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Neuropsychology

a specialty field in clinical psychology that seeks to treat patients with cognitive impairments from aging, disease, and injury

Neuropsychologists

licensed doctoral level clinical psychologists who have a special training

often work in collaboration with neurologists

Neuropsychological assessments

develop an informed treatment plan

choice of method depends on issue

standardized testing

Standardized tests for neuropsychological assessments

Halstead-Reitan battery - measures language, abstract thinking, memory, motor dexterity, etc. often used as first baseline exam

comparison tests with population

comparison tests with abilities unaffected by condition

If injury causes swelling, will test again after swelling has reduced

Neurocognitive disorders

in DSM-5 as when a patient experiences a decline in functioning in one or more cognitive domains following a known challenge to the nervous system

attention, executive function, learning and memory, perception and movement, social cognition

Brain tumors

independent growths of new tissue that lack purpose

Primary tumors of the brain

very rare

causes are unknown, but radiation increases risk

typically arise from glial cells

Secondary tumors of the brain

miss growth in glial cells, meninges, and ependymal cells

most common type of tumor until age 19

Malignant tumors

no distinct boarder, hard to remove in surgery

cancerous tumor that can cause harm

may metastasize

Benign tumor

noncancerous tumor that doesn’t harm

has distinct boarder

cannot metastasize

Brain tumor development

most brain tumors are infiltrating, growing diffusely throughout surrounding tissue

about 10% of brain tumors are metastatic, typically originating in the lungs

Symptoms of brain tumors

very late onset in development of tumor

headache, vomiting, double vision, decreased heart rate, decreased alertness, pressure on the skull

Treatment for tumors (well developed treatments)

surgical removal

whole brain radiation

Treatment for brain tumors (more experimental)

stereotaxic radio surgery (targeted radiation in very specific cancerous locations)

Ultrasound therapy (heat used to damage tumor tissue)

trying to develop chemo that can get through blood brain barrier

Thalidomide used to starve tumors of blood supply

Delivery of stem cells with anticancer genes

Types of brain tumors

about 70% are Gliomas

about 20% are more specifically meningiomas

Gliomas

cancerous brain tumor composed of one type of glial cells

Meningioma

encapsulated tumor in the meninges

usually benign, surgically removed

What cells cause brain tumors

Not nerve cells, as they are incapable of dividing

either from other cells in the brain or the metastasize from elsewhere in the body

Stroke

a sudden onset cerebrovascular even that causes brain damage

5th leading cause of death in the US

Leading cause of adult disability in the US

Infarct

Dead tissue resulting from stroke

lacks any function

Penumbra

surrounds infarct

decreased function at first, but typically function will return

Cerebral hemorrhage

blood vessel ruptures, causing bleeding in the brain

Cerebral ischemia

disruption of blood flow due to blockage

Transient ischemic attack (TIA)

mini ischemic episodes

no permanent damage

can be a sign of full ischemic event soon if no treatment

Aneurysm

weakened point in blood vessel that makes a stroke more likely

may be congenital (since birth) or due to poison/infection

Thrombosis

blockage forms in blood circulating brain, causing cerebral ischemia

Embolism

blockage forms elsewhere in the body and moves into the brain, causes ischemia

Arteriosclerosis

wall of blood vessels thicken, usually due to fat deposits

Damage due to cerebral ischemia

does not develop immediately

most damage is due to consequence of excess glutamate release

blood deprived neurons become overactive and release glutamate

Glu over activates receptors (NMDA receptors) leading to an influx of Na⁺ and Ca²⁺

Result of Na⁺ and Ca²⁺ influx in cerebral ischemia

release even more glutamate downstream

sequence of internal reactions that ultimately lead to apoptosis

Ischemia induced brain damage

takes about 10 minutes

does not occur equally in all parts of the brain

mechanisms of damage vary by brain structure

NMDA antagonists block damage → administered following ischemic event to minimize negative effects of the ischemia

Contrecoup injuries (coup is primary impact to head)

contusions are often on the side of the brain opposite a blow

torn and twisted axons

ruptured blood vessels

cerebrospinal fluid can distort the walls of the ventricles

traumatic brain injury can lead to development of a chronic seizure disorder several months after the blow

Contusions

closed-head injuries that involve damage to the cerebral circulatory system

hematoma

due to contusion

clotted blood in organ or tissue

causes bruising

Concussion

disturbance of consciousness following a blow to the head

no evidence of structural damage

multiple concussions can result in chronic traumatic encephalopathy (CTE) which causes dementia type symptoms

Encephalitis

resulting inflammation from a brain infection by microorganisms

Bacterial brain infections

often lead to cerebral abscess (pocket of pus)

may inflame meninges, causing meningitis

treated with antibiotics

Viral infections of the brain

some viral infections preferentially attack neural tissue

Syphilis

bacterial brain infection

lays dormant for years

produces symptoms of insanity and dementia

Rabies

viral brain infection

high affinity for the central nervous system

Mumps and herpes

typically attacks tissues other than the brain

can produce sclerosis in the brain

Zika virus

can be transferred to fetus in the womb

leads to microcephaly → severe brain developmental delays and small head

Neurotoxins

from environment

may enter general circulation through GI tract, lungs, or skin

Toxic psychosis

chronic insanity produced by neurotoxins

seen in people who worked with mercury

Tardive dyskinesia

motor disorder involving uncontrolled smacking of the lips caused by antipsychotic drugs

Some neurotoxins are endogenous (make by body and attack nervous system)

Recreational drugs, like alcohol, can cause brain damage (thiamine deficiency from alcohol)

Epilepsy

primary symptom is seizures, but not all seizures are a result of epilepsy

seizures are generated by own brain dysfunction

epilepsy is not due to drugs or external factors

affects about 1% of the population

very diverse and complex epileptic seizures makes it hard to diagnose

Convulsions - Tremos (clonus) and Rigidity (tonus)

motor seizures

clonus produces tremors

tonus produces rigidity

loss of balance and consciousness

Some seizures can simply be subtle changes of thought, mood, or behavior

Causes of epilepsy

Brain damage

over 70 known genes correlated with epilepsy

Diagnosis of epilepsy

electroencephalogram (EEG)

seizures associated with high amplitude spikes

inhibitory control over activity doesn’t stop brain activity properly

Aura

smell, hallucination, or feeling that warns epileptic of an impending seizure

Partial and Generalized epilepsy

partial doesn’t involve the whole brain

generalized involves the entire brain

Treatment of epilepsy

often treated with anticonvulsants (like benzodiazepines - GABA action)

anti seizure medications (ASMs) can be used for daily epilepsy control

more sleep and no alcohol are behavioral treatments

Simple partial seizures

symptoms are primarily sensory or motor

can be both (Jacksonian seizures)

symptoms spread as epileptic discharge spreads

Complex partial seizure

often restricted to the temporal lobes (temporal lobe epilepsy)

automatisms - patient engages in compulsive and repetitive simple behaviors

more complex behaviors can seem normal

automatism

compulsive and repetitive simple behaviors due to partial complex seizure

Grand mal

generalized seizure

loss of consciousness and equilibrium

tonic-clonic convulsions

resulting hypoxia may cause brain damage

petit mal

generalized seizure

not associated with convulsions

disruption of consciousness and cessation of ongoing behavior (abruptly zoning out from current behavior)

Multiple sclerosis

progressive autoimmune disease that attacks CNS myelin, leaving hard scar tissue (sclerosis)

periods of remission are common (plateau for a while then worsen again)

nature and severity of deficits vary with the nature, size, and position of the sclerotic lesions

Symptoms of multiple sclerosis

visual disturbances

muscle weakness

numbness

tremor

ataxia - loss of motor coordination

Who is vulnerable to MS

those that grow up in a cool climate are more likely to have MS

Africans and Asians have very low rates of MS

strong genetic predisposition and many genes involved

drugs may slow progression or stop some symptoms

higher rate in women than men (3:1)

interferon β

protein that modulates responsiveness of the immune system

reduces frequency and severity of MS attacks

reduces immune system activity, which reduces frequency of MS

glatiramer acetate

mixture of synthetic peptides composed from tyrosine, glutamate, alanine, and lysine

first produced in an attempt to induce MS symptoms in laboratory animals, but ended up reducing symptoms of MS

interferon β and glatiramer acetate only help prolong remitting-relapse form of MS, no drugs can help progressive MS

Alzheimer’s disease

most common cause of dementia

likelihood increases with age (only 10% at 65 but 50% at 85)

progressive, with early stages characterized by confusion and selective decline in memory

neurofibrillary tangles and amyloid plaques

autopsy to diagnose or some blood tests and spinal taps

Familial forms Alzheimer’s

several genes correlated with early onset of AD

all affected genes are involved in the synthesis of amyloid or tau, which are found in the tangles

early onset AD suggests amyloid proteins come first, then neuro-fibrillary tangles form

declined acetylcholine levels is an early change seen in early onset AD

Tau protein

serves as a component of microtubules, which provide cell transport mechanism

due to Alzheimer’s, phosphate ions become attached to strands of tau proteins, which changes its molecular structure

abnormal tau proteins prevent transportation of substances, so apoptosis occurs, leaving tangles of protein filaments

lots of cell death in the hippocampus due to Alzheimer’s

Transgenic mouse model of AD

transferred human AD genes into mice

genes accelerate amyloid synthesis

plaque distribution comparable to Alzheimer’s

but no neurofibrillary tangles

mice showed memory deficits

Parkinson’s disease

movement disorder affecting about 1-2% of the elderly population

2.5X more likely in males than females

pain and depression commonly seen before full disorder develops

tremor is the most common symptom

dementia is not typically seen

no single cause

Symptoms of Parkinson’s

progressive difficulty in all movements

muscle tremors

frozen facial expressions

dopaminergic neurons of the substantia nigra begin to degenerate

Causes of Parkinson’s

still widely unknown

genetics play a role in early-onset but not late-onset (~10 gene mutations that disrupt function of mitochondria)

correlation with lack of coffee use

some exposure to environmental toxins and head injury

Autopsies of patients with Parkinson’s

almost no dopamine in the substantia nigra

Lewy bodies (protein clumps) in the DA neurons of the substantia nigra

Treatment of Parkinson’s

temporary treatment with L-dopa (precursor to dopamine that can get through blood-brain barrier)

L-dopa treatment is less effective as condition progresses

Deep brain stimulation (DBS) of the sub thalamic nucleus is effective for motor symptoms

Lesion of Globus Pallidus also effective for motor symptoms but has adverse effects

More Parkinson’s treatment

Glutamic acid decarboxylase (GAD) - enzyme responsible for synthesis of GABA. attempt to implement gene responsible for GAD into Globus Pallidus

can implant fetal cells into the basal ganglia, although often led to severe dyskinesia (new cells had a-synuclein - a miss folded protein)

Huntington’s disease

deterioration of caudate and putamen in the basal ganglia

progressive motor disorder with strong genetic basis (jerky movements of limbs)

associated with dementia

death usually occurs within 15 years of symptoms

1st symptoms usually not seen until age 40

caused by single dominant gene on chromosome 4

Genetic basis for Huntington’s

repeated sequence of bases that code for the amino acid glutamine

causes protein called huntingtin to contain elongated stretch of glutamine

Huntingtin normally facilitates the production and transport of brain-derived neurotrophic factor

Abnormal folding of Huntingtin triggers apoptosis

Migraines

caused by low levels of serotonin

high blood flow in migraine generator located in the brainstem activates trigeminovascular system

causes release of glutamate and calcitonin gene-related peptide (CGRP)

produces increased blood flow and pain in brain and meninges

Migraine symptoms

excruciating head pain

nausea

vomiting for 4-72 hours

Treatments of migraines

triptans prevent release of CGRP

Botox injections

behavioral adjustments

Can also have migraine auras like you can have epilepsy auras

Mental disorder

a syndrome characterized by clinically significant disturbance in an individual’s cognition, emotion regulation, or behavior that reflects a dysfunction in the psychological, biological, or developmental processes underlying mental functioning

Animal studies show gut microbiome can influence anxiety and social behavior

people who have major depressive disorder showed a larger improvement in Beck Depression Inventory with use of probiotic

Psychological disorders are more subtle changes in brain pathology and are suggested by the effectiveness of treatments

psychological disorders are less well understood than neurological disorders

Schizophrenia

splitting of the psychic functions

onset of about 18-25

positive symptom = presence of abnormal

negative symptom = absence of normal

Diagnosis of schizophrenia - must have two of these symptoms for most of the time during a single month to receive a 6 month diagnosis

hallucinations

delusions

disorganized speech

grossly disorganized or catatonic behavior

negative symptoms (decreased motivation, emotions, etc)

catatonic behavior

physically frozen, don’t move

Basis of Schizophrenia

48% genetic basis in schizophrenia

C4 gene causes too much synaptic pruning in schizophrenia patients

GRIN2A gene is involved in glutamate receptors

some genetic overlap with bipolar and autism

early sickness can cause (infections, autoimmune reactions, toxins, traumatic injury, stress)

Diathesis-Stress theory in Schizophrenia

patients susceptible to schizophrenia still need some traumatic incident to cause onset of schizophrenia

Antipsychotic drugs

Chlorpromazine - calms many agitated schizos and activates emotionally blunt (effective for positive and negative symptoms)

Reserpine - also effective but not approved in US due to drops in heart rate

both drugs take 2-3 weeks to work and induce Parkinson-like motor effects

Dopamine theory of schizophrenia

antipsychotic drugs work by decreasing dopamine levels

Chlorpromazine antagonizes DA activity by binding and blocking DA receptors

Reserpine depletes brain of DA and other monoamines by making vesicles leaky

Amphetamine and cocaine cause acute schizophrenic symptoms

degree that anti schizophrenic drugs (neuroleptics) bind to D₂ receptors is correlated with their effectiveness

Haloperidol has a high affinity for D₂ receptors

Problems with D₂ theory in schizophrenia

Clozapine is an effective neuroleptic, but it primarily binds to D₁ and 5HT receptors than it does D₂

Neuroleptics lower DA levels at the synapse but don’t alleviate symptoms for weeks - some slow acting change occurs

Schizophrenia is associated with cortical cell damage, not DA circuitry

May be best to think of schizophrenia as multiple disorders with multiple causes

positive symptoms are likely D₂ related b/c of drug effectiveness

negative symptoms may be cause by brain damage or hypofrontality (decreased activity of the dorsolateral prefrontal cortex) which may be caused by decreased DA in this region

schizos have enlarged ventricles and greater loss of grey matter

hypofrontality

associated with negative symptoms of schizophrenia

decreased activity in the dorsal-prefrontal cortex

Negative symptoms and glutamate

increasing activity at NMDA receptors decreases negative symptoms

glutamate hypo function is related to negative symptoms

PCP or Ketamine, which decrease glutamate activity, can induce negative symptoms in normal people

Depression

normal reaction to loss when acute

abnormal when it persists or has no cause

Unipolar - depression only

reactive - triggered by negative event

endogenous - no apparent cause

bipolar disorder

depression with period of mania