Sub-Saharan African countries are the most profoundly impacted
    • Up to one quarter of young adults being HIV seropositive
  • In US (1999 numbers)
    • 850,000 are living with HIV/AIDS
    • 430,000 have died from it


Two Factors

  • History of Clinical Conditions
    • Category A: Patients who have remained medically asymptomatic or have had only a transient illness at seroconversion or persisting hymphadenopathy
    • Category B: Patients with more serious HIV-related conditions (minor opportunistic infections)
    • Category C: Patients who have had more serious AIDS-defining illnesses such as Pneumocystis carinii pneumonia
  • Degree of Immunosuppression (based on CD4+ T-lymphocyte cell count per microliter of blood)
    • Category 1 (the healthiest): CD4 counts of greater than 500
    • Category 2: CD4 cell counts from 200-499
    • Category 3: CD4 counts below 200
  • AIDS is diagnosed in those with CD4<200 and /or a category C complication


  • Some people develop symptoms similar to those of infectious mononucleosis a few weeks after first contracting HIV infection
  • A fever, rashes, swollen lymph nodes, and general discomfort can last 3 to 14 days
  • Most symptoms then disappear, although the lymph nodes may stay enlarged
  • Additional symptoms may not appear for years.
  • However, large amounts of the virus circulate in the blood and other body fluids immediately, so a person becomes contagious soon after becoming infected
  • Within several months of contracting HIV, people may repeatedly experience mild symptoms that don’t yet fit the definition of full-blown AIDS.
  • A person may have symptoms of HIV infection for years before developing the distinctive infections or tumors that define AIDS
    • These symptoms include swollen lymph nodes, weight loss, a fever that comes and goes, an unwell feeling, fatigue, recurring diarrhea, anemia, and thrush (fungal infection of the mouth)
    • Weight loss (wasting) is a particularly troublesome problem
  • By definition, AIDS begins with a low CD4+ lymphocyte count (less than 200 cells per microliter of blood) or the development of opportunistic infections (infections by organisms that don’t cause disease in people with a healthy immune system)
    • Cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma may also develop
    • Both the HIV infection itself and the opportunistic infections and cancers produce the symptoms of AIDS
    • However, only a few people with AIDS die from the direct effects of HIV infection.
    • Usually, death is caused by the cumulative effects of many opportunistic infections or tumors.
    • Organisms and diseases that normally pose little threat to healthy people can rapidly lead to death in those with AIDS, especially when the CD4+ lymphocyte count drops below 50 cells per microliter of blood

Common Opportunistic Infections

  • Thrush
    • Often one of the first infections to appear
  • Vaginal Yeast Infections
    • Often one of the earliest symptom of HIV infection in a woman
    • May be frequent that aren’t easily cured.
    • However, recurring vaginal yeast infections are commonly seen in otherwise healthy women and may be caused by other factors, such as oral contraceptives, antibiotics, and hormonal changes
  • Cryptococcal Meningitis
    • Results from infection with Cryptococcus neoformans (a yeast)
    • Characterized by headaches, altered mentation, fever, and nausea
  • Pneumocystis Carinii
    • Pneumonia caused by this fungus is a common
    • Often one of the first serious opportunistic infection to develop
    • It was the most common cause of death among HIV-infected people before methods to treat and prevent the pneumonia were improved
  • Toxoplasmosis
    • The most common cause of mass lesions in AIDS patients
    • Usually results in multifocal abscesses in both hemispheres, particularly in the basal ganglia
    • Characterized by a fever, altered mentation, seizures, and focal signs that develop in a few days
    • When it reactivates in patients with AIDS, Toxoplasma causes severe infection primarily in the brain.
  • Tuberculosis
    • More frequent and more deadly in people who have HIV infection and is difficult to treat if the strains of the tuberculosis bacterium are resistant to several antibiotics
  • Mycobacterium Avium Complex
    • A common cause of fever, weight loss, and diarrhea in people with advanced disease
    • It can be both treated and prevented with recently developed drugs.
  • Cryptosporidium
    • Gastrointestinal infection that is also common with AIDS
    • It is a parasite that may be acquired from contaminated food or water, causes severe diarrhea, abdominal pain, and weight loss
  • Progressive Multifocal Leukoencephalopathy (PML)
    • A viral infection of the brain
    • A demyelinating disorder
    • Usually occurs in subcortical regions, but occasionally may affect the gray matter
    • Lesions do not produce a mass effect
    • The first symptoms are usually a loss of strength in an arm or leg and loss of coordination or balance
    • Within days or weeks, the person may be unable to walk and stand, and death usually occurs within a few months
  • Cytomegalovirus (CMV) Encephalitis
    • Highly endemic in American homosexual men (95%)
    • Became a common, uncontrolled problem in advanced AIDS before the advent of HAART
    • There appear to be a distinct dementia associated with CMV-E
    • People with AIDS are also highly susceptible to many other bacterial, fungal, and viral infections
  • Common Tumors
    • Kaposi’s Sarcoma: A tumor that appears as painless, red to purple, raised patches on the skin, affects people with AIDS, especially homosexual men
    • Lymphomas: Tumors of the immune system which may first appear in the brain or other internal organs
      • Typically, patients present with slowly progressive neurological deterioration and may die within 3 months
      • Focal lesions may develop
      • Difficult to differentiate lymphomas from toxoplasmosis
    • Women are prone to developing cancers of the cervix
    • Homosexual men are prone to developing cancer of the rectum


  • HIV enters the CNS early in the course of the disease
  • A small subset of individuals may develop severe dementia as the initial manifestation of AIDS, but it is primarily a late stage phenomenon
  • Milder forms of cognitive sequelae are more common
  • 50-66% of AIDS patients may develop some form of CNS disease as a result of the direct or indirect effects of HIV
  • It does not appear that HIV directly infects neurons
  • It is hypothesized that damage to neurons may be mediated my macrophages and microglia
  • The presence of HIV may lead to chronic activation of macrophages/micrglia, which can result in increased prodection of cytokines such as IL-1, IL-6, and TNF-alpha by these cells
    • These cytokines may then damage neuronal structures directly or set off disturbances in other cells (e.g., astroglia) that are important in maintaining the viability of neurons
  • Neuroimaging shows abnormalities frequently seen as atrophy, white matter lesions, and abnormal metabolism
  • HIV is predominantly found in the subcortical brain regions
  • However, neocortical regions are also affected by HIV


  • Neurocognitive complications can be classified as being primary or secondary
    • Primary complications are linked directly to HIV infection of the brain
    • Secondary complications are linked to immunodeficiency or other adverse events associated with HIV disease or its treatment
      • Delirium is a common secondary complication (well covered in the book)
  • Grant and Atkinson (1995) Taxonomy
    • Neurocognitive deficit: One cognitive area is impaired
    • Neurocognitive impairment: Deficits in at least two domains
    • Neurocognitive disorder: Impairment is “clinically meaningful”; definite symptoms such as problems at work or difficulties with other aspects of social or day-to-day functioning
  • Grant and Atkinson (1995) Diagnostic Schema
    • Mild Neurocognitive Disorder/Minor Cognitive Motor Disorder MND/MCMD (coincides with neurocognitive impairment)
      • Characterized by difficulty in concentrating, unusual fatigability, subjectively slowed down, and mild memory problems
      • May by seen as anxiety, depression, or hypchondriasis
      • Cognitive testing reveals difficulties with information processing speed, divided attention, sustained effortful processing, deficiencies in learning and recalling new information
      • Problem solving, abstract reasoning, and motor speed are occasionally seen
      • Verbal skills are less affected (although may have slower fluency)
    • HIV-Associated Dementia [HAD] (coincides with neurocognitive disorder)
      • Characterized by severe impairments in cognitive functioning with marked interference in social occupational performance
      • Impairments commonly see in learning and recall, psychomotor speed, fluency, and executive functioning
      • Affective lability, irritability, withdrawal, apathy, or inappropriateness may be present
      • As dementia advances, delirium is often present
      • Ataxia, weakness, and incoordination can be prominent
      • Decreased survival rate
      • Dementia in AIDS patients is strongly correlated with a decrease survival time
      • Occurs almost exclusively in more advanced AIDS patients
  • Sidtis and Price (1997) AIDS Dementia Complex (ADC) Staging Scheme
    • Stages
      • Stage 0 (normal): Normal mental and motor function
      • Stage 0.5 (equivocal/subclinical): Either minimal or equivocal symptoms of cognitive or motor dysfunction characteristic of ADC or mild signs, but without impairment of work or capacity to perform ADLs (e.g., may show slowed extremity movement); Gait and strength are normal
      • Stage 1 (mild): Unequivocal evidence of functional, intellectual, or motor impairment characteristic of ADC, but able to perform all but the more demanding aspects of work or ADL; Can walk without assistance
      • Stage 2 (moderate): Cannot work or maintain the more demanding aspects of daily life, but able to perform basic activities of self-care; Ambulatory but may require a single prop
      • Stage 3 (severe): Major intellectual incapacity or motor disability
        • Cannot follow news or personal events
        • Cannot sustain complex conversation
        • Considerable slowing of all output
        • Cannot walk unassisted, requiring walker or personal support, usually with slowing and clumsiness of arms as well
      • Stage 4 (end stage): Nearly vegetative
        • Intellectual and social comprehension and responses are at a rudimentary level
        • Nearly or absolutely mute
        • Paraparetic or paraplegic with double incontinence
    • At the early stages, we see complaints of lapses in concentration, increased difficulty in performing tasks that were once routine, forgetfulness, difficulty walking, diminished legibility in writing, loss of interest in daily activities, and social withdrawal
    • We do not see an initial amnestic state
    • Progresses to a final stage that is nearly vegetative, with only rudimentary intellectual function


  • Quality of life changes (driving skills may or may not be affected)
  • Medication management is significant (if cognition is deficient, may not be able to management own medications)
  • Work functioning decreases
  • Increased substance abuse (either as a risk factor or subsequent to the diagnosis) – may also impact cognitive functioning
  • Stigmatism
    • Threat of loss of employment
    • Threat of denial of medical benefits and or life insurance
    • May affect immediate social support


  • Adjustment Disorders
  • Anxiety Disorders: GAD, Panic D/O, OCD
  • Mood Disorders: Depression, Mania (i.e., Bipolar)
  • Psychosis
    • May or may not be pre-existing
    • People with Schizophrenia are at a higher risk for contracting HIV
    • Brief Reactive Psychosis, Depression with Psychotic Features, Psychoactive Substance Use Disorders, and organic sources
  • Substance Use Disorders
    • May or may not be pre-existing


  • Exposure to HIV doesn’t always lead to infection, and some people who have been repeatedly exposed over years remain uninfected
  • Moreover, many infected people have remained well for over a decade
  • Without benefit of current drug treatments, a person infected with HIV had a 1 to 2 percent chance of developing AIDS in the first several years after infection
    • The chance continued at about 5 percent each year thereafter
    • The risk of developing AIDS within 10 to 11 years of contracting the infection was about 50 percent
  • An estimated 95 to 100 percent of infected people will eventually develop AIDS, but the long-term effects of newly developed drugs used in combination may improve this outlook
  • The first drugs used to treat HIV, such as AZT (zidovudine) and ddI (didanosine), have reduced the numbers of opportunistic infections and increased the life expectancy of people with AIDS, and combinations of these drugs produce even better results
  • Newer nucleoside drugs, such as d4T (stavudine) and 3TC (lamivudine), and HIV protease inhibitors, such as saquinavir, ritonavir, and indinavir, are even more potent
  • In some, combination therapy reduces the amount of virus in the blood to undetectable levels. Cures, however, have not been proven
  • With the development of new antiviral drugs and improved methods to treat and prevent opportunistic infections, many people retain their physical and mental abilities for years after the diagnosis of AIDS

History of Neuropsychology


First Uses of the Term

  • 1913: Term first used by Sir William Osler
  • 1936: Entered psychology nomenclature after use by Karl Lashley
  • 1949: Term used by D. O. Hebb in his book, The organization of behavior: A neuropsychological theory. The term was undefined, however.
  • 1957: The term became a recognized designation for a subfield of the neurosciences when Heinrich Kluver (Behavior Mechanisms in Monkeys) suggested the book would be of interest to neuropsychologists. Did not use the term in the 1933 edition.
  • 1960: Term given wide publicity when it appeared in Karl Lashley’s writings (The Neuropsychology of Lashley). The term was still undefined.


  • The study of the relation between brain function and behavior
  • The field draws on information from many disciplines, but its central focus is the development of a science of human behavior based on the function of the brain
  • Its contemporary definition is strongly influenced by two traditional foci for experimental and theoretical investigations in brain research: the brain hypothesis, the idea that the brain is the source of behavior; and the neuron hypothesis, the idea that the unit of brain structure and function is the neuron


  • American (actuarial)
    • Based primarily on psychometric properties. Normative data and “organicity”
    • Developed out of behavioral/actuarial methods at the time
    • Statistical evaluation
    • Standardized
    • Deemphasized individual difference
    • Protocol
  • Russian (clinical-theoretical, Luria)
    • Heavy reliance on clinical expertise, minimal normative data, observation key
    • single case studies
    • Lesion identification and localization
    • Lacks objective standardization or procedures
    • Detailed clinical evaluation
    • Unique behavioral product
    • Hypothesis testing


500 B.C.

  • Almaceon of Croton: Located mental process in the brain, subscribing to what is now called the brain hypothesis

495 B.C.

  • Empedocles: Located mental process in the heart, subscribing to what could be called the “cardiac hypothesis”

460 B.C.

  • Hippocrates: Argued that the brain was the organ of intellect and controlled senses and movement. Lesions affected the contralateral side

427 B.C.

  • Plato: Developed the concept of the tripartite soul and placed its rational part in the brain because that was the part that was closest to the heavens

384 B.C.

  • Aristotle: The heart was warm and active, and the source of mental processes; the brain, because it was cool and inert, served as a radiator to cool the blood

130 A.D.

  • Galen: Spent 5 years as a surgeon to gladiators
    • Aware of the behavioral consequences of brain damage
    • Refuted Aristotle by pointing out that nerves from sense organs go to the brain and not the heart
    • Also completed experiments looking at effects of pressure on the heart and brain


  • The notion that given behaviors are controlled by specific areas of the brain
  • Today, the term generally means functions are distributed among different segments of the neocortex
  • Two problems: are mental processes the products of the brain or mind; & where are the controls for different aspects of behavior located within the brain?

300 B.C.

  • Herophilus: Believed the brain was the source of intellect, the third ventricle the source of cognition, the fourth ventricle the seat of the soul, and posterior regions responsible for memory

130 A.D.

  • Galen: Believed that the substance of the brain was responsible for intellect, not the ventricles


  • Vesalius: Noted that the brains of all animals have similar structures and very only by size


  • Descartes: Replaced the Platonic concept of the tripartite soul with that of a unitary mind that is the reasoning or rational soul
    • Originator of the mind-body problem
    • First to locate mental processes precisely within brain tissue; the pineal gland


  • Gall & Spurzheim: Different human faculties were located in different centers of the brain
    • Vital forces were located within the brainstem and intellectual capacity within the cerebral hemispheres, connected by the corpus callosum
    • Personal characteristics determined by the shape of the skull (Phrenology)
    • Made important discoveries in neuroanatomy: cortex composed of functioning cells that are connected with subcortical structures, crossing of the pyramids, white and grey matter composition of the spinal cord, and connectedness of the cerebral hemispheres by commissural fibers
    • Gall also gave the first complete account of a relation between left frontal brain damage and aphasia


  • Bouillaud: Presented a large series of cases of loss of speech following frontal lesions
    • Suggested left hemisphere controlled various right-handed acts
    • Provided a method for determining localization of function, which moved neuropsychology from the descriptive to correlational level


  • Dax: Reported, in an unpublished paper, on 40 patients over a 20-year period, noting the association between left-hemispheric damage, right hemiplegia, and aphasia


  • Auburtin: furthered Bouillaud cause, when he presented at the Anthropological Society of Paris


  • Broca: Offered the first model of the neuropsychology of language
    • 4 contributions to study of cortical functions
      • Described a syndrome consisting of an inability to speak despite intact vocal mechanisms and normal comprehension (Broca’s aphasia)
      • Coined the term aphemia
      • Correlated aphemia with an anatomical site (Broca’s area)
      • Elaborated the concept of cerebral dominance of language in the left hemisphere
    • Widely criticized by many historians, many of whom judged his contributions as not original, not enduring, or not accurate


  • Fritsch & Hitzig: Produced contralateral movement through mechanical and electrical stimulation of the brain
    • Resulted in notion that cortex is excitable, cortex plays a role in producing movement, & function is localized (“On the electrical excitability of the cerebrum”)


  • Bartholow: Was the first to perform electrical stimulation of a human cortex


  • Penfield: Mapped sensory & motor regions of the cortex
    • Experimented with electrical stimulation


  • Connectionist theories hypothesized that a relatively small number of basic centers in the brain could be combined through connections to explain a wide variety of higher functions


  • Wernicke: Made findings devastating to strict localization
    • There is more than one language area (sequential programming of various behaviors) & damage that spares an area could result in deficits that are indistinguishable from those resulting from damage to the area (concept of disconnection)
    • This type of theorizing was known as associationism or connectionism
  • Meynert: Was an associate of Wernicke and the first to suggest the cortex behind the central fissure is sensory in function
    • Provided thorough account of brain structures and their possible functional significance
    • Described thalamus, hypothalamus, hippocampus, lateral geniculate nucleus, and nucleus basilis of Meynert


  • Dejerine: Identified the first callosal syndrome, & alexia w/o agraphia
  • Liepman: Described apraxias and, he and Maas, callosal apraxia in connectionist terms


  • Geschwind: Supported connectionist explanations of aphasia, apraxia, alexia, etc.

HIERARCHICAL ORGANIZATION (but still connectionist in nature)


  • Hughlings Jackson: Viewed the nervous system as an organized and interactive whole, with functional hierarchy in several levels (spinal cord, basal ganglia & motor cortex, & frontal cortex)
    • Adopted the theory of hierarchy from Spencer’s evolution of the brain argument
    • Studied focal seizures, and proposed the homunculus notion
    • Ideas were too complex for his time…
    • Dissolution, the notion that disease or damage would produce the reverse of evolution (the organism still has a repertoire of behaviors, but the behaviors are simpler in nature)
  • Vygotsky: Cultural historic theory (greatly influenced Luria)
    • Suggested cultural, historical, and social influences are important for adaptation
  • Luria: Lesions lead to disintegration of functions but may tell you little about the functional system
    • Need to understand how brain structures contribute to functional systems of behavior
    • Three Functional Units
      • Brain Stem Structures (arousal unit): Responsible for regulating cortical tone
      • Cerebral Cortex Posterior to Central Sulcus (input): Responsible for receiving, organizing, and storing visual, auditory, and tactual stimuli
      • Cerebral Cortex Anterior to Central Sulcus (organization & planning unit): Responsible for emitting motor responses, formulating intentions, planning and evaluating behavior
      • 2nd and 3rd blocks are also divided into primary, secondary, and tertiary areas.
    • Five Stages of Development of Higher Cortical Functions
      • RAS
      • Primary sensory & motor areas, biologically more than environmentally
      • Single modality secondary association areas
      • Intermodality integration
      • Prefrontal regions
    • Problems with Luria’s Theory
      • Not all cortical areas are hierarchically linked.
      • Difficult to make firm distinctions between sensory and motor functions
      • Unclear how much behavior goes through direct sequential process
      • Doesn’t take into account the parallel systems in the brain



  • Flourens: Generally credited with the demolition of Phrenology
    • Argued for an equipotentiality approach
    • First scientific studies related to brain function (pigeons & chickens)

Late 19th & Early 20th Centuries

  • Marie, Head, Goldstein, & Lashley’: Move toward holism, attacked strict localization
    • Gestalt psychology was influential in this movement
    • Social and political influences around WWI also contributed
    • Lashley proposed theory of mass action and equipotentiality.


Late 19th Century

  • Vogt, Campbell, Brodmann: Produced first cytoarchitectonic maps
  • Ribot: Introduced the distinction between anterograde and retrograde memory; also, Ribot’s law.


  • Munk: Ablation of occipital cortex of dogs – Lissauer and visual agnosia


  • Bender: Neurologist (Bender-Gestalt)
  • Golden: Standardized Luria’s Neuropsychological Investigation
  • Goodglass: Study of language and aphasia
  • Halstead & Reitan: Developed the most widely known battery, based on a series of tests devised by Halstead in the 1940’s
  • Kaplan: Originator of the Boston Process Approach
  • Mishkin: Interaction between amygdale and hippocampus in recognition memory; independence of these structures in associative learning
  • Pribram: Hologram model of memory
  • Teuber: Double dissociation of function; “Kennard principle”
  • Zangwill: Theory of equipotentiality


Why was Neuropsychology so Slow in Developing?

  • Neurologists persisted in rejecting the brain-behavior correlation positions of Broca, Wernicke, etc.
  • Two world wars intervened…
  • Psychology directed its attention to behavior, psychophysics, and psychoanalysis

Why did Neuropsychology Develop?

  • Neurosurgery: Horsley-Clarke (stereotaxic device), Scoville (H.M.), Milner (surgically treated epileptics), Sperry (split brain studies)
  • Psychometrics: Objective measurement and statistical analysis
  • Technology: CT, MRI, functional neuroimaging
  • Experimental Psychology

General Pharmacology


Tricyclic Antidepressants (TCAs)

  • Common TCAs
    • imipramine (Tofranil)
    • clomipramine (Anafranil)
    • amitriptyline (Elavil)
  • Mechanism of Action
    • NE and 5-HT receptors
  • Uses
    • Somatic and vegetative symptoms of depression, panic attacks, agoraphobia, and obsessive states
  • Side Effects
    • Anticholinergic (e.g., dry mouth, blurred vision, pupil dilation, urinary retention, nasal congestion, skin rash, cardiovascular effects, memory, confusion, and insomnia)

Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Common SSRIs
    • fluoxetine (Prozac)
    • sertraline (Zoloft)
    • paroxetine (Paxil)
  • Mechanism of Action
    • 5-HT
  • Uses
    • Depression, obsessive compulsive disorder, and eating disorders
  • Side Effects
    • Sexual problems, gastrointestinal symptoms, headache, and dizziness
    • Less severe side effects than TCAs
    • Less potential for a lethal dose
    • In combination with other serotonergic compounds, can result in central serotonin syndrome that can be fatal


  • Types
    • bupropion (Wellbutrin)
    • nefazodone (Serzone)
    • venlafaxine (Effexor)
  • Side Effects
    • Less anxiety and sexual side effects than SSRIs

Monoamine Oxidase Inhibitors (MAOIs)

  • Common MAOIs
    • phenelzine (Nordil)
    • tranylcypromine (Parnate)
  • Mechanism of Action
    • NE
  • Uses
    • Atypical depression, hostility, anxiety, and hypochondriasis
  • Side Effects
    • Tremor, hypotension, dizziness, dry mouth, upset stomach, weight gain, blurred vision, and headache
    • Must avoid foods with tyramine due to possibility of developing hypotensive crisis

Mood Stabilizers

  • Types
    • lithium (Lithobid)
    • divalproex sodium(Depakote)
  • Mechanism of Action
    • Unknown
  • Uses
    • Mania and mood swings
  • Side Effects
    • Hand tremor, gastric distress, weight gain, fatigue, and mild cognitive impairment
    • Vomiting, abdominal pain, diarrhea, severe tremor, ataxia, and coma can appear at toxic levels


  • Types
    • chlorpromazine (Thorazine)
    • thioridazine (Mellaril)
    • haloperidol (Haldol)
    • clozapine (Clozaril)
    • risperidone (Risperdal)
  • Mechanism of Action
    • Dopamine
  • Uses
    • Positive symptoms of schizophrenia and psychotic reactions
  • Side Effects
    • Anticholinergic and extrapyramidal effects (Parkinsonian symptoms) and tardive dyskinesia
    • Risk of agranulocytosis with clozapine
    • Neuroleptic Malignant Syndrome (e.g., high fever, severe muscle rigidity, altered consciousness, and ANS dysregulation)



  • Types
    • diazepam (Valium)
    • alprazolam (Xanax)
    • clonazepam (Klonipin)
    • lorazepam (Ativan)
    • Triazolam (halcion)
  • Mechanism of Action
    • GABA
  • Uses
    • Anxiety, seizure disorder, and sleep
  • Side Effects
    • Sedation/drowsiness, confusion, disorientation in the elderly, disturbed sleep, potential for a withdrawal syndrome


  • Types
    • thiopental (Pentothal)
    • amobarbital (Amytal)
    • secobarbital (Seconal)
  • Mechanism of Action
    • Reticular Activating System
  • Uses
    • Acute agitation
  • Side Effects
    • Addictive
    • Synergistic effects with alcohol consumption


  • Types
    • propanolol (Inderal)
  • Mechanism of Action
    • Beta-adrenergic
  • Uses
    • Physical manifestations of anxiety (anticipatory)
  • Side Effects
    • Gastric distress, hypotensive episodes, sexual dysfunction, numbness, and some memory impairment


  • Types
    • Morphine
    • Percodan
    • Darvon
    • Methadone
  • Mechanism of Action
    • Enkephalin receptors
  • Uses
    • Pain relief
  • Side Effects
    • Pupil constriction, decreased visual acuity, perspiration, gastric distress, respiratory suppression, constipation, and addictive


  • Types
    • methylphenidate (Ritalin)
    • pemoline (Cylert)
    • Dexedrine
  • Mechanism of Action
    • Catecholamines (i.e., DA, NE, Epinephrine)
  • Uses
    • ADHD, narcolepsy, and treatment resistant depression
  • Side Effects
    • Anorexia and dry mouth
    • Overdose can lead to paranoid state, tachycardia, and anxiety


  • Types
    • carbamazepine (Tegretol): Can also be a mood stabilizer
  • Side Effects
    • CNS (i.e., drowsiness, confusion, ataxia, hyperreflexia, clonus, tremor)
    • GI (i.e., n/v, diarrhea, constipation, anorexia)
    • Blood dyscrasia (rare)
    • Cardiovascular
    • Dermatologic problems


  • Cholinergic Therapies
    • tacrine (Cognex)
    • donepezil (Aricept)
    • eldepryl (Selegiline)
    • Estrogen
    • Ibuprofen
    • Vitamin E (&C) nerve growth enhancers
  • Rationale
    • Cholinergic deficit has been the most commonly observed neurotransmitter deficits in Alzheimer’s Disease and is hypothesized to underlie the cognitive deficits; although the precise relationship remains unknown
    • Cholinesterase inhibitors approved for use are Cognex and Aricept
    • Aricept has less hepatotoxicity than Cognex


  • Growing Population
    • Individuals > than 6 comprise 12% of the population but receive 33% of all prescription drugs
    • Elderly patients take on average of 3-4 prescription drugs per day
    • The > 65 age group is growing
  • Physiology of Aging
    • Diminished Physiologic Reserve
      • Changes in CNS function may not become apparent until patient confronts a physiologic challenge (acute illness or medical intervention)
    • Aging Impacts the Pharmacokinetics of Drugs
      • Absorption is influenced by gastric pH, intestinal blood flow, GI motility, # of cells to absorb
      • Altered nutritional status in the elderly, consumption of other drugs can also affect absorption
      • Distribution: 3 compartments (fat tissue, body water, binding to plasma proteins)
      • Increased proportion of body fat to water with age
      • Increased total body fat which increases the volume of distribution of lipid soluble drugs which can impact the ½ life
      • Intravascular protein levels drop in the elderly and this impacts distribution
      • Psychotropics generally bind extensively to plasma proteins
      • Malnutrition, protein wasting, and concomitant administration of other drugs that compete for protein binding sites leads to drop in amount of circulating proteins
      • Metabolism (liver is principal site of metabolism)
      • Decreased hepatic blood flow, competing drugs may impact metabolism
      • Excretion (kidney is major organ for excretion)
      • Renal clearance is a problem with dehydration which is common in the elderly
    • Pharmacodynamics and the Elderly
      • Age related alteration in neuronal cell # and neurotransmitter production and break down
      • Selective alteration in pre or post-synaptic receptors e.g., decrease in # and sensitivity of serotonin receptors may impact sleep/appetite in the elderly
      • Age related alterations in receptor binding
      • Less efficient blood brain barrier
      • Decreased cerebral circulation and metabolism
      • Autonomic neurodegenerative changes, predisposing to orthostatic hypotension and thermal dysregulation
    • Specific Risks
      • AD: Degeneration of the cholinergic system where anticholinergic drugs have amplified negative effect on an already compromised memory system
      • PD: Profound DA depletion
  • Drug Induced Neuropsychiatric Disorders in the Elderly
    • Seven categories of adverse effects of commonly encountered agents used with geriatric patients (e.g., Coffey & Cummings, APA Textbook of Geriatric Neuropsychiatry, 1994)
      • Depression
      • Mania
      • Anxiety or agitation
      • Delirium
      • Psychosis
      • Visual hallucinations
      • Dementia-like syndrome
  • Medical Conditions Producing Psychiatric Symptoms
    • Cognitive
      • Delirium may arise from intracranial or extracranial causes
      • Dementia: Must involve cerebral dysfunction, whether primary or secondary, may have treatable causes (e.g., neurosyphilis, thyroid disease, vitamin deficiencies, medication-induced)
    • Mood
      • Neurological (e.g., Parkinson’s, MS, Huntington’s, dementia, hydrocephalus, infections, trauma)
      • Cerebrovascular disease (MID)
      • Endocrine (e.g., thyroid, adrenal, menses or post-partum related)
      • Infections or inflammatory disorders (e.g., HIV, mono, chronic fatigue syndrome, pneumonia, lupus, rheumatoid arthritis, etc.)
      • Miscellaneous (e.g., cancer, uremia, nutritional deficiencies)
    • Psychotic Symptoms
      • Neurological (e.g., epilepsy, neoplasm, trauma, hydrocephalus, HD, herpes encephalitis, neurosyphilis)
      • CBVS Disease
      • Many other disease states (e.g., nutritional deficiencies, delirium syndromes, heavy metal poisoning, lupus, acute intermittent porphyria)
    • Anxiety
      • Neurological (see above)
      • Hypoxia due to cardiovascular disease, pulmonary disease, anemia
      • Endocrine (e.g., thyroid, pituitary, adrenal, virilization disorders in females)
      • Inflammatory disorders (e.g., lupus, rheumatoid arthritis)
      • Nutritional deficiencies
      • Miscellaneous (e.g., hypoglycemia, cancer, mono, etc.)

Frontal Lobes

Frontal Subcortical Circuits


Frontal_Lobes_1The General structure shared by ALL frontal-subcortical circuits (direct connections) (CSGT: Cortex, Striatum, Globus Pallidus, Thalmus)

There are 5 frontal-subcortical circuits that provide a neuroanatomical basis for movement and behavior, named by either function or cortical site of origin.

  • Each circuit uses the same transmitters at each anatomic site.
  • The relative anatomic positions of the circuits are preserved in each circuit structure (i.e., dorslateral PFC projects to dorslateral region of the caudate).

The 1st two circuits are motor:

Motor (Supplementary Area-Subcortical) Circuit

General control of preparatory premovement activity and serial/parallel processing of movements initiated in the cortex: somatomotor system governing movement of limb and body in space.

Oculomotor (Frontal eye fields-subcortical) Circuit

Visuomotor system for orienting the head and eyes to the environment.

The other three are more behaviorally related, each with signature neurobehavioral clinical syndromes.

The Dorsolateral Circuit

Damage typically results in Executive Dysfunction including:

  1. poor organizational strategies,
  2. poor memory search strategies,
  3. Stimulus-bound behavior/environmental dependency,
  4. impaired set shifting & maintenance,
  5. verbal-manual dissociation.


Frontal_Lobes_2Figure A: Origin of the Dorsolateral Curcuit.

Orbitofrontal Circuit

Has two parallel subcircuits Lateral & Medial. Personality Change is the hallmark of orbitofrontal dysfunction, including:

  1. irritability,
  2. lability,
  3. fatuous euphoria,
  4. inappropriate response to social cues,
  5. undue familiarity,
  6. lack of empathy.
  • These pts. often perform normally on the WCST.
  • Acquired OCD may result from OF lesions.


Frontal_Lobes_3Figure B: Origin of the Orbitofrontal circuit (Lateral in green, medial in red & blue).

The Anterior Cingulate circuit

Mediates motivated behavior, thus damage to this circuit results in an apathetic syndrome. Bilateral lesions often results in akinetic mutism. Other symptoms may include,

  1. psychic emptiness,
  2. poverty of spontaneous speech,
  3. indifference to pain,
  4. poor response inhibition,
  5. reduced creative thought.

Frontal_Lobes_4Figure C: Origin of the Anterior circuit

Direct and Indirect Pathways

Each direct circuit is modulated by an indirect pathway


Frontal_Lobes_5The direct and indirect frontal subcortical loops (red = excitatory connections; blue = inhibitory connections).

  1. Excitatory glutaminergic corticostriatal fibers
  2. Direct loop’s inhibitory GABA/substance P fibers (associated with D1 receptors) from the striatum to the globus pallidus interna/substantia nigra pars reticulata
  3. Indirect loop’s inhibitory GABA/enkephalin fibers (associated with D2 receptors) from the striatum to the globus pallidus externa
  4. Indirect loop’s inhibitory GABA fibers from the globus pallidus externa to the subthalamic nucleus
  5. Indirect loop’s excitatory glutaminergic fibers from the subthalamic nucleus to the globus pallidus interna/substantia nigra pars reticulata
  6. Basal ganglia inhibitory outflow via GABA fibers from the globus pallidus interna/substantia nigra pars reticulata to specific thalamic sites.
  7. Thalamic excitatory fibers returning to cortex (shown in contralateral hemisphere for convenience).

The Direct connection Disinhibits the thalamus. The Indirect connection Inhibits the thalamus.

Open and closed loops

Although each of the 5 circuits comprises a closed loop, there are also open elements in each circuit. This allows for posterior association cortices to affect frontally mediated behavior or to serve as communiction points between the three circuits.


The numerous structures and the many transmitters, receptors, and modulators involved in these circuits account for the observation that lesions in different brain regions may have similar behavioral effects.

Endocrine Disorders



  1. Endocrinology is the study of chemical communication systems that provide the means to control a huge number of physiologic processes
  2. Two systems control all physiologic processes
    1. The nervous system sends electrical messages to control and coordinate the body
    2. The endocrine system uses chemicals to communicate, called hormones

Three general classes or groups of hormones (classified by chemical structure, not function)

  1. Steroid hormones (e.g., the sex hormones)
  2. Amino acid derivatives (e.g., epinephrine)
  3. Peptide hormones (e.g., insulin)

Endocrine System (the following are the major human endocrine glands)

Hypothalamus and Pituitary Gland

  1. Much of the endocrine system is controlled by hormones produced by cells in the hypothalamus
  2. A small but very crucial vascular system interconnects the hypothalamus and the anterior pituitary gland
  3. The hypothalamic hormones are secreted by specialized neurons called neurosecretory cells, located near the base of the pituitary stalk
  4. These hormones are carried by the blood vessels to the pituitary gland and stimulate it to secrete its hormones
  5. Pituitary gland is called the master gland because it controls many endocrine functions
  6. Most of the anterior pituitary hormones control the secretions of other endocrine glands (e.g., gonadotropic hormones to stimulate the gonads to release male or female hormones; also produces growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, and prolactin)
  7. The hypothalamus also produces the hormones of the posterior pituitary gland and control their secretion (e.g., oxytocin for ejection of milk and uterine contractions at the time of childbirth; vasopressin [antidiuretic hormone] for regulation of urine output by the kidneys)

Thyroid Gland (and Parathyroid Gland)

  1. Thyroid hormones affect three fundamental physiologic processes (cellular differentiation, growth, and metabolism)
  2. Thyroid gland also produces calcitonin, and the parathyroid gland secretes the parathyroid hormone
    1. Both participate in control of calcium and phosphorus homeostasis and have significant effects on bone physiology


  1. Two functions
    1. It serves as a ducted gland, secreting digestive enzymes into the small intestines
    2. It also serves as a ductless gland by secreting insulin and glucagon to regulate the blood sugar level
      1. a. Glucagon tells the liver to take carbohydrates out of storage to raise a low blood sugar level that’s too low
      2. b. Insulin tells the liver to take excess glucose out of circulation to lower a blood sugar level that’s too high

Adrenal Glands

They sit on top of the kidney and consist of two parts

  1. Cortex, which secretes corticosteroids (e.g., cortisone)
    1. Well-known as being anti-inflammatory
    2. But they also suppress the immune system and can lead to susceptibility to infections
    3. Known to raise blood pressure
  2. Medulla, which secretes epinephrine (a.k.a., adrenaline) and other similar hormones
    1. Responds to stressors such as fright, anger, caffeine, or low blood sugar


  1. The anterior pituitary gland secretes to the gonads, and the gonads secrete their own hormones (in addition to producing gametes)
  2. These hormones are called sex hormones
    1. Both sexes make some of each of the hormones, but testes secrete primarily androgens (e.g., testosterone), and ovaries make estrogen and progesterone

Pineal Gland

  1. Located near the center of the brain in humans and is stimulated by nerves from the eyes
  2. It secretes melatonin at night when it’s dark, thus secreting more in winter when the nights are longer
    1. Melatonin promotes sleep
    2. It affects reproductive functions by depressing the activity of the gonads
    3. It affects thyroid and adrenal cortex functions
    4. It is tied in to the circadian rhythm, annual cycles, and biological clock functions
    5. Linked to seasonal affective disorder – too much melatonin is produced

Common Endocrine Disorders

Diabetes Mellitus

Definition – DM is a disorder in which blood levels of glucose are abnormally high because the body doesn’t release or use insulin adequately

Types/Causes of DM

  1. Type I (IDDM)
    1. Pts. develop little or no insulin
    2. Of the 6% of the population with diabetes, only 10% have this type
    3. Diagnosis is before the age of 30
    4. Environmental factors (e.g., viral infection or nutritional factor in childhood or early adulthood) is thought to be the cause
    5. Some genetic predisposition is most likely needed for this to happen (e.g., short arm of chromosome 6)
  2. Type II (NIDDM)
    1. The pancreas continues to manufacture insulin, sometimes at even higher levels, but the body develops resistance to its effects, resulting in insulin deficiency
    2. Diagnosis is most typically after age 30, although children and adolescence can have it
    3. The prevalence becomes progressively more common with age
    4. 15% of people over 70 have Type II DM
    5. Obesity is a risk factor (80-90% of the obese have it)
    6. Blacks and Hispanics have a 2-3 times increased risk
    7. Tends to run in families
  3. Other causes
    1. High level of corticosteroids
    2. Pregnancy (i.e., gestational diabetes)
    3. Drugs
    4. Poisons that interfere with the production or effects of insulin
  4. Discuss Brittle Diabetes

Medical Symptoms

  1. Frequent urination – polyuria (kidneys are trying to dilute the glucose in urine)
  2. Excessive thirst – polydipsia
  3. Excessive hunger – polyphagia (loss of calories through urination causes weight loss, and the body needs to compensate for it).
  4. Other symptoms include blurred vision, drowsiness, nausea, and decreased endurance during exercise
  5. Those with poorly controlled DM have greater susceptibility to infections
  6. Weight loss almost always occurs before treatment in Type I, but most ppl with type II don’t lose weight
  7. In type I, sx begin abruptly and may progress rapidly to diabetic ketoacidosis (DKA)
    1. A condition in which fat cells begin to break down, producing ketones (toxic chemical compounds that can make the blood acidic)
    2. Initial sx include excessive thirst and urination, weight loss, nausea, vomiting, fatige, abdominal pain (esp. in kids), deep and rapid breathing, and coma if not treated
    3. DKA can occur even after starting insulin if they miss an injection or become stressed by an infection, accident, or serious medical condition
    4. Ppl with type II may not have sx for years or decades
      1. First sx of urination and thirst are mild at first and gradually worsen over weeks or months
      2. DKA is rare
      3. If blood sugar becomes very high, usually as a result of some superimposed stress (e.g., infection), the person may develop severe dehydration, which may lead to mental confusion, drowsiness, seizures, and a condition called nonketotic hyperglycemic-hyperosmolar coma


  1. Over time, elevated blood sugar levels damage blood vessels, nerves, and other internal structures
  2. Poorly controlled blood sugar also tend to cause the blood levels of fatty substances to rise, resulting in accelerated atherosclerosis
  3. Poor circulation through large and small blood vessels can harm the heart, brain, legs, eves, kidneys, nerves, and skin (making healing injuries slow)
  4. Long terms complications include things like MI, CVA, diabetic retinopathy, diabetic polyneuropathy, impotence in men, kidney failure, skin ulcers, gangrene of hands and feet, and amputations

Psychiatric Symptoms

Children and adolescents

  1. Kids are difficult to regulate medically
  2. Research has suggested that kids are quite resilient to psychopathology
  3. Longitudinal study by Kovacs et al. (1990)
    1. 14% of kids (out of 95) had premorbid dx
    2. 36% had dx within 3 mos. of onset – mostly adjustment disorder
    3. 93% of them had complete remission within 9 mos.
    4. As kids age, there may be a small increase in sx of depression, and in girls an increase in sx of anxiety
    5. Children who reported more difficulties in managing their diabetes also showed more symptoms of psychological distress
  4. Most cross-sectional studies have found no evidence of severe behavior or psychological problems in kids or adols.
  5. Some studies have suggested “tendencies toward anxiety and depression,” but not severe enough to meet diagnostic criteria


  1. Not as much research, but depression seems to be higher in adult DM compared to general population, but it is usually comparable to other chronic illnesses
  2. Type of diabetes does not appear to make a difference
  3. Certain concomitant medical factors appear to increase the risk of developing a psych disorder (e.g., macrovascular disease, retinopathy, peripheral neuropathy)

Neuropsychological Disorders

  1. Early onset in kids
    1. Early studies were able to show that IQ scores are significantly lower if diagnosed before the age of 5 – cause is thought to be organic
    2. Younger kids tested b/t 6 and 14, but dx by 4, show performance decrements (not just in IQ, but in other visuospatial measures)
    3. Girls more affected by boys
    4. By adolescence, impairments are across a broader range of domains
      1. IQ, attention, learning, memory, visuospatial ability, mental and motor speed
    5. 25% of adols. dx by age 5 met criteria for clinically significant impairment compared to only 6% of those dx after 5 and 6% of the nondiabetic comparison group
    6. Early onset kids and adols. have higher rate of severe hypoglycemia and have greater occurrence of seizures or LOC
    7. These kids also are more likely to show EEG abnormalities
  2. Later onset in kids
    1. These kids are much more comparable to their nondiabetic controls, with the exception of verbal IQ (more in girls) and academic achievement (more in boys)
      1. School absence was the greatest predictor of decline
      2. These kids may have undetected hypoglycemic events and miss stuff in class
  3. Cognitive function in adults with type I
    1. Evidence suggests that chronic hyperglycemia does have a negative impact on cognitive functioning once the type I-ers are in adulthood
    2. Deficits have been shown in complex novel problem solving ability, effortful learning, memory, attention, psychomotor speed, spatial information processing
    3. Theory is that chronic hyperglycemia may induce a “central neuropathy” that is characterized primarily by mental and motor slowing – deficits tend to be relatively small and unlikely to aversely affect ADLs
    4. Diabetic adults have slower brain stem auditory evoked potential latencies
    5. More likely to show abnormalities on MRI

End Stage Renal Disease (ESRD)


  1. Condition involving irreversible failure of excretory and regulatory functions of the kidneys
  2. Kidneys no longer sustain normal body functioning
  3. Requires renal replacement therapy for survival
  4. Associated cognitive deficits

Essential functions of the kidneys

  1. Controls the volume and composition of bodily fluids
  2. Excretes metabolites
  3. Produces or metabolizes hormones

Stages of renal failure

  1. Diminished renal reserve
    1. A measurable loss of renal function is noted
    2. Homeostasis is preserved at the expense of some hormonal adaptation (e.g., hyperparathyroidism)
  2. Renal insufficiency
    1. A slight retention of nitrogenous compounds (azotemia), which are reflected in elevated plasma urea and creatinine
  3. Uremia
    1. It’s the accumulation in the blood of constituents normally eliminated in the urine that produces a severe toxic condition
    2. Disturbed fluid and electrolyte balance
    3. Increased azotemia
    4. Systemic manifestations occur
      1. Pulmonary, cardiovascular, neurological, dermatological, gastrointestinal, hematological, and immunological systems

Most common causes of ESRD (top two are the most common in the US)

  1. DM
  2. HTN
  3. Chronic glomerulonephritis (one of the glomerulopathies)
  4. Chronic pyelonephritis
  5. Polycystic kidney disease

Early symptoms of ESRD

  1. Fatigue, drowsiness, apathy, lethargy, social withdrawal, personality changes, decreased concentration, diminished attention span

Progressed neuropsychological symptoms

  1. Confusion, inability to concentrate, decreased mental alertness, fatigability, intellectual impairment, impaired memory, sensory perception deficits, diminished perceptual-motor coordination

Common physical complaints

  1. Chronic fatigue, sexual dysfunction, headaches, nausea, leg cramps, sleep disturbances

If untreated, ESRD may result in delirium, coma, and eventually death


  1. The cognitive deficits associated with chronic renal failure may not be explained solely by uremia, but also by the anemia that almost invariably accompanies it
  2. It’s detected in 90 percent of patients
  3. There are many contributing factors to this complication, but the most important cause is a decrease in erythropoietin production by the failing kidneys
  4. Severe anemia has been shown to be associated with cognitive dysfunction, reduced energy, and mood disturbances
  5. Recombinant human erythropoietin (rHuEPO) has provided effective treatment in reversing anemia in ESRD patients, thereby improving attention, mental processing speed, learning, memory, and mood


  1. Hemodialysis
  2. Peritoneal dialysis (a.k.a., continuous ambulatory peritoneal dialysis)
  3. Kidney Transplantation

Neuropsychological Functioning

  1. Before treatment – reduced mental alertness, decreased concentration, fatigability, intellectual impairment, memory deficits, decreased psychomotor speed, and reduced perceptual-motor coordination
  2. After Treatment – dialysis improves cognitive functioning, but most studies report persistent deficits after the onset of dialysis, particularly in attention and concentration

Psychosocial Factors

  1. Depression
  2. Quality of life issues
  3. Interference with work, school, etc.
  4. Sexual dysfunction
  5. Marital and family discord
  6. Noncompliance with treatment


It is a condition in which the thyroid gland is overactive and produces too much hormone

  1. Many causes (some include:)
    1. Immunologic reactions (believed to be the cause of Graves’ disease)
    2. Thyroiditis – an inflammation of the thyroid gland that typically goes through a phase of hyperthyroidism
    3. Toxic thyroid nodules (adenomas) – areas of abnormal tissue growth within the thyroid gland
    4. Toxic multinodular goiter (Plummer’s disease) – a disorder in which there are many nodules
    5. Uncommon in adolescents and young adults and tends to increase with age
  2. Onset of hyperthyroidism can occur at any time during life span
    1. Peaks during the 3rd and 4th decades
    2. Occurs 7-10 more often in women (reason for sex difference is unknown)
    3. Regardless of the cause, the body’s functions speed up
  3. Symptoms include
    1. Heart palpitations, hypertension, person may feel warm even in a cool room, moist skin and diaphoresis, tremor, nervousness, fatigue and weakness, increased level of activity, increased appetite (but with weight loss), impaired sleep, frequent bowel movements, with occasionally with diarrhea
    2. Older adults may not show the above symptoms, but they may become weak, sleepy, confused, withdrawn, and depressed (sometimes called apathetic or masked hyperthyroidism)
      1. Heart problems, especially abnormal heart rhythms, are seen more often in older people
      2. Can cause changes in the eyes (puffiness, increased tear formation, irritation, unusual sensitivity to light, and the person appears to stare)
  4. Treatment is usually by medication, but other options include surgically removing the thyroid gland or treating it with radioactive iodine

Neurocognitive Effects

  1. Slower reaction time
  2. Impaired motor tasks, likely due to fatigue
  3. Mild deficits in attention, memory, and complex problem solving
  4. With proper treatment, most cognitive problems remit (although maybe not fully)
  5. Affective Features (improve or remit after euthyroidism is restored)
    1. Hyperthyroidism is believed to be accompanied by emotional instability/lability, general hyperactivity, irritability, easy fatigability, heat intolerance, feelings of apprehension, restlessness, and inability to concentrate


A condition in which the thyroid gland is underactive and produces too little thyroid hormone. Very severe hypothyroidism is called myxedema


  • The most common cause is Hashimoto’s thyroiditis (an inflammation of the thyroid gland in which, for unknown reasons, the body turns against itself in an autoimmune reaction, creating antibodies that attack the thyroid gland)
    • The condition occurs eight times more often in women than in men and may occur in people with certain chromosomal abnormalities, including Turner’s, Down, and Klinefelter’s syndromes.
    • Many people with Hashimoto’s thyroiditis have other endocrine disorders such as diabetes, an underactive adrenal gland, or underactive parathyroid glands, and other autoimmune diseases such as pernicious anemia, rheumatoid arthritis, Sjögren’s syndrome, or systemic lupus erythematosus (lupus).
  • The second most common cause is treatment of hyperthyroidism
    • Both radioactive iodine treatment and surgery tend to produce hypothyroidism.
  • The common cause of hypothyroidism in many undeveloped countries is a chronic lack of iodine in the diet that produces an enlarged, underactive thyroid gland
    • Since salt manufacturers began adding iodine to table salt and iodine-containing disinfectants are often used to sterilize cow’s udders, this form of hypothyroidism has disappeared in the United States.
  • Even rarer causes of hypothyroidism include some inherited disorders in which an abnormality of the enzymes in thyroid cells prevents the gland from making or secreting enough thyroid hormones.
  • In other rare disorders, either the hypothalamus or the pituitary gland fails to secrete enough of the hormone needed to stimulate normal thyroid function.


  1. Insufficient thyroid hormone causes bodily functions to slow down.
  2. In sharp contrast to hyperthyroidism, the symptoms of hypothyroidism are subtle and gradual and may be mistaken for depression.
  3. Symptoms include dulled facial expressions, hoarse voice, slow speech, eyelids droop, puffy and swollen face and eyes, weight gain, constipation, inability to tolerate cold, hair that is sparse, coarse, and dry, and the skin that is coarse, dry, scaly, and thick.
  4. Many people develop carpal tunnel syndrome, which makes the hands tingle or hurt.
  5. If untreated, hypothyroidism can eventually cause anemia, a low body temperature, and heart failure.
    1. This may progress to confusion, stupor, or coma (myxedema coma)
  6. Treatment with thyroid hormone replacement therapy (oral medication) for life
  7. Neurocognitive effects
    1. Cognitive deterioration
    2. Onset and development of the cognitive impairments are usually subtle and insidious
    3. The patient becomes sluggish, lethargic, and suffers concentration and memory disturbances (and effects on motor speed)
    4. Some people, especially older people, may appear confused, forgetful, or demented–signs that can easily be mistaken for Alzheimer’s disease or other forms of dementia.
    5. Replacement therapy improves performance, but it may not completely reverse the effects
  8. Affective Features (reversed or greatly improved by thyroid replacement therapy)
    1. Hypothyroidism may be accompanied by symptoms of depression, emotional lability, mental sluggishness, indifference, self-accusatory ruminations, and suspiciousness
    2. Psychiatric presentation may be the first sign of hypothyroidism



Acute inflammation of the parenchyma secondary to viral infection

Herpes Simplex Virus Encephalitis

  • most common sporadic encephalitis
  • no age, sex, racial, seasonal, or geographical predilection

Neonatal Presentation

  • vertical transmission
  • recognized during the 1st – 3rd week
  • diffuse neurological signs, seizures, hypotonia, diminished responsiveness, poor feeding, irritability, systematic manifestations

Children & Adults

  • predilection for medial temporal and orbital areas
  • neurologic presentation – altered consciousness, seizures
  • neuropsych outcome – memory deficits, social problems; Kluver-Bucy like symptoms
  • less than half of survivors have normal developmental or intellectual outcomes
  • 75-85% show significant personality and behavioral changes
  • 30-50% show motor disorders, seizures

Arboviruses (Arthropod-Borne Viruses)

  • outcome dependent upon age at onset, illness type, clinical course, etc.
  • incubation approximately 4-10 days
  • typically occur from May to October in N. Hemisphere

Eastern Equine Encephalitis (EEE)

  • 153 confirmed cases in the U.S. since 1964
  • most common along Atlantic and Gulf coasts
  • mortality – 30-60%
  • pediatric cases – 50-70%

Western Equine Encephalitis (WEE)

  • 639 confirmed cases in the U.S. since 1964
  • most common in western and central US and Canada
  • mortality – 2-5%
  • disease severity increases with age

California Encephalitis (caused principally by the LaCrosse virus strain)

  • roughly 70 cases per year
  • most common in midwest
  • mortality 1%
  • male>female 2:1
  • typically affects young children (peak 5-10 years)
  • sx: paresis, abnormal EEG’s, seizures (40-50%), status epilepticus (10-15%)
  • neurologic outcomes: residual seizures (20%), EEG abnormalities (33-75%)
  • neuropsych outcomes: typically mild sequelae, unless especially ill at presentation



(review articles & studies) Hemispheric Specificity


Blonder, Bowers, Heilman (perception of facial express and prosody)

  • Florida Affect Battery
  • RHD impaired on perception of facial expression and prosody
    • not due to VS properties b/c stim were presented verbally
    • not due to inability of RBD to interpret emotional signif of events b/c able to comprehend emotional sentences (i.e., mom was pissed at the dog for tracking in mud)
    • not due to fact that RBD lost ability to perform cmplx inferential processing b/c reading level at same as NC and LBD
  • 2 interpretations can be made from data:
  1. may be 2 indep systems that are impaired following RBD: system to decode cmplx aud/ visual patterns present in nonverbal emotional expression, other system which assoc beh with emotion
  2. hierarchical system mediates comprehension of nonverbal communicative stim (what they favor)

Cohen (perception of gestures, emotional comprehension, prosody)

  • RTLE<NC=LTLE (all 3 measures); children
  • RH dominant for affective comprehension and that the organization of affective

Borod et al. (facial expression- expressive communication)

  • R and LBD; spontaneous expression of emotions (to slides), posed expression of emotion (look happy), perception of pos/ neg facial emotions
    • Ss with RHD have deficits in processing facial emotion compared to LHD and NC. Further, the notion of valence distinction and hemi. differences was not supported.

Wechsler (emotional memory)

  • immediate recall of 2 stories (amnt recalled and affective content recalled)
  • BD recalled fewer items than the NC on both stories.
  • BD (neutral>affective material)
  • RHD>LHD & BD (overall recall)
  • LHD made fewer errors on the emotionally laden story than the RHD group
  1. cerebral brain damage results in a greater impairment of recall of emotionally charged, verbally presented material than for neutral material
  2. LHD- quantitative errors (recalling less items), did better at emotion content recall than RHD -RH -dominant role in recalling emotionally charged, verbally presented material.

Cimino et al. (series of studies) (emotional memory)

1. RHD & NC

  • describe an event from own life related to cue word (neutral or emotional), decide when the event occurred, how emotionally signif, rated for emotional expression.
  • RHD <NC (emotional reports, less specific)

2. NC presented lateralized pos, neg & neut words/ nonwords (to L and RVF)

  • overall so RVF/ LH adv (expected b/c verbal material)
  • recognition data provided strong support for valence model (LH more accurate for pos than neg words and neg words adv for RH)
  • free recall and perception data provided partial support (LH more accurate for pos, trend for RH more accurate for neg for perception, no diff in free reall)

Babinski (contributions of amygdala to emotional memory)

  • case study of bilateral TL damage (mostly amygdala)
  • intact intelligence, general memory, and other cog domains intact
  • specific, affect-related memory ds
  • conclude that amygdala’s role is to process events in a way that is of specific emotional significance and plays a bottleneck fx for affect-related LTM

Components of Emotion & Studies

Physiological arousal (studied via experience)


  • Gainotti (1st to show this); Babinski and Golstein first to suggest this

RBD (euphoria, indifference)

LBD (catastrophic rxn, depression)

  • specifically: catastrophic rxn (62% L; 10% R) euphoria/ indiff (38% R; 11% L)
  • note, although sensitive, lacks specificity
  • WADA studies: injection into LH (catastrophic rxn) RH (euphoria) when drug wore off)
  • MMPI studies have shown that more LBD are depressed compared to RBD (Gasparrini)
  • Robinson found that LFD and LSC damage after stroke (depression), but often resolved
    • sxs were worse the closer the LH were to F lobes
    • showed that RBD showed reverse (posterior more depressed than anterior strokes)
  • Starkstein : LF & L caudate D more assoc with depression, closer to the frontal pole-worse
  • also see section on prosody (expression)


  • Davidson has done the majority of the work here with NC and depressed looking at EEG with respect to mood valence:
  1. depressed students have lower resting activation levels in LF
  2. induced depressed mood assoc with lower LF activation
  • PET studies have also shown hypometabolism in LF in depressed pts (Bench et al.) esp in L anterior cingulate and DLPF


  • lesions to the F, limibic and amygdala regions all result in emotional changes (see notes)

Overt behavior (studied via expression)


1. NC

  • Moscovitch & Olds recorded facial expresions: L-sided (more)
  • in lit, L hemiface reported more intense production of emotions

2. BD

  • Kolb: anterior lesions causes greater reduction in freq/ intensity of facial expressions than posterior damage (consistent with monkey studies); i.e., FD worse off than TD
  • Kolb also showed chanbed in spontaneous talking: RFL (incr); LFF (decr)
  • Ursual Bellugi showed decreased gestural expression in deaf signers with RBD
  • general conclusions: RBD may reduce facial express, but method differences including:
    • site of lesion in R vs LH
    • size of lesion
    • time since onset of lesion/ disturbance
    • age & sex of Ss
    • means of measurement and induction tech


  1. NC
  2. BD
  • Tucker found that RBD severely impaired in saying semantically neutral stmt (They boy went to the store) sad, happy, indifferent prosody; spoke in monotone voice
  • often see aprosody of speech after RBD:
    • flat when speak sentences with tone
    • accuracy and intensity of prosody decreases
    • no valence difference found
  • Motor aprosodia and sensory have been distinguished:

a.) motor A analogous to BA (but RH)- inability to produce prosody

b.) sensory A have deficit in ability to comprehend prosody (R WA)

  • have shown d.dissoc of both and can have both (with RBD)
  • Ross argued that LH responsible for propositional aspects of language whereas RH responsible for emotional prosodic elements of speech
  • many areas have been suggested as important in prosody: F, P and pre-rolandic, T, BG

GSR (autonomic)

  • RH see decrease in response to emotional stimuli


  • see sct on deaf signers (Bellugi)

Cognitive Processes (studied via evaluation)

Visual-nonverbal material

1. NC (RH advantage)

a.) Bryden (T-scope); found LVF superiority (match expression even after covary face matching

b.) Priming studies show LVF advantage for affective ladden words (interactions with valence; RH-sad; LH-happy)

c.) Chimeric face studies show: judgment of which face looks happier (fill in the emotion)- LVF (judgment)- so L side of face

2. Clinical (RH damage impairs eval, LF too)

a.) Split brain studies show: impaired ID facial expression with LH (Benowitz et al.)

b.) WADA testings show: LH rate faces as less emotional than RH

c.) RBD:

  • overall have shown impaired:
  • comp/ appreciation of humor without captions (Gardner et al.; Brownell et al.)
  • impaired word & sentence id, word discrim (emotional content) – (Borod et al.) so role in lexically based emotional stim
  • Blonder: impired match. scenarios to facial, vocal & gestural emotional expression
  • Bowers suggests not perceptual deficits (vs intact) &b/c impaired when verbally described (e.g., “her eyes widened, he raised his fist- )
  • also suggests it’s not due to deicits in breakdown of emotional semantic knowledge (able to infer that tracking in mud on carpet would make mom mad)

3. impaired evaluation of emotional facial expression

  • RBD only (no valence effect):
    • Borod et al.- also found same impairment in SZ with neg sx suggesting that it’s assoc with RH dysfnct)
    • Borod et al. (found RBD impaired in both perception and expression of emotion; no valence effect compared to LBD)
  • No evidence
    • Hirschman & Safer also found no valence or HS effect (NC Ss only and T-scoped naming and rating intensity of facial)
  • (Valence effect)- typically stronger for L (pos) if found:
    • Duda & Brown: T-scope (NC); RT (indicate happy/ sad)
    • RT quicker for happy faces (LVF-RH)
    • RT (no difference for sad); so partial support
  • Lorenz & Davidson (same set up as Duda study)
    • RT quicker for happy faces (LVF-RH)
    • RT quicker for sad faces (RVF-LH)
  • Davidson & Fox (EEG diff in perception of pos/ neg faces in infants)
    • LF>RF and P (happy segments)
    • sad stimuli (no difference)

Auditory- Prosody

1. NC

  • on dichotic listening task, show LEA-RH for discriminating emotional tones

2. Clinical

  • RBD impaired comprehension of affective prosody (Heilman et al.)- while they found nonaffective prosody not to differ from LBD (both grps worse on this than NC); (Bowers et al.)
  • Heilman had R and LBD rate mood of speaker (R worse)

Emotional memory (not a lot out there)

  • typically show either RBD worse (Wexler- see other notes on this study)
  • have shown partial support for valence notion (Cimino- see other notes on this study)

Disconnection Syndromes


The term “disconnection syndrome” is applied to the effects of lesions of association pathways, either those which lie within a single cerebral hemisphere or those which join the two halves of the brain (Geschwind,1965). Often the disconnection syndromes are talked about more generally as Collosal Syndromes. Of course, the corpus callosum is by far the largest of the nerve fiber bundles that directly connect one cerebral hemisphere with the other. These are generally called cerebral commissures and include the anterior and hippocampal commissures. These syndromes occur when the corpus callosum is partially or fully surgically divided. Syndromes of hemisphere disconnection can also occur when there is a partial disconnection such as in naturally occurring diseases/condition such as stroke (thrombosis etc.) Callosal lesions are often accompanied by damage to neighboring structures. Therefore “neighborhood signs” may overshadow signs of callosal disconnection.

Split-Brain Effects

  1. Just after complete cerebral commissurotomy patients respond well and can write letters to simple commands. Easily confused by three or even two-part verbal commands. Seen as mildly akinetic. A seeming imperviousness is observed. Often patients may write short and usually one-word answers. Considerable variation from one patient to another in terms of neurologic outcome and deficits.
  2. After a few months symptoms of hemisphere disconnection are compensated for to a large degree and seen in improved personality functioning, interactions and social situations and on neurologic exam.

a.) Visual material: visual material presented selectively to a single hemisphere by fixing gaze on some picture or object. Can describe or read various kinds of material in the right half-field at the level substantially the same before surgery. When presented to left half-field usually reports they see nothing or a flash of light.

b.) Inability to describe verbally left half-field stimuli includes hemialexia, where subject can’t read individual words flashed to the left half-field. Some recovery occurs over a period of years where word is recognized by right hemisphere as a symbol for something, albeit diffuse semantic information. Semantic information transferred to the speaking left hemisphere which approximates the stimulus word.

c.) Auditory Suppression: Right-handers identify single words if presented to one ear at a time. If different words presented during dichotic listening tasks, right ear information will be reliably reported. Left ear words poorly reported although occasionally appropriate actions are made by the left hand indicating some perception. Repeated testing indicates that your asymmetry may decrease particularly if patients attention is directed to left ear or if information load is reduced.

d.) Motor function: left-sided apraxia to verbal commands noted. Left limb apraxia seen because of poor comprehension by right hemisphere and poor ipsilateral control by left hemisphere. Compensatory mechanisms may emerge including increased right-hemisphere comprehension of words and increased left-hemisphere control of left hand.

e.) Somesthetic Effects (including touch, pressure, and proprioception). Unseen objects in right hand are handled, named and described in normal fashion. In contrast, naming of objects held out of sight in left hand are consistently failed. Despite inability to name the object in left hand, the left hand is able to manipulate the item and show how it’s used ;or they retrieve the object with the left hand from among the collection of objects screened from the patient sight (implicating that the object is also being identified by the right hemisphere.)

f.) Cross-replication of hand postures: One patient told to make postures with one hand, can’t mimic same posture with the opposite hand . When a specific posture is flashed in one visual half-field, can be copied by hand on the same side but not by the other hand.

g.) Inter-manual point localization: After a complete commissurotomy, there is a partial loss of ability to name exact points stimulated on left-side of body. Defect is least apparent in the face and most apparent and distal parts (e.g. fingertips). To test for this, while hand is shielded, the patient is asked to identify which finger tip was touched by examiner and to touch that finger with their own thumb (on the same side touched by examiner). Then when asked to identify the same fingertip on the opposite hand, (and once again to touch it with the thumb on that hand) they are unable to do it. Cross localization can be done by split-brain patients at a level not much better than chance.

h.) Right-hemisphere Verbal Comprehension: Auditory comprehension of words by disconnected right hemisphere is seen in the patients ability to retrieve, with the left hand, various objects if they are named aloud. Visual comprehension of words is accurate especially with short, and high-frequency words. So if a word name of an object (e.g. the word key) is flashed to the left visual half-field, patient can retrieve the item with the left hand from a group of objects hidden from view. Typically incorrect verbal descriptions are given after the word is presented, implicating that only the right hemisphere knew the answer. Right hemisphere language capabilities in right-handers are more evident when left hemisphere has been removed. If removed during infancy these capabilities may seem nearly normal as child develops language capabilities. Left hemisphere disease later in childhood that affects language abilities typically shows less intact language function since right hemisphere does not compensate as well. After split brain surgery and the left hemisphere is present and relatively intact, most linguistic abilities of disconnected right hemisphere are largely absent or suppressed. The disconnected right hemisphere’s receptive vocabulary can grow considerably and reach levels comparable to that of the vocabulary of the 10-to 16 year-old. Right hemisphere language has limitations: such as poor syntactic ability which is rudimentary at best. The rich lexical structure of language in right hemisphere diminishes significantly.

Other Disorders Following Hemisphere Disconnection

  1. Unilateral verbal anosmia:unable to named odors presentd to the right nostril even when readily presented to the left. Not a defect of smell in right nostril.
  2. Double hemianopia
  3. Hemialexia and Alexia without agraphia: When printed letters or short words are presented to left half-field patient unable to read information. Can readily read it when presented in the right half-field. Left hemialexia when combined with right homonymous hemianopia results in Alexia without Agraphia. For example, stroke patients can write but are unable to read even when they have just written correctly to dictation. Occurs in about 75% of righthanders with left posterior cerebral artery infarcts. Typically the patient has a right homonymous hemianopia resulting from a left occipital lobe lesion. In this case nothing can be seen, much less read in the right half-field. Visual information can reach the left hemisphere language only from the left half-field via the right occipital cortex and spelenium. Since there is a lesion typically in this region, it has disconnected the right occipital cortex from the left hemisphere. The left hemisphere still retains the ability to right to dictation even though it does no longer have access to information arriving in the right occipital lobe from the left visual half-field.
  4. Auditory Suppression
  5. Unilateral (left) ideomotor apraxia: This was the first described callosal symptom in the literature. In response to a verbal command the right-handed individual can’t carry out with the left hand some behavior which the right hand can do. Important to distinguish upon examination that the problem doesn’t have to do with a loss of dexterity or mild weakness. Also distinguished from ideational apraxia
  6. Unilateral (right) constructional apraxia: The inability to organize several parts into a configuration despite normal ability to handle or draw the individual parts. This type of apraxia can be quite prominent in the right hand of right-handers with callosal lesions. Have the patient copy with one hand, and then with the other hand, various geometric figures. Hemisphere disconnection in a right-hander is strongly suggested if patient can copy designs better with left hand.This may only be the case when there is no other right hemisphere involvement (e.g., left hand is paretic or ataxic)…in this instance they probably do no better with one hand vs. the other.
  7. Spatial acalculia: Since hemisphere disconnection can cause right-handed disability for spatial forms patient may have difficulty using pencil and paper to solve arithmetic problems. This deficit typically progressively received with recovery. Sometimes they can do mental calculations even though they cant to written ones.

Summary of Disconnection Syndromes based on the work of NORMAN GESCHWIND..

(if you want to read this these are the syndromes he covers)

  1. Word blindness without agraphia: Regarded as the first example of a callosal disconnection syndromes for which clear anatomical evidence was established.
  2. Pure Word Deafness: A lesion, located subcortically in the left temporal lesion typically destroys the left auditory radiation as well as callosal fibers from the opposite auditory region. The lesion has the effect of preventing the speech area (that part of the auditory association cortex that is Wernicke’s area) from receiving auditory stimulation. Although the right primary auditory cortex could receive auditory stimuli it can’t convey them to the speech area because the callosal connections from the right side were destroyed in the left temporal lobe.
  3. Lesions of Wernicke’s Area: although verbal comprehension is impaired, speech is also impaired. The loss of Wernicke’s area can be regarded as the destruction of a memory store as it was in fact regarded classically. Presumably it functions importantly as the “storehouse” of auditory associations. Geschwind describes that “a name” passes through Wernicke’s area then via the angular gyrus which arouses associations and other parts of the brain. Wernicke’s area attains its essential importance and comprehension as it is also involved in the arousal of associations. (maybe we should discuss this and talk about whether this is phenomena is discussed in this way anymore).
  4. Tactile aphasia: A disturbance characterized by an inability to name objects tactilely in the preservation of the ability to name on the basis of visual or auditory stimulation and spontaneous speech.