Lectures 34-36, 38, Basal Ganglia and OCD Flashcards Preview

Brain and Behavior > Lectures 34-36, 38, Basal Ganglia and OCD > Flashcards

Flashcards in Lectures 34-36, 38, Basal Ganglia and OCD Deck (108):
1

Basic basal ganglia connectivity

Cerebral cortex--> striatum --> globus pallidus / substantia nigra --> thalamus --> cortex

2

Inputs to BG and corresponding NTs

Cortex (glu), thalamus (glu), midbrain (DA), raphe nuclei (5-HT), locus coeruleus (NE)

3

Major cortical input to BG is from which lobe?

Frontal lobe

4

Thalamic inputs to BG (3)

Ventral, intralaminar, medial dorsal

5

Two parts of the SN and their NTs

SN pars compacta = DA; SN pars reticulata = GABA

6

LC and Raphe are located in which brainstem region?

Pons

7

Parts of the striatum. Basic function?

Dorsal (C + P); Ventra (NAS, olfactory tubercle); receives most extrinsic projections

8

Where is the nucleus accumbens located? What NT?

Leans on septum pellucidum in the ventral portion of the striatum; GABA

9

Where is the olfactory tubercle located? What NT?

Medially, below the anterior commissure; GABA

10

Where is the subthalamic nucleus located?

Medially to BG, caudal to thalamus

11

What cell type in the striatum receives inputs and projects outputs? What NT?

Medium spiny neurons; GABA

12

Two types of medium spiny neurons (organize via their respective NTs and receptors)

1. substance P, D1 (excitatory via adenylyl cyclase); 2. enkephalin, D2 (inhibitory via adenylyl cyclase)

13

Where does the dorsal striatum project to? (2)

Globus pallidus (internal and external segments); Substanti nigra (pars reticulata and compacta)

14

Where does the ventral striatum project to? (2)

Ventral pallidum and VTA

15

More likely to visualize which segment of GP in cross section?

GPe

16

Where is the ventral pallidum?

Ventral to the GP (beneath anterior commissure)

17

The major outputs from the BG are all ________ and arise from? (3)

GABAergic; GPi, SNpr, VP

18

Where do the major outputs from BG system project to? What do you notice about this?

Mostly thalamus: Ventral groups, MD, ILN; same areas as major inputs!

19

Fiber bundles from BG to thalamus...combine with what?

Thalamic fasciculus w/ cerebellar efferents

20

Then where does the thalamus project?

The same frontal lobe structures that input into BG (mostly motor)

21

Inputs to BG are mostly what? Outputs are mostly what?

Excitatory, inhibitory

22

What are the functions of the five loops of the BG

Motor, oculomotor, cognitive (2), limbic

23

Model of BG function states...Which family of medium spiny neurons?

Direct (striatonigral) Path facilitates movement through disinhibition of thalamocortical activity; substance P/D1

24

The end of the direct path stimulates where, which loops back to where? And who projects DA to where?

VA/VL --> cortex; SNpc to striatum

25

How is the indirect pathway different?

SNpc projects to D2 receptors in striatum, which is inhibitory --> GPe --> disinhibits STN --> excites GPi/SNpr --> inhibits thalamus and cortex

26

What does the indirect pathway result in?

Inhibits BG output by increasing inhibition of thalamocortical pathway

27

What is the hyperdirect pathway? Describe the path.

Fast way to repress undesired behaviors (because indirect would be slower); Ctx --> STN --> (+) output structures of thalamus (GPi/SNpr)

28

What happens to the direct pathway in PD, broadly and specifically.

DECREASED, SNpc is damaged, so striatum is less active, so it does NOT disinhibit output structures, leading to inhibited thalamus/cortex

29

What happens to the indirect pathway in PD?

INCREASED, SNpc is damaged, so striatum is MORE active, suppressing GPe, disinhibiting STN, more activity in output structures, suppressing activity of thalamus and cortex

30

Huntington's Disease is characterized by what change to the BG?

Atrophy of medium spiny neurons in dorsal striatum

31

HD is primarily thought to affect what pathway? How?

Indirect pathway; loss of striatum leads to overactive GPe, an inhibited STN, so no excitation to the output structures, so no inhibition of the thalamus/cortex

32

Hemiballismus is characterized by what symptom and what nucleus damage?

Wild, flailing muscles; STN

33

Describe the pathway in Hemiballismus

No STN in indirect pathway means no excitation of the output structures, so overactive thalamus and and cortex

34

Parkinson symptom constellation (4)

Bradykinesia, rigidity, postural instability, tremor

35

Parkinson ancillary features (3)

Freezing, hypophonia, bradyphrenia (slow thinking)

36

Parkinsonian Tremor

Asymmetrical onset, pill rolling, 3-5 Hz, postural re-emergent tremor, resting, chin/tongue, disappears in sleep

37

What other disease has a postural re-emergent tremor?

None!

38

Parkinsonian bradykinesia

Poor dexterity with decrementing (worsening) rapid alternating movements, micrographia, hypomimia, infrequent blinking

39

Rigidity (definition)

Increased resistance to passive movement (ratcheting)

40

Parkinsonian gait

Short strides, multipivot turn, loss of postural reflexes (>2 steps to recover from push = impaired)

41

Cardinal feature of PD? (and 4 related symptoms)

Asymmetric: rigidity, tremor, slowness, postural instability

42

Supportive features for PD diagnosis

Proressive and marked improvement with levadopa

43

Name and describe the major pathological finding of PD

Lewy body! Eosinophilic inclusion in neuron containing ubiquinated protein, alpha synuclein and neurofilament; forms due to misfolded alpha synuclein that cannot be cleared

44

What do misfolded alpha synuclein proteins form into?

Amyloid fibrils

45

Is the Lewy Body itself pathogenic?

No! Attempt to deal with oxidative stress, etc caused by amyloid fibrils

46

T/F: Lewy Bodies can be transferred between neurons?

True!

47

Genes related to PD are in which organelles? Early or late onset?

Mitochondria and degradation system; early

48

T/F: All PD patients have Lew Bodies

False! Those w/ mitochondrial-related genetic factors do not

49

What medications are first given? And SEs...

Levodopa (motor fluctuations, dyskinesia), dopamine agonists (sedation, impulse control issues, hallucinations), MAOB inhibitors

50

Why don't we give young patients levodopa right away?

Can cause motor issues with increased use. Also cycle through periods where it works, periods of ON (dyskinesia) and periods of OFF time.

51

Older patients will get what drug "up-front"

Levodopa

52

What regions are targeted with deep brain stimulation for PD? How much can tremor be decreased? What is NOT improved by DBS?

GPi or STN; 75-90%; freezing/postural issues/cognitive issues

53

Prodromal (non-motor) symptoms (4)

Constipation, anosmia, REM behavioral disorder, psych

54

Lewy Body/PD Dementia symptomology (4); Lewy Bodies are where?

1. Visual hallucinations; 2. Dementia; 3. Fluctuations of attention/arousal; 4. Parkinsonism that begin ~1 year of dementia; cortical regions

55

Define Multiple System Atrophy

Autonomic Dysfunction (orthostatic hypotension, incontinence, impotence) w/ PD or Cerebellar symptoms

56

Age of onset of MSA

40-60s

57

Parkinson's signs of MSA

Asymmetric w/ major gait disorder

58

Cerebellar signs of MSA

Gait disorder, limb ataxia, nystagmus

59

Pathology of MSA

Alpha synuclein inclusions in oligodendrocytes

60

Define Progressive Supranuclear Palsy and onset (one big difference from PD). What are the other PD-like symptoms? What's missing?

SYMMETRICAL bradykinesia; 70s; early balance problems (falls w/in a year); no tremor

61

Eye movement signs of PSP

Supranuclear vertical palsy (cannot look up)

62

Cognitive signs of PSP

Frontal lobe dementia

63

Pathology of PSP

Accumulation of tau

64

Define Corticobasal Degeneration, PD-ike symptoms, and onset

Asymmetric bradykinesia and rigidity in one limb (useless, alien limb); gait/postural instability; 60s-70s

65

Is CBD responsive to levodopa?

No

66

Cortical signs of CBD

Apraxia (cannot perform purposeful actions), cortical sensory loss (cannot identify objects by touch), dementia

67

PSP imaging

"Humming-Bird Sign" (atrophy of midbrain, flat tectum)

68

MSA imaging

"Hot cross bun" in pons and "hyperintense putaminal rim"

69

CBD imaging

Asymmetric cortical atrophy (opposite to symptomatic side)

70

Secondary etiologies in PD and some examples

Meds (neuroleptics, anti-seizure), toxins (MO, CO, CN, pesticides), structural (tumor), infection (HIV, syphilis)

71

T/F: Removing exposure to secondary etiologies always removes symptoms?

Sometimes, depending on the cause; often NOT with toxins

72

Define tremor

Rhythmic, oscillatory mov't of a body part

73

Define essential tremor; what happens when they drink?

Kinetic tremor condition = tremor during tasks, various frequencies; tremor attenuates w/ ETOH

74

Name 3 other tremor conditions

Enhanced physiological tremor (postural); Cerebellar Tremor (slow, kinetic tremor); PD tremor (pill rolling, primarily at rest)

75

Define dystonia

Involuntary, sustained muscle contractions causing twisting/repetitive movements

76

What are some variations in dystonia?

Age of onset, focal (tend to be adult), generalized (tend to be child), hemidystonia (pallidal injury), etiology (genetic, degenerative, secondary)

77

Is dystonia associated with rigidity of muscles?

Nope

78

Define chorea

Involuntary, irregular flitting movements flowing across body movements

79

Huntington's Disease is...(cause and threshold)

Autosomal dominant repeat in HTT gene on chromosome 4, threshold number of repeats is 40

80

What's the association b/t repeat number and age of onset?

More repeats, younger onset

81

Treatment for HD

Tetrabenazine, neuroleptics, benzodiazepines

82

What's an important co-morbidity for HD?

Neuropsychiatric problems, including irritability, psychosis, suicide

83

Besides chorea, what kind of movement disorders do you see with HD?

Parkinsonism (early onset), dystonia

84

How does someone with HD die?

Respiratory complications

85

HD pathology

Atrophy of spiny neurons in striatum (atrophy of caudate)

86

Define tic disorder. What is special about tic disorder?

Quick, stereotype movements/vocalizations that can be temporarily suppressed; only mov't disorder that persists through sleep

87

Define myoclonus and how is it different from tic disorder

Involuntary, very brief muscle jerks that interrupts voluntary movements generated anywhere in CNS but NOT suppressible

88

Two sources of physiological myoclonus

Hiccups, hypnic jerks

89

What's an important pathological etiology of myoclonus?

Epilepsy

90

Define Wilson's Disease. Age of onset?

Copper accumulation disorder related to AR disorder on chromosome 13; 20s - 30s

91

Describe the common neurological feature of Wilson's

Tremor (80%): if child presents w/ essential tremor, screen for Wilson's

92

How do you test for Wilson's?

Low serum cerulosplasmin, very high 24hr urine copper, low normal total serum copper and genetic testing

93

OCD is filed where in the DSM-5?

Obsessive-compulsive & related disorders

94

What is the time consuming threshold for OCD?

1 hour

95

When does OCD typically onset?

Childhood (50% before age 14)

96

Obsessions; contrast to hallucinations

Recurrent, intrusive, disturbing thoughts; recognized as own thoughts

97

Compulsions; what can a compulsion NOT be in the book of OCD?

Repetitive, obsessive acts often driven by obsessions; pleasurable

98

What proportion of patients with Tourette's develop OCD symptoms? What about the converse (OCD patients w/ tics)

50%; 10-20%

99

Two predominant theories of OCD

NT-based (5-HT/Glutamate) and Cortico-striato-thalamo-cortical loops

100

Serotonin Hypothesis

Some role for 5-HT in OCD, based on the fact that SSRIs are helpful for OCD

101

Role of glutamatergic involvement in OCD

Genetic, animal models of OCD, elevated glutamate, but no data for glutamate treatment efficacy

102

Abnormal OCD circuits

Increased activity in OFC, striatum, ACC

103

OCD animal model

SAPAP3 scaffolding protein at excitatory synapse in striatum deleted --> OCD that responds to SSRIs

104

Main treatments for OCD

SSRIs (other classes ineffective) or CBT (exposure and response prevention)

105

For OCD non-responders

Different SSRI, add an antipsychotic, neurosurgery

106

Describe ablation surgical OCD treatment

For severely impaired patients, ablated anterior capsulotomy/anterior cingulotomy

107

Where do the leads go in DBS for OCD?

Stimulate anterior limb of internal capsule (ventral capsule), deepest point on NA/ventral striatum

108

Currently, what does research say about success rate for DBS and OCD? What about AEs?

About two-thirds; generally well-tolerated, but stimulation-specific adverse effects (hypomania), especially during programming

Decks in Brain and Behavior Class (56):