Higher Cortical Processing, Aging

Front 1

What is neocortex?

Back 1

Cortex that has 6 cellular layers/laminae.

Front 2

T/F Cells with similar functions tend to be arrayed in radially aligned groups that span all the cortical layers and receive inputs that are often segregated into radial bands or columns.

Back 2

T

Front 3

What are the outputs of the following:
A) Layers 1-3
B) Layers 5-6

Back 3

A) Other cortical areas
B) Subcortical strutures, thalamus

Front 4

Contains mainly neuropil

Back 4

LAyer 1

Front 5

Stellate cells located primarily in what layer?

Back 5

4

Front 6

What type of stain is best for seeing layers? For seeing cell types?

Back 6

Nissl (not good for individual cells); Golgi (good for individual cells)

Front 7

What is the defn of primary cortical areas? What %age of brain are these?

Back 7

Regions responsible for encoding sensory info and commanding movements; 20%

Front 8

What is the defn of association cortical areas? What %age of brain are these?

Back 8

regions responsible for attending, IDing, recognizing, and planning appropriate responses; 80%

Front 9

Which lobe is largest? Smallest?

Back 9

Frontal > Temporal > Parietal ~= Occipital

Front 10

Which side is generally more analytical? More abstract?

Back 10

L; R

Front 11

Plays a role in emotion, taste, and homeostatic regulation of autonomic activity

Back 11

insula lobe

Front 12

Includes medial aspect of cerebral hemispheres, forms a rim around corpus callosum and diencephalon and includes the paraterminal, cingulate, parahippocampal gyri. Central role in memory, learning, emotion, some neuroendocrine fxn, and autonomics

Back 12

Limbic lobe

Front 13

Essential for planning and executing learned and purposeful behaviors

Back 13

Frontal lobe

Front 14

What are the four functionally distinct areas of frontal lobe?

Back 14

1) Primary motor cortex
2) Premotor and supplementary motor areas
3) Broca's area
4) Prefrontal cortex

Front 15

Their axons comprise the corticospinal tract. Damage to them causes weakness/paralysis on contralateral side.

Back 15

Precentral gyrus

Front 16

Location of primary motor cortex

Back 16

Precentral gyrus

Front 17

What are Betz cells?

Back 17

pyramidal cell neurons located within the fifth layer of the grey matter in the primary motor cortex, M1.

These neurons are the largest in the central nervous system, sometimes reaching 100 μm in diameter.[2][3] Betz cells send their axons down to the spinal cord where in humans they synapse directly with anterior horn cells, which in turn synapse directly with their target muscles.

Their axons form corticospinal tract.

Front 18

In What layer are Betz cells?

Back 18

Within the fifth layer of the grey matter in primary motor cortex

Front 19

What would be a sx of damage to premotor areas?

Back 19

Loss of ability to plan motor movements

Front 20

In general, what are some sx of frontal lobe deficits?

Back 20

Impulsivity, lack ofmotivation, inability to plan, general lack of concern for oneself or others. Disturbed affect.

Front 21

Expressive language is associated with _________ area while receptive language is associated with _____ area.

Back 21

Broca's; Wernicke's

Front 22

In what parts of the frontal lobe is Broca's area?

Back 22

LEFT (or right if right is dominant) Inferior frontal gyrus - opercular and triangular pars

Front 23

4 main gyri of parietal lobe

Back 23

1) Postcentral
2) Intraparietal
3) Supramarginal
4) Angular

Front 24

Involved in somatosensation, vision, attention

Back 24

parietal lobe

Front 25

What is the primary somatosensory cortex?

Back 25

Postcentral gyrus

Front 26

Mediates complex aspects of spatial orientation, perception, and attention; Contributes to analysis of motion and spatial relationships

Back 26

Superior parietal lobule (aka the dorsal "Where" pathway).

Front 27

Unilateral damage to angular gyrus can result in what?

Back 27

Alexia (problems reading); Anomia (problems naming); Agraphia (inability to write)

Front 28

Unilateral damage to the nondominant (usually R) parietal lobe can result in what?

Back 28

Contralateral neglect syndrome.

Front 29

Contralateral neglect syndrome is typically associated with damage to what?

Back 29

RIGHT parietal cortex. R parietal cortex mediates attention to both left and right halves of the body and extrapersonal space, whereas left hemisphere mediates attention primarily to the R

Front 30

What produce more severe neglect sx - L or R parietal cortex lesions?

Back 30

R. There will be severe L neglect

Front 31

Sx of R parietal lesion

Back 31

Severe L neglect

Front 32

Sx of L parietal lesion

Back 32

Mild/Minimal R neglect

Front 33

Sx of partial bilateral parietal lesion

Back 33

Severe R neglect

Front 34

Involved in hearing, vision, language, memory

Back 34

temporal lobe

Front 35

Four functionally distinct areas of temporal lobe

Back 35

1) Wernicke's area
2) Primary auditory cortex
3)Inferior region involved in higher order visual processing
4) Medial part concerned with learning and memory

Front 36

Where is primary auditory cortex?

Back 36

Superior temporal gyrus

Front 37

Where is wernicke's area?

Back 37

posterior portion of superior temporal gyrus of the dominant (usually Left) hemisphere

Front 38

Have difficulty with language comprehension but may speak fluidly

Back 38

Wernicke's aphasia

Front 39

Part of the ventral "what" pathway and contributes to analysis of form. Involved in recognition of color, faces, etc.

Back 39

Inferior occipital region

Front 40

Medial/inferior temporal lobe is essential for _________

Back 40

learning and memory

Front 41

Two major parts of occipital lobe. Essential for vision

Back 41

Cuneus and lingual separated by calcarine sulcus

Front 42

T/F Speech and language are localized and lateralized

Back 42

T.

Front 43

Inability to properly move the muscles of the tongue and mouth to produce speech

Back 43

Dysarthria

Front 44

Halting speech; perseveration; disordered syntax, grammar, structure of individual words with preserved comprehension are characteristic of

Back 44

Broca's aphasia

Front 45

Fluent speech, with adequate grammar and syntax, but impaired comprehension is characteristic of

Back 45

Wernicke's aphasia

Front 46

Results from damage to arcuate fasciculus, a bundle of nerve fibers that lies below the supramarginal gyrus in temporal lobe and connects broca's and wernicke's areas

Back 46

Conduction aphasia

Front 47

Patients have intact auditory comprehension, fluent but paraphasic speech production, and poor speech repetition. will understand speech but give inappropriate responses to spoken word

Back 47

Conduction aphasia

Front 48

Random, intuitive, holistic, synthesizing, subjective, looks at wholes

Back 48

Right brain

Front 49

Logical, sequential, rational, analytical, objective, looks at parts

Back 49

Left brain

Front 50

Lexical and syntactic language

Back 50

Left hemisphere

Front 51

Writing and speech

Back 51

Left hemisphere

Front 52

Spatial abilities

Back 52

Right hemisphere

Front 53

Emotional coloring of language

Back 53

Right hemisphere

Front 54

Macroscopic changes occurring in normal aging

Back 54

Reduction in brain weight; Thinning of cortex; Widening of subarachnoid space; Dilation of ventricles; changes and reduction in myelin

Front 55

T/F There is an atrophy of large neurons during aging

Back 55

T

Front 56

What are the most vulnerable neurons to damage and /or age-related stress?

Back 56

Large neurons with high energy requirements. Cells that have large surface area that increases exposure of cells to toxic conditions. Pyramidal neurons in entorhinal and neocortices, hippocampus

Front 57

What occurs in dendritic atropyhy

Back 57

Overall regression of dendritic tree, including loss of dendritis spines, thus decreased excitatory input; reduced potential for plasticity and sprouting

Front 58

Where does the most severe loss of myelin occur?

Back 58

Forebrain/Anterior regions

Front 59

Loss of myelin is a primary pathology of what cell type?

Back 59

Oligodendrocytes

Front 60

What does accumulation of reactive oxygen species (ROS) lead to?

Back 60

Oxidative modification of DNA, proteins and lipids and results in abnormal gene expression, inactivation of enzymes, abnormal protein aggregation, etc; Mitochondrial dysfunction

Front 61

Impaired memory, problem solving, judgment, visual-spatial perception, sometimes hallucinations and delusions are sx of what?

Back 61

Alzheimer's disease

Front 62

when do AD sx usually get bad enough to affect quality of life?

Back 62

6th - 7th decade of life, though mild cognitive impairments start much earlier.

Front 63

T/F 90% of AD cases are familial

Back 63

F. 90% are sporadic.

Front 64

How is AD dxed?

Back 64

Pt history, neuro exam, behavioral tests and MRI/PET

Front 65

What histopathologies are seen in AD?

Back 65

Neurofibrillary tangles (NFT) - aggregated Tau protein

Amyloid plaques (AP) - aggregated beta-amyloid protein

Front 66

Where are NFTs most prominent?

Back 66

large hippocampal neurons, entorhinal cortex, other neocortical sites

Front 67

What role does phosphorylation play in tau?

Back 67

Hyperphosphorylation leads to aggregation and destabilization of microtubules --> death of neurons. Uncertain if these are cause of disease or not.

Front 68

NFT are (extra,intracellular) while amyloid plaques are (extra,intracellular)

Back 68

intra; extra

Front 69

What comprises amyloid plaques?

Back 69

Core of beta-amyloid protein surrounded by degenerated neuronal process, reactive astrocytes and microglia (inflammatory).

Front 70

How do amyloid plaques arise?

Back 70

They evolve from small clusters of beta-amyloid protein (oligomers). These are what is toxic, not the plaques. The compromise of neurons is happening long before aggregations.

Front 71

What happens in the enzymatic processing of beta amyloid?

Back 71

Beta-amyloid peptide is contained within the amyloid precursor protein (APP).

APP is normally cleaved by alpha-secretase that cuts thru beta amyloid sequence and releases soluble APP.

However, APP cleavage by gamma and beta secretase generates the toxic beta-amyloid fragment --> neuronal death.

Front 72

alpha-secretase

Back 72

normally cleaves APP ; cuts thru beta amyloid sequence and releases soluble APP

Front 73

gamma and beta secretase

Back 73

cleavage of APP by these enzymes generates toxic beta-amyloid peptide

Front 74

T/F Severity of AD dementia correlates with overall plaque load

Back 74

FALSE. Correlates with the level of beta-amyloid oligomers because these are what's toxic, not the plaques themselves. The mature plaques represent an end stage.

Front 75

T/F Majority of human gene mutations linked to early AD either involve APP protein or the cleavage enzymes

Back 75

T

Front 76

Oligomers of beta-amyloid target ________

Back 76

synapses

Front 77

T/F Extracts of AD brain reduce LTP and spine density, perturbing memory tasks

Back 77

T (extracts of non-amyloid associated dementias did NOT have this affect)

Front 78

T/F Mutations increase the likelihood that toxic forms of beta-amyloid will be generated

Back 78

T

Front 79

What type of enzyme is alpha-secretase?

Back 79

metalloprotease

Front 80

Gamma-secretase is a protease complex including what?

Back 80

presenilins (PS1 and PS2). Mutations in either of these leads to increase in toxic forms of beta amyloid

Front 81

What is Apolipoprotein E (ApoE)? What are implications for AD?

Back 81

Cholesterol chaperone in bloodstream. Produced by liver and astrocytes in brain. Binds beta-amyloid and may affect aggregation.

Front 82

What are the ApoE isoforms? What's their relation to AD?

Back 82

E2 (rare); E3 (most common, 65% of population); E4 (less common, associated with increased risk to AD)

Front 83

Earliest AD-related changes may occur up to _____ years before dx.

Back 83

20

Front 84

Treatment of AD

Back 84

Inhibitors of acetylcholinesterase (e.g., Aricept)

Front 85

Where does AD begin?

Back 85

in hippocampus. Then it spreasd out

Front 86

What is Pittsburgh compound B (PiB) ?

Back 86

a fluorescent analog of thioflavin T, which can be used in positron emission tomography scans to image beta-amyloid plaques in neuronal tissue. Due to this property, Pittsburgh compound B may be used in investigational studies of Alzheimer's disease.

Front 87

What cross the BBB, binds to amyloid aggregates, and can be imaged by PET?

Back 87

pittsburgh compound B

Front 88

Why do acetylcholinesterase inhibitors slow declines in cognitive function in AD?

Back 88

Loss of neurons in basal forebrain (nucleus basalis) causes decline in ACh. Inhibiting breakdown of ACh by AChE improves cognition.