Midterm 1 PSYC 301 Flashcards

Question

MSE: Language Problems

Answer 1

``` Aphasia = Problems with language production and/or comprehension Alexia = Problems with reading Agraphia = Problems with writing ```

Answer 2

Focal or diffuse damage to the left hemisphere language network depending on handedness

Answer 3

Working or short term memory: Digit span - live a list of number and person must list numbers back Ideally 7+/-2 numbers Pointing span - point to different corners in the room in the same order doctor as given Verbal, visual object learning Past public/personal events - e.g. who’s the president right now? Factual knowledge Important in neurodegenerative disorder, dementia

Answer 4

Medial temporal structures (e.g., hippocampus), thalamus, basal forebrain, prefrontal cortex (less common)

Answer 5

Line cancellation - given a piece of paper with lines, and asked to draw lines to create X’s with lines Contralateral neglect - only cross right side of the page Copy of geometric designs Judgment of line orientation Object/face/color recognition

Answer 6

Prosopagnosia = Failure to recognize faces even though they can see the separate features Agnosia - name for a number of visual perception disorders Regions involved: Ventral side of temporal lobe (e.g. fusiform gyrus) Constructional Apraxia = Difficulty putting pieces of an object together Dressing Apraxia = Difficulty getting dressed especially when requested

Answer 7

Right hemisphere’s attention network | Apraxias tend to be problems with the parietal lobe especially with right hemisphere although not always

Answer 8

collection of all the most important things that we need in order to be successful in human society (e.g. balancing a number of responsibilities, incorporating new info into our model of the world, making decisions with appreciative social behaviors, being able to deal with immediate and long term goals at the same time, self control, etc.) Judgment Verbal fluency Tests of perseverative behavior (inflexibility of behavior):

Answer 9

Test: clear real life scenarios - what to do with dropped mail -> put in mailbox

Answer 10

E.g. List as many words as you can starting with the letter F

Answer 11

place fist on table and palm down and alternate fist-edge–palm behaviour repeatedly

Answer 12

E.g. copying figures with multiple loops - patients with perseveration problems may draw extra loops

Answer 13

Recite the alphabet and numbers from 1 to 26 and recite them in alternating order “A1B2C3D4….”

Answer 14

Prefrontal cortex and/or associated projections mainly to do with executive function

Answer 15

Tumours (aka neoplasms- new growth) - cells that grow and multiply Encapsulated: membrane around tumour

Answer 16

Encapsulated tumours Grow between the meninges If you remove it - low likelihood that it will grow back And high likelihood that all of the tumour will be removed Benign: if removed, little likelihood that it will grow back

Answer 17

(majority of tumours) Grow diffusely through surrounding brain tissue Does not have membrane Removing the tumour - must remove some tissue and some tumour will be left behind If failed to remove or destroy them completely, they will grow back Malignant: invading, recurring, and difficult to remove/destroy completely

Answer 18

(type of infiltrating tumour) Some infiltrating brain tumours grow from tumour fragments carried to the brain from another body part via the bloodstream Commonly originate from a breast cancer or a lung cancer

Answer 19

most common type of malignant (infiltrating) brain tumour in adults (aka: glioma) Most malignant Short survival rate: Median survival rate is around 14-15 months

Answer 20

Strokes are sudden-onset cerebrovascular disorders (problem with blood flow in head) that cause brain damage 2nd or 3rd leading cause of death Most common cause of adult disability No redundancy in blood flow to the brain In 3-4 mins of restricted blood flow, the area that is directly affected by the stroke is lost/dead tissue (infarct)

Answer 21

area of dead/dying tissue | Irreversible damage from stroke

Answer 22

dysfunctional area surrounding the infarct from stroke tissue in penumbra may either recover or die Even after the cerebrovascular event has finished weeks later it may die This area would have had a little but not a lot of oxygen Doctors try to save this area since infarct is already dead

Answer 23

Ischemic | Hemorrhagic

Answer 24

resulting from cerebral ischemia More common (80%) Problem with blood flow to the area The further up the artery (thicker), the larger the infarct will be

Answer 25

resulting from cerebral hemorrhage Blood leaking in brain Severe - blood is toxic (bacteria + viruses) Pressure from the blood - spraying fire hose at jello

Answer 26

Can be congenital or develop later Common as people get older People who are up to age 40, have a very low prevalence of aneurysm At 40-60, about 3.5% of people that are scanned may have an aneurysm 60 and onward, over 5% of people that are scanned may have an aneurysm Aneurysms are extensions of the arterial wall Placing pressure in arterial wall -> ballooning effect (bubble At a certain point, the balloon may rupture, leading to hemorrhagic stroke

Answer 27

``` Usually artery (not veins) - Commonly at base of brain (e.g. Circle of Willis) Circle of willis: Internal carotid and Vertebral artery are connected into a circle ```

Answer 28

diabetes, hypertension, smoking cigarettes, alcoholism, aging

Answer 29

to stop the balloon from growing and rupturing 1. Clipping Requires craniotomy (opening up skull) 2. Endovascular coiling

Answer 30

Requires craniotomy (opening up skull) slightly lower rate of recurrence than option 2 Older type High tension titanium clip at the neck of balloon so that the balloon has no blood flow and will not expand More successful in the long run Risky procedure Go through skull and move brain bits out of way and clip Exposing brain to air and infection Patients must be under anaesthesia for a while which can be dangerous especially for older people

Answer 31

Much less invasive (less likelihood of infection by exposing brain to air) slightly higher rate of recurrence than option 1 Create an opening/ put a catheter (tube) in their femoral artery (leg) The catheter tube runs all the way up to the heart, through the aorta, to the brain Monitor process with a real time x-ray to watch it go up The end of the catheter has metal in it (platinum coil) -> push out platinum coils into the inside of the artery Fill the artery with platinum coils The metal platinum induces clotting and causes blood to harden, turning the aneurysm into a hard thing without blood flow Can be dangerous because it forms clots in artery but mostly successful Sometimes does not stop the aneurysm from growing Can do on individuals with higher risk

Answer 32

A disruption of blood supply to some area of the brain Blockage of an artery, preventing the blood flow, any of the areas that are downstream are not getting the blood The neurons of those brain areas quickly start dying

Answer 33

1. Thrombosis: a plug (thrombus- blood clot) 2. Embolism: a moving thrombosis (piece of fat, oil, air bubble, tumour cell fragment in blood stream) When the arteries are wide, there won’t be a problem but at some point the arteries narrow and will be blocked 3. Arteriosclerosis The walls of the blood vessels are thickening and the channels are narrowing Deposits or build up inside the arterial wall The thickening of the walls increases the likelihood of a thrombus blocking the artery

Answer 34

1. It takes a while to develop (can be days) Much of the damage from ischemia take 1-3 days to develop fully Should prevent when not fully blocked artery Better chance of saving more tissue earlier 2. Damage is more likely in some parts of the brain (e.g. hippocampus - sensitive to damage) When it is not a full blockage yet (there is still some O2), some areas are more susceptible than others 3. The mechanisms of ischemia-induced damage vary between brain structures (one example: excitotoxicity and apoptosis) - The penumbra may or may not die -> reason: can be due to other mechanisms not simply lack of O2

Answer 35

toxic effect caused by too much excitation in the brain | Happens with severe head trauma, apoptosis, epilepsy

Answer 36

programmed cell death Glutamate receptors NMDA receptor, which lets in calcium NMDAR are important for memory formation (strengthen the synapse) If these NMDAR are too excited, it will let in too much calcium -> high level of calcium will act as a different signal to self destruct Under normal healthy conditions, apoptosis plays a good role During a stroke, apoptosis may be triggered and healthy cells will die

Answer 37

When not getting or limiting oxygen and glucose from blood flow, one of the first things to fail is the Na+/K+ pump (not functioning properly) Since Na+/K+ pumps are important for maintaining resting membrane potential -> cell starts to depolarize -> triggering action potentials and NT release in some areas Drugs to block activity of NMDAR (NMDAR antagonist) -> to block calcium from getting into cell -> apoptosis will not occur NOT SUCCESSFUL - calcium has other ways of getting into the cell (calcium channels) and related to depolarization Alcohol and ketamine are also NMDAR antagonist

Answer 38

aka Penetrating (enters skull) or perforating head injuries (something passes through one side to the other) ¾ of people shot in head die immediately, and 20% more die at hospital Typically very severe (~90% chance of lethal) High risk of infection, complications

Answer 39

E.g. Phineas Gage - almost died, went through times of infection and coma for awhile Had confusion and other problems High velocity worse than low E.g. Ron hunter -> landed on drill (1.5 in diameter) face first, penetrating and perforating him Conscious as flown by helicopter to hospital Moved drill bit through his head Did not damage any of his brain only pushed it away thanks to his meninges Ended up bankrupting himself from medical costs

Answer 40

contusion essentially just means “bruise” Closed-head injuries that involve damage to the cerebral circulatory system, producing internal hemorrhaging and a resultant hematoma (solid swelling of clotted blood) Occurs where the brain slams against the skull with huge impact Considered traumatic brian injury Contusions (and closed-head injuries in general) are frequently coup contrecoup injuries Contusions will be visible with imaging

Answer 41

Epidural Subdural Intracranial- most severe (in the brain)

Answer 42

Place where head hit = coup If hit hard enough, the brain will bounce off the coup and slam into the the other side (countercoup) If something hits you standing still-> coup injury If you run into something stationary -> coup contrecoup injury

Answer 43

a syndrome - a collection of symptoms that may arise from mTBI Problems with sleep, concentrating, mood, irritability, fatigue

Answer 44

When there is a blow to the head but no evidence of contusion or other structural damage with imaging Typically synonymous with concussion, which is a syndrome (concussive mTBI) but you can injure your brain without getting a concussion (subconcussive mTBIs) Couple of concussions are okay - generally

Answer 45

aka Dementia pugilistica, punch-drunk syndrome A progressive, irreversible neurodegenerative disease Caused by repeated blows to the head ⅓ or more of amateur athletes show evidence of CTE Not just professional athletes There is no cure and essentially causes dementia - declining mental abilities, memory problems Preventible form of neurodegenerative disorders - avoid getting head hit Not just concussion They saw evidence in teenagers with signs of CTE -> repeated hits to head

Answer 46

parkinsonism (looking like someone with Parkinson's disease: problems initiating voluntary behaviours, slow to get up, sit down) changes to cognition: not withholding inappropriate comments, explosive behaviour, volatility, extreme pathological jealousy or paranoia, suicidality, mood problems

Answer 47

110; Any high contact sports | Shows in people with epilepsy, autism (head-bangers), people with domestic abuse

Answer 48

Does not correlate with concussions A number of people diagnosed post-mortem with CTE who never reported having concussions or few concussions It is the repeated blows to the head

Answer 49

Can only diagnose suspected CTE while alive | Must look at the stain of post-mortem brain to diagnose

Answer 50

Tau (protein) binds and stabilizes the cytoskeleton When tau comes off the cytoskeleton, the cytoskeleton comes apart Normal as cell and cytoskeleton must change shape at times When tau is hyperphosphorylated and stop binding to the cytoskeleton, it aggregates and the cytoskeleton becomes unstable and breaks apart The tau starts binding to each other and clumps to make neurofibrillary tangles Not necessarily cause of CTE only correlation It could be that as neurons die, the tau come off the cytoskeleton and aggregate, and the tangles increases Also seen in AD, PD - so increase in neurofibrillary tangles does not mean someone has CTE The fibrillary tangles is a good marker of CTE, but relies on postmortem staining Tau is probably a marker that cells are dying Removing tau is not going to get rid of CTE

Answer 51

The tangles form in the sulci first and then spread out Early indicators of mild CTE are in the sulci Some say that CTE is from mini hemorrhages which cause iron deposits since the arteries are on the sulci Tau progression is different for CTE vs. AD (can tell the difference between the two CTE: primarily in the cortex - where the sulci are AD: seen in brainstem first, locus coeruleus, reticular activating system nuclei

Answer 52

Trying to develop PET tracer for CTE (tau) diagnosis in the living, but not there yet There would be lots of tau in individuals with CTE They found that the PET and post-mortem stain lined up pretty well This tracer molecule for tau does not bind to tau equally well across the brain Binds well in brain stem but not in cortex -> not useful for CTE Cannot diagnose CTE with PET tau tracer “Taupathy” Result: neurofibrillary tangles

Answer 53

Some sort of microorganism thing is going in the brain

Answer 54

Bacteria are single-celled organisms Can cause inflammation of the brain (encephalitis) When bacteria attack the brain they often lead to the formation of cerebral abscesses (pus pockets) Bacteria often attack the meninges, producing an inflammation known as meningitis

Answer 55

Quite common Might look like cold or flu: headache, stiff muscles, sensitivity to light or sound In children: confusion, drowsy, irritable Not clear what the problem is Dangerous Bacterial meningitis in humans adults is fatal about 25% of the time if not treated Can be treated with antibiotics BUT viral meningitis cannot be treated with antibiotics

Answer 56

They created natural products to treat illness Their own 13-month son got sick: confused, irritable, drowsy, trouble maintaining consciousness Son did not get better They did not take their child to the hospital even though the child had meningitis It was too late and their son died Charged with criminal negligence

Answer 57

Was a commonly passed on disease commonly by genital contact Targets Nervous system tissue Asymptomatic for years and syphilis will be on their skin A type of bacteria that can attack the brain. General paresis Can treat with antibiotics, even later stages can use IV treatment

Answer 58

the syndrome of psychosis/dementia that results from a syphilitic infection of the brain Later stages of syphillis Paresis: losing touch with reality, a form of psychosis Hallucinations, delusions, loss of mental faculties Around 15-20 years after infection of syphilis

Answer 59

virus is not a cell, but a small collection of protein with DNA or RNA inside and get animal’s cells machinery to reproduce themselves Two types: 1. Those that have a particular affinity for neural tissue (e.g. rabies) 2. Those that attack all tissues indiscriminately, including nervous tissue (e.g. herpes simplex) Many types of viruses infect a variety of cell types Viral infections of the brain can cause encephalitis and meningitis

Answer 60

The rabies virus has an affinity for the nervous system Rabies transmitted through bites Later stages of rabies: confused, aggressive, disoriented Rabies spread by getting into axons of motor neuron and gets into spinal cord Most bites do not lead to rabies (15%) But if infected and once it is in CNS, it is lethal Takes about a month for virus to travel around and into the brain to cause all lethal effects Symptoms are not clear: Disoriented, General feeling of unwell, headache, Fever, Violent movement, Pain, Uncontrolled agitated movement, Painful swallowing, Intense periods of manic, Eventually coma, destroy cells in hindbrain and medulla, leading to death A couple of people who have somehow survived this

Answer 61

Eukaryotic parasite Dangerous for unborn child Spends some of its life outside the cat and travels back into the cat Rats may encounter feces of cats where they acquire toxoplasma gondii from the cat and become infected In rats, toxoplasma gondii will change in the animals’ brain, affecting the amygdala (fear, fear learning) and destroys the circuit that causes rats to be afraid of cats The rats become unafraid of cats - selective removal of the fear of cats The rat becomes more likely to encounter the cat -> the cat kills the rat -> toxoplasma gondii will go back into the cat and complete its life cycle Lot of people will test positive of toxoplasma gondii (25-30%) Some personality studies suggest people with toxoplasma gondii are more likely to score higher on certain personality traits: High on Schizoaffective traits Slight significant effect on personality

Answer 62

Tapeworm in the brain Increasingly common The worm normally stays in the gut If tapeworm is ingested at a particular time in their lifecycle, it can invade soft tissue (skin, brain) They feed off the immune system Must wash hands and do not eat undercooked pork

Answer 63

Mercury can accumulate in the brain and permanently damage it - producing a toxic psychosis People who made hats use mercury -> mad hatter When mercury is vaporizes and inhaled Can cause Psychosis Most common place to run into mercury is in your teeth The substance that dentists use to fill your teeth is silver, mercury (40-50%) which have no neurological consequences Methyl mercury is more dangerous Found in fish, seafood, and ocean Still uncommon to have neurological problems from methylmercury Minamata disease

Answer 64

caused by severe methylmercury poisoning; ataxia, numbness, muscle weakness, damage to vision/hearing/speech, paralysis, coma, death congenital effects Chemical factory at the coast were dumping large amount of methylmecury and affecting the local waters and fish, and other animals Happened for almost 30 years methylMercury is devastating to the nervous system at high doses and is suggested to be related to some neurological disorders

Answer 65

Methylmercury poisoning is thankfully rare in North America, now, but still sometimes occurs Methylmercury in skin lightening cream and women used it for years Agitated delirium - she was applying cream at high doses

Answer 66

Small amounts of ethylmercury are present in vaccines as a preservative, BUT no evidence whatsoever to suggest harmful neurological effects

Answer 67

Wakefield did study to suggest that the MMR vaccine was bad and causes autism but it was a bad study but the public had already absorbed fake news 104k people killed by measles in 2018 worldwide because of this news and people refusing to get the vaccine

Answer 68

Lead can also lead to toxic psychosis (“crackpots”) In england, the poor would often use ceramic pots with lead core and if the pot was cracked, then the lead would leak out and expose people to lead Lead was removed from everything because it was in a lot of products such as paint, makeup, gas, and other household. lead is toxic at much lower levels as well

Answer 69

Lead poisoning is especially deleterious to children, where it impairs physical and mental development Lower IQ and other physical developmental impairments, learning difficulties, abdominal pain, constipation It can also cause a variety of neurological problems in adults Blood pressure, joint pain, headaches, mood disorder, increases likelihood of spontaneous miscarriage or premature births

Answer 70

2019 in Canada: many places had serious high levels of lead in canada Older homes with lead pipes - ingesting lead with running hot water Water in prince Rupert Canada is much higher than flint Michigan Home built in the 1960s, the paint on the wall is lead based paint Lead sped up the drying and increased durability of the paint, and the moisture resistant Not so dangerous on the walls but taking it off the walls or putting on the walls can be Home built in 1980s, the paint in the interior will not have lead but may for exterior wall paint Homes built in 1992, there would be no lead based paint Pipes and water supply is where lead is mostly nowadays Flint michigan has contaminated water supply -> high levels of lead

Answer 71

A progressive disorder that primarily attacks the myelin of axons in the CNS, but there is also cell loss Signals can no longer travel down axon - can no longer conduct, the AP is lost The immune system often appears to attack the CNS myelin as if it were a foreign substance Myelin being attacked by the immune system Sometimes there is an immunological response and sometimes not

Answer 72

1. Axons traveling from the body to the brain (afferent) - loss of sensation visual disturbances, numbness 2. Axons travelling from the brain to the body (efferent) - loss of movement muscular weakness, tremor, and loss of motor coordination

Answer 73

Multiple Sclerosis (MS)

Answer 74

1. Relapsing-remitting - some periods where symptoms are severe and other periods of remission where you are asymptomatic Alternating period of symptom and no symptoms 2. secondary progressive - happens after relapsing-remitting; symptoms all the time 3. primary progressive- do not have relapsing-remitting MS; symptoms of MS are chronic

Answer 75

1. Primarily an autoimmune disease (“outside-in” theory) Immune system starts attacking own cell 2. Primarily a neurodegenerative disease, with inflammation in some patients (“inside-out” theory) Newer more supported theory Neurodegenerative disease, perhaps Schwann cells or oligodendrocytes are dying, or neurons that are dying -> loss of cells (cytodegeneration) Debris from dying cells in the NS - so the immune system is responding to the debris, leading to inflammation in some patients

Answer 76

1. Inflammation is present in some individuals and not all people with MS Do not need immune response Primary progressive MS - they do not have much immune response 2. If this disease was an autoimmune disease, you could theoretically target the immune system and block the progression of the disease Immunosupressors or immunomodulators were given to patients -> they removed the symptoms of MS for many individuals with inflammation BUT does not slow down the progression of the disease 3. If it were an autoimmune disease, your immune cells would be attacking the myelin Would expect the outermost layer of the myelin sheath would be damaged first The inner layer is damaged first - which are not even accessible to the immune system (inside-out theory)

Answer 77

CIS = clinically isolated syndrome RRMS = Relapsing-remitting MS SPMS = Secondary progressive MS Diagonal line = loosing more and more cells across the life - neurodegeneration X-axis = time Dotted horizontal line = clinical threshold - if these events cross over the dotted line, the person will have symptoms Anything under the dotted line, the person will be asymptomatic Cytodegeneration for most of the time course is under the dotted line As cells die, they leave debris and there is an inflammatory response from the immune system Immune activity + underlying cytodegeneration (dotted bar) -> enough to put the symptoms above the clinical threshold 1st bar: CIS (clinically isolated syndrome) - the first time the symptoms present for MS Happens to many in their 20s more commonly in women Few days of numbness, weakness, loss of coordination 2nd bar: Once the immune activity goes down a bit -> not enough to exceed the clinical threshold even with underlying cytodegeneration This causes relapsing-remitting MS Over time cytodegeneration gets higher and higher until eventually, the cytodegeneration alone is enough to cross the clinical threshold (secondary progressive MS) Symptoms of MS will be chronic Less immune response

Answer 78

Inside out theory

Answer 79

PPMS = Primary progressive MS For years and years, there is building up neurodegeneration/loss of cells in the brain There is no immune response -> so not enough to reach the clinical threshold (asymptomatic) Eventually neurodegeneration is so severe that the patient becomes symptomatic -> primary progressive MS

Answer 80

High the further away from the equator People who are of African or Asian descent, even if they grew up in northern climates, there is very low risk of developing MS Northern countries prevent and Australia The most northern states (least amount of sun) furthest away from the equator have highest rates of MS

Answer 81

Low vitamin D levels put you at a higher risk of developing MS Being exposed to the sun causes the production of vitamin D in your skin Vitamin D supplements decrease the likelihood of MS Where you lived the first 15 years of life is important for risk of MS Being far from the equator puts you at higher risk Anywhere north of southern Ontario or northern California -> not getting enough vitamin D Closer to the equator, can get all of your vitamin D from the sun

Answer 82

If MZ twin has MS, you have high risk of MS

Answer 83

1. Vitamin D supplements? (lack of is more a risk factor) Useful for first 15 years of life Less useful once you already have MS 2. Corticosteroids - way to modulate the immune system Reduce neuroinflammation Used for a variety of autoimmune disorders But cannot stay on them for a long time as they cause problems with blood pressure, insomnia, bone density 3. Immune system modulators Help for relapse and remitting Not helpful for secondary progressive and primary progressive 4. Cannabis (Sativex) Spasticity: high muscle tone/stiffness and rapid muscle contraction - common in people with MS Cannabis can help with spasticity - relaxes muscle Sativex - spray to reduce pain of MS 5. Physical therapy Maintaining quality of muscle tone 6. Muscle relaxants 7. “Liberation treatment” of the veins? (No) They thought MS had to do with insufficient vein system- i.e. insufficient way for getting blood out of the brain The problem with MS was not with insufficient vein flow or blood removal from head Does not help with MS and it is quite dangerous 8. High-dose biotin? (maybe) In final phase (3) of clinical trial High does of vitamin H -> 10,000x higher than the recommended dose Supposed to stimulate myelin production and/or increase the ability for neurons to be myelinated - Hopefully more/better soon - not many great treatments Must figure out the basis of cytodegeneration in MS to treat the core problem not the effects of the problem

Answer 84

no, with stroke, CTE, parkinson’s disease etc. those neurons are gone and cannot recover completely although the can adapt

Answer 85

the people look fine and well and their symptoms are not obvious (fatigue, impulsivity, aggression, irritability) -> bad symptoms to have Many people misattribute a behaviour (e.g., fatigue, aggression) that is the result of brain dysfunction to the person’s personality or life stage Social psychologists have shown that people are more forgiving of a person’s behaviour if they have a bandage or a visible scar on their head Many people falsely believe that emotional problems after brain injury are usually not related to brain dysfunction Changes in mood are common to large global changes to brain function and dysfunction E.g. CTE often accompanied by changes in mood - severe chronic depression, suicidal

Answer 86

no, Often people with amnesia will suffer other functions as well Memory, mood, cognitive function are all somewhat interconnected -> brain is not compartmentalised In many cases of brain dysfunction, brain dysfunction is not perfectly localised and impacts multiple regions - Many people falsely believe that people with amnesia have no trouble learning new information (i.e. they believe their amnesia is entirely retrograde - loss of memory for events prior to brian injury) Anterograde amnesia - inability to create new long term memory

Answer 87

a brain dysfunctional where the patient is truly unaware of impaired neurological or neuropsychological functioning, which is obvious to the clinician

Answer 88

One arm is paralyzed from stroke During the anosognosia, the patient uses denial/freudian defence mechanisms to explain why they are not paralyzed The patient confabulates (comes up with a reason why they are paralyzed without saying they are paralysed) Anosognosia is completely recovered after a few days -> the patient has come out of the denial After anosognosia is gone, Ramanchanran asked the patients what they told him yesterday when they asked if the patient can move their arm After a week of denial, the patient comes out of denial -> the patient claims they told the doctor they were paralyzed yesterday -> denying the denial The patient is rewriting the script to match the current belief system

Answer 89

1. Movement disorders E.g. the arm is paralyzed as the part of brain that normally controls the arm is damaged 2. Contralateral neglect: not paying attention to the left side of the world 3. Memory disorders: amnesia Unaware that they have a memory disorder 4. Dysexecutive syndrome (frontal lobe syndrome) - often

Answer 90

Frontal lobe damage -> executive functions are impaired Disinhibition, aggression, impulsiveness, and disruptions in sequencing, planning and certain types of memory (i.e. working memory) Impairment in staying on track Often lack of self awareness of impairments disexecutive syndrome Anosognosia when damage first occurs but they recognize their impairment Since symptoms are somewhat subtle, anosognosia is common

Answer 91

Impairs functional recovery If someone has an injury and has anosognosia -> they have poorer recovery With anosognosia, prediction will likely be wildly inaccurate -> they will predict that they will perform much better than they actually will Researchers make the participants predict over and over until prediction improves When a prediction of performance improves, the likelihood of achieving rehabilitation goals improves The better they are able to predict their performance/their impairments, the better their rehabilitation/ability to recover Individuals who are demonstrating clear anosognosia (bad prediction of performance) did not reach their rehabilitation goals People who did not have anosognosia recovered better than those with anosognosia

Answer 92

The poorer self awareness (the worse the anosognosia) participants had in the beginning, the worse their recovery over time + poorer their functional outcome At 3m, all the patients did not have anosognosia anymore but the worse the anosognosia in the first 10 days of recovery was a major predictor of their recovery

Answer 93

Rehabilitation progress not as strong when anosognosia is present, over 60 days Hospitalised patients: Anosognosia -> poorer recovery Aware patients had better recovery

Answer 94

“Awareness intervention program” (AIP) Participants were given education on their own deficits, regularly given experiential knowledge of their inability to do some functions, practice predicting performance enhance self-awareness and remove anosognosia faster AIP group showed improved self-awareness but was not associated with improved functional outcome

Answer 95

her brain was removed when she was young so the brain was able to rewire due to plasticity during development (synapses/connections between areas are more easily formed) She still had functioning hippocampus, amygdala Redundancy of hemispheres allowed her to get by She has regular social interaction, married, thoughtful Having 2 hemispheres allows for compensation if one hemisphere is lost or damaged and other reasons Often, damage to a younger brain will lead to better recovery than an older brain (brains are relatively fixed when older) Adult brains are fixed (inflexible) because we want stable personalities, stable memories Plasticity of child’s brain leads to better recovery but also childhood amnesia and unstable memories

Answer 96

the best recovery depending on extent of brian injury | recovery diminishes as age increases

Answer 97

Prefrontal lesions before 16 months may be associated with an inability to learn social and moral rules later in life (lifelong change more severe than adult damage) Psychopathy: (neurodevelopmental disorder) symptoms start to present early in life with indications of different developmental trajectory (social and moral transgression) Thinner prefrontal cortex; connections from PFC is weaker to other parts of the brian Adult prefrontal cortex damage shows relatively few impairments and relatively few changes to their personality

Answer 98

TBI is around 1% before the age of 5 they recover well due to brain plasticity Rate goes down after 4 years of age and raises in adolescent years and goes back down in adulthood

Answer 99

There is a direct relationship between the size of the brian lesion and the extent of recovery: Larger lesions generally result in more functional impairments Patients with bilateral lesions show less recovery than patients with unilateral lesions Mostly the brain is redundant in both hemispheres (e.g. hippocampus is responsible for memory on both sides) There is some lateralization for language and some for attention The hemispheres deal with different halves of the world but they can compensate for different hemispheres after damage e.g. hippocampal lesions Unilateral hippocampal lesion -> mild impairments in memory Bilateral hippocampal lesion -> ability to form explicit long term memories will be devastated (anterograde amnesia)

Answer 100

little impairment Slow growing -> brain adapts and rewires and compensates for change Eventually some impairments may show up and some symptoms (headaches) Look at brain -> substantial lesion from tumour

Answer 101

Sudden stroke with associated damage (of a comparable size), functionally devastated Acute dysfunction is more noticeable No time to adjust or compensate for change

Answer 102

not permanent damage; areas around the infarct where the tissue may be healthy but have dysfunctions for other reasons - edema - diaschisis

Answer 103

Swelling (edema - Cerebral spinal fluid) after stroke may mask or distort functions in essentially intact regions of the brain Edema can cause further damage Much of the hemisphere is swollen -> tissue does not function properly Dissipation of these effects may account for substantial early recovery As the edema subsides -> there is restoration of function as tissue may still be healthy No neurons are coming back - the neurons in the swelling were never damaged or lost Individuals rapidly recover

Answer 104

Our brain areas are all connected together (many inputs and outputs) A brain lesion can cause dysfunction in an area remote to it because of its strong connections with that area Remote area was not damaged but hypofunctional due to loss of inputs from damaged brain area Brain adjusts to new types of inputs and outputs and strengthens connections -> diaschisis goes away -> rapid functional recovery Recovery can occur because of a spontaneous reduction of diaschisis (i.e. reduction in metabolic depression in cerebral areas remote to the lesion) Areas that were hypofunctional for a secondary reason have come back

Answer 105

recovery after brain injury animals: rats: tubes, wheels, social interaction Humans: crosswords, regular exercise, social interaction Social world is an enormous predictor of functional recovery Rich environmental circumstance tends to lead to much better recovery Rehabilitation and physical theory, therapy environmental factors is a major rehabilitation predictors With brain dysfunction often comes social isolation and loneliness -> lead to poorer recovery

Answer 106

constraint-induced movement therapy: cover one hand (good hand) and force the patient to use the other hand (impaired hand by stroke) regularly to promote recovery Monkeys with a focal strokes to the motor with focal strokes to the motor cortex that were restrained in skilled hand use Using hands that they weren’t as good at using led to better recovery than monkeys who were allowed to use their good hand -> allow brain to rewire

Answer 107

100% true recovery where brain function the same as it did before injury Mild TBI and didn’t lose any tissue with some swelling -> restitution is possible

Answer 108

(more common) compensatory strategies, substituting new brain areas to accomplish the same old goals Stroke and other brain injuries that are more severe Goal of substitution is not to get back to the way brain function but to get back to near the same function Can sometimes get back to the same functional level but with different sets of functions or behaviours A patient learns strategies to adapt to his or her new motor sensory or cognitive impairments

Answer 109

Severe sensorimotor impairment with lesions to rats brain at first but over time will adapt gain function and cross beam perfectly well altered pattern for use of limbs (placing feet or order of movement, etc) -> substituting new activity/behaviour to make up for loss of function

Answer 110

Our whole representation of the world is mapped onto our cortex -True for touch, sound, vision, and other sensory info Can touch different fingers and stimulate different parts of the cortex, or vice versa - All 5 digits are relatively equal size in cortical representation - Larger cortical representation for hand since hand needs to be sensitive Functional areas (cortical representations) are flexible - Can change in shape or size depending on the use of the hand Representation is based on use -> can grow and shrink based on use

Answer 111

No input coming to D3 due to loss of finger -> no purpose in having a cortical representation of a finger that does not exist Neurons will not do anything -> those neurons in the D3 cortical representation area will start to take on representations of the next strongest inputs When they had a 3rd finger, they got most inputs for D3 and weak inputs from D4 and D2 The animals D4 and D2 are larger and removes D3 region -> cortex rewires/reshapes Individuals born without third finger will have never had a D3 area in their brain

Answer 112

Stimulus disk -> learn how to stop disk with 2 fingers when there is a particular bump With regular practice and use of the D2 and D3, the somatosensory region for the digits D2 and D3 will grow larger Animal is performing a task that requires inputs form D2 and D3 They get better at task partly because fingers get more sensitive to the stimulus The digits that are not doing anything in the task (D4) will get smaller Representation of the hand changes size based on importance/use but not create new tissue

Answer 113

their threading hand has larger cortical representation and is much more sensitive than in a non violin player

Answer 114

there are different parts of cortex with different types of cells Each subsection like the somatosensory cortex will be somewhat limited -> brain wants to maximise function for more important useful parts

Answer 115

Young individual - higher degree of neuroplasticity and flexibility of brain (shifting of inputs- better for substitution) If you lose a limb (e.g. hand), quite a large amount of somatosensory cortex is no longer receiving inputs -> reorganisation and neuroplasticity occurs: cortical areas adjacent to the hand are larger Entire somatory path representing the lost limb -> adjust to the next strongest input As an adult, you form stable cortical representations - the rewired/reorganised cells are now responding to a different body part Report that they feel their hand when touched in other parts of their body - Phantom limb can be stimulated when other parts of the body are stimulated Reorganisation is not perfect leading to impaired perception the recovery process is slower and less efficient Phantom limb: getting sensation from limb that is no longer there Phantom limb pain is common -> dysfunctional or damaged nerve ending from where the hand (or other limb) was cut off

Answer 116

adjacent brain areas

Answer 117

Meta analysis shows that therapy is beneficial and leads to recovery More therapy -> more recovery (so therapy is beneficial even after a long time after injury)

Answer 118

used to make sure the data good -> reveal if there is publication bias if it is closer to funnel shape X-axis: observed outcome (right = beneficial ; left = not beneficial) Y-axis: Standard error related to quality of study (e.g. sample size) As standard error gets larger (lower on y-axis) -> more false positives and false negatives Lower N size, lower statistical power As standard error gets smaller (closer to 0 - higher on y-axis) -> better study, larger sample size, and higher statistical power

Answer 119

Often the left half of the funnel plot is missing -> publication bias when only one half of the funnel is present with dots Researchers are withholding or failing to report undesired results

Answer 120

Plan to move - guided by thoughts and self and under conscious control (voluntary) Cortex plays a big role in these top-down processes Movement of eye is mediated by supplementary eye field and the frontal eye field (main one sending major motor signals for controlling your eyes) E.g. parkinson’s disease, huntington’s disease

Answer 121

Moving elicited outside of conscious control Movement guided by salient features of the stimulus (e.g. bright TV) Not very cortical in nature - areas outside of control are generating movement Activity mediated by activity in the superior colliculus (tectum of the midbrain)

Answer 122

Sensory system is an essential part of movement Abstract intention/decision/goal -> motor plan (maps our body) -> motor signal (how to control certain movements in muscles) -> movement -> sensory information (vision, touch reception, skin stretch receptors) Sensory info (incl. proprioception) sends info back to motor plan and/or motor signal Proprioception: Skin stretch receptors allows you to know where your body is in space A lot of this sensory feedback is affecting systems that are outside our conscious awareness -> affecting lower levels of motor hierarchy

Answer 123

Damage to somatosensory nerves of his arms (afferents) but normal motor control of muscles (afferents) Numerous problems with movement Fine motor skills affected Holding briefcase - Maintaining muscle contraction If patient G.O. was not paying attention to hand, the briefcase would fall out of hand Buttoning up shirt Could not adjust to disturbances in the environment (e.g. holding a cup of coffee and someone hits us, he cannot adjust and hold tighter and will almost certainly spill the coffee)

Answer 124

ballistic response (super fast movements where there is not enough time to get sensory feedback and adjust) -> open loop movement

Answer 125

Lowest level: spinal motor circuits - reflexes -> controls muscles Brain stem motor nuclei (cranial nerves related) -> influenced by primary Primary motor cortex - signals from cortex to voluntarily control our muscles -> sending motor signals out to muscles Secondary motor cortex - mainly sending info to primary motor cortex -> turning plan into concrete sets of actions Association cortex - top level/planning for future movement

Answer 126

Once you have learned a movement well, the higher levels are free and the lower levels take over Higher levels handle the complex functions (e.g. playing guitar) More sophistication as you move higher up the hierarchy

Answer 127

Basal ganglia; cerebellum

Answer 128

1. The lower levels of the sensorimotor system hierarchy possess “sensorimotor programs” Sensorimotor programs represent particular patterns of activity (e.g. contracting fingers/hand muscles in certain ways) 2. A particular movement is produced by activating the appropriate combination of these sensorimotor programs Programs built on programs built on higher level plans 3. Once a particular level of the sensorimotor hierarchy is activated, it is capable of operating on the basis of sensory feedback without direct control by the higher levels Most of the actions in life use cortex to get started but do not need a lot of cortex to keep going (at least not association level or even secondary level) -> movements are offloaded to lower levels of motor hierarchy

Answer 129

(spinal animal - no afferents or afferents with brain) Spinal animal held up on a treadmill - the animal will step with its legs (coordinated movement) Spinal cord has relatively coordinated control of the body The animal cannot stand without additional help Reflexes, e.g. stepping responses, limb approach or limb withdrawal to tactile stimuli, stretch reflex

Answer 130

put weight on hand -> the sensory info (activation of stretch receptors in muscles) elicits movement to keep weight up right and counteract added weight afferent signals synapsing onto motor neurons/interneurons that act on motor neurons -> signal travels through the motor neurons back out and controls muscle groups

Answer 131

Series of simpler movements into something that is much more complex Take preparatory movements Abstract -> concrete More than one way to carry out a movement

Answer 132

signing your name with your toe Motor equivalence - same movement can be performed by different muscle groups Motor programs are independent of body Outside of primary motor cortex -> secondary motor areas are active (where motor programs independent of the body are stored) Similar pattern of brain activity when signing name with toe and fingers

Answer 133

Practice can create and/or modify sensorimotor programs Learning a new skill requires higher level associations Larger pattern of activity when learning a new task in many areas of the brain Harder to multitask two tasks when the higher-level association cortex is focused on a specific task

Answer 134

1. Response chunking- grouping series of movements for efficiency (e.g. learning to read - recognize letters and eventually read/ recognize words without needing to focus and go through each letter) Chunks can be grouped again to form bigger chunks of complex movements 2. Shifting control to lower levels- frees up higher levels to do other tasks As you learn and getting better and better at actions the control shifts from higher levels of motor control to lower levels More automatic and unconscious -> become faster at tasks Free higher levels to do other tasks and multi task easier by freeing up higher levels

Answer 135

Involved in most abstract level of behaviour Dorsolateral prefrontal cortex: involved in working memory, decision-making, other aspects of cognition but also motor region Posterior parietal cortex: sensory processing, body awareness, proprioception but also motor region There are a variety of subareas for these areas but are considered the sensorimotor association cortex

Answer 136

Provides information on where body parts are in relation to the external world Receives input from visual, auditory, and somatosensory systems (incl. Stretch receptors in muscle) Output goes to secondary motor cortex and some to dorsolateral PFC not considered top most part of motor hierarchy

Answer 137

Secondary motor cortex is where you are storing motor programs independent of limbs (intermediate step between most abstract and most concrete) Secondary motor cortex receives inputs from the posterior parietal cortex to provide info on spatial awareness and body awareness -> helps secondary motor cortex to select the right kind of actions

Answer 138

Stimulation of the posterior parietal cortex (on scalp) makes the subject feel they are performing an action at low currents, patients experience the feeling that they are going to perform a behaviour (intention) “I feel like I'm going to move my arm” At higher currents, patients feel that they have performed a behaviour “I feel like i just moved my arm” even if action did not happen

Answer 139

Involved in a variety if cognition, sensation perception, and behaviour -> some part of dorsal stream Knowing where you are in space (starting point) for whatever actions Lots of sensory inputs (somatosensory, auditory, vision, and body awareness/ proprietary) Sending signals to the dorsolateral prefrontal cortex and the secondary motor cortex Some impairments can be changes in visual perception There are subregions that are easier to outline than the dorsolateral prefrontal cortex

Answer 140

Damage has a strong lateralizing effect I.e. see one type of deficit with damage to one side vs. the damage to the other side 1. apraxia 2. contralateral neglect

Answer 141

(inability to perform movements on command) Occurs when posterior parietal association cortex is lesioned Great difficulty imitating a gesture especially if the gesture or movement is meaningless, like pretending to hold something Difficulty performing gestures on command though they could do it on their own Difficulty using tools outside its use (e.g. painting on canvas is fine but not on a rock) Associated with left hemisphere damage (posterior parietal cortex) Spontaneous movements tend to be fine with sometimes some problems with accuracy Symptoms are bilateral - happens to both sides of body

Answer 142

(fail to respond to visual, auditory, or somatosensory stimuli) Produced by very large right parietal lesions Some of the world is mapped bilaterally (i.e. if you damage the left parietal, the right parietal can take over and pay attention to the right side, but not the other way around) Attentional impairment NOT visual impairment Individuals only attend to the right side of body or items in environment They will not pay attention to the left side of the world (e.g. shave the right side of the face, eat the right side of the plate) Egocentric left is not paid attention to (not an issue with vision) without realising they are not paying attention to the left side of the world Individuals are capable of unconsciously perceiving objects on the left (Subcortical systems; e.g. superior colliculus could still grab people's attention to the left side of the world and move their eyes left even if they are consciously unable to perceive it) Not interfering with other aspects of cognition (e.g. puts all numbers on a clock face but only on the right side of the clock)

Answer 143

Top most part of motor hierarchy where the initiation of voluntary action begins Receives projections from posterior parietal cortex (finding out info on where we are in space and our orientation, and appetitive/motivational info) and other sensory information, and other inputs related to values, decision-making Evaluated all the different types of stimuli and decides what to do (behavioural choices) Projects to secondary motor cortex, primary motor cortex, and frontal eye field If you record activity from the DLPFC, some of the neurons are firing when performing certain actions, or to the characteristics of an object that leads to an action Involved in assessments of external stimuli - certain stimuli are more valuable Some of these motor neurons are firing in response to an object, (combination of) characteristics of the object, location of object All the different aspects of environment are represented in the DLPFC -> building simulation of the world - critically involved in so many other functions (e.g. problem-solving, maths, working memory, explicit learning)

Answer 144

Lots of areas have activity that precedes a behaviour or movement - predicts whether a movement is going to occur May work with posterior parietal cortex in decisions regarding voluntary response initiation dlPFC fires first in motor chain - when a particular action is being decided, the earliest activity in the DLPFC Decision making, voluntary movement (top-down) -> firing in anticipation of movement occuring

Answer 145

damage here affects a number of sophisticated cognitive functions listed above Variety of types of errors in cognition or motor can occur Damage depends on the extent of damage, the extract subregions damaged, whether the interactions between posterior parietal or other regions are damaged

Answer 146

2 areas of premotor cortex Externally guided behaviour (e.g. dancing with partner) Not exactly bottom-up 3 supplemental motor areas Activity recorded in these areas seems to be internally guided (top-down) in motor planning Voluntary spontaneous behaviours 3 cingulate motor areas

Answer 147

They receive inputs from the posterior parietal and the dorsolateral prefrontal Projects to primary motor cortex, each other, and brainstem Sometimes completely bypass primary motor cortex entirely Produce complex movements (before and during voluntary movements) stored here - motor Important for stringing together chains of complicated movement Separation of specific subaspects of movement Exact role of these areas is unclear There are mirror neurons in these areas - Both premotor and Supplementary MA contain mirror neurons

Answer 148

planning, internally guided -> generation of voluntary movement Damage causes loss of voluntary behaviours Secondary motor cortices

Answer 149

externally guided -> e.g. follow cursor around on screen Premotor areas encode spatial relations Secondary motor cortices

Answer 150

aka the (anterior) precentral gyrus, M1 (most posterior section of frontal lobe right before central fissure leading to parietal lobe) While Somatosensory cortex (postcentral gyrus - after central fissure) Somatotopic organisation: motor homunculus Disproportionately large portion of our motor cortex is devoted to our hands, and lips - where the finest motor control is Receives feedback from muscle and joints (sensory input) - not solely motor about Neurons code for preferred patterns of movement/direction (e.g. extending, twistin, curling), not muscles per se even though muscles are the last step

Answer 151

Damage to M1 is not as disruptive as you might think Manifest in different ways Loss of limb separation or Independent movement (e.g. can open and close their hand but may have difficulty moving one finger) Astereognosia -> Losing the ability to use touch and movement of object to identify object Sensory and motor impairment - to recognize the object type in hand, you must move it around Reduced speed/ accuracy/force most affected - less efficient movements, slower movement Not too great of an effect on voluntary behaviour - there are multiple levels of control of the system that bypassed by the M1 Suggests SMA/premotor control

Answer 152

Alcohol effect - change in coordination and movement Cerebellar disorders Parkinson’s disease - changes in substantia nigra and dopamine level Huntington’s disease - individuals can’t stop initiating movement Stereotypy and impulsivity in psychostimulant addiction (cocaine, amphetamine, meth)

Answer 153

10% of brain volume with 50% of all neurons Individuals born without cerebellum -> deficits are not very noticeable Part of motor control system Axons from the primary motor cortex through the pons, the medulla, the spinal cord, to muscles The primary cortical neurons send another axon (branches/collateral) to the cerebellum Cerebellum receives somes of the motor signals Compares our intended movements to our actual movements, and then corrects our motor behaviour based on discrepancy outside of conscious control (corrects movement ~7times/sec (Hz)) Cerebellum corrects movement, coordination, and course correction and improves motor output -> closed loop Critical for timing and sequence (both motor and cognitive) E.g. rhythm in music Ipsilateral control of body -> i.e. left half of the body is responsible for the left half of the body, unlike most of the brain which is contralateral control

Answer 154

(interaction between efferents and afferents) Sensory inputs (somatosensory system, vision, stretch receptors, vestibular system, proprioceptive info) Primary and secondary motor cortex - motor inputs Information about descending motor signals front the brain stem nuclei - cerebellum knows intention and planned movement Feedback from motor responses via the somatosensory and vestibular systems

Answer 155

loss of ability to precisely control the direction, force, velocity, and amplitude of movements (wobbly uncoordinated movement) Must manually adjust movement using eyes and other parts of cortex Loss of automatic correction loss of ability to adapt patterns of motor output to changing conditions difficulties in maintaining steady postures (e.g., standing) - often how to recognize people have cerebellum damage The hand may be wobbly to grab a glass of water disturbances in balance, gait, and the control of eye movement impairments on measures of attention and executive control, procedural memory, working memory, language, timing sequence, emotion, and visual-spatial processing Impairments in closed-loop movements where there is feedback and movement and sensory input over and over impairments in the learning of new motor sequences Impairments in coordination and control and motor learning Not much impairment in ballistic movement Cognitively, some impairments in attention and executive control (normally there would be bold activity in the cerebellum during these tasks)

Answer 156

No cerebellar damage: accurate With glasses that change the angle of vision: less accurate but over time they adapt and hit the target Take glasses off and angle shifts back and they have less accuracy again until they adapt back to accuracy Cerebellar damage: relatively accurate With glasses: less accurate and they do not adapt to improve accuracy When they take prism goggles off, they do not overshoot, they go back to shooting relatively accurate because they did not adjust with goggles Cerebellum is important in adjusting with feedback happening moment to moment and on a larger scale

Answer 157

``` 2 regions: Striatum (with 2 subregions: caudate nucleus, putamen) Ventral surface of the striatum -> nucleus accumbens - important for addiction and motivated behaviours globus pallidus (pale globe - white matter) with 2 components: internal segment (GPI), external segment (GPE) 2 Other regions intimately connected to the basal ganglia Subthalamic nucleus (STN) - has extensive connections to striatum and globus pallidus, and many consider it to be a part of basal ganglia Substantia nigra - Midbrain nuclei that produces dopamine which all goes to basal ganglia Damage to substantia nigra that causes parkinson’s is causing changes through changes to basal ganglia circuit ```

Answer 158

Distinction between movement and cognition/motivations is blurred Modulates motor output (classical view) - modulate function of secondary motor cortex (change intensity or timing) Critical to habit formation “Muscle memory” and skills Many cognitive roles Motivated behaviours - seeking out rewards

Answer 159

How brain regions interact to produce different types of output Frontal cortex include secondary motor areas, association cortex like dorsolateral prefrontal Various parts of the cortex = sensory cortex, dorsolateral, secondary motor, etc Green arrows = excitatory (glutamate) Red arrow = inhibitory (GAGAergic) Blue arrow = dopamine Direct pathway: GO: facilitates disinhibition of frontal cortex; increasing activity Indirect pathway: STOP: maintains the tonic inhibition of frontal cortex; decreasing activity Basal ganglia must decide which circuit or which patterns of activity should be elicited at any given moment Piano: some fingers must move and some not (coordinate patterns of activity)

Answer 160

``` frontal cortex (secondary motor areas) Whether or not voluntary or spontaneous movement occurs will have to do with our frontal cortex Frontal cortex activity will have to do with the thalamus If the thalamus is sending lots of glutamate signal to the cortex, then elicit lots of voluntary spontaneous movements ```

Answer 161

Motor/premotor areas in frontal cortex are normally tonically inhibited (thalamus being kept silent and inhibit movement) Result: no movement The default is to have a low level of spontaneous movement indirect/STOP pathway: maintains the tonic inhibition of frontal cortex DEFAULT: The globus pallidus internal sends this gabaergic signal to the thalamus tonically -> strong inhibitory signal Inhibits the thalamus -> the thalamus does not send its glutamate signal to the frontal cortex -> relatively low amount of spontaneous voluntary movement Increase the amount of tonic inhibition coming from the GPi Parts of the cortex synapse on another cell of the striatum part of indirect pathway -> send glutamate onto cells of the indirect pathway -> those striatal neurons fire lots of action potentials -> release lots of GABA onto GPe (inhibits) -> GPe is not inhibiting the GPi -> GPi has no inhibition on it -> GPi is free to sends a strong gabaergic signal to the thalamus -> inhibits thalamus -> thalamus send less excitatory signal to the frontal cortex -> less movement/less activity in motor cortex Parts of the cortex synapse on another cell of the striatum -> send glutamate onto cells of the indirect pathway -> those striatal neurons fire lots of action potentials -> release lots of GABA onto GPe (inhibits) -> GPe is not inhibiting the subthalamic nucleus STN -> STN sends strong excitatory signal in the GPi -> GPi more strongly sends inhibitory signals (GABA) to the thalamus -> thalamus sends less glutamate sent to frontal cortex -> less movement overall Net result: more go, less stop -> movement

Answer 162

To activate motor cortex, we need to inhibit the inhibition: this is called disinhibition (release inhibition) -> movement Direct/Go pathway: facilitates disinhibition of frontal cortex Cortex sends a glutamatergic signal to the striatum (excited striatal neurons) -> send more action potentials to release GABA onto the globus pallidus internal -> inhibition of the GPi -> not gonna have many AP -> removing tonic inhibition -> thalamus free to send glutamate signals to frontal cortex without inhibition by GABA from the GPi -> motor cortex more likely to fire Result: movement; more activity in particular circuit Whether or not movement occurs depends on balance of activity in these 2 pathways There are more than 2 circuits -> within the two, there are subcircuits of controlling specific hands, fingers, or body parts

Answer 163

Dopamine releasing region is the substantia nigra par compacta (SNc), releasing dopamine onto the whole striatum Monoamines are not super targeted -> the whole striatum receiving dopamine Neurons in the go and stop pathway are receiving dopamine The two pathways have different dopamine receptors

Answer 164

Primarily D1 receptors in the go/direct pathway -> excitatory Dopamine D1-family receptors have a positive modulatory role -> increases activity within neurons When dopamine is released onto the striatum -> activate striatal neurons and bind to D1R and increase activity -> increase amount of GABA released into GPi D1R activity increases transmission in the direct/GO pathway

Answer 165

Primarily D2 receptors in the indirect/stop pathway -> inhibiting Dopamine D2-family receptors have a negative modulatory role -> more inhibition of activity When dopamine is released onto the striatum -> bind to the D2R and inhibit the neurons that project to GPe -> less GABA released into GPe -> less activity in stop pathway D2R activity decreases transmission in the indirect/STOP pathway (indirect pathway)

Answer 166

The release of dopamine leads to more GO/direct and less STOP/indirect -> leads to more movement

Answer 167

In PD, most of the dopaminergic neurons of the SNc die Lack of voluntary spontaneous behaviour Death of SNc -> no activity in the D1 and D2 receptors dopamine is not released onto the striatum This decreases transmission in the GO pathway This also increases transmission in the STOP pathway -> increase in tonic inhibition (inhibiting the thalamus) Net result: without dopamine -> less go, more stop -> diminished voluntary movement

Answer 168

Restoring dopamine signal on the striatum should hopefully restore the movement (L-dopa) 1. L-DOPA (precursor to dopamine) is the gold standard Dopamine pill does not cross the BBB but L-dopa does cross the BBB Enzymes in the brain will convert L-dopa into dopamine, increasing dopamine in the striatum and all across the brain -> increase in activity of D1R and D2R -> restore some of the activity in the GO (more GO) and reduce activity in the STOP (less STOP) 2. Deep brain stimulation (DBS) of the STN Electrode in brain and stimulate (turns that part of brain off - silences) Generally inhibits brain region -> improve symptoms seen in Parkinson’s disease Reduce activity of STN by DBS -> less excitatory signals to the GPi -> less GABA released from the GPi -> less inhibition of the thalamus -> more glutamate released from the frontal cortex

Answer 169

Tremors, inability to stop spontaneous voluntary movement, constantly moving or clenching Constantly moving exhausts the muscles even when tired -> huge build-up of lactic acid -> painful Purely genetic in nature - we know who has the genotype in infancy Opposite of Parkinson’s disease Specifically, damage within the basal ganglia circuitry Damage neurons especially in the indirect pathway This decreases transmission in the indirect/STOP pathway the striatal neurons that project to GPe die (i.e. neurons in the indirect pathway damaged - normally more tonic inhibition, reduction in movement) Freeing the direct pathway to remove tonic inhibition HD affects neurons across the brain, but especially the striatum Net result: no stop -> excessive movement

Answer 170

Unfortunately very little Must find out the way to prevent the gene from being expressed into a protein Fatal disease 100% of the time Can only ease symptoms

Answer 171

Highlighting the opposite of Parkinson’s problem where dopamine activity is lost Gain of function: All drugs of addiction increase the amount of dopamine functioning of the brain indirectly or directly All the drugs are going to increase the amount of dopamine being released from SNc to Striatum Ventral tegmental area (VTA) also releases dopamine onto the motivation related part of the basal ganglia Drugs are considered habit/habitual (basal ganglia circuit) - seeks drugs (motivation/reward) Excessive drug use -> increase dopamine release -> bind to D1 (strong positive modulatory effect- more activity in the direct pathway GO, increasing movement) and D2 (block activity in indirect pathway -> disinhibition- less STOP) Drug users are behaviourally more active At low doses, it can help you stay motivated or on task- goal directed behaviours (e.g. ADHD) At higher doses, rats will perform more rat-like behaviour (more grooming); in humans, more primate like behaviour (e.g. biting nails, picking skin, tweaking, grinding teeth) -> species specific behaviour

Answer 172

The ventral tegmental area has another basal ganglia circuit that is more related to motivated behaviours -> biggest change when drug addiction develop

Answer 173

All drugs of addiction directly or indirectly increase dopamine transmission from SNc and the other main dopaminergic region, the VTA change in behaviour to seek out more of the drug by shaping the way in which our basal ganglia work Effects of prolonged use is that they fundamentally change how the basal ganglia are working the pathways shown are normally thought of for movement, but they apply somewhat (and are analogous to other pathways) for reward and motivation these drugs can shape our behaviours such that we seek out more of them (e.g. addiction - drug habit) psychostimulant drugs like cocaine or amphetamines increase goal-directed behaviours (low doses), impulsivity, and (at higher doses) repetitive behaviours (called stereotypy (in animals) or punding (in humans) Long term use will change basal ganglia circuits (rewires brain), which changes behaviour

Answer 174

New implantable pulse generators (e.g. allowing storage of electrophysiological data and eventual adaptive stimulation), as well as new electrode configurations, are now available high-resolution structural imaging, including high-field MRI and diffusion tensor tractography, will facilitate both the planning of DBS procedures, and the optimization of postoperative outcomes by aiding stimulation programming Clinically, we have achieved a deeper understanding of outcomes, thus facilitating the process of target and patient’s selection. The recent technological advantages of neuromodulation have opened new avenues toward new targets and indications

Answer 175

Parkinson’s disease, dystonia and tremor and as an off-label treatment for many other movement disorders

Answer 176

clinical and technological.

Answer 177

Most of published studies have been conducted on patients with Parkinson’s disease, in whom DBS produces a consistent and sustained improvement of motor function and quality of life an early and sustained improvement of quality of life in patients receiving DBS STN DBS in patients without motor fluctuation (disease duration <4 years), but this approach is less compelling as it exposes patients to potentially dangerous side-effects without improving the motor function and quality of life and an unclear impact over the long term

Answer 178

1. DBS produces motor improvement of signs responding to dopaminergic drugs, whereas unresponsive features often predominate in the late stages of the disease 2. older patients are more likely to develop surgical complication and/or worsening of axial motor functions 3. performing DBS at advanced stages of illness can alleviate certain aspects of motor dysfunction without addressing the ongoing difficulties in well-being and social relations with themselves, spouses, families and socio-professional environment

Answer 179

The motor benefits can be similar with each target favoring STN for greater benefit in the severity of off symptoms and cost-efficacy Whereas, Dyskinesias Suppression and Long-term effects on stability and cognitive favor GPi

Answer 180

the long-term (beyond 10 years) outcome of early open-label series of STN DBS patients have consistently shown an enduring beneficial effect of surgery on motor fluctuations STN DBS may improve patients’ survival STN DBS does not appear to halt Parkinson’s disease progression and the phenotype of the ‘long-term DBS syndrome’ emerges over the years The clinical picture of these patients is dominated by axial motor problems (dysarthria, freezing of gait and postural instability)

Answer 181

Although a number of experimental and clinical observations support the role of pedunculopontine nucleus (PPN) in the pathophysiology of gait and stability impairment in humans, PPN DBS is still considered an investigational procedure