Neuro Test 4

6 Common Causes of Brain Damage

1) Brain tumor

2) cerebrovascular disorders (stroke)

3) closed head traumatic brain injury (TBI)

4) infections

5) Neurotoxins

6) Genetic Factors

Tumors

from dysregulated cell growth

encapsulated: grown w/n own membrane

infiltrating: grow diffusing thru surrounding tissue

benign: low risk, easy remove

malignant: regrow, difficult removal

Types of Tumors (spcfc)

metastic: tumor originates in organs and spreads to other

• multiple brain tumors in brain: sign of LUNG cancer

meningiomas: grow in meninges

• encapsulated, benign

Gliomas: common infiltrating tumor

Cardiovascular Disease (CVD) (stroke)

sudden CVD onset that disrupts brain supply

• infract: area of dying tissue

• penumbra: vulnerable area surrounding infract

2 Types CVD:

1) Cerebral hemorrhage: bleeding in brain

2) C. Ischemia: loss blood supply to brain

C Ischemia Causes

Arteriosclerosis: thick wall and fat buildup on vessels impede blood flow

Thrombosis: plug of blood clot

embolism: clot blocks smaller vessels

Closed Head Injuries

concussion

MTBI: concussion, mild traumatic brain injury

4 Neuroplastic Changes in Repsonse to Brain Damage

1) Neural degenerations:

• Axotomy: axon cut

• Anterograde: in, distal (far from) degenerates

• retrograde: out, proximal (close to, cell body) degen

2) Neural Regen: degen A cause collateral sprouting of B

3) Neural Reorg: Rats vibrissae muscles out, associated areas activate other

• gradual collateral sprouting, release from inhibition

• Neurogenesis: making new neurons

4) Function recovery

• obscured by 2 phenomena: improve from waning after effects (swelling/edema), substitution of function

• cognitive reserve: tasks accomplished in new ways

• rehab goal: exercise recover CNS and no further damage

• growth factors: + dendrite branching

Motor vs Cognitive Dysfunction

No clear cut boundary btw two

motor: Parkinsons and Huntington’s, speed and selection of mvmnt

• Park: dementia

• HD: Always dementia

cognitive: Alzhiemers (also motor impair)

• Basal Ganglia: input from cortex output thalamus drives cortical activity, DA modulated, DA from substantia nigra

Parkinsons (PD)

tremor, diffuicult initiate movement, slow, rigid face

dementia: 20-30% W/ PD, 50% depression

degen of substantia nigra (where DA release, not stored)

• Lewy Bodies: surviving FNA neurons

treatment:

• 2 DA, DA agonists (short lived)

• DBS (cognitive impairmnt, small improve)

• MPTP model: drug induced compare heroin w/ MPTP, MPTP degen sn, DA agonists, Frozen addicts!

slow, low DA, treat: L DOPA and DBS

Neurotransplantation (stem cell transplant)

effective on MPTP monkey, but at large there where side effects (dyskinesia: inv mvmnt)

Human embryonic cell transplant (ES)

• pluripotent: can become any cell

• in vitro (glass lab grown) long term= genetic defects and too many divides damage DNA

Induced Stem Cells (iSCs): skin cells show promise to be ES but not ready

Ideal but Not the case bc:

• neurotrophic factors (BDNF) and guidance mlcls (CAMS), chemicals releases to support surviving factors

• dvlpmnt glial cells (brain repairs self)

Huntingtions disease

Rare

Basal Ganglia disorder: unwilled limb movemnt

Protein aminos: 37-80 repeats in genes (triplets all x2)

Autosomal Dominant Gene: Gene= have

Large hole in BG

no treatment

dementia: low cogn function

Alzhiemers (AD)

dementia

plaques and tangles

emerging biologics

amyloids!

Epilepsy

rare

SYNDROME (collection of symptoms)

difficult diagnose, amy symptoms

seizures symptoms

• symptomatic: w/ cause (tumor or virus)

• idiopathic: spontaneous w/o cause in CNS

seizures produced by aura: hallucin,smell feeling

• suggest epileptic focus (brain area)

• warns of seizure

Seizures produce convulsions: physical, behavioral manifest of neuronal firing (muscle contract,etc). Observable seiz comp, progress to epileptic

2 Main Types of Seizures

Generalized: no localized onset, both hemispheres at same time

• -tonic w/ motor, sitff and rigif

• Atonic w/ motor: loss of muscle tone:

• twitches: myotonic seiz. may occur with automatisms (action w/o aware)

• -absence: w/o motor

• change in sensations, ANS, or behavioral arrest

• -3 per sec spikes and wave discharge (bilaterally symmetrical)

Focal: 1 brain area

• F aware: awake and aware

• F impaired: confused and impaired, complex partial seizure

Seiz Fix/ Analysis

EEG detects electrical activity and action potential (large amplitide spikes)

Case of Julia: amygdala origin, TLE seiz, violent

• treat: electrode implant, stimulated amygdala lesion, controversial

Kindling Model (induced seiz activity)

• Leech Model: daily amygdala stim= sub convulsions then seiz then permant changes

• repeated focal onset: impaired awareness seiz (temp lobe)

• vs human (epiloptegensis)

• high excite (Na, K, Glut)

• anticonvulsant drugs

3 Components of Emotional Experience

1) Physiological arousal: changes heart rate, respiration, sewat

2) Behavior: facial, startle

• expressionL vestigal tailbone

• universal across culture

• emotions biological hardwired

• voluntary facial paresis: can’t control face muscles

• duchene: genuine face

• orbicularis: eye wrinkle

• zygomaticus": corner mouth

• pyramidal: false

3) Cognition: memories, planning, feeling

Limbic System: Controls Emotions

Papez Circuit: hippo and mammillary bodies (relayed and memory processing), anterior nucl thalamus (signal to cortex), cing gyrus (emotional experience)

Behavior and decision: temporal, amygdala, prefrontal

Kluver- bucy Syndrome: Bilateral removal of temporla lobe (amygdala and hippo), inappropraite, hyperorality (mouth) and hyperphagia (eat)

Parietal: Where, control and decisions

Temporal: what

Anterior Cingulate Cortex (ACC): conflict monitor and error detect

Corticolimbic Circuit: danger, response

thalamus/sensory cortex to amygdala to PFC (attention and control)

Amygdala to: hypo, brainstem, and forebrain

disfunction: high amy, low PFC activity

Corticostriatal Circuit: reward and goal directed

Ventrial Striatum- VTA midbrain dopamine to N Accumbens- (makes reward and pleasure) to PFC Top Down- Motor System and Action

Top down inhib: control loss, low DA and low NA/contextual response

Pavlovian Associative Learning

Amygdala

UR: fear response

CS: neutral

CS + VS (shock)= CR

Fear Conditioning Paradigm: before learn, learn trials, recall (high bp and recognize at end)

Pathways and Structures in Fear

Paths:

1) direct: MGN- amygdala (adaptive advantage)

2) indirect: MGN-cortex-amygdala (fear circuits)

MGN: auditory thalamus lesion, blocks FC (fear response)

Auditory CORTEX lesion: NOT block FC

Amygdala

common site of abnoram electrical activity=seizure

focal seiz: emotion disturb w/ comordity (multiple diseases)

surgical removal reduce symptoms

important in social behavior

Urbach Wiethe diseas: calcify amygdala, natural lesion

Patient Sm: fear deficit amygdala bad hippo (memory) good

Amygdala connections with PFC:

• feeling

• T-D process! Pfc control/terminate amygdala output

• PFC important for extinction of fear, activates GABA in amygdala (no fear without shock, etc), restores resting state

Autism (ASD)

neurodevelopmental, genetic

extreme variability

poor eye contact and facial expression, repetitive behavior, BOYS 4x more likely

Phenotype variation in other symptoms:

anxiety and mood, intellect disability, seizures, sleep disorders, allergies, digestions

NO LINK MMR vaccination with autism

ambiguous commonality to our gen

Estiology (causes ASD)

Pathology: brain areas involved (amygdala, PFC, cerebellum)

genetics

Early ASD hypothesis: social disengage and hyposensitivity hallmark

• early fMRI support blunt emotion and hyposensitivity NEGLECTED poor eye contact

Gaze aversions: (looks at mouth), amygdala high activity, sees object faces/facial sensitivity (more time eye contact=more anxiety= more facial processing)

ASD Accelerated Brain Growth and Enlargement

volume in amygdala and PFC

develop changes in functional connectedness (not straight)

social impare areas: amyg, PFC, ACC (bridge PFC with limbic)

synaptic abnoraml: neurligns and neurexins not line up properly

• proteins crucial for synaptic activation

• NT changes (Serotonin, glut, gaba)

• Oxytocin change

PFC HYPOactivity: NOT turn off amygdala (shows severity_

SMA spine back, ACC, OFC

Anxiety and depression related

1) dep have anxiety

2) with anxiety higher risk dep

3) similar pharmacotherapic

Anxiety

disorder: duration and intensity

MOST prevalent of psych disorders and MOST difficult to trat, leads to other disorders

Anxiety Interacting Mechanisms:

• transmitter symptoms

• endocrine changes

• corticolimbic dysfunction

FORMER anxiety disorders: ptsd and ocd

Anxiety Medications

antideppreseents!

SSRI (ocd) serotonin

• reduces 1A 5HT autoreceptors: (5HT= serotonin, increase IA brakes on Serotonin release, +SSRIS desensitize 1A and weakens so more rlease)

• Mice: +1A= more anxiety

• therapeutic lag, receptor desensitization

Anxiolytics: Benzodiazepines, +BDZ, +GABA, block Anxiolytics/anxiety effects

Anxiety Endocrine factors

endocrine changes:

1) HPA axis controls endoc stress response (high Cortisol high stress

• GR returns cortisol levels

2) early life experiences: shape HPA

• more HPA= more cortisol= maternal separation and less maternal nurturing behaviors

• more nurture: +GR= resilient

hypo release CRH- Pituitary A release ATCH- adrenal gland release cortisol and glucocorticoids- hippo GCR feedback (neg= stop)

Affective Mood Disorders

BD and major depress MDD

intesnity and duration

MDD: neg emotion, suicide

• anhedonia: low self worth and interes

• cognitive impairment: inflexibility

BD: cycle btw depression and mania (hyperactive, +self-esteem, loss sleep)

Diathesis Stress Model: interaction btw genes and env

• stress precedes MDD, strong MDD genetic

• + genetic vulnerability +stress

MDD and BD Treatment

MDD:

antidepress: +synaptic levels of MONOAMINE transmitters like NE and %HT

SSRIS: fluox and sentraline, block 5HT reuptake ONLY

TCA/tricyclice: imrpimine, block reuptake 5HT and NE

MAOi: inhib MAO, hypertensive crisis (cheese +tyramine)

BD:

Lithium: gold standard (works for all issues: manic and depress)

anticonvulsant: seiz for mood, Vaporic acid (mania0 and Lamotrigine (depress)

• alternative

Atypical: Lurasidone and Cariprazine (help for immediate)

Monoamine theory of depression

MDD from underactivity of 5HT and NE WRONG

based on antidep medi, not account for therapeutic lag (and feel better for weeks)

(treat how and circuits?

Dexamethasone Suppression Test

DEX not lower cortisol= disfunction

HPA axis can sustain high levels cortisol, disrupted neg feedback

Neurogenic hyptthesis

stress: high cortisol, low BDNF (helps neuron connections), low atrophy (health) and loss of neurogenesis (new growth)

antidep: +5ht= +BDNF

Schizophrenia (SZ)

neurodevelopmental disorder, psychotic

6 month symptom diagnosis: no essentials!

M-F 20s

social withdrawl in teens

Strong genetic component (NOT purely genetic, would be 100%)

Treatment: Neuroleptics: 1st antipsych drug, dopamine D2 antagonists (prohibit bind)

• Chlorpromazine and hazoperidol

• effects: motor (parkinsons), endocrine (+prolactin/lactation)

Dopamine Theory of Sz

excess DA

reserpine: herbal, -DA

cocaine and amph: +Da induce Sz symptoms

NOT true: therapeutic lag and NOT overactivity (other receptors contribute)

early dvlpmnt maters: perinatal complications and stress

maternal malnutrition: Dutch Famine 1944

Clozapine new: makes simple Sz explain insufficient b/c f atypical meds and brain changes and genetics

Atypical Antipsychotics

Clozapine, Zyprexa, Sereoquel, Ablify

Most FDA approved as BD monotherapy and depression

off label use

what makes atypical: low Parkinson side effects and recpetor affinity (low DA bloc, high 5HT block)

Atypical side effects: sedation blocking a, cardiometric problems (weight, diabeties, heart)

Clozapine: can cause agranulocytosis (lethal blood disorder)

Sz changed to brain

enlarged ventricles (produces CSF) M>F

low brain volume (PFC and hippo and total)

disorganized anatomy (PFC and hippo)

heritable factor: twins and fam

synapse structure disorganized, NT synthesis and inactivation

risk distribution across 1000s of genes

Sz Neurodevelopmental disorder

Diathesis

perinatal

PFC dvlpmntl errors: negative symptoms (no regulate)

• deficits in corticosteroid circuit controlling DA= +symptoms