Midterm 3 Flashcards
______ is an age-related cognitive decline that reaches a pathological level
Dementia
Alzheimer’s, Parkinson’s, and Huntingtin’s disease are all a form of ______
Dementia
What are the symptoms of Alzheimer’s disease?
Memory: Retrograde amnesia as well as deficits in storing new memories (anterograde amnesia)
Deficits in executive function (complicated tasks with multiple tasks) ex. cooking
Agnosia: failture to recognize objects
Apraxia: impaired motor function
Aphasia: impaired langage function
What is the survival time after diagnosis of AD?
~8 years after diagnosis
Cognitive deterioration is slow during the early and alter stages but quite rapid during the middle stage
As the disease progresses, symptoms become more severe and at the final stage the individual is typically completely dependent on caregivers
What is the progression of AD?
Starts mild absentmindedness and language becomes more simpler and more concrete
As it progresses, language skills decline, LTM deficits occur, affection and emotion become affected (irritable, aggressive, outburst, childlike), and become confused and wander around
What is Anosogonsia?
A lack of awareness that one has Alzheimer’s, often seen in people with mid-stage AD
What is the typical age of onset of AD?
Appears between 60s-70s
Early-onset AD can appear as early as 40s, also known as pre-senile dementia
What is the purpose of long-term potentiation and depression?
It maintains a record of activation - synapses that are frequently stimulated become stronger and easier to stimulate in the future
Neurally, how are brains thought to store memories?
Each unique experience activates a combination of neurons and synapses
Each network or ‘trace’ is unique thus storing a memory
As you experience the same thing over and over, this network becomes stronger, which is how people become good at something
What analogy did Dr. MacKay use for storage of memories?
Walking down a laid pathway in the winter
Each time someone walks on the path, the path becomes worn in, and easier to travel
If you learn something and then during aging a crucial neuron in your circuit or trace dies, what will happen?
Your brain will take an alternative route. The entire circuit is not lost, but it does mean the circuit will work less efficiently
What happens to the brain of someone with AD?
- shrunken cortical gyri,
- reduced gray matter
- massively enlarged ventricles
- increase CSF
What causes neuronal death in AD?
Post-mortem analysis finds increased clusters of amyloid-B plaques
These are neurotoxic and as they accumulate they choke off adjacent neurons, leading to cell death
There are also increased neurofibrillary tangles which are defective neurofibrils that occurs due to an excess of hyperphophorylated Tau proteins
Neurofibrillary tangles occur in the axons
True or False
False
It occurs in the cytoskeleton
How is AD diagnosed?
Using a PET, imaging can quantify amyloid-B in a living brain using radioactive dye
Until recently it was only diagnosed post-mortem
What is the purpose of the cytoskeleton?
It functions as a flexible scaffold that’s solution allows a neuron to maintain their 3D structure
It also transports proteins and molecules across vast distances
What are the 3 main components to the cytoskeleton?
Neurofilaments - control & transport of membrane proteins
Microtubules- control the transfer/movement of substances and organelles through the cytoplasm
Microfilaments - provides structural support to axons & dendrites
What are Tau proteins? What are hyperphoshorylated tau proteins?
Tau proteins are involved in the stabilization and flexibility of microtubules and microfilaments
They are a highly soluble protein that are activated through phosphorylation and promote assembly of microtubules
However, hyperphosphorphyated tau proteins begin to accurate which eventually form neurofibrillary tangles inside cell bodies
Microtubules disintegrate and destroy the cytoskeleton - collapsing the transport system, causing biochemical malfunction, leading to cell death
What is the pattern of neural degeneration in AD patients?
Begins in the frontal, posterior parietal lobe, and temporal lobes and then spreads to other regions
This is why earliest symptoms are cognitive impariemtns, memory loss, and reduced impulse control
The majority of AD cases are inherited
True or False
False.
Twin studies suggest a 40% concordance rate which means there are some genetic component:
- Mutations in the gene coding from amyloid precursor protein (APP) can increase the risk of AD
- Apolipoportein E is another protein involved in the genetic risk
How can chronic stress impact AD patients?
Chronic stress leads to neurodegeneration and increases the build up of amyloid-B plaques
The combination of stress and amyloid-B show impaired memory
What is the treatment of AD?
There is no pharmacological treatment to death with pathology of AD
Medication can only temporarily mitigate some deficits
- Acetylcholinesterase inhibitors increase levels of ACh which is lost in AD patients
- NMDA antagonists block the NMDA glutamate receptors: dying neurons dump excess glutamate which are toxic and can lead to a chain reaction
These treatments do not extend the life of a person with AD but it increases their time before becoming severely impaired
What is ALS?
Amyotrophic Lateral Sclerosis is a progressive degenerative disease that affects neurons controlling voluntary muscles
No muscle nourishment on the spinal cord where sclerosis (scarring/hardening) occurs
ALS is hereditary
True or False
True
Some cases are inherited but there are also sporadic cases
What is the common death in someone diagnosed with ALS?
Respiratory failure 2-4 years after diagnosis
What are the symptoms of ALS?
Loss of motor neuron function result in: stiff muscles, muscle twitching, weakness due to decreased muscle size, difficult speaking, swallowing and breathing (1st symptoms to appear)
People eventually lose the ability to control all voluntary movements
Cognitive dysfunction are present in less than half of cases
What causes ALS?
Results from a degernation of both the upper (motor cortex) and lower (brainstem & spinal cord) motor neurons
The cause of degeneration is unknown in ~95% of cases
Familial cases involve genetic mutations in superoxide dismutase leading to oxidative stress
No specific environmental factors have been identified
Which types of neurons are more susceptible to damage?
long neurons such as lower motor neurons
The ________ is the primary control systemm for precise voluntary movements. Where is it located?
corticospinal tract
It begins in the precentral gyrus (aka primary motor cortex) and crosses to the contralateral side of the body at the level of the medulla a(decussation of the pyramids)
If a person hits their head on the left side of their brain injuring the left motor cortex. What symptoms of injury would you expect to see?
Injuries on the right side of the body since the injury is upward of the desiccation of the pyramids
What types of neurons are located in the primary motor cortex? How do they project throughout the body?
Large projection neurons known as pyramidal neurons that send their axons through the internal capsule (a chokehold for motor neurons)
They then pass through the cerebral peduncle in the midbrain
Then through the pyramids in the medulla and 90% cross over at the decussation of pyramids and 10% stay ipsilateral
The ones that cross over join the lateral corticspinal tract
The ones that do not join the anterior corticospinal tract and then decussate at the spinal cord before they connect with their lower motor neurons
What are the difference between upper and lower motor neurons?
Upper motor neurons (UMN) are pyramidal cells that synapse onto interneurons in the spinal cord and live in the primary motor cortex
Lower motor neurons (LMN) are efferent nerve fibers that carry signals from the spinal cord to the muscles and live in the ventral horns of the spinal cord
What happens at a neuromuscular junction?
It is where the lower motor neurons attach to a striated muscle
The motor neurons release ACh which binds to either nicotinic or muscarinic ACh receptors to cause a muscle contraction
How does botox interact with ACh to cause paralysis?
Botox is taken up selectively by peripheral cholinergic nerve terminals, including those at the neuromuscular junction
Botox interferes with ACh release, blocking the release of ACh from their synaptic vesicles which results in muscle weakness or paralysis
What is the function of acetylcholinesterase?
Acetylcholinesterase is an enzyme that cleans up and disposes of ACh after it has been dumped in the neuromuscular junction
What are nerve agents?
They permanently block acetylcholinesterase which results in a rapid build up of ACh at the neuromuscular junction so the muscles cannot relax and the individual loses complete control of their body
Death occurs by suffocation as you need muscles to breathe
Ex. sarin and VX
What is the motor unit?
The LMN cell body, axon and the multiple fibres it innervates
An AP will depolarize one motor units muscle fibres and multiple APs will overlay each other, leading to larger muscle contractions
What is the pathway involved in starting the shower and determining if the water is hot enough?
- Sensory endings in the skin detect temperature
- AP is sent to the sensory neurons in the dorsal root ganglia
- The sensory axon enters the spinal cord and synapses with a interneuron in the brain (medulla)
- Sensory pathways continues with second neurons projecting to the thalamus
- sensory pathway reaches cerebral cortex
- UMN from the cortex executes a motor command
- UMN connects to a LMN in the spinal cord
- The LMN causes contraction of the target skeletal muscle
What are the pathways of an afferent sensory input?
The afferent sensory sobers enter the dorsal root bringing sensory info from the receptors
They then go 1 of 3 ways:
- Directly to the CNS
- Synapse with LMN to elect an immediate response
- Synapse with an interneuron
Why are reflexes tested?
Simple reflex tests can help identify damage to the upper or lower motor neurons
Ex. A weakened/absent knee jerk reflex indicates LMN damage; an exaggerated knee jerk indicates UMN damage
What is the pathophysiology of ALS?
ALS has an increased presence of inclusion bodies in the cytoplasm of motor neurons. Aggregations lead to dysfunctional motor units and cause cell death
Which proteins aggregate differ depending on the type of ALS (sporadic vs. familial)
How is SOD involved in ALS?
superoxide dismutase (SOD is an enzyme that catalyzes the disputation of the superoxide radical (O2-) into a less toxic chemical
If not regulated, O2- can cause many types of cell damage
People with familial ALS have disruptions in SOD1 functioning causing O2- levels to rise
How is ALS diagnosed?
Based on patient history, neurological exams (reflexes), and EMG testing
Muscle injuries results in smaller motor unit potential measures (EMG) ; injury to axons result in larger motor unit potentials
What is the treatment of ALS?
There is no cure for ALS
Riluzole, an anti-glutaminergic drug, may extend life expectancy and QoL by preventing excitotoxicity caused by increased Ca2+ due to excessive release of glutamate
Contrast nociceptive and neuropathic pain
Nociceptive pain arises from tissue damage (adaptive)
Neuropathic pain arises from damage to the damage-reporting system in the nervous system
How do we perceive pain?
- A nociceptor is a sensory neuron that responds to damaging stimuli by sending possible threat signals to the spinal cord where it synapses with a secondary neuron in the dorsal horn
- This neuron crosses to the contralateral side where it travels through the medulla to the thalamus where in synapses and passes through the internal capsule
- The signals is then sent to the sensory cortex in the parietal lobe
- If the brain perceives this signal as a threat, it will create the sensation of pain and initiate a cascade of events to deal with it (known as nocicpetion)
What is the dorsal columns tract?
It is used for precise fast information in the cuneatus and gracilias nucleus
What is the difference between free nerve an encapsulated nerve endings?
Free nerve endings are embedded in tissues
Encapsulated nerve endings synapse with tissues
What is the difference between afferent and efferent signals?
Afferent is incoming - they come through the dorsal horns
Efferent is outgoing - they come through the ventral horns
DAVE - Dorsal Afferent, Ventral Efferent
What are the different types of afferent fibres?
C Fibres: small unmyelinated fibres that carry nociceptive info
ABeta, ADelta Fibres: medium, myelinated fibres that carry nociceptive and non-nocicpetive info
Alpha Fibres: large myelinated fibres that carry light touch and proprioception info
What are the different types of pain?
Somatic pain refers to localized injury to skin, muscles, bones, joints, and connective tissues (outside); fast and slow pain (A and C fibers)
Visceral pain refers to poorly localized pain that results from the nociceptors of internal cavities such as thoracic, pelvic, or abdominal viscera; slow pain only (C fibers)
Which structures in the CNS respond to pain?
Dorsal horn - site where pain is modulated and afferent fibers are sent to thalamus
Sensory homunculus - in the somatosensory cortex where we consciously perceive localized pain
Limbic system - Emotional arousal
Midbrain - Autonomic activation (increased HR, BP)
In response to pain what does gating refer to?
Gating is one way in which humans modulate pain
The gate theory suggests that non-painful stimuli close the ‘gates’ to painful input which prevents pain sensation from travelling to the brain
Ex. shaking your hand after you hit with a hammer
There is a projection neuron in the dorsal horn: C-fibers send a pain signal and ABeta fibers send proprioception info to that projection neuron
However, if the ABeta fibers send a signal at the same time as the C fibers the ABeta fibers activate an inhibitory neuron which inhibits the signal of the pain (closing the gate)
How does the brain modulate pain (top down influence)?
The brain will activate descending neural pathways to dampen afferent signals in response to pain stimulus
Starts in the periaqueductal gray matter -> Medulla -> spinal cord -> synapse with secondary neurons in the dorsal horn and inhibit firing of afferent neurons
This occurs due to 5-HT, NE, cannabinoids and opioids
What is inflammation?
Inflammation is a localized physical condition in which the body becomes reddened, swollen, hot and often painful
It occurs due to the release pro-inflammatory cytokines =, it makes peripheral nerves, dorsal horn, and thalamus/somatosensory cortex more excitable
These are ongoing processes which up regulate pain
What is sensitization?
When your pain is unregulated due to:
An increase # of glutamate receptors, making post-synaptic membranes are hyper excitable and now, even normal stimulus will be perceived as noxious
Broken/damaged cells release pro-inflammatory cytokines (prostaglandin, bradykinins) that up regulate receptors leading to hyper excitability and CNS sensitization
Hyperalgesia occurs when a slightly painful stimulus is very painful due to the hyperactiation of peripheral nerve fibers (overactive C-Fibers)
Allodynia occurs when a stimulus that should not be painful is painful due to A-fibers send inaccurate signals
How do NSAIDs work?
They inhibit the production of prostaglandin to stop inflammatory cascade
What are the cogntive inhibiting and sensitizing factors to pain?
Inhibiting:
- anticipation of relief from pain
- distraction
- positive outlook
- cognitive contextualization of stimulus
Sensitizing:
- expectation of pain
- attention to pain
- depression/anxiety
- lack of understanding or context for stimulus
What typically causes neuropathic pain?
Since it is not due to injury it is typically caused by an up regulation or dysfunctional ion channels (Na channels) which can lead to hyper excitability and cause painful signals in absence of injury
How is pain managed?
Pharmacological agents:
- locally acting agents: local anaesthetics (blocking neurons), topical NSAIDs
- Non-opiates: COX inhibitors, acetaminophen, neuropathic agents, cannabinoids, antidepressants
- Opiates: codeine, morphine, hydromorphone, fentanyl, methadone
Non-pharmacological:
- Local: fixation of tissue (pressure), surgical excision, physio/massage therapy, hot/cold compress, exercise
- Central: psychological support, stress management, distraction, DBS, exercise, physio
What is PTSD?
A mental health disorder that develops after a traumatic experience
It is thought to be a disturbance of memories and is characterized as a stress response that won’t turn off
PTSD is more common in women
True or False
True
Which type of trauma is more likely to result in PTSD?
Interpersonal trauma (e.g., sexual assault)
What are symptoms of PTSD?
Symptoms are likely to arise up to a year after the event and include:
- Anxiety, intrusive memories, dreams/flashbacks, irritability, poor impulse control, social isolation, emotional numbness
- Patients with PTSD will attempt to avoid and trauma-related cues/triggers
How are flashbacks triggered?
They are triggered automatically by situations that reflect aspects of the traumatic event
E.g. noise of an ambulance activates a response that leads to re-experiencing of intrusive event
How is PTSD diagnosed?
It is a DSM-5 disorder
Diagnosis requires exposure to traumatic event along with:
- Event is persistently re-experienced in memories, nightmares, flashbacks, etc.
- Avoidance of trauma-related stimuli
- Negative thoughts/feelings that began or worsened after the events
- Trauma-related arousal and reactivity
- Symptoms must last longer than 1 month
Can people be predisposed to developing PTSD?
Not really
Only 28-41% genetic concordance rate for MZ twins
However, personality can put you at a higher risk:
- People with minimal education and people who act out are more likely to encounter trauma
What causes PTSD?
We don’t really understand the pathophysiology but people with PTSD show:
- Shrinking hippocampus (memories)
- Increased amygdala activity (emotion)
- Shrinking of ventromedial PFC (regulation of emotion)
- Neuroendrocrine disruptions
What types of neuroendocrine disruptions to people with PTSD display?
They sympathetic division of the ANS involves the release of epinephrine from the adrenal medulla responsible for fight or flight response
Epinephrine strengthens formation of emotional memories via activation of amygdala
PTSD patients show higher levels of circulating epinephrine and/or stress catecholamines; remaining in increased activation and sensitized system following traumatic events
Why does the hippocampus shrink in PTSD patients?
When an individual is stressed their adrenal cortex releases glucocorticoids which send signals to the hippocampus
High levels of glucocorticoids damages the neurons in the hippocampus which increases the sensitivity to stress (no longer able to turn off the HPA axis) and the stimulation results in atrophy - an example of a positive feedback loop
However, it appears that decreased hippocampal volume is an inherited risk
Why is the amygdala overactive in PTSD patients?
The amygdala (in the temporal lobe) plays a role for processing emotions
Epinephrine directly and indirectly activates Beta-adrenergic receptors; thus when you are stressed and have increased epinephrine your expereinced memories are more likely to be associated with stress
Epinephrine is released from adrenal medulla -> Stimulates the Vagus nerve -> Stimulates the neckless of the solitary tract (NTS) in brain stem -> activates the amygdala leading to memory storage
Why is the PFC affected in PTSD patients?
Epinephrine at high levels can impair the PFC function
People with PTSD show a hypo-responsiveness in the PFC, which normally provides inhibitory control over the amygdala
What is fear conditioning? What is extinction?
A lab technique in which a fear response is associated with a conditioned stimulus
Ex. fear is associated with a tone as it was paired with an electric shock for many trials
Extinction occurs when the animal eventually forgets about the association as the tone has been played in absence of the shock for many trials
How long after a traumatic event do people become to extinct their stress response?
PTSD includes a failure of extinction
Without treatment, potentially never
How is fear conditioning developed in people with PTSD? Why do they have trouble with extinction?
Sensory info reaches amygdala throughout the thalamus
The amygdala sends signals to the hypothalamus and midbrain to stimulate the behavioural and physiological fear response
The PFC and hippocampus (contextual info) work to suppress or modulate conditioning fear
Since the PFC and hippocampus are smaller in people with PTSD, these structures are less effective in extinguishing fear conditioning
What are the three processes of LTM?
- Encoding/consolidation: to process of converting sensory info in your WM to LTM
- Storage: long term storage of memories
- Retrieval: the process of re-accessing stored memories and temporarily returning them to WM
What does synaptic plasticity refer to?
Higher level brain regions are capable of re-arranging themselves and increasing/decreasing efficacy in which they transmit info
Contrast the terms long-term potentiation (LTP) and long-term depression (LTD)
LTP is when NMDA glutamate receptors are stimulated which causes changes in gene expression and potential synthesis at the synapse. This results in more AMPA receptors that make the synapse more sensitive to glutamate in the future
- These changes are maintained by the enzyme PKMzeta
LTD is the opposite which occurs after persistent weak stimulation of the synapse
Neurons that fire together wire together
How does the brain consolidate memories?
It uses the hippocampus and happens mainly at night
Intense emotions are consolidated more readily than ‘cold’ memories
Our emotional state ‘tags’ our memories which is mediated by hormones in the HPA axi; in stressful situations levels are high, the brain then stamps in these memories
Propranolol is an effective PTSD vaccine
True of False
As a beta-blocker it interferes with Beta-adrenergic receptors making them unable to respond to NE
However, this drug has found mixed results. It can be used to block reconsolidating of traumatic memories
How does playing Tetris after a traumatic event assist with trauma?
Distracting stimuli compete for cognitive resources and interfere with memory consolidation leading to less flashbacks from traumatizing events
Debriefing a trauma victim immediately after a traumatic event leads to a significant decrease in risk of PTSD
True or False
False - It appears to increase risk of developing PTSD
What is the connection between cannabis and PTSD?
Cannabis can increase risk of experiencing PTSD later in life
However, it can also be used as a treatment due to blocking dreams, helping with impulse control, inducing sleep, facilitating memory extinction, interferes with memory
In the Alzheimer’s article what blood protein was identified and believed to be response for initiating the destructive cascade leading to the appearance of neurological dysfunction
A) Transforming growth factor beta (TGFb)
B) Albumin
C) Astrocytes
D) Sentinel cells
B) Albumin
Albumin simulates astrocytes by binding to a receptor that usually docks TGFb
If too many albumin slips in TGFb increases which activates inflammation, damaging chemicals
Older people have more albumin levels
In the Alzheimer’s article Kaufer and Friedman’s initial research was importance because:
A) They found stress doesn’t impact the BBB
B) They found that stress strengthens the BBB
C) They found stress undermines the structural integrity of the BBB
D) They Found that stress increases inflammation
C) They found stress undermines the structural integrity of the BBB
According to the pain article, if Alice has pain in her lower back but no sign of tissue or nerve damage, she is suffering from:
A) Nociplastic pain
B) Alloplastic pain
C) Nociceptive pain
D) Neuropathic pain
A) Nociplastic pain
According to the pain article, what is the biggest challenge facing pain researchers?
A) No single measure exists to test pain, as it is too subjective
B) Different types of pain are no easily distinguished from one another
C) It is not ethical to test opioids on pain patients, as they are too addictive
D) Pain responses are observable across several brain regions
A) No single measure exists to test pain, as it is too subjective
According to the pain article, neuropathic pain typically results from:
A) A pinched nerve of diabetes
B) Stubbing your toe
C) No obvious cause
D) Stretching of tendons or ligaments
A) A pinched nerve of diabetes
According to the PTSD article, amnesia that arises in the wake of childhood trauma and severs to act as a defence mechanism is known as?
A) Selective amnesia
B) Anterograde annesia
C) Dissociative amnesia
D) Transient global amnesia
C) Dissociative amnesia
According to the PTSD article, pathological communication between the ________ and the __________ likely give rise to the severe dissociative symptoms found in women diagnosed with PTSD stemming from childhood trauma
A) Default mode network; Midcingulo-insular network
B) Occipital network; Midcingulo-insular network
C) Default mode network; Frontoparietal network
D) Occipital netowrk; pericentral network
C) Default mode network; Frontoparietal network
According to the PTSD article, MRI studies conducted on amnesia arising from trauma exhibit reduced activity in the _______ and increased activity in the ________
A) Amygdala, PFC
B) PFC, amygdala
C) Hippocampus, amygdala
D) Amygdala, PVC
A) Amygdala, PFC
According to the epilepsy article, seizure forecasts are said to:
A) Predict the probability of a seizure happening over a given time
B) Predict not just the probability of a seizure but the time of it
C) Alert the user of a potential seizure 3 days in advance with 100% accuracy
D) Alert the user of a potential seizure 1 day in advance with 100% accuracy
A) Predict the probability of a seizure happening over a given time
According to the epilepsy article, what class of drugs is considered to be one of the main therapeutics used to prevent seizures, and what is their drawback with LT use?
A) Hallucinogens, development of psychosis
B) Barbituates, development of dependence
C) Benzos, loss in therapeutic efficacy
D) Depressants, development of addiction
C) Benzos, loss in therapeutic efficacy
According to the epilepsy article, seizures are associated with which type of rhythm:
A) Circadium rhythm
B) Circannual rhythm
C) Ultradian rhythm
D) Infradian rhythm
A) Circadium rhythm
According to the Alzheimer’s article, which drug causes the Gulf War Syndrome? Why?
Pyrodpstigamine
This was not supposed to cross the BBB but when people are stressed the BBB leaks allowing the entry of Pyrodpstigamine
According to the Alzheimer’s article, what is the state of an Alzheimer’s patients BBB?
It shows excessive and progressive BBB leaking
According to the Alzheimer’s article, what is the criticism of beta-amyloid being the dominant cause of the disease?
- Reduced levels of beta-amyloid does not affect mental decline
- Drugs that target beta-amyloid fail to help the disease
According to the Alzheimer’s article, which type of drug may be effective in protecting individuals from cognitive decline due to aging?
TGFb blockers (IPW)
According to the pain article, during an MRI people with fibromyalgia hav either ______ and ______ act up at the same time
Default mode network; insula (salience network)
This is because the default mode network turns on during topics involving oneself and the insult turns on when someone is experiencing a new sensation
The pain experienced in fibromyalgia is so chronic that pain becomes a part of ones identity
What is Epilepsy?
A broad term that includes a large group of neurological disorders characterized by epileptic seizures
It is defined by the occurrence of at least one epileptic seizure, but characterized by recurrent seizures
What is an epileptic seizure?
A brief episode of abnormally excessive cortical neuronal activity
Excessive discharges within the brains gray matter or out of control action potentials result in brief undetectable seizures to vigorous shaking
Why was epilepsy stigmatized?
People thought it was contagious via ‘evil breath’ as people can almost appear possessed
Until 1956, people with epilepsy could not marry in 17 states ‘eugenics’
What are the 2 major different types of epileptic seizures?
Generalized seizure: typically have no apparent local onset
- they mostly grow from a focus to a widespread seizure that involves activation of entire cortex
Partial seizure: have definite focus or sources of irritation
- typically begin in specific area in the motor/sensory cortex and involve only a small, circumscribed area of the cortex
What are the 3 types of generalized seizures?
- Tonic-clonic (grand mal): most severe
- Absence (petite mal): unresponsiveness, blinking repeatedly
- Atonic: loss of muscle tone, temporary paralysis
What are the different types of partial seizures?
Simple: no major change in consciousness
- localized motor seizure
- motor seizure with progression of movements as seizure spreads along motor cortex
- sensory (seeings/hearing things)
- psychic (forced thinking, fear, anger)
- autonomic (sweating, salivating, chewing, etc.)
Complex: Includes altered consciousness and includes subtypes 1-5
Partial seizures however can develop into generalized seizures
What are the stages of a grand mal seizure?
- Tonic phase
- muscles contract forcefully all over the body
- patient is unconscious
- rigid posture (~15s) - Clonic phase
- Muscles tumble then start jerking
- eyes roll into back of head
- face is contorted, tongue may be bitten off
- Intense activation of ANS
- ~30s muscles relax and patient resumes breathing
When do convulsions occurs during a seizure?
Occurs when the abnormal activity involves the entire motor cortex
What is the Jacksonian March?
Electrical activity slowly marches across the motor cortex causing sequential progression of clonic movements in a seizure
Typically begins with foot, hand, or face
What is an Aura?
Changes in mood, abnormal motor movements, or other sensory anomalies that occur prior to a seizure
Dogs can be trained to sense auras
What causes epilepsy?
The cause of most cases is unknown
Certain factors are associated with development:
- brain injury, stroke, neurological-trauma, neurological-infections, birth defects/genetic abnormalities
Most common cause is scarring that irritates the brain tissue surrounding it causing an increase in neural activity
Environmental factors: - flashing lights, infections causing high fevers
What is Kindling?
An animal model for the development of seizures and epilepsy, in which the duration and behavioural involvement of induced seizures increases after seizures are induced repeatedly
Seizures generate plastic changes in cortical circuit which make them more common and severe due to sensitization
These effects are more or less permanent
What are the genetic causes of epilepsy?
One cause is a mutated sodium channel
- Mutation leads to dysfunctional inactivation of Na channels in presence of elevated temperature (eg. fever) causing seizures
Another cause is synaptic inhibition
- Mutations that affect synthesis or release of GABA, enzymatic degradation or its activity
How do you treat epilepsy?
Anticonvulsant drugs are typically used to
- enhances GABA neurotransmission to reduce/counter excitability, benzos, barbiturates
Surgery can also be effective when epilepsy is unresponsive
- removal of brain region where seizures originate or disconnect hemisphere to avoid spreading hyperactivity
Who is HM?
A man who suffered from severe epilepsy and had his medial temporal lobe (amygdala, hippocampal and associated subcortical structures) removed
He showed severe anterograde amnesia, retained an average IQ, complete loss of explicit memory but implicit memory was intact
Are seizures harmful?
Yes they can cause brain damage (~50% of patients), and physical damage to your body
What is Status epilepticus?
A condition in which a patient undergoes a series of seizures, without regaining consciousness
Causes excessive glutamate release and significant hippocampal damage
Which drugs can cause epileptic seizures? Why?
Withdrawal from alcohol or barbiturates
The body adapts to the presence of the drug and upon cessation the brain is hyper excitable which can lead to a seizure
How is epilepsy diagnosed?
Done via EEG recordings that will demonstrate unique patterns that are suggestive of hyper excitability
However 1/10 patients show normal EEG recordings
According to the epilepsy article, how are seizure focecases predicted?
By using an EEG to monitor interictal epileptiform discharges - pathological spines in brain activity that occur between seizures
According to the the epilepsy article, what are the advantages and disadvantes to seizure forecasting?
Pros: People could take benzos only when they are high risk to make them more effective
Cons: Reorganizing your day/week because you expect to have a seizure but then don’t could be very frustrating
What is the key limitation for the forecasting technique used in epileptic seizure forecasting?
It requires a brain implant to record neural activity
According to the epilepsy article, which other was can seizures be forecasted?
- Subscalp EEG can record neural activity
- multiday cycles in HR
In lecture, Dr. MacKay described ____ as the unique trace of neurons that are joined together with LTP-strengthened synapses, or the physical substantiation of memory in the brain.
A) Hippocampal trace
B) Hebbian theory
C) Engram
D) Hebbian trace
C) Engram
In lecture, a study was mentioned about rats injected with amyloid-B and subjected to stress. What did the results of this study suggest?
A) Stress may increase the neurodegenerative effects of amyloid-B
B) Amyloid-B and stress can act synergistically to impair memory
C) Neither stress nor amyloid-B alone can impair memory, but together they can
D) All of the above
D) All of the above
How can a high fever contribute to the development of epilepsy?
A) Elevated temperatures upregulate glutamate release
B) Elevated temperatures inhibit GABA synthesis and release
C) Elevated temperatures induce synchronous neuronal activity
D) Elevated temperatures lead to impaired inactivation of sodium channels
D) Elevated temperatures lead to impaired inactivation of sodium channels
Which is not a characteristic of neuropathic pain?
A) Pathological pain function
B) High levels of pain tolerance
C) Resulting from neural damage
D) Low threshold pain sensitivity
B) High levels of pain tolerance
ccording to article #7 - The Unexpected Diversity of Pain, osteoarthritis is associated with what type of pain?
A) Nocieptive
B) Neuropathic
C) Central sensitization
D) Nociplastic
A) Nocieptive
According to the article, ‘Damage to a Protective Shield around the Brain’, which of the following does NOT contribute to the aging deterioration of the Blood Brain Barrier (BBB)?
A) TGFB
B) Albumin
C) Astrocytes
D) Resident microglia
D) Resident microglia
Nociceptive pain results from
A) A disease such as shingles
B) Injury or tissue damage
C) Nerve damage
D) Central sensitization
B) Injury or tissue damage
Alzheimer’s disease follows a fairly predictable trajectory, beginning with neural degeneration in the ___ and then spreading to other brain regions.
A) Frontal and temporal lobes
B) Cerebellum and entorhinal cortex
C) Hippocampus and thalamus
D) Insula and occipital lobe
A) Frontal and temporal lobes
Which of the following is known to induce seizures?
A) Barbiturate withdrawal
B) All options can lead to seizures
C) mTBI
D) Meningitis
B) All options can lead to seizures
SOD typically contributes to breaking down ________________.
A) Cholinergic drugs
B) Exsessive CA2+ in the cytoplasm
C) Free radicals
D) Inclusion bodies in the cytoplasm
C) Free radicals
A missing stretch reflex is a sign of _______.
A) Upper and lower motor neuron damage
B) Lower motor neuron damage
C) Damage that would only be seen in various sensory neurons
D) Upper motor neuron damage
B) Lower motor neuron damage
Which is not a pathological hallmark of ALS?
A) Insufficient clearance of intracellular proteins
B) Mutations in the region of the genome that codes for SOD1
C) Decreased catalysis of O2 into a less reactive chemical
D) Loss of dopaminergic neurons in the substantia nigra pars compacta
D) Loss of dopaminergic neurons in the substantia nigra pars compacta
Lower motor neurons can be found in both the ventral horns of the spinal cord and ________________-
A) Pyramidal nuclei of the brain stem
B) Primary motor cortex
C) Interneurons in the spinal cord
D) Motor nuclei of the crainial nerves
D) Motor nuclei of the crainial nerves
Alzheimer’s disease was first characterized by:
A) Hans Alzheimer & Sigmund Freud
B) Auguste Deter & Alois Alzheimer
C) Herman von Helmholtz & Albert Alzheimer
D) Alois Alzheimer & Emil Kraeplin
D) Alois Alzheimer & Emil Kraeplin
Which of the following is NOT a symptom associated with Alzheimerís disease?
A) Apathy
B) Retrograde dementia
C) Affect and emotion
D) Executive function deficits
B) Retrograde dementia
An individual has recently been experiencing seizures. When describing the symptoms to their physician, they say that they stare off into space with a vacant look and blink. What type of seizure would the physician say this individual is suffering from?
A) Atonic seizure
B) Grand mal seizure
C) Petit mal seizure
D) Myoclonic seizure
C) Petit mal seizure
Individuals that have Alzheimerís disease as early as the 40s is considered to have _____.
A) Pre-senile dementia
B) Preliminary amnesia
C) Anterograde dementia
D) Premature Alzheimer’s disease
A) Pre-senile dementia
Which best describes botulinum toxin’s mechanism of action
A) A reduction of Ach release at nerve terminals
B) The impairment of vesicular fusion between synaptic vesicles and nerve terminal
C) Selectively taken up by cholinergic nerve terminals
D) All of these describe important parts of the mechanism
D) All of these describe important parts of the mechanism
Jacksonian March refers to:
A) A specific walking technique that can help minimize the impacts of a seizure.
B) The tendency for seizures to spread along the motor cortex, causing a cascade of visible motor symptoms following a stereotyped progression.
C) The tendency for individuals with epilepsy to have more seizures in the late winter/early spring months.
D) Jacksonian March was a 19th Century physician who described the first anti-convulsive drug.
B) The tendency for seizures to spread along the motor cortex, causing a cascade of visible motor symptoms following a stereotyped progression.
Which is not a characteristic of nociceptive pain?
A) Results from inflammation
B) Results from acute trauma
C) Results from central nervous system dysfunction
D) Results from injury
C) Results from central nervous system dysfunction
An individual consciously executes a command to squeeze their right hand, which is the proper order in which the information would travel?
A) Right precentral gyrus, Spinal Cord, Ventral Root, Right Hand.
B) Left precentral gyrus, Spinal Cord, Dorsal Root, Right Hand.
C) Left precentral gyrus, Spinal Cord, Ventral Root, Right Hand.
D) Right precentral gyrus, Spinal Cord, Dorsal Root, Right Hand.
C) Left precentral gyrus, Spinal Cord, Ventral Root, Right Hand.
Which of the following gene is linked to Alzheimer’s disease?
A) Growth hormone secretagogue receptor 1A (GHSR1A)
B) Acetyl-CoA carboxylase (ACC)
C) Amyloid precursor protein (APP)
D) Monoamine oxidase A (MAOA)
C) Amyloid precursor protein (APP)
According to the article, Forecasts of Epilepsy Seizures Could Become a Reality, how do circadian rhythms influence seizures?
A) Seizures are more likely during certain times of day
B) Individuals with epilepsy tend to have more seizures in years with large cicada swarms
C) Seizure likelihood is influenced by the phase of the moon
D) All of these are circadian signals known to influence seizures
A) Seizures are more likely during certain times of day
According to Dr. MacKay, an episode of Pokémon was taken off the air because it featured ________________ which is considered to be ________________.
A) Strobe effects; excitotoxic
B) Flashing lights; epileptogenic
C) An optical illusion; seizure-inducing
D) High frequency sounds; excitotoxic
B) Flashing lights; epileptogenic
Sensory nerves are described as ____, and enter through the ____ of the spinal cord
A) Efferent, Dorsal Root
B) Afferent, Ventral Root
C) Efferent, Ventral Root
D) Afferent, Dorsal Root
D) Afferent, Dorsal Root
Which of the following statements regarding kindling is false?
A) It demonstrates that those with epilepsy have reduced brain plasticity
B) The effects of kindling are permanent
C) It is an animal model for seizures and epilepsy
D) Over time, less stimulation is needed to induce a seizure
A) It demonstrates that those with epilepsy have reduced brain plasticity
An individual with epilepsy has been unresponsive to pharmacological treatment. Their physician suggests surgery in order to reduce the amount of cortical hyperactivity that spreads from the left hemisphere to the right hemisphere during a grand mal seizure. What brain region should the surgeon transect?
A) Corpus Callosum
B) Cingulate Cortex
C) Hippocampus
D) Thalamus
A) Corpus Callosum
Which is incorrect?
A) Lower Motor Neurons are efferent nerve fibers
B) Upper Motor Neurons originate in the precentral gyrus
C) Lower Motor Neurons are afferent nerve fibers
D) Upper Motor Neurons synapse onto interneurons within the spinal cord
C) Lower Motor Neurons are afferent nerve fibers
Which neurons control the reflex arc ?
A) Primary motor cortex neurons
B) Secondary motor cortex neurons
C) Upper motor neurons
D) Lower motor neurons
D) Lower motor neurons
Which of the following can lead to inherited epilepsy?
A) Mutations in the EPI gene and mutations in the enzyme that degrades glutamate
B) Mutations of the GABA channel and mutations affecting sodium conductance
C) Mutations that impair glutamate reuptake by astrocytes
D) Mutations in ionotropic sodium channels and mutations affecting GABA production
D) Mutations in ionotropic sodium channels and mutations affecting GABA production
An individual is experiencing synchronous neuronal activity in the orbitofrontal cortex, the hippocampus and the primary somatosensory cortex. It is unknown which brain region the abnormal activity originated from. What type of seizure is this individual experiencing?
A) Focal seizure
B) Complex partial seizure
C) Simple partial seizure
D) Generalized seizure
D) Generalized seizure
According to the article, ‘Damage to a Protective Shield around the Brain’, which of the following statements is FALSE?
A) Increased albumin levels in the brain leads to increased TGFB in astrocytes
B) Inflammation due to TGFB started before albumin appeared in the hippocampus
C) TGFB blockade in mice had reversed cognitive impairment due to aging
D) Experiments reducing B-amyloid had no effect on disease or mental decline
B) Inflammation due to TGFB started before albumin appeared in the hippocampus
H.M.’s seizures originated in his _________________ and after a bilateral resection of this region, he experienced complete _______________ amnesia.
A) Lateral temporal lobe; anterograde
B) Lateral temporal lobe; retrograde
C) Medial temporal lobe; anterograde
D) Medial temporal lobe; retrograde
C) Medial temporal lobe; anterograde
Acetylcholine receptors are densely expressed in _______.
A) Neuromuscular junction
B) Lower and upper motor neurons
C) Tight junctions
D) Upper motor neurons
A) Neuromuscular junction
If a neuroscientist were to lesion the region of the right premotor cortex corresponding to the hand, what part of the body would see impaired function?
A) The Right hand because the corticospinal tract decussates at the midbrain
B) The Left hand because the corticospinal tract decussates at the hindbrain
C) The Right hand because the corticospinal tract decussates at the hindbrain
D) The Left hand because the corticospinal tract decussates in the midbrain
B) The Left hand because the corticospinal tract decussates at the hindbrain
According to the article, ‘Damage to a Protective Shield around the Brain’, blockade of the TGFB receptor in rodents after a concussion alleviated the following EXCEPT for ____.
A) Increased tight junctions
B) Inflammation
C) Cognitive decline
D) Seizures
A) Increased tight junctions
Which of the following cytoskeletal elements is implicated in Alzheimer’s pathology?
A) Neurotubules
B) Microtubules
C) Neurofilaments
D) Microfilaments
B) Microtubules
Quantitative sensory testing is a
A) Individualized diagnostic that can measure when a stimulus becomes painful to a patient
B) A categorical quality of life scale in which patients report impairments due to their pain
C) A diagnostic tool a clinician can use to determine a patients pain level by the appearance of their face
D) Patient feedback questionnaire that evaluates their current pain on a scale of 10
A) Individualized diagnostic that can measure when a stimulus becomes painful to a patient
Individuals with Alzheimer’s disease who do not realize they are ill are said to have ____.
Anosognosia
____________________ drugs are prescribed to treat epilepsy. They are classified as a GABA _____________ and work by _______________ the amount of inhibition throughout the brain.
A) Convulsant; agonist; decreasing
B) Anti-convulsant; agonist; increasing
C) Anti-convulsant; antagonist; increasing
D) Anti-convulsant; antagonist; decreasing
B) Anti-convulsant; agonist; increasing
Trephination, the process in which burr holes are drilled into the skull, is the earliest known surgical intervention for which disease?
A) PTSD
B) Alzheimer’s Disease
C) Epilepsy
D) Chronic pain
C) Epilepsy
According to the article, Forecasts of Epilepsy Seizures Could Become a Reality, what is the current downside to seizure forecasting?
A) The technology used to determine the computational modelling requires weekly updates
B) Seizure forecasting is extremely expensive and therefore unattainable for many with epilepsy
C) Seizure forecasting is accurate for less than 5% of people with epilepsy
D) It requires a neurostimulation device to be implanted in the brain
D) It requires a neurostimulation device to be implanted in the brain
Excitotoxicity can lead to a chain reaction of cell death. What type of drugs used in the treatment of Alzheimer’s disease can help protect neurons from this chain reaction?
A) Glutamate release inhibitors
B) Glutamic acid decarboxylase antagonists
C) Acetylcholinesterase inhibitors
D) NMDA antagonists
D) NMDA antagonists
According to the article, Forecasts of Epilepsy Seizures Could Become a Reality, what did Rao et al. use to predict future seizures?
A) Sleep-wake cycle data from each participant
B) EEG readings of the pathological spikes in brain activity that occur between seizures
C) Self-report assessments of auras
D) Cortisol levels throughout the day
B) EEG readings of the pathological spikes in brain activity that occur between seizures
Which of the following is true about the neurobiology of memory formation in the brain?
A) LTP makes synapses easier to stimulate, while LTD makes synapses harder to stimulate
B) All of these things are true
C) Synapses that are frequently stimulated become stronger and easier to stimulate in the future
D) In a neural network, sensory neurons are typically the input neurons while the motor neurons are typically the output neurons.
B) All of these things are true
