Exam 2

Question 1

What kind of people does Alzheimer’s affect and what are some general risk factors?

Answer 1

It affects older people. Alzheimer’s leads to dementia.
Age is the biggest risk factor though there are some environmental and genetic risk factors.
Genetic factors for ApoE is the biggest genetic risk factor.

Question 2

How is amyloid-beta formed?

Answer 2

A𝛽 is caused by the cleavage of the amyloid precursor protein (APP).
When cleaved by 𝛽 secretase and 𝛾 secretase, A𝛽 peptide is the result.

Question 3

How are neurofibrillary tangles formed?

Answer 3

Neurofibrillary tangles are caused by phosphorylated tau.
When tau is phosphorylated, it can’t regulate the microtubules, leading them to aggregate.
The neurofibrillary tangles seem to be a secondary issue to the A𝛽.

Question 4

What does amyloid-beta impact?

Answer 4

Interacts with TLRs and can activate the immune system.
Cause mitochondrial dysfunction.
This can lead to the production of ROS.
Damage to the BBB leads to increased permeability.
This can allow more immune cells in.
Increased Ca2+ influx.
This can lead to apoptotic pathways.
Dysregulated excitation and inhibition ratio.
Kill or weaken glial cells.

Question 5

What are cognitive functions?

Answer 5

Abstract problem-solving (fluid reasoning)
Processing speed.
Maintaining information (working memory)
Episodic memory
Learning
Using and applying rules (crystallized knowledge).
Ex: Societal or cultural rules. 
Procedural memory.

Question 6

Can we measure general intelligence?

Answer 6

No, not really. Intelligence changes with age and circumstances such as low SES and education status. There are a lot of different cognitive functions and someone may be better at one rather than the other.

Plus, measuring general intelligence is highly rooted in eugenics.

Question 7

How do cognitive functions change over time?

Answer 7

Process abilities peak in early adulthood.
Fluid reasoning, episodic memory, and processing speed.
Product abilities peak in late adulthood.
Ex: Crystallized knowledge, procedural knowledge, and specialized professional skills.

Question 8

What areas does AD impact?

Answer 8

It hits the temporal lobe first, specifically the hippocampus. That causes deficits in spatial and episodic memory.

Deficits in other areas of the cortex such as the Nucleus Basalis Myenert which is involved in sleep, attention, and consciousness.

Question 9

Why is it hard to diagnose AD?

Answer 9

Because there are many subtypes of dementia. AD symptoms also only appear after a lot of neuronal death and after amyloid-beta levels have plateaued so it is hard to catch early.

Question 10

What are risk factors for PD?

Answer 10

Age.

alp-synuclein.

Question 11

What does alp-synuclein have to do with PD?

Answer 11

alp-synuclein forms aggregates of Lewy bodies.

Question 12

What cells does PD affect?

Answer 12

It affects the substantia nigra in the basal ganglia. It affects the dopamine system in general, so it could affect the VTA as well which connects to the PFC.

The cholinergic, serotonergic, and noradrenergic networks can be disrupted as well.

Question 13

What are motor symptoms of PD?

Answer 13

Bradykinesia=hard time initiating movement. 
Rigidity=muscle stiffness.
Resting tremor
Postural instability
Gait disturbance
Speech and swallow troubles.

Question 14

What are non-motor symptoms of PD?

Answer 14

Lack of smell
Sleep disturbances
Insomnia and REM sleep disorder
Cognitive dysfunction
Mood disorders
Anxiety and depression. 
Constipation
Bladder dysfunction
Orthostatic hypotension
Sexual dysfunction
Changes in thermoregulation

Question 15

What are typically the first symptoms of PD?

Answer 15

Sleep problems, then motor, then dementia later.

Question 16

What crossover is there between PD and AD?

Answer 16

1/2 of PD patients with dementia form amyloid-beta plaques.

Question 17

What treatments are there for PD?

Answer 17

General treatments for symptoms.
Dopamine agonists are given first.
L-dopa is not given until later because its effectiveness eventually wears off. C
Cholinesterase inhibitors are given to help improve cognitive decline.
DBS is becoming a more popular option.
Surgery is a last-ditch option.

Question 18

Why do you have to be careful about the dopamine medications for PD?

Answer 18

You also have to be careful because dopamine medication and lead to impulse disorders or dopamine dysregulation syndrome.
The impulse syndrome can lead to executive dysfunction.

Question 19

What is the parallel circuit model?

Answer 19

Parallel circuit model:
The parallel circuit model says that the information from different inputs stays in different tracks around the basal ganglia as they encode different information.
Striatum takes input from the VTA and cortex.
The direct pathway allows movement to happen.
The indirect pathway inhibits movement.
Information can go back through the loop and possibly cross-talk with other channels.

Question 20

What is the center surround model?

Answer 20

To execute an action other competition possible options must be suppressed.
In PD, there is excessive activation of the GPi and STN and decreased activity in GPe.

Question 21

What could be underlying mechanisms for PD?

Answer 21

Changes in synchronization of firing and changes in aberrant neural activity could contribute to PD pathophysiology.

Question 22

What animal models exist for PD?

Answer 22

Rotenone is only used in rodents.
Affects mitochondria.
MPTP is only used in primates.
Selective for SN neurons and produces ROS toxic for DA neurons.
Inhibits mitochondrial complex I, II, and III.
6-OHDA can be used in rodents of C. elegans.
Direct injection of SN via surgery.
Oxidized and leads to ROS and cell death.
⍺ synuclein and PARKIN model better replicate protein dysfunction.
It leaves the DA neurons fine.

Question 23

What is epilepsy?

Answer 23

It is a broad term for a bunch of disorders that have seizures.

Question 24

Who does epilepsy typically affect?

Answer 24

Children due to genetic risks.

Older people due to cerebrovascular damage.

Question 25

What discrepancies are there in epilepsy diagnosis and treatment?

Answer 25

There is also a big discrepancy in how epilepsy is treated in high-income countries vs middle and low-income countries. In low and middle-income countries it is a lot harder to access healthcare and to get or afford the medication that would work best for the individual.

Question 26

What can lead to mortality in epilepsy?

Answer 26

There are a lot of comorbidities for epilepsy and they are usually more likely to lead to mortality than the actual seizures themselves. There is the sudden unexpected death in epilepsy (SUDEP) that seems to be death caused by seizures. It is very rare and little is known about it.

Question 27

What is generalized epilepsy typically caused by vs focal seizures?

Answer 27

Generalized epilepsy has a stronger genetic component. Many are due to genes that affect inhibition and excitation regulation. Focal epilepsy is more likely to be caused by structural problems.

Question 28

What do criteria are there to get diagnosed with epilepsy?

Answer 28

2 unexplained seizures with an eyewitness. | Brain imaging to check for structural abnormalities and an EEG.

Question 29

What treatments are there for epilepsy?

Answer 29

Anti-convulsants Surgery for those with structural abnormalities Neuromodulation- Vagus nerve stimulation and DBS could be a treatment.

Question 30

What are partial focal seizures and what are the subtypes of it?

Answer 30

Partial/focal seizure=one hemisphere or lobe is impacted. Simple=retain consciousness. Usually knows something is happening and remembers the seizure. Complex=impaired consciousness. May not remember what happened.

Question 31

What is a generalized seizure and what are the subtypes of it?

Answer 31

Generalized seizure=both hemispheres affected with a loss of consciousness. Secondary generalized seizure=partial seizure → generalized seizure. Tonic seizure=muslce become flexed. The muscles become stiff and the patient tends to fall backward. Atonic=muscles relax. The muscles relax and the patients tend to fall forward. Clonic=lots of convolutions. Tonic-clonic seizures are the most common generalized seizure. Myoclonic=short muscle twitches. Absence=loss of consciousness and quick regaining of consciousness. The person looks like they spaced out.

Question 32

How does epilepsy occur?

Answer 32

Abnormal activity in cortical neurons. Epilepsy is not thought to be a simple balance in excitation and inhibition but rather cause be activity-dependent disinhibition. Excitatory signals may get too high and pass a seizure threshold, overwhelming the system. Inhibition does not occur like it normally would.

Question 33

What molecular changes could lead to epileptogenesis?

Answer 33

Abnormal short-term plasticity may lead to seizures. Especially, if there are mutations in presynaptic docking proteins. Mutations in postsynaptic proteins usually lead to longer seizures and act on longer time scales. Disinhibition may also be caused by abnormal changes in ionic concentration extracellularly and intracellularly. Increases in K+ extracellularly or intracellular influx of Ca2+ can cause seizures. GABA receptors are permeable to Cl- and HCO3-. If there is a lot of synaptic activity, max Cl- transport rate will be reached and more bicarb may be pulled in instead. However, CO2 is equal on both sides of the membrane so pulling in HCO3- will be more electroneutral as it is converted to CO2. Imbalance circuit: This can be caused by an injury or cortical dysgenesis Overactivity of the mTOR pathway is linked to some epilepsy. Overactivation can decrease autophagy processes. Connectivity issues can arise due to abnormal synaptic plasticity, migration, and process outgrowth. Mutations in ARX lead to decrease migration and could contribute to this. Mutations in SC1NA lead to fewer Na+ channels in inhibitory neurons which makes it harder to start an action potential. Abnormal neuronal homeostasis.

Question 34

What are some risks to developing autism?

Answer 34

There are some genetic risks of autism and some environmental risks such as increased parental age.

Question 35

What are the social symptoms of autism?

Answer 35

Impaired social ability Social responses are not deemed to be normal. Non-verbal communication difficulties. Hard time making and maintaining relationships. Spend less time looking at faces.

Question 36

What are the behavioral symptoms of autism?

Answer 36

Repeated stereotyped behaviors. Focus on routine or sameness. Special interests. Can be hyperactive or hypoactive at times.

Question 37

What are the most common comorbidities of ASD?

Answer 37

ADHD, anxiety, other mood disorders, irritability, and aggression.

Question 38

What is the neurological basis of autism?

Answer 38

There is a significant genetic component → ~70-90% risk heritable. Elevated risk for younger siblings. Brain overgrowth during early development. Overgrowth in the amygdala in childhood. Neuronal connectivity issues. Has a lot of connectivity in some areas and less in others. Social and attentional deficits.

Question 39

What is some treatment for autism?

Answer 39

Parent-mediated interventions with how to better interact with their child. Some pharmacological interventions to treat comorbidities such as ADHD or aggression. Speech and occupational therapy could help the individual.

Question 40

What did the Avino et al., 2018 paper find with amygdala differences between NT and ASD people?

Answer 40

Amygdala neurons increase with age in NT people. ASD children start with more neurons than NT children. ASD adults have fewer neurons than NT adults. Decrease in immature neuron numbers in the paralaminar nuclei with age in both groups.

Question 41

Why are the differences in amygdala growth seen in ASD and what could it mean?

Answer 41

The amygdala continues to grow post-birth due to activity-dependent experiences. The difference in amygdala growth could be due to altered pre and postnatal neurodevelopmental processes A hyperactive amygdala in adulthood could decrease neuron number due to excitotoxic effects. Altered amygdala function leads to increased anxiety and social impairment.

Question 42

Why is it important to get a diagnosis of ASD and why is it hard to get a diagnosis?

Answer 42

A diagnosis can be very helpful for an individual to understand themselves for family members to understand them. Problems with getting a diagnosis: ASD is very heterogenous so diagnoses are usually missed for those who are verbal and do not have intellectual disability comorbidity. Also, factors, like having younger siblings, being female, a family of a low SES, and being a racial or ethnic minority, will lead to more missed diagnoses.

Question 43

Why does den Houting promote the social model of disability for autistic people?

Answer 43

Autistic people are disabled. The social model of disability should be followed because the environment does not meet or accommodate the needs of autistic people and thus accommodations should be made to give them opportunities to thrive and for others to listen to them.