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At what age is it that men do better cognitively than women?
After you cross the threshold of 80/85
Do old rats do worse than young rats in cognitive experiments?
Yes, for the most part. However there is a subset of about 30% that does just as well if not better than the younger rats
Why is it that reduced caloric intake leads to longer life?
Reduced caloric intake, there is less nutrients for mitochondria to make ATP which means that it is also going to be making less free radicals.

Free radicals are the identified main culprits in aging.
What are the three main steps that people notice with aging?
1. Cognitive slowing
2. Issues with attention and working memory
3. Poor learning and melh ability, especially with recent events and information
Often times older peolpke have issues with SEMATIC knowledge.
The have information at the tip of their tongue. This is indicative of a problem in which lobe?
Indicative of an issue with the frontal lobe
What is more impaired in the older population, free recall or recognition?
Free recall is more impaired
Where do older people exhibit neuronal loss?
NOT IN THE C1 region of the hippocampus.

Loss in the subiculum and dentate hilus of the hippocampus (loss reported in humans, and no loss was reported in rats)
What has been associated with neurogenesis in people of old age?
Exercise
Compare the sensitivity of hippocampal neurons to glutamate in old and young rats?
The sensitivity is the same
What neurotransmitter transmission was attenuated by 50% in older rats?
Cholinergic transmission
What is a key hypothesis as to why we age?
The calcium hypothesis of aging.
Excess intracellular calcium actives proteases that destroy the cytoskeleton and lead to cell death.
What is the part of the action potential that is most delayed in the aging neuron?
The late deoolarizing plateau in Calcium potentials

This in turn leads to a slow after hyperpolarization which in turn leads to reduced neuronal excitability
What can you give to increase the baseline excitability of aging hippocampal neurons?
L type Calcium channel blockers

They also have been shown to increase the learning rate of old, but not young neurons
What does the beta amyloid hypothesis have to do with?
Alzheimer's
How does beta amyloid deposition lead to Alzheimer's
Leads to neurofibrillary tangles, Cl loss and cognitive disfunction, which are all markers of Alzheimer's disease

Also believed that it leads to increased Ca deposition
What may help to deal with enhanced neuronal calcium load and reduced cholinergic neurotransmitter seen in aging neurons?
Estrogen.

Especially in aging rats. However, this could lead to an increased risk of developing heart disease and cancer
How much of a factor do genetics play in AD?
Only 20-30%!

Environmental stimuli, including trauma to the head have been shown to play a part in developing AD
What is dementia pugilistica?
The cognitive deficits that some boxers exhibit. It is very simila to AD
Where are the concentration of amyloid plaques found in patients with AD?
In the temporal lobe
At what age does the incidence of AD increase dramatically?
65
What must be present clinically in order to diagnose someone with AD? 3
1. Dementia
2. Memory
3. Slow onset
Is there a definitive diagnosis for AD?
No. You can only know for sure post mortem
Can Alzheimer's patients learn some procedural tasks?
Some. However they will not remember having learned the task at hand
What happens to the motor and sensory systems in AD?
Much of them is spared, as is the cerebellum
Amygdala is often involved in patients with AD which explains
The emotional flattening that is often seen in patients with AD
What are three things that provide some protection against Alzheimer's disease?
1. Education
2. Immunization with beta amyloid
3. Blocking APP cleavage that is required in order to yield beta amyloid at the BACE site
If you exercise,what happens to BDNF?
BDNF will go up, it is a growth factor that is good for brain health
Where does AD tend to begin?
AD tends to begin in the limbic system
What part of the frontal lobe is in charge of the internal sequencing of motor actions?
The premotor cortex
What part of the frontal lobe selects the appropriate movements given the time and space?
The prefrontal cortex
An injury in the lateral prefrontal cortex is associated with what?
Issues with WORKING MEMORY.

Need to inspect closely though, because at first sight the patients seem to not be impaired cognitively
What did the experiment on delayed response on monkeys show? This is where they show a cross and ask them to associate it with a cross, versus asking them to remember under which card it is located.
Lateral prefrontal cortex injury
DOES NOT affect monkeys ability to associate the cross with food

NOT ABLE TO REMEMBER under which card the food was located, which is an issue with working memory
The example of the monkey being able to associate the cross with food is similar to object permanence that children develop when they are 1 year old, once the development of what is complete?
Once the development of the frontal lobe is close to being complete
What is the Wisconsin Card Sorting Task?
It is a test that was developed to see the functioning of adults Lateral Prefrontal Cortex.

They show you s bunch of cards and you have to sort them by color, number, or shape.
Does an injury to the prefrontal cortex affect long term memory?
NO. It only affects the long term storage site for memories used in solving delay tasks.
When will the neurons in the prefrontal cortex fire during a delayed response task?
They will only fire AFTER the stimulus is removed.
Besides issues with working memory, what's another major issue that people with prefrontal cortex damage have?
1. Working memory
2. Temporal memory
What does it mean that patients with prefrontal forts have issues with Temoral memory?
It means that when they are presented with a series of objects they can remember having seen them, but they can't remember in what order they saw them
With regards to the action potentials elicited by neurons in the prefrontal cortex, what explains the faulty temporal memory?
Excitatory response is not inhibited as well as it should be.

Normally after seeing an object your neurons fire and then they stop. Becaus there is not a secondary inhibition the objects mesh with one another
Utilization behavior and imitative behavior are often seen in patients with frontal lobe injuries. What is utilization?
Exaggerated tendency to use environmental cues to guide behavior
What is the ventromedial prefrontal cortex tightly associated with?
Ventromedial prefrontal cortex is tightly associated with the amygdala
What I Descartes error
He failed to recognize that many of the decisions we make from day to day are NOT entirely rational, but also carry an emotional significance.

Something that is lacking in patients that have an injury in the centromedian prefrontal cortex
With regards to the frontal lobe, what do schizophrenic patients show?
Reduced activity in the frontal lobe, especially the lateral regions
With regards to the frontal lobe what do people with depression exhibit?
OVERACTIVE prefrontal regions
Did frontlal lobotomy help schizophrenic patients?
NO, it did make the depressed and anxious patients feel a little bit better, but they were left nonfunctional.
When looking at a dot in the center of your field of vision, and paying attention to the center although you can see something in the periphery what two areas light up?
V2 and V4
If you go from looking at the center of the visual field while seeing something in the periphery, THEN you shift your attention to that which is found in the periphery, you see increased activity in what part?
V4
As far of attention, there are 2 main subdivisions: bottom up and top down. Describe them
Bottom up: stimulus driven, unimodoal sensory cortex

Top down: cognitively driven (frontal, pareital, cingulate, limbic).
"Spotlight that highlights information of interest"
Attention and arousal are similar. What does arousal do?
Enhances neuronal processing in general.
Arousal DOES NOT bias neurons to process particular information.

Also, arousal ALWAYS affects attention, but attention does not necessasrily affect arousal.
Anatomically, what are the 2 structures at the core of the arousal/attention system?
1. mesencephalic reticular formation
2. thalamus (reticular and intralaminar nuclei)

Brainstem nuclei also play a role: substantia nigra, ventral tegmental area, raphe nuclei and locus ceruleus and basal forebrain nuclei also play a role.
During arousal the mesencephalic reticular formation (MRF) plays a key rolde doing what (2)
MRF
1. Inhibit the thalamus
2. Excites the cortex

Thalamus is inhibitory, so by inhibiting it you are allowing the flow of information.

Alos allowing flow of information via the cortex.
The two hierarchies for attention were bottom up and top down, the two main types are Matrix and Vector.

Can you describe the matrix functions of attention? What type of hierarchy is it associated with
Hs to do with level of attention, resistance to interference
Related to bottom up type of attention (in association with unimodal areas, MRF, thalamus)
Can you describe the vector function of attention?

What type of hierarchy is it associated with?
Direction of attentional focus: actual space or thought (thought: deciding to focus on color rather than shape)

Associated with top down mechanism
What are the 3 most common defects that have to do with attention?
1. Confusinal state (most common distrubance of mental status)
2. Partial attentional syndromes
3. Hemispatial neglect
What are the main clinical presentations of someone in a confusional state?
1. change in overall attention tone, disoreinted, faulty memory
2. Issues encoding learning and retreieving information
What kind of symptoms would you find in someone with a Partial Attention deficit?
Reduced performance in one or more cognitive domains
Eg:
-Visual stimuli
-verbal fluency

--> need to be able to differentiate someone that is having a hard time expressing themselves from having aphasia to having a problem with attention.
What would explain the fact that with injury to the right lobe you can't see the left visual field, but with an injury to the left lobe you can still see the right field?
Thought that
-right himsphere distributes attention to BOTH LEFT AND RIGHT
-left hemisphere only to the right
Are motor and sensory deficits necessary for hemispatial neglect to occur?
NOOOOOOOOO

indepenendent of motor and sensory areas
How do patients with hemispatial neglect do with "Extinction" tests?
When a dot appears and disappear on the left side,they see it.

Appears and disappears on the right side, they see it.

Appears and disappears on both sides -> they DO NOT see it on the left side.
Is it Wernicke's or Broca's that provides a linkage between auditory and vertbal word forms and their associated meanings?
Wernicke's
Does the brain have "centers" for individual concepts?
NO, but it does appear to have specific gateways to access the information.

Think of the diagram with pictures of the brain that light up for different words.
Will a lesion affecting the auditory cortex cause apahsia?
NOOO. Aphasias are NOT simple sensory or motor disorders.
What does paraphasia mean?
Errors in word production
Saying mable instead of table is an example of what type of paraphasia?
Literal paraphasia
Do Broca's and Wernicke's patients have issues with:
repetition, naming, reading and comprehension, writing?
YES
What type of aphasia has problems with repetition and naming, but CAN read, write and comprehend auditory signals?
Conduction Aphasia: impaired repetition and naming only
What is aphemia?
Deficit caused by injuring the area that is just above Broca's and it results in a very noticeable deficit in speech, but not language.

Patients could even be mute, but they can recover
What patients display a two way naming deficit?
Wernicke's patients.

This means that they can't spontaneously generate the correct word, nor can they select if if they are given multiple choices
If a patient does not have issues with repetition, what kind of aphasia do you think they might have (2)?
Trans cortical
Atypical
If a patient has preservations of speech and auditory comprehension, what type of aphasia do they have and what is it caused by?
Conduction aphasia.

Caused by
Damage to supramarginal gyrus
Damage to left auditory cortex

Often accompanied by mild right facial weakness
If you have auditory comprehension and no fluent speech, what kind of aphasia do you have
Transcortical aphasia
Global aphasia is when patient's Wernicke's area and Broca's areas are affected.

What is this normally caused by?
Besides the typical symptoms you see, what's another thing?
Global aphasias are normally caused my injury to the left middle cerebral artery.

Global aphasia: brocas plus Wernicke's symptoms.

Also, Contralateral hemiplegia
What are the two types of aphasia where repetition is not impaired?
Transcortical
Atypical
The is damage to the body or tail of the caudate, what kind of aphasia will you see?
None.

However, if the head of the LEFT caudate nucleus is injured there will be a deficit
What do lesions to the superior chiamsatic nucleus do with regards to the length of spontaneous waking episodes?
Lesions to the superior chiamsatic nucleus DECREASE the length of spontaneous waking episodes.
The superior chiamsatic nucleus promotes
Maintenance of wakefulness
When do SCN nucleus fire the most?
They fire the most during the day, and the least during the night.

Note that this remains the case regardless of the environmental cues
What are the three afferent pathways to the SCN and what are the neurotransmitters involved?
1. Photic, glutamanergic retinohypothalamic
2. Photic, NPY geniculohyoothalamic
3. Non photic, serotinergic fibers from raphe nucleus
The connection from the SCN to the locus Ceriulus allows the SCN to do what?
Allows the locus ceruleus to modulate alertness and sleep
How long is the frequency of oscillation of the human endogenous circadian rhythm?
24.2 hours..

This is why the SCN needs to synchronize itself.
Retinal ganglion cells that relay the information to the SCN contain melanesian, which is most sensitive to what kind of light?
Melanopsin is most sensitive to short wavelength in the blue green range
Exposure to light in the morning will do what to your circadian rhythm?
It will phase advance the circadian rhythms.

Light in the night will do the opposite and result in phase delay.
What can be thought of as the bodies internal dark signal?
MELATONIN this is an important zeitgeber that relates inversely to body temperature
What are the two main final destinations of the retinohypothalamic tract?
1. Pineal gland
2. Sub ventricular zone of the hypothalamus
Describe the path from the retinohypothalamic tract to the pineal gland
Retinohypothalamic tract to the SCN of the hypothalamus, medial forebrain bundle, intermediolateral gray column of the spinal cord, cervical ganglion, pineal gland
Melatoning given in the early evening causes what?
Phase advance
Melatoning given in the early morning results in what?
Results in phase delay
Biochem. Melatonin produced in the pineal gland does what?
Projects directly back to the SCN
When do melatonin levels start to rise??
1-3 hours before your usual sleep time
When does the highest circadian alerting system occur?

When does the largest homeostatic drive for sleep occur?
They BOTH occur about 12 hours after you wake up.

Usually around 9 pm
What are the main four zeitgebers?
LIGHT
Melatonin
Exercise
Food
Light during the late evening 9PM, at the peak of your most active period will do what to your circadian rhythms?
It will permanently delay the circadian rhythms.
Light in the middle of your sleep will do what?
It will advance your circadian rhythm
There are two melatonin receptors MT1 and MT2.
What do they do?
MT1: inhibits SCN firing rate
MT2: changes circadian phase
If you are completely blind, what is likel to happen to your circadian rhythm?
Likely to be delayed