Exam 3 Deck 1 Flashcards
1
Q
What is the function of the cerebellum?
A
Key structure for motor learning and coordination
2
Q
What is the main symptom of cerebellar damage?
A
Ataxia - issues synthesizing smooth, well-timed and proportional movements
3
Q
What are the cerebellar lobes?
A
Anterior, posterior, flocculonodular
4
Q
What are the Identify the anterior lobe of the cerebellum.
A
5
Q
Identify the posterior lobe of the cerebellum
A
6
Q
Identify the flocculonodular lobe of the cerebellum
A
7
Q
What is a folium?
A
Equivalent to a gyrus in the cerebellum
8
Q
What is a cerebellar lobule?
A
A combination of multiple folia in the cerebellum
9
Q
Identify the primary fissure of the cerebellum
A
10
Q
Identify the postero-lateral fissure of the cerebellum.
A
11
Q
Idnetify the horizontal fissure of the cerebellum
A
12
Q
What connections pass through the inferior cerebellar peduncle?
A
Connections fromthe medulla and spinal cord to the cerebellum
13
Q
What information passes through the middle cerebellar peduncle?
A
Connections from the pontine nuclei to the cerebellum
14
Q
What information passes through the superior cerebellar peduncle?
A
Exiting efferents from the cerebellum (except vestibular), and afferent ventral spinocerebellar tract axons
15
Q
Where is the fastigial nucleus found?
A
In the vermis
16
Q
Where is the interposed nucleus found?
A
Between fastigial and dentate nucleus
17
Q
Where is the dentate nucleus found?
A
Lateral cerebellum
18
Q
Identify the fastigial nucleus
A
19
Q
Identify the interposed nucleus
A
20
Q
Identify the dentate nucleus
A
21
Q
What is the spinocerebellum?
A
Vermis and intermediate hemisphere
Contains somatotopic representations of the head nad body and sends efferents to spinal motor nuclear tracts
22
Q
Which part of the spinocerebellum receives axial body input and projects through medial descending motor systems?
A
Vermis
23
Q
Which part of the spinocerebellum receives distal body inputs and projects through lateral descending systems?
A
Paravermis (intermediate hemisphere sections)
24
Q
What are the lateral hemispheres of the cerebellum responsible for?
A
Cerebrocerebellum - receive input from cerebral cortex via the pontine nuclei and do not receive direct somatosensory input
25
What is the flocculonodular lobe of the cerebellum responsible for?
The **vestibular** cerebellum.
Connectivity breaks all the rules of the other cerebellar structures
26
What is the part of the cerebellum responsible for vestibular functions?
flocculonodular lobe
27
What are the four spinocerebellar tracts?
Dorsal spinocerebellar tract - lower boddy proprioception
Ventral spinocerebellar tract - lower boddy error signal
Cuneocerebellar tract - upper body proprioception
Rostra spinocerebellar tract - upper body error signal
28
Which spinocerebellar tracts are involved with proprioception?
Cuneocerebellar tract (upper body)
Dorsal spinocerebellar tract (lower body)
29
Which spinocerebellar tracts are involved with transmitting error signals?
Rostral spinocerebellar tract (upper body)
Ventral spinocerebellar tract (lower body)
30
Which spinocerebellar tracts go to the lower body?
Dorsal and ventral spinocerebellar tracts
dorsal = proprioception; ventral = error signal
31
Which spinocerebellar tracts go to the upper body?
Cuneocerebellar tract = proprioception
Rostral spinocerebellar tract = error signal
32
What is the dorsal spinocerebellar tract?
Ipsilateral lower body proprioceptive tract
Muscle spindle afferents carry proprioception from lower body climb up the fasciculus gracilus and terminate in Clarke's nucleus. Project through ipsilateral dorsolateral funiculus and inferior cerebellar peduncle to the intermediate zone of cerebellum
33
What is the cuneocerebellar tracts?
Proprioceptive upper body spinocerebellar tract
Ipsilateral
Muscle spindle afferents carry proprioceptive info to external cuneate nucleus. These axons travel up with teh dorsal spinocerebellar tract and end in intermediate zone of cerebellar cortex
34
What is the ventral spinocerebellar tract?
Lower body error signal spinocerebellar tract
**Contralateral ascent, re-cross in cerebellum**
GTO afferents project to spinal interneurons. Cross in spinal cord and ascend in the ventrolateral funiculus
Travel through superior cerebellar peduncle and recross midline
Cerebellar projection is ipsilateral
****
35
What is the rostral spinocerebellar tract?
Upper body error signal tract
GTO to interneurons through inferior cerebellar peduncle to cerebellum
36
Which spinocerebellar tracts course through the inferior cerebellar peduncle?
Cuneocerebellar, dorsal spinocerebellar, rostral spinocerebellar
Ventral spinocerebellar courses through the superior cerebellar peduncle
37
Which spinocerebellar tract courses through the superior cerebellar peduncle?
Ventral spinocerebellar tract
Dorsal, cuneocerebellar, and rostral course through inferior peduncle
38
What are the inputs to the cerebellum?
Spinocerebellar tracts (4 of them)
Reticular formation
Vestibular nerve, nuclei
Pontine nuclei
Inferior olivary complex
39
What are the layers of the cerebellar cortex?
Molecular = closest to pia
Purkinje = middle
Granular = deepest
40
Which cells are the key to the cerebellar cortex?
Purkinje cells
Reside in the purkinje layer
GABAergic, inhibitory neurons
41
What cells reside in the molecular layer?
Purkinje cell apical dendritic trees (perpendicular to long axis)
Climing fiber axon terminals - which provide direct, convergent input to purkinje cells
Stellate cells = inhibitory interneurons to Purkinje dendrites
Basket cells = inhibitory interneurons to Purkinje cell bodies
Excitatory parallel fibers (course parallel to long axis)
42
What are the climbing fibers?
Synapse **directly** to Purkinje cells and arise from the Inferior Olivary Complex
Provide convergent excitation (one purkinje cell receives input from one climbing fiber; but each climbing fiber innervates only a few Purkinje cells; however, the climbing fibers make thousands of synapses on each Purkinje)
43
What are mossy fibers?
Provide input from all sources except inferior olivary complex
Provide **indirect** input to purkinje cells. Relayed via parallel fibers of granule cells located in glomeruli
These convey excitatory information to large number of Purkinje cells
44
What is a cerebellar glomerulus?
Located in granular layer
Comprised of mossy fiber axon terminal (excitatory; Golgi cell axon terminal (inhibitory) and several post-synaptic granule cell dendrites
45
Describe the inputs of cerebellar cortex
46
What are the outputs of the cerebellar cortex?
Purkinje cell is the only output
Project to cerebellar nuclei or to the vestibular cerebellum
47
How doe the cerebellum control pusture?
Flocculonodular lobe and vermis project to the vestibular nuclei of the brainstem (bilaterally) with **no cerebellar relay**. From here goes to reticulospinal and vestibulospinal tracts to the axial, neck muscles
Some vermis projections to the vestibular nuclei relay through the fastigial nucleus
48
How does the cerebellum control motor control?
Paravermis nuclei (interposed nuclei = globulose and emboliform nuclei) project through the superior cerebellar peduncle to the contralateral red nucleus (decussates)
Activate rubro-olivary tract (red nucleus to inf. olivary complex, to cerebellar peduncle and climbing fibers)
Activate rubrospinal tract (red nucleus to midbrain decussation to distal misculature)
49
How does the cerebellum control motor planning?
Lateral hemispheres of the cerebellum project to the dentate nuclei which send axons through superior cerebellar peduncle to the VLp in the thalamus (contralateral). These go to the cerebral cortex which send projections to the distal musculature through corticospinal tract
Dentate nuclei also project to red nucleus , which lets the red nucleus integrate info from paravermal intermediate zone and lateral hemispheres
50
Why are cerebellar deficits always ipsilateral to the lesion?
All outpus (except vestibular) course through the superior cerebellar peduncle. This decussates as it ascends and targets the red nucleus and cerebellar cortex through the thalamus. The resulting descending tracts also cross (back) to the muscles of the ipsilateral side of the lesion
51
What are cardinal features of cerebellar dysfunction?
Ataxia
Decomposition of movement
Dysarthria
Dysdiadochokinesea
Dysmetria
Hypotonia
Nystagmus
Scanning Speech
Tremor
52
What is ataxia?
Reeling, or wide-based gait
53
What is decomposition of movement?
Inability to correctly sequence fine coordinated acts
54
What is dysarthria?
Inability to articulate words correctly with slurring and inappropriate phrasing
55
What is dysdiadochokinesia?
Inability to perform rapid altering movements
56
What is dysmetria?
Inability to control range of movement (abnormal trajectories through space)
57
What is hypotonia?
Decreased muscle tone
58
What is scanning speech??
Slow enunciation with a tendency to hesitate at the beginning of a word or syllable
59
What is tremor?
Rhythmic, alternating, oscillatory movement of a limb as it approaches a target (intention tremor)
60
What are features of Vermis Syndromes?
Symptoms that affect the trunk
Wide-based gait and stance
Truncal titubations (staggering)
Arm and leg coordination are spared
Gait abnromalities not improved by visual orientation (indiscriminate falling)
Eye movement disturbances
Rotated postures of head
Test by tandem toe-heel walking; walking backwards; hop on each foot; romberg
61
What is the most common cause of midline (vermis) cerebellar syndromes?
Chronic alcohol use
62
What are symptoms of hemispheric cerebellar syndromes?
Appendicular ataxia - loss of coordination of limbs ipsilateral to lesion
Impaired rapid alternating movements
Gait abnormalities not improved by visual orientation - fall toward lesion
Dysdiadochokinesia, Dysarthria, Dysmetria
Tremors
Hypotonia
Test with rapidly alternating movements (finger to nose, heel-knee-shin), check and rebound, past pointing
63
What are common causes of cerebellar hemisphereic syndromes?
Metastasis, infarcts, abcesses
64
What are pancerebellar syndromes?
Combination of vermis and hemispheric syndromes
Can be caused by infectious processes, hypoglycemia, paraneoplastic disorders, drunkenness
65
What oculomotor dysfunctions are commonly seen in cerebellar disorders?
Nystagmus (gaze evoked, upbeat, rebound)
66
What is the Romberg Sign?
Close eyes and stand still
Patients will fall with both cerebellar and posterior column disease
With eyes open, patients with cerebellar disease will fall.
Posterior column defecits will present with eyes closed (falling out of shower)
67
What do cerebellar tremors present as?
Intention tremors
Occur during purposeful/directed movement (especially near end)
Usually slow frequency, coarse, and broad
68
What do non-cerebellar tremors present as?
Resting tremors, usually
Occur maximally at rest and decrease with activity
69
What structures are likely affected in a patient with a resting tremor that improves with motion?
Not cerebellum!
70
What structure is likely affected in a patient with a tremor that worsens with movement and is worse at the end of a movement towards an object?
Cerebellum!
71
What is a resting tremor?
Maximal at rest
Decreases with activity
Usually symptom of Parkinson's
72
What is a postural tremor?
Maximal with limb in a fixed position against gravity
Gradual onset suggests physioloic or essential tremmor
Acute onset suggests toxic/metabolic disorder
73
What is an intention tremor?
Maximal during movement toward a target (finger to nose)
Suggests cerebellar disorder but may be due to somethign else (MS, Wilson's)
74
What is asterixis?
Flapping "tremor" in wrist due to liver failure (think metabolic)
Caused by interruptions of contraction in wrist extensors
75
What is a pill-rolling tremor indicative of?
Parkinsons!
76
What do dysfunctions of the basal ganglia present as?
Motor behavior and reward seeking deficits
Tremor, rigidity, dyskinesias, loss of postural reflexes, chorea, ballismus, dystonia, addiction
Parkinson's, Huntingtons, Tourette's, hemibalismus are diseases
77
What are the components of the basal ganglia system?
Striatum (dorsal = caudate nucleus + putamen; ventral = nucleus accumbens septi)
Pallidum (external, internal, ventral)
Substantia nigra (compacta, reticulata)
Ventral tegmental area
Subthalamic nucleus
78
What are the major inputs to the basal ganglia system?
Cerebral cortex (huge) - glutamatergic
Thalamus - glutamatergic
Midbrain - dopaminergic
Raphe nuclei - serotinergic
Locus ceruleus - noerepinephrine
79
How is cerebral cortical input to the basal ganglia organized?
Topographically
from all areas, but especially the frontal lobe
80
Where does thalamic input to the basal ganglia originate from?
Ventral group (VA/VM; VLa)
Inrtralaminar nuclei (CM)
Medial Dorsal Nucleus (MD)
81
What are the main efferent cells of the striatum?
Medium Spiny Neurons (GABA-ergic)
82
What are the two subtypes of the medium spiny neurons of the striatum?
Substance-P colocalizing neurons with D1 receptors (excitatory)
Enkephalin colocalizing neurons with D2 receptors (inhibitory)
Project to Globus Pallidus and Substantia Nigra
83
What are the components of the striatum?
Dorsal = caudate and putamen
Ventral = nucleus accumbens septi, olfactory tubercule
84
What is the dorsal striatum?
Putamen and caudate nucleus
85
What is the ventral striatum?
Nucleus accumbens and olfactory tubercule
86
What is the subthalamic nucleus?
STN - pod-shaped, located rostral and lateral to substantia nigra
Output is excitatory (Glutamatergic)
87
What is the globus pallidus?
Located lateral to the interanl capsule and medial to the putamen
3 parts: External, internal, ventral
External (GPe) and inner (GPi) are dorsal pallidum; ventral pallidum (VP) is ventral to anterior commissure
All are GABAergic
88
What is the substantia nigra?
Two parts (pars reticulata (SNpr), and pars compacta (SNpc))
SNpr is caudomedial extension of GPi = both are GABAergic
SNpc is midbrain dopaminergic cell group that provides input to striatal MSN
89
Which are the major output centers of the basal ganglia?
GPi, SNpr and VP
90
Which basal ganglia output center contorls head and neck motor control?
SNpr
91
Which basal ganglia output center controls motor body function?
GPi
92
How does output to the pyramidal system occur from the basal ganglia?
GPi/SNpr axons travel to thalamus via ansa lenticularis and lenticular fasciculus
93
What are the important functions of the ansa lenticularis and lenticular fasciculus?
Tracts of output from the GPi/SNpr axons to the thalamus
94
What are the pathologic hallmark of parkinson's disease?
Lewy bodies
95
What is a lewy body?
Pathologic hallmark for Parkinson's Disease
Eosinophilic inclusion in neuron made of alpha synuclein and ubiquitin
Classically in Substantia Nigra, but also found elsewhere
96
How is Parkinson's diagnosed?
Clinically
Cardinal signs:
Bradykinesia, rigidity, tremor, postural instability
97
What is the characteristic parkinson's tremor?
3Hz, 3-5Hz, pill rolling
98
How is Parkinson's treated?
Symptomatically - no cure
Levodopa (precursor to dopamine that crosses BBB)
MAOI -B inhibitors - increases dopamine levels
COMT inhibitors - keep plasma levodopa levels high
Amantadine - antiviral agent that keeps endogenous dopamine levels high
Anticholinergics
Deep brain Stimulation
99
What is Lewy Body Dementia?
Parkinsonism, dementia, fluctuations in arousal and attention, myoclonus, **visual hallucinations**
100
What is progressive supranuclear palsy (PSP)?
**Symmetric** Parkinsonism
**Early postural instability** with falls
Typically onset after 70 years old, and no response to levodopa
101
What is Cortical basal ganglionic degeneration?
Rare condition with onset in 60s or 70s with **rapid** course
Asymmetric, atremulous parkinsonism
Cortical involvement with issues writing, aphasia
no response to levodopa
102
What is multiple system atrophy?
Onset in 40s-60s and can mimic Parkinson's
parkinsonian, cerebellar, or autonomic
**early autonomic dysfunction** (orthostatic, incontinence)
**symmetrical** parkinsonism, with **rapid** progression
103
What is Wilson's Disease?
Movement disorders that present at 10-25 years old with liver disease
(**liver + neuro/psych = wilsons)**
Can lead to renal failure, retardation
Dysarthria, dystonia, tremor, parkinsonism, Kaiser Fleischer rings (copper in cornea),
**Autosomal recessive** caused by mutations in copper transporter ATPase. Causes copper accumulation
If under 50 with parkinsonism = test for Wilsons!
Treat with chelators!!!!
104
What is Huntington's Disease?
Chorea - starts as clumsiness/fidgetiness progresses to full chorea
Dysarthria, dysphagia, motor impersistence
Parkinsonism
Depression, psychosis, dementia
**Slowed saccades**
Atrophy of the striatum - particularly caudate
Initially degenerates indirect pathway, eventually both
Treat with Dopa antagonists and Dopa depleting agents
Autosomal dominant - CAG repeats in huntingtin gene (Chr 4 \>38 repeats
105
What is chorea?
Involuntary continual irregualr and unsustained movements
Not predicatable or suppresable
Motor impersistence, mild hypotonia
In Huntingtons, side effect of L-Dopa, antipsychotics
106
What are tics?
Unvoluntary production of movements, sounds
Premonition sensation, suppressible, suggestible, stereotyped
Childhood onset, co-occurs with OCD, ADHD (Tourette's)
107
What are tremors?
Involuntary rhythmic oscillations, usually 3-12 Hz
Essentail tremor = head, hands voice (6Hz)
Cerebellar dysfunction = 3 Hz
Parkinsonism = 3Hz
Alcohol improves essential tremor
Treat with DBS, botulinum, anticonvulsants
108
What is dystonia?
Slow, twisting, repetitive movements that produce abnormal postures
Task specific, persist over time, spread
Sensory tricks can aleviate
Dopamine, ACh dysfunction in basal ganglia
109
What happens in hypokinesis?
Indirect pathway dominates over direct pathway - net inhibition of thalamus - decreased cortical output - decreased quality of movement
Parkinsons = loss of Dopaminergic SNpc neurons
110
What happens in hyperkinesis?
Direct pathwya predominates over indirect pathway with net **disinhibition** of the thalamus - increased cortical signals - increased movement
Huntingtons - death of neurons that initiate indirect pathway; D1 Substance P MSNs are spared, but lost over time
111
What two main category of symptoms is OCD characterized by?
Obsessions and compulsions
112
What are obsessions?
Recurrent, persistent thoughts, urges, or images experienced as intrusive and unwanted, usually causing marked distress
Affective individuals attempt to ignore, suppress or neutralize such obsessions with another thought or action
113
What are compulsions?
Repetitive behaviors or mental acts that a person feels driven to perform in response toa n obsession or according to rules that must be rigidly applied
Aimed at preventing or reducing distress or preventing some dreaded event or situation
Usually unrealistic, excessive and may reduce anxiety, but are not pleasurable.
114
What are the features of obssessions and compulsions that meet the diagnostic critera for OCD?
Time consuming, lasting more than one hour per day
Associated with significant distress or impairment
Insight can vary, and OCD patients usually recognize/acknowledge at some point that their obsessions/compulsions are unrealistic or excessive
Some have lifetime history of chronic tic disorder
115
What is the lifetime prevalence of OCD?
2-3%
116
When is onset of OCD most common?
Childhood (over 50% of new cases in children)
Course is typically chronic and sometimes disabling
Men and women are affected equally
117
What is the gender distribution of OCD?
Equal
118
What are some typical obsessions in OCD patients?
Contamination
Aggression
Safety/harm
Sex
Religion (scrupulosity)
Somatic Fears
Need for symmetry or exactness
119
What are typical compulsions in OCD?
Cleaning/Washing
Checking
Ordering/Arranging
Counting
Repeating
Hoarding/Collecting
120
What is Tourette's Syndrome?
Disorder in which affected individuals have motor and vocal tics that occur many times a day nearly every day for at least one year
Onset is usually before 18 years old
Significant comorbidity with OCD, likely due to the role of basal ganglia and genetic factors that overlap in the two disorders
121
What are primary headache syndromes?
Physiological disruption
Migraine
Tension type
Cluster
122
What are secondary headache syndromes?
Pathology + physiology
Neoplasm
Infection
Aneurysm
123
What is the most common type of headache?
Tension headache
124
What is the most common type of headache that physicians see?
Migraines
125
What defines a migraine without aura?
At least 5 attacks
Headache lasts 4-72 hours
Two of: unilateral, pulsatile, moderate/severe pain, aggravation or avoidance of physical activity
One of: N/V, photophobia and phonophobia
Not attributable to somethign else
126
What defines a migraine with aura?
At least two of:
Aura with fully reversible visual, sensory, or dysphasic speech symptoms
Homonymous visual or unilateral sensory symptoms; 1 aura symptom developing over 5 minutes, or different symptoms in succession over 5 minutes
Headaches fulfill criterea for migraine without aura
127
How does cerebral blood flow correlate with headache?
Prodrome - nothing
Aura - nothing
Headaceh - increased flow
128
How do you determine whether the origin of a headache is opthalmic?
All ocular causes of headache are associated with changes in the external apperance of the eye
129
How do the timing and topography of cerebral blood flow, aura, and headache relate to each other during migraine attacks?
Pain begins during hypoperfusion phase
Hyperperfusion may outlast pain
130
What is cortical spreading depression?
Devleopment of waveform in brain that causes period of activation followed by refractory period of depression
Crawls at 3mm/minute from brainstem, up to occiput, and then forward through brain
I.e. activation = aura; depression = blindness
131
Describe threshold of transcranial magnetic stimulation of a patient with migraines compared to normal.
Migraines - lower thereshold (brain is 'excitable')
132
What brain structures get activated at the onset of migraines?
Brainstem centers - periaqueductal grey turns on during migraine attack
133
What structures is primarily involved in migraines that can explain symptoms?
Meninges!
Cortical spreading depression causes release of vasodilatory mediators in the brain that cause meninges to expand/be inflamed
134
What is the cheiro oral phenomenon?
Numbing/tingling of cheek and hand (which then spreads)
Almost pathognomonic for migraines
135
If a patient walks in with headache symptoms and a tingling/numbing of the mouth and a hand, that progressively spreads up arm, what are you thinking?
Migraine
136
What is the funciton of glial cells, and what about their normal physiology is important to migraines?
They redistribute K, Mg, and excitatory amino acids
Lowest numbers in primary occipital cortex (i.e. if glia aren't working well, the occipital lobe will take a hit)
137
What is the role of astrocytes in migraines?
Astrocyte calcium waves could mediate propagated cortical phenomena of migraine via release of neuroactive and vasoactive messengers
Astrocyte waves can explain cortical activity changes in the absence of cortical spreading depression
138
What is a tension-type headache?
Bilateral, band-like pressing headache
Not aggravated by activity
Little or no nausea, photophobia, or phonophobia
139
What are the diagnostic criteria for tension-type headache?
Essentially: not a migraine
Bilateral, steady non-pulsatile pain, not affected by movement,
Not associated with N/V, nor photophobia nor phonophobia
140
Can migraines present with neck pain?
yes
Migraines are often misdiagnosed because of neck pain leading to the diagnosis of tension headache
141
What is the physiology of neck pain that can be seen in migraines?
It is a referred pain phenomenon
Trigeminal nucleus caudalis extends to dorsal horn C2, C3, C4 =\> causes neck pain and posterior head pain.
142
What is the trigeminal autonomic reflex?
Irritation of trigeminal nerve causes activaiton of parasympathetic nucleus which causes lacrimation, rhinorrhea, nasal congestion
143
What is the tearing/sniffling/congestion reaction to cold/spicy/etc called?
Trigeminal autonomic reflex
144
What are some symptoms of children with migraines?
Benign paroxysmal vertigo of childhood
Alternating hemiplegia
Cyclic vomiting
Recurring abdominal pain
Benign torticollis
Acute confusional migraine
Car sickness
145
What is sinus headache?
**NOT actually a thing.**
Commonly diagnosed as headache secondary to sinusitis in the US - leads to overprescription of antibiotics
146
What are more serious complications of migraines?
Progression in severity
Migrainous stroke
Persistent aura without infarction
Epilepsy
147
What neurological issues does migraine put you at an elevated risk for?
Stroke
Epilepsy
148
What are you likely to see if you order an MRI for a migraine patient?
White matter changes that may be misdiagnosed as MS plaques, vasculitis, etc.
149
Generally speaking, what is the timeframe of primary headache syndromes?
Months to years
Shorter is likely to be a secondary headache
150
Which structures in the head are pain sensitive?
Meninges
Neural Structures (Trigeminal, Glossopharyngeal, Vagus CNs)
Scalp + Superficial structures
Vasculature
151
What are red flags that a headache is not a primary headache syndrome?
• A new or different headache
– ≤5 years old
– ≥50 years old
* Abrupt onset
* Cancer, HIV, pregnancy
* Abnormal physical exam
* Neuro symptoms ≥ one hour
* Headache onset
– With seizure or syncope – With exertion, sex, or
Valsalva
152
How do headaches due to brain tumors present?
Similar to tension headaches in most patients
Can be migraine like
"Classical" brain tumor headache is only 8%
153
What type of headache do patients with brain abscesses get?
Same as brain tumor
Fever in 1/2 of cases
154
Patient with frontal headache which increase with straining and are awekening out of sleep. Also papiledema, and dysmenorrhea. What type of headache?
Idiopathic intracranial hypertension
Pseudotumor cerebri
155
What are characteristics of headaches of idiopathic intracranial hypertension?
brain tumor headache
Visual complaints (diploplia, TVOs, photopsias)
Cranial bruits, noises in head, pulsatile tinnitus
N/V
radiculopathies
156
What do you treat idiopathic intracranial hypertension with?
Try to correct predisposing factors (weight loss, diuresis, shunting)
Try to preserve vision - optic nerve sheath fenestration
Symptoms
157
What is a hypnic headache syndrome?
Rare disorder in older people (40-84 y/o)
Bilateral throbbing headache
Recurring 1-3 times nightly with no other associated symptoms
Treat with lithium, caffeine, flunarizine
158
What types of headaches are seen with patients who had strokes?
Abrupt or gradual
Severity not associated with size of infarct
Headache can be multifocal or migratory - pain can move down arms, etc)
Not migraine in older patients (would have had a history)
159
What must you consider in a patient with "complicated" migraine presentation who is older?
Not only migraine (but may be less likely due to age)
Consider tumors, strokes, sensory seizures, etc.
160
How do sub-arachnoid hemmorage present as?
Abrupt onset of severe headache (reaches full intensity instantly - or close)
(Aneurysm burst)
Seizures and diploplia can be seen
Perform non-contrast CT, LP
161
What is thunderclap headache?
Headache seen in survivors of Berry aneurysm
Can be caused by aneurysmal or nonaneurysmal subarachnoid hemmorrage
162
What distinguishes a thunderclap headache from a subarachnoid hemmorrhage?
Seizures adn diploplia seen in SAH
163
What is a cluster headache?
Intense, boring (knife-like pain, very severe), unilateral pain
Quicker onset (over span of minutes)
Eyes tear and nose runs - autonomic involvement
Horner's Syndrome (ptosis and miosis)
Episodic - bouts of headache that last 1-4 months. Follow circadian pattern within and between cycles
Chronic - may evolve from episodic form or be chronic from onset. Absence of circadian patterns
Headaches with manic symptoms - almost opposite of migraine
164
What is temporomandibular dysfunction?
Pain that can be around the ear while chewing
Can go away quickly, but can persist too
Click may be heard over ear while jaw opening.
165
What type of headache can present with giant cell arteritis (temporal arteritis)?
Generalized, throbbing, temporal pain
Claudication - worsens with exertion
Polymyalgia rheumatica in 50% (aches and pains, maybe fever)
Visual scintillations
CRP or ESR abnormalities indicate biopsy
TREAT WITH CORTICOSTEROIDS
166
What type of headaches can be seen with angina?
Jaw, tip of nose, brow, bregma, occiput, palate, .... (anywhere really)
Extremities, shoulder pain
Rarely below umbilicus
167
What type of headache do you see with sexual activity?
Explosive, throbbing, occipital or frontal
Lasts for hours
Confusional state or symptoms of ischemia
(occur with valsalva too)
168
What symptoms can you see withs pontaneous carotid artery dissection?
Seen in young and middle age
Risk factors include trauma, arteriopathies, family history, respiratory infection
**Headaches, neck pain, horner's syndrome**
Cerebral ischemia
Tx: anticoagulation
169
If a patient presents with unilateral throbbing headache with pain of the face, neck, worse with movement, Horner's Syndrome, and a recent URI; what do you suspect?
Spontaneous carotid artery dissection
170
What can cause low-pressure headache?
Meningeal diverticula
Dural root sleeve tears
Excessive coughs
Erosion of dura from adjacent lesions
Head trauma
overshunting/carbonic anhydrase inhibitors
**Lumbar puncture (esp. in thin females)**
171
What is a common issue that can develop in thin female patients who have lumbar punctures?
Low-pressure headacehs
172
How do you treat low-pressure headaches?
IV Na caffeine benzoate
Epidural blood patch (if post-LP)
173
What is beta-2-transferrin?
Indicator of CSF
If seen in rhinorrhea, indicative of CSF leak
174
What do you suspect if you identify beta-2-transferrin in rhinorrhea?
CSF leak
175
What is POTS?
Postural orthostatic tachychardia syndrome
Seen in young post pubertal females
See orthostatic and non-orthostatic headache
Fatigue, decreased concentration, exercise intolerance, syncope
176
How do you treat POTS?
Hydration and salts
Elastic stockings
Beta blockers, fludrocortisone, minodrine, indomethacin
177
72 year old male, developed sharp pains in his right cheek and lip. These increased with light touch and he was nearly unable to shave or eat. His neurological examination was entirely normal. What do you suspect?
Trigeminal Neuralgia
178
What is trigeminal neuralgia??
Brief paroxysms of electric-like, lancinating pains (stabbing)
Usually affects V2 and V3
Stimulation of trigger points induces attacks
Suggest structural disease - demyelinated nerve-root area
Seen more in older patients. In younger patients think neurodegenerative disease
179
How does trigeminal neuralgia occur in older patients?
Superior Cerebellar Artery rubs against trigeminal nerve root and causes demyelination - origin of pain
180
How does trigeminal neuralgia occurs in younger patients?
Demyelinating process of trigeminal nerve
181
What is primary stabbing headache?
New onset, sharp, shooting pain in temple and behind eye
Not triggered by cutaneous stimuli
Preceded by days of euphoria
182
What sequence of events occurs during excitotoxicity?
Injury (ischemia, trauma, etc) leads to a decreased ATP state in the neuron.
This causes increased Na and Ca levels, depolarizing membrane potential.
Glutamate is increased extracellularly, exciting neighboring neurons.
183
What is chromatolysis?
Apoptosis of neurons
Shown here surrounded by healthy neurons with intact Nissl bodies
184
What is neurapraxia?
Focal demyelination of a neuron
Leads to a loss in conduction velocity of the axon - neuron stays in tact
185
What is axonotmesis?
Axon is cut and the distal part is lost via Wallerian degeneration
Nerve can regrow back to original target (takes months)
186
What is neurotmesis?
Loss of axon and surrounding wrappings (endoneurium, perineurium, epineurium)
Poor prognosis, surgery may help
187
What is disrupted in neurotmesis?
Wrappings of the nerve beyond the myelin (endoneurium, perineurium, and/or epineurium)
188
What can you see in nerve conduction studies/electromyography in demyelination?
Decreased conduction velocity
189
What do you see in nerve conduction studies/electromyography in axonal loss?
decreased action potential amplitude
190
What occurs during wallerian degeneration?
Intra-axonal organelle and microtubule breakdown (mins-hours)
Schwann cells begin breakdown of axons and recruit macrophages
Macrophages do their thing
Then the path is cleared for axons to regrow from proximal to distal
191
Which is more conducive to nerve regeneration, CNS/PNS?
PNS
192
Does Wallerian degeneration occur in the PNS? CNS?
PNS only!
Oligodendrocytes not as good at initiating degradation as Schwann cells
CNS - astrocytes and microglia not as helpful as macrophages
193
Which cells (PNS/CNS) have greater intrinsic growth potential and why?
PNS cells - have greater expression of regeneration-associated genes (RAGs)
PNS neurons possess receptors and signal transduction machinery allowing them to grow in response to neurotrophins - retrograde injury signals
194
What are neurotrophins?
Retrograde injury signals - promote growth towards higher concnetration
195
What is a growth cone?
Very tip of a regenerating axon - sense the milieu and decide to grow or not (sense neurotrophins, for instance) and direct growth of axon
196
What is the molecular basis of a growth cone?
Cytoskeletal rearrangement - actin bundles and microtubules
Attachment of cytoskeleton to the signal transduction machinery is key
197
What are retraction bulbs (of Cajal)?
Failed regeneration growth cones of the CNS
198
What types of changes are seen in CNS plasticity?
Molecular and structural changes
Molecular include synapse, receptor, transmitter regulation
Help adapt instead of regrowing in CNS
199
What opportunities arise from the complexity of neuronal connetions in the brain?
Complexity allows for recovery in the case of injury - you can reroute or use other mechanisms - don't have to fix the original pathway
200
How does activity help lead to neuronal plasticity?
Leads to increases in grwoth factors, especially BDNF (important in exercise)
Leading to increased neurogenesis, glial cell support.
Also, angiogenesis, synaptogenesis
201
What parallels are there between normal brain developmenta nd recovery from injury?
Birth-\>child age -\> maturity
Injury-\>regrowth-\>consolidation
You need to prune the neuronal connections
202
What types of activities are best for helping regrow/recover from neuronal injuries?
A variety of skilled, task-specific, repetitive tasks - these are better than general exercise alone
e.g. real life skills (reaching into cupboard)
203
What are natural sources for stem cells?
Embryonic - inner cell mass from 4-5d blastocyst - usually from excess IVF cells - plurpotent
Fetal - from extra-fetal or fetal tissue (amniotic, cord blood, placental tissue) - multipotent
Adult - from BM, skin, GI, fat, heart, brain, dental pulp - multipotent or oligopotent - huge advantage is they are autologous
204
What is a difference between adult, fetal and embryonic stem cells?
adult - oligo or multipotent - autologous
fetal - multipotent
embryonic - pluripotent
205
What is somatic cell nuclear transfer?
Take nucleus from adult somatic cell and insert it into enucleated egg cell - get early embryo
Not 100% autologous - mitochondrial genome is still present
206
What are induced pluripotent stem cells (iPS) and their advantages?
Turn on four genes - myc, sox, oct, nanog - in a somatic cell and you get a stem cell
Pluripotent
100% autologous
207
What are the best targets for stem cel therapies?
Neurodegenerative diseases - Huntington's (one type of neuron, isolated), ALS, Parkinson's, Alzheimers (but it is very diffuse)
Stroke
Traumatic Brain Injury, Spinal Cord Injury
208
How many approved indications are there for pluripotent stem cells?
ZERO
Hematopoeitic stemm cells are used in bone marrow transplants
209
What are dysmyelinating diseases?
Disease where myelin sheath is abnormally **formed** (mostly related to inherited metabolic disorders)
210
What are demyelinating diseases?
Disease wher ethe myelin sheath is normally formed but is the target of **destruction** (e.g. MS)
211
What cells comprise the gray matter?
Neuron cell bodies
Dendrites
Synapses
Axons
212
What comprises the white matter?
Myelinated axons
213
What makes up the myelin of the CNS?
Oligodendroglial cells wrapped around the axon
214
Where in the brain are grey and white matter generally located?
Cortex - grey matter
Tracts underneath - white matter (including corpus callosum)
215
What are examples of dysmyelinating diseases?
Adrenoleukodystrophy - primarily affects white matter
Tay Sachs disease - primarily involves ccumulation of myelin byproducts in neurons
216
What is the general course of MS?
Initially begins with relapse/recover periods (something like IBD)
Then morphs into a progressive disease (something like Alzheimers)
217
What is multiple sclerosis?
Inflammatory, autoimmune disease of CNS
Characterized by relapsing neurologic symptoms, and progressive impairement of function
Variable symptoms and signs - monocular vision loss, brainstem, motor/sensory impairments, imbalance
218
What are common early features of MS?
Motor weakness, parasthesias, impaired vision, double vision, intention tremor, ataxia
These are symptoms common of other diseases, so you must work it up or look back at it later
219
What is Charcot's triad?
Intention tremmor, nystagmus, scanning speech
Points to white matter pathways to and from cerebellum (vulnerable to demyelination)
Common presentation of MS
220
What is the most common form of involvement of the visual pathway of MS?
optic neuritis
Inflammation of optic nerve - **painful**
221
What is a very common first presenting feature of MS?
Optic neuritis - inflammation of optic nerve - presents with pain
222
What type of eye involvement is common in MS?
Optic neuritis - painful upon movement
Common to have a scotoma - isolated area of visual field with absent vision
223
What is the prognosis of optic neuritis that is seen early in MS?
1/3 will recover completely, the rest will improve substantially
Half of patients who present with optic neuritis alone will develop other signs of MS
224
What is RR-MS?
Relapsing-remitting MS
Relapses, recovery, and **stability** between
225
What are the different clinical patterns of MS?
Relapsing-remitting, secondary progressive, primary progressive, progressive relapsing
226
What is secondary progressive MS?
Relapse with recovery, then gradual worsening of symptoms over time
227
What is primary progressive MS?
gradual worsening of symptoms - no cardinal features of relapses
228
What is the relationship between brain lesions and disability in MS?
We can see lesions more readily than attacks, and are indicators of progression of MS
Looking below the surface of symptoms reveals worsening picture of lesions in the brain
229
What is clinically isolated syndrome?
First presentation of what is liekly to become MS - (singular sclerosis)
Within 10 years, 50% wil develop secondary-progressive MS
230
Who gets MS?
young people: 20-40 (big spread)
Particularly women (3:1)
231
What is the most common cause of medical disability in young adults?
MS
232
In what ethnicity is MS more common?
North European descent
Seen more common in latitudes further from equator too
233
What are the genetic fators of MS?
Complex - but twins at 30% chance of getting MS, siblings 2-5%
Both more common than general population
234
What helps you make the diagnosis for MS?
Dissemination in space and time of disease activity
Based on history and neurological exam
No single diagnostic test
MRI can help
235
What is the significance of contrast-enhanced lesions in the brain on MRI?
Indicate **active** inflammation. Lesion associated with MS
In non-contrast MRI - indicate history of MS lesions
236
In non-contrast-enhacned MRI, what is the significant of lesions in white matter tracts?
Old MS plaques. Active inflammation can be seen by contrast enhancement
237
What is this MRI indicative of?
**Multiple Sclerosis**
Periventricular lesions - radiating upward and outward from ventricles + white matter tracts
Radiating upwards from corpus callosum
Brainstem, cerebellum lesions
238
How do MRI lesions predict development of MS after presentation with optic neuritis (or other first attack)?
Increased likelihood
239
What must you be sure of before diagnosing MS?
That there is no better explanation, e.g.:
Infectious: Lyme, Syphilis, HIV, HTLV-1, PML
Inflammatory: SLE, Sjogren’s syndrome, vasculitis,
sarcoidosis, Bechet’s syndrome, APLS
Metabolic: Vitamin B12 deficiency, dysmyelinating
diseases (lysosomal/leukodystrophies), toxins, CPM,
mitochrondrial disorders, Copper deficiency,
Vascular: CADASIL, susac’s syndrome
Neoplastic: CNS lymphoma, metastatic disease
Structural Spine disease: AVMs, degenerative disc
disease, syrinx, arnold-chiari
Genetic- hereditary spastic paraparesis
**Psychogenic**-Depression, anxiety, conversion
240
What occurs from an immunological perspective in Multiple Sclerosis?
Th1 cells become activated and self-reactive T cells enter brain and mistake myelin for antigens
Without regulatory cells, they are reactivated and release proinflammatory cytokines that increase inflammation, cause edema, and damage myelin and nerves
241
What type of disregulation is thought to occur in MS with respect to Th cells?
Th1 more than Th2 (inflammatory more than anti-inflammatory)
242
What do you see in the CSF of MS patients?
Oligoclonal bands - identified by electrophoresis of CSF
Two or more bands needed to be seen for it to be useful
IgG bands
243
What are oligoclonal bands?
When you electrophorese CSF in MS patients, you will see excess of bands instead of smear, of IgG
244
What is seen in histological sections of MS lesions?
Peri-venular inflammatory infiltrates
245
What are the goals of treating MS?
Treat relapses and exacerbation
Prevent relapses
Reduce devleopment of disability
Treat symptoms
246
What can be used to directly treat MS relapses/exacerbations?
High dose IV steroids - remember, this is an inflammatory event.
247
What are some limitations of treating MS?
Disease modifying agents are only partially effective
All injectible (IV)
Side effects of interferons (flu-like, headche, fever)
Risk/Benefit
248
How can you identify an acute exacerbation of MS that you should treat?
Must distinguish from Uhthoff's phenomenon (which is sudden onset of neurological dysfunction as a result of elevated body temperature)
Episode of neurological dysfunction lasting more than 24 hours in the absence of fever or infection
249
What is Uhthoff's phenomenon?
A sudden onset of neurological dysfunction as a result of elevated body temperature
250
What drug do you use to treat acute exacerbations of MS?
IV methylprednisone - high dose
251
When is the onset of Tourette's Syndrome?
Before 18 years old
252
What is a common comorbidity seen with Tourette's Syndrome?
OCD
253
What is an effective psychological treatment for COD?
Cognitive Behavioral Therapy (CBT)
254
What is the learning theory explanation of OCD?
Symptoms are a result of a person developing learned negative thoughts and behavior patterns towards previously neutral situations
255
What is the neurotransmitter based model for the etiology of OCD?
Based on the findings clinically that selective serotonin reuptake inhibitors (SSRIs) and glutamate receptor blockers are efficacious
Also that glutamate is found in elevated levels in some brain areas
Not fully well understood
256
What is the circuit-based hypothesis for the etiology of OCD?
It is hypothesized that OCD involves an imbalance between the direct and indirect pathways of the basal ganglia, leading to relatively greater excitation of the circuit, and resultant stereotyped behavior
257
What is the infection-triggered hypothesis for the etiology of OCD?
It is has been observed that there is a subset of children with rapid onset of OCD symptoms and/or tic disorders and it is hypothesized that these symptoms are caused by group A beta-hemolytic streptococcal infections- an initial autoimmune reaction to the strep infection produces antibodies that interfere with basal ganglia function.
258
What organism has been implicated in the development of some cases of OCD in children?
group A beta-hemolytic streptococcus
259
What evidence suggests the role of genetics in the etiology of OCD?
Family aggregation studies show it is familial - especially early-onset and tic-related forms
Twin studies
One glutamate transporter gene (SLC1A1) has been associated and replicated
Little from GWAS
260
What are the two well established mainstays of OCD treatment?
Serotonin reuptake inhibitors (SRIs) - either clomipramine or fluvoxamine (SSRI)
Cognitive Behavioral Therapy - exposure and response prevention therapies -\> shown to have a higher rate of resopnse
261
What proportion of patients respond to OCD treatment (either pharmacologic of CBT)?
50% and full remission is uncommon
262
What are some options for OCD patients for whom traditional serotonin therapies or CBT is not working?
Changing SSRI
Adding antipsychotic drugs
If all other treatments are not working, deep brain stimulation and in some cases neurosurgery could be attempted - but must get full consent from patient
263
When can DBS be used for the treatment of OCD patients?
Failed CBT
Failed multiple medication treatments including SSRIs, clomipramine, and SSRI + antipsychotic
Must get full consent (and often IRB approval, etc) - still experimental/not proven efficacious
264
What are the two major divisions of the cerebral cortex?
Allocortex - including the archicortex (e.g. hippocampus) and paleocortex (parahippocampal cortex)
Isocortex - referred to as neocortex nowadays
265
What are the components of the allocortex?
Archicortex (hippocampus) and paleocortex (parahippocampal cortex)
266
What is the isocortex?
Neocortex
267
Which brain region is primarily responsible for conscious thought?
Cerebral cortex
complex sensory processing, motor control, decision making, introspection
268
Which brain region is responsible for complex sensory processing, motor control, decision making, introspection?
Cerebral cortex
269
What accounts for over 90% of the cerebral cortex in humans?
The neocortex
270
What is the basic unit of information processing in the neocortex?
Cortical column - includes all essential cellular and synaptic elements of intrinsic cortical circuitry
271
What is a cortical column?
The basic unit of information processing in the neocortex
Includes the essential cellular and synaptic elements of intrinsic cortical circuitry
272
What are the two most important types of projections to a given cortical area?
Thalamocortical inputs - provide primary sensory input to the neocortex
Corticocortical input that interconnect functionally linked cortical areas
273
What inputs do thalamocortical connections provide to the neocortex?
Primary sensory input
274
What do corticocortical inputs provide to the neocortex?
Interconnect functionally linked cortical areas
Establish broad distributed systems that are well suited for complex information processing
275
What are the inputs that the neocortex receives?
* *Thalamus - sensory**
* *Other neocortical areas - linked functional systems**
Extrathalamic subcortical afferents - regulation of mood and attention
Amygdala - emotional tone to neocortical functions
Parahippocampus - primary association cortex - role in memory
276
Where do cholinergic projections to the neocortex originate?
Nucleus basalis
277
Where does the dopaminergic projections to the neocortex originate from?
Substantia Nigra/Ventral Tegmental Area
278
Where do the serotinergic projections to the neocortex originate from?
Dorsal Raphe nucleus
279
Where do the noradrenergic projections to the neocortex originate from?
Locus Ceruleus
280
What is a difference between the organization of thalamic cortical inputs and extrathalamic cortical inputs?
Thalamic cortical inputs are highly topographic with a narrow field of termination
Extrathalamic inputs are highly divergent, innervating huge areas of the neocortex and regulating functions such as mood, sleep, wakefulness, attention, alertness, etc.
281
Which inputs to the neocortex are highly topographic and well-organized?
Thalamic inputs
282
What are the major efferents of the neocortex?
Mostly reciprocal projectiosn of the major afferents:
Extrathalamic afferents are not reciprocal, largely
Major non-reciprocal cortical efferent system from motor and frontal association areas to the caudate.
Also non-reciprocal projections to brainstem nuclei and spinal cord that are important for motor control
283
What are the non-reciprocal efferent tracts from the cortex?
Basal ganglia - from the motor and prefrontal cortices
To brainstem and 'downstream' motor areas - Pons, brainstem motor nuclei, tectum, spinal cord
284
What are the six layers of the neocortex?
I - Molecular (plexiform)
II - External granule layer
III - External pyramidal layer
IV - internal granule layer
V - Ganglionic layer (internal pyramidal)
VI - multiform layer (polymorphic)
285
What is layer IV of the neocortex associated with?
Sensory information (inputs)
286
What is layer V of the neocortex associated with?
Motor outputs
287
How are cortical layers different in different brain areas?
For instance- primary motor and frontal premotor have larger layer V (motor)
Sensory areas (occipital, for example) have larger layer IV (sensory)
288
What is significant about the neocortex in the primary visual cortex?
It is highly specialized to receive initial sensory input from teh thalamus
Large layer IV of the neocortex
289
What is significant about the neocortex in the primary motor cortex?
Directly drives motor centers of the brain stem and spinal cord - large layer V
290
What are pyramidal neurons?
Principal **output** neurons
The main axon leaves the cortex and they are generally **excitatory (signal with glutamate)**
Spiny - have great capacity for integration of information form multiple sources
291
What is significant about the spines on pyramidal neurons?
They each receive excitatory signals (glutamatergic)
These are modified in the context of learning and memory and are implicated in plasticity and their loss is associated with aging
292
What are non-pyramidal neurons?
Interneurons that have fairly local projections
**Mostly inhibitory (signal via GABA)** - some are excitatory spiny-stellate (in layer IV of visual and somatosensory cortices)
Three types: Chandelier, Basket, and Double Boquet
They modulate excitability throughout the entire receptive surface of pyramidal neurons
293
What are chandelier cells?
Inhibitory interneurons (non-pyramidal) that synapse on the axon initial segment and inhibit the action potential
294
What are basket cells?
Inhibitory interneurons (GABAergic, non-pyramidal) that synapse on the cell bodies of pyramidal cells
295
What are double bouquet cells?
Inhibitory interneurons (GABAergic, non-pyramidal) that synapse on the dendritic shafts and spines
296
What is the basic scheme of columnar organization of the neocortex?
Activation of the pyramidal cell via incoming excitatory afferent, which is modulated by the GABAergic interneurons' inhibitory signals.
Thought to arrange in radial columns of interconnected neurons that form integratory circuit that processes bits of information
297
How do the types of circuits of the brain reflect the neurotransmitters through which they signal (GABA, Glutamate, 5-HT, NE, DA)?
Local interneurons control pyramidal cell output via inhibitory GABAergic synapses
Thalamocortical and corticocortical circuits are heirarchical excitatory circuits via glutamatergic synapses
Brainstem projections to the cortex are broadly modulatory via monoamines (5HT, NE, DA)
298
What types of functions do GABAergic neurons play?
Locally inhibitory interneurons that modulate pyramidal cell signaling
299
What types of functions do glutamatergic neurons play?
Excitatory links of thalamocortical and corticocortical pathways. Heirarchical
300
What types of functions do monoamine (5HT, DA, NE) neurons play?
Broadly modulatory from the brainstem to cortical areas.
301
What are association cortices?
can be linked to a particular sensory modality (unimodal) or can be a center for convergence of multiple modalities (polymodal)
Required for interpretation and elaboration of sensory information
Prime example is visual cortex
302
What are the two major streams of visual processing?
Occipito-parietal stream - processes visuospatial information and **motion** detection
Occipito-temporal stream - processes form and color
303
What information does the occipito-parietal stream process?
visuospatial information and **motion** detection
304
Which visual processing stream processes visuospatial information and motion detection?
Occipitoparietal stream
305
What information does the occipito-temporal stream process?
Form and color information for the visual system
306
Which visual processing stream processes form and color information?
Occipito-temporal stream
307
What is the "where" visual processing system?
Occipito-parietal stream
308
What is the "what" visual processing system?
Occipito-temporal stream
309
[...] cells are involved in the processing of "where" visual informaiton (motion, spatial relations)
Magnocellular cells are involved in the processing of "where" visual informaiton (motion, spatial relations)
Occipito-parietal stream
310
[...] cells are involved in the processing of "what" visual information (form, color)
Parvocellular cells are involved in the processing of "what" visual information (form, color)
Occipito-temorpal stream
311
Which visual processing stream is involved in the recognition of faces?
occipito-temporal stream
312
What is visual agnosia?
Incapability of recognizing visual stimuli
May be able to recognize objects presented to other sensory modalities
313
What is prosopagnosia?
Inability to recognize previously known human faces or to learn new ones
Can perform complex perceptual tasks and do not have visual spatial disturbances
Correlated withd amage to the occipito-temporal region
314
What lesions can cause prosopagnosia?
Damage to the occipito-temporal region
315
What is the term for the inability to recognize previously known human faces or to learn new ones?
Prosopagnosia
316
What is the term for the inability to recognize objects visually?
Visual agnosia
317
What is visual object agnosia?
In addition to prosopagnosia, patients have inability to identify or recognize the generic class to which an object belongs
Also correlated with damage to the ventral and medial parts of the occipito-temporal visual areas
318
What is Balint's syndrome?
Three components:
Optic ataxia (impairment of target pointing under visual guidance)
Ocular ataxia (inability to shift gaze at will toward new visual stimuli)
Simultanagnosia (perception and recognition of only parts of the visual field)
-- Strongly correlated to bilateral damage of the occipito-parietal region
319
What is optic ataxia?
impairment of target pointing under visual guidance
320
What is the term for impairment of target pointing under visual guidance
optic ataxia
321
What is the term for the inability to shift gaze at will toward new visual stimuli?
Ocular ataxia
322
What is ocular ataxia?
The inability to shift gaze at will toward new visual stimuli
323
What is simultanagnosia?
Perception and recognition of only parts of the visual field
324
What is the term for perception and recognition of only parts of the visual field?
Simultanagnosia
325
What syndrome is related to bilateral damage of the occipito-parietal region?
Balint's Syndrome
326
What types of lesions is Balint's Syndrome related to?
Bilateral occipito-parietal region damage
327
What functions does the prefrontal cortex serve?
Working memory
Planning
**Executive function**
Top-down cognitive control (forming rules)
Modifying these rules
Response inhibition
328
Which area of the brain is more developed in humans than in other species?
Prefrontal cortex
329
What modalities send signals to the prefrontal cortex?
All higher level association areas project to the prefrontal cortex
Auditory, somatosensory, motor, visual, affective (amygdala)
330
What information about the prefrontal cortex can be elucidated from delayed response task studies in monkeys? (The task consists of a visual cue, then obligated to delay their response but remember the cue's location and then generate an appropriate response for a reward)
Different neurons fire during different parts of this task
The prefrontal cortex neurons are active during the delay phase! (D below)
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331
What are key characteristics of prefrontal cortex neurons in delayed-response task studies?
They are active duriing the delay
They are spatially selective (others are object selective)
They are resistant to distraction
332
What neurons are important for tasks such as adjusting to cars traveling on the left side of the road when in England (i.e. changing the rules)
Prefrontal cortex
333
What cognitive impairments are associated with prefrontal cortex damage?
Problem solving deficits
Impaired temporal order judgements
Difficulty in attending to a task
Enhanced sensitivity to distraction
Perservation
Impulsive behavior
Poor planning
Impaired decision making
Working memory defecits
Impaired executive functioning
- Heavily compromised in disorders such as Alzheimers
334
What brain region is likely damaged in patients presenting with problem solving deficits, impaired temporal order judgments, difficulty in attending to a task, enhanced sensitivity to distraction, perservation, impulsive behavior, poor planning, impaired decision making, working memory deficits and impaired executive functioning?
Prefrontal Cortex
As in Alzheimer's Disease
335
What brain regions is Alzheimer's Disease associated with?
Compromised prefrontal cortex
336
What are the two core clinical components of consciousness?
Arousal - level of consciousness - are the lights on?
Awareness - content of consciousness - is anyone home?
337
Which brain structures are important in mediating arousal?
Ascending reticular activating system (ARAS) - in brainstem
Thalamus
Thalamocortical Relays
338
What is ARAS?
Ascending reticular activating system
Origininates in nuclei in the ponto-mesencephalic junction
Transmits via Acetylcholine
339
What neurotransmitter is used by ARAS?
Acetylcholine (ACh)
340
Where are the source nuclei of the ARAS located?
Ponto-mesencephalic junction
341
Which brain structure important in mediating arousal has its source nuclei located in the ponto-mesencephalic junction?
Ascending reticular activating system (ARAS)
342
Which brain structures are important in mediating awareness?
The cerebral cortex
343
How can lesions to the cortex impair consciousness?
Large, bilateral lesions
344
What areas, if disrupted, can cause an impairment of consciousness?
ARAS
Thalamic relays
Cortex (bilaterally)
345
What are possible etiologoies of consciousness impairment?
Structural - trauma, mass lesions (neoplasm, hematoma, abscess)
Functional - ischemia, seizure, metabolic, endocrine, inflammatory, infectious, iatrogenic, toxic
346
What are the six levels of arousal?
Awake
Drowsy/somnolent
Lethargic
Obtunded
Stupor
Coma
347
What does it mean to be awake?
Full wakefulness
348
What does it mean to be drowsy/somnolent?
Able to be stimulated to full arousal by non-noxious stimuli
349
What does it mean to be lethargic?
Resonsds to non-noxious stimuli but unable to be brought to full arousal
350
What does it mean to be obtunded?
Responds to non-noxious stimuli but more depressed level of consciousness
351
What does it mean to be stuporous?
Requires noxious stimuli to raise level of arousal
352
What does it mean to be comatose?
Unresponsive, reflexive response to all stimuli
353
What is the Glascow Coma Scale (GCS)?
Quantitative scale to asses level of **arousal** on verbal responsivity, eye opening, motor responsivity
Scores range from 3-15. 3 is deep coma, 15 is fully awake
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What is a quantitative descriptor of arousal?
Glascow Coma Scale
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What are the components of consciousness?
Arousal
Awareness
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How is awareness described?
From alert/attentive to inattentive (distractible or dissociated) to vegetative
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What are the three principal features used to localize the source of an arousal dysfunction?
Respiratory pattern
Eye function
Motor responsivity
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What is Cheyne-Stokes respiration? What is it indicative of?
Crescendo-decrescendo respiratory pattern with apnic period
Indicative of diffuse forebrain dysfunction
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What type of brain lesion is hyperventilaiton indicative of?
Midbrain injury
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What type of breathing pattern will you see in a diffuse forebrain dysfunction?
Cheyne-Stokes
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What type of breathing pattern will you see in a midbrain injury?
Hyperventilation
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What type of breathing pattern will you see in a rostral pons injury?
Apneusis
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What region of the CNS do you suspect a lesion if a patient's respiratory pattern is apneusis?
Rostral pons
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What is apneusis? What type of CNS injury is it indicative of?
Large breaks of apnea. Rostral pons injury
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What type of breathing pattern do you expect to see in a caudal pons injury?
Ataxia - dyscoordinated, irregular respiratory pattern
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What type of CNS lesion do you suspect if a patient has an ataxic respiratory pattern?
Caudal pons
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What is the difference in the respiratory pattern of a patient with an injury to the rostral vs caudal pons?
Rostral = apneusis - large periods of apnea
Caudal = ataxia - disorganized, irregular
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What type of respiratory pattern do you expect to see in a patient with a medullary injury?
Respiratory arrest
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Where in the CNS do you expect to find a lesion for a patient in respiratory arrest?
Medulla
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What eye functions are important in helping identify arousal dysfunction?
Corneal reflex
Pupil size/reactivity
Extra-ocular movements
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What is a thalamic pupil?
Small, reactive, symmetric
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What types of pupils are small, reactive, and symmetric?
Thalamic
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What types of pupils are fixed and dilated?
Pretectal pupils
(Edinger-Westphal damage)
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What are pretectal pupils?
fixed, dilated
(damage to Edinger-Westphal)
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What are pontine pupils?
Pinpoint
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What types of pupils are pinpoint?
Pontine pupils
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What types of pupils are fixed at mid-size?
Midbrain pupils
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What is a midbrain pupil?
Fixed, mid-size
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What is a herniation pupil?
1 fixed, dilated pupil
This suggests a mass effect and is an **emergency**
****
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What does one fixed, dilated pupil indicate?
Herniation pupil - indicates mass effect - **emergency**
****
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What is responsible for the afferent limb of the corneal reflex?
CN V1 - localizes to the pons
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What is responsible for the efferent limb of the corneal reflex?
CN VII - localizes to the CNVII nucleus in the pons
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Which brain structure is important for the corneal reflex?
PONS
Afferent - CN V1
Efferent - CN VII
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What can the vestibulo-ocular reflex tell you about a person's lesion in arousal dysfunction?
VOR requires in tact brainstem
Lateral pontine lesion - PPRF on side of lesion is dysfunctional and the eyes do not move horizontally when the head is turned in the direction that is contralateral to the lesioned PPRF (cold water in ipsilateral ear makes no eye movement)
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What changes in the VOR would you expect with a lateral pontine lesion?
PPRF of lesion side is not functinoal - eyes do not move horizontally when head is turned in contralateral direction
Colt water in ipsilateral ear = no movement; contralateral ear = movement
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What do you suspect when cold water into the right ear produces no horizontal eye movements?
Right lateral pontine lesion - lesion of PPRF on right side
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Identify the lesion:
Right lateral pontine lesion
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Identify the lesion:
Bilateral midbrain lesion
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Identify the lesion:
Brainstem is intact!
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What occurs in a bilateral midbrain lesion?
Bilateral CNIII nuclei are not able to function properly so they are unable ot activate the medial rectus as to adduct the appropriate eye during head turns/calorics
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What innervates the meninges?
Trigeminal nerve
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What are components of cognition?
Attention
Language
Memory
Perceptual processing
Praxis - process of learning
Thought content
Executive function
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What is akinetic mutism?
Medial frontal lobe dysfunction
Loss of initiative/agency/motivation
Anterior cingulate
Can be caused by stroke, medial frontal mass lesion, trauma, degeneration
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What determines hemispheric dominance?
Language lateralization - handedness is an indicator
R-handed = 98% L-hemisphere language dominance
L-handed = 60% L hemisphere language dominance (more likely to have bilateral
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What cerebral hemisphere is more likely to be dominant for language in all patients?
Left
98% in right handers
~60% in left handers
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Patients with [...] handedness are more likely to have bilateral language representation in their hemispheres
Patients with left handedness are more likely to have bilateral language representation in their hemispheres
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What are the three parameters used to evaluate language dysfunction?
Fluency (grammar, syntax)
Repetition
Comprehension
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What is Broca's Area involved in?
Expression of language
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What is Wernicke's Area involved in?
Understanding spoken language
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What is the function of Wernicke's Area?
Detects auditory stimuli and identifies them as having linguistic value
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What is the function of the transcortical sensory areas?
They determine what information identified by Wernicke's area as having linguistic value actually mean
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What areas of the brain are important in comprehension of language?
Wernicke's Area - identifies auditory stimuli as having linguistic value
Transcortical Sensory Area - determines what this information means
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What areas of the brain are important for expression of language?
Broca's area - mediates final output for language
Transcortical motor area - assembly of language (syntax, etc)
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What areas of the brain are important for language repetition?
Arcuate fasciculus - connects Broca's and Wernicke's area
(it is possible to repeat something without understanding its meaning)
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Which area of the brain is important for the final output for language?
Broca's Area
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Which area of the brain is important for assembling language for output?
Transcortical motor area
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What is the function of the transcortical motor area?
Assembly of language for production (sends to Broca's area)
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What is Broca's Aphasia?
Non-fluent speech
Effortful/frustrated
Missing relational words (articles, conjunctions)
(may indicate emergence of non-dominant hemisphere expressive laguage)
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What would a lesion like this produce? 
Broca's Aphasia
Effortful/frustrated non-fluent speech that misses relational words
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What is a transcortical motor aphasia?
Expressive dysphasia
Impaired fluency
Preserved comprehensoin and repetition
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What would a lesion like this produce? 
Transcortical motor aphasia
Impaired fluency (preserved comprehension and repetition)
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What is Wernicke's aphasia?
Receptive dysphasia (impaired comprehension)
Expressive features are syntactically correct but semantically/lexically empty
Patients circomlocute (talk around words)
Paraphasic errors (semantic, phonemic)
Neologisms
Dictionary/lexicon is embedded in and around Wernicke's area
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What would a lesion like this produce?
Wernicke's aphasia
Impaired comprehension and repetition
Expressive features are syntactialy correct but may be circomlocutions (talking around objects) since Wernicke's area has the dictionary/lexicon in and around it
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What is Transcortical Sensory Aphasia?
Receptive dysphasia with impaired comprehension, but preserved fluency and repetition
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What would a lesion like this produce?
Transcortical Sensory Aphasia
Receptive dysphasia with impaired comprehension, but preserved fluency and repetition
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What is a conduction aphasia?
Impaired repetition but preserved fluency and comprehension
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What would a lesion like this produce?
Conduction aphasia
Impaired repetition but preserved fluency and preserved comprehension
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What are the steps that go into producing a memory?
Attention
Registration
Working memory
Evaluation for reference
Encoding
Storage/consolidation
Retreival of memories
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What are the different types of memory?
Echoic - \<5 seconds
Short term - seconds-minutes
Working memory - seconds-minutes
Long term minutes (explicit or implicit) - minutes-years
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What is echoic memory?
Lasts for 5 seconds or less, and is basically a perceptual echo - may facilitate registration
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What is short term memory?
Passively on-line maintenence of information over a period of seconds to minues
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What is working memory?
Complex concept that involves attentional circuits, task control and short term memory systems
Active on-line maintenence over a period of seconds to minutes
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What is long-term memory?
Covers a period of time from minutes to years
2 types:
Explicit/declarative - conscious or preconscious and can be semantic (factual) or episodic (from events)
implicit - non-conscious and includes procedural memory (skilled motor tasks), classical conditional, and emotional
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What is anterograde amnesia?
Impaired ability to form new memories
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What is retrograde amnesia?
loss of old memories (with or without temporal gradient)
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What is complete unilateral apperception?
Perceptual deficit that produces a visual field cut
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What is attentional asymmetry?
Perceptual deficit that produces neglect of one side - have in tact acuity, but need very effortful preservation of lesser preserved side to see what is happening there
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What is a sensory field cut?
Complete unilateral apperception (perceptual deficit)
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What is neglect?
Attentional asymmetry (perceptual deficit)
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What is extinction?
Asymmetry of perception of simultaneously presented stimuli (perceptual deficit)
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Which parietal lobe mediates attention only to the contralateral hemispace?
The dominant one (usually left)
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What parietal lobe usually mediates attention to bilateral hemispace?
The non-dominant one (usually right)
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To what does your dominant parietal lobe mediate attention?
The contralateral hemispace
(usually left parietal lobe)
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To what does your non-dominant parietal lobe mediate attention to?
Bilateral hemispace
(usually your right parietal lobe)
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What is the neuroanatomical basis for neglect?
Lesions to the non-dominant parietal lobe, since it is in charge of bilateral hemispace attentional capacity
Dominant parietal lobe only mediates attention to contralateral hemispace
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Lesions to which parietal lobe will produce neglect?
Non-dominant - it mediates attention to bilateral hemispace
Dominant lobe only mediates attention to contralateral hemispace
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How do you clinically assess neglect?
Line bisection task
Clock-drawing task
Writing
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What is agnosia?
Intact peceptual production but dysfunction of associational sensory processing which leads to **impaired recognition**
I.e. visual agnosia where there is an inability to visually recognize an object (can sometimes recognize object presented in other sensory modalities)
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What is anosagnosia?
The inability to recognzie one's own deficit, especially neurological ones
E.g. hemi-body neglect (will only dress half of yourself, etc)
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What is Anton's syndrome?
Cortical blindness + unaware of deficit due to occipital + parietal association area dysfunction
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What is dyspraxia?
The inability to perform a previously learned motor task
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What is the praxicon?
The store of motor programs (analogue of lexicon, but for actions)
Mostly found in the dominant side in the temporal-parietal regions
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Where is the praxicon typically located?
Dominant parietal lobe
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What is the neuranatomical basis of praxis?
Praxicon (dominant side) sends projections to SMA and other premotor areas
This will then send projections to the motor strips (bilaterally via corpus callosum), which then send projections down corticospinal system and to body
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What is constructional apraxia?
Inability to properly form objects
(i.e. inability to draw intersecting pentagons)
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How do you asses construction apraxia?
Ask patient to draw intersecting pentagons/cubes
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What are the three subdivisions of the prefrontal cortex?
Medial prefrontal cortex/Anterior cingulate - provides go/motivation/initiative/agency (dysfunction can cause aboulia - lack of desire/motivation)
Orbitofrontal cortex - provides brake/no-go (dysfunction = disinhibition syndrome)
Ventrolateral and dorsolateral prefrontal cortex - direct the 'how to go' - executive function (dysfunction = dysexecutive syndrome)
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Which subdivision of the prefrontal cortex is involved with directing motivation, initiative/ "go"?
Medial prefrontal cortex (anterior cingulate)
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Which prefrontal cortex subdivision is responsible for applying the brakes/"no-go"/inhibitoin?
Orbito-frontal cortex
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Which prefrontal cortex subdivision is responsible for providing executive function/"how to go"?
Ventrolateral /dorsolateral prefrontal cortex
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What is abulic-akinetic syndrome?
Dysfunction of medial prefrontal cortex/anterior cingulate
Loss of "go"/initiative/motivation center
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What is disinhibition syndrome?
Dysfunciton of the orbitofrontal cortex
Loss of inhibitory/'no-go' / brakes functionality
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What is dysexecutive syndrome?
Dysfunciton of the dorsolateral prefrontal cortex/ventrolateral prefrontal cortex
Loss of executive function/ "how to go"
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What is a great test for executive dysfunction?
Ask a patient to draw "ten after eleven" on a clock:
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What is a difference between Alzheimer's disease memory impairment and age-related memory impairment?
Alzheimer's has significant selective neuron death
Age-associated memory impairment has no significant neuron loss, but the synapse may be the site of the changes leading to functional decline
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What proteins are in neurofibrillary tangles of AD?
Tau
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What proteins are in the plaques seen in AD?
Beta amyloid protein
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What is thought to disrupt cortical-cortical circuits in AD?
Both tangles and plaques
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Where do tangles appear early in AD?
entorhinal cortex and CA1 - then become abundant in association cortex
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What is the function of the entorhinal cortex?
Gets input from the association areas and then informaiton flows through the hippocampus where new memories are laid down
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Where does neuron death start in AD?
Entorhinal cortex
When the circuit dies, access to neocortical information for new memories is compromised
The circuit also suffers in normal aging
Disruption of neocortical circuits is **required** for the dementia of AD
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What is required for the development of the dementia of AD?
Disruption of neocortical circuits
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Is it abnormal to find neurofibrilary pathology in the entorhinal cortex in patients over 55 years old?
Yes
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Which circuits are most vulnerable in AD?
Cortico-cortical circuits that mediate cognition (especially those in the temproal-prefrontal areas) are most vulnerable
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What happens to neurons that have tangles form in them?
They die
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What is the basis for the dementia of Alzheimer's Disease?
The inability of cortical regions to funciton together as a cohesive system
Complex thought requires complex circuitry and once the cortical connections deteriorate, it is not possible
(Tau bundles, Beta amyloid plaques)
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What cognitive functions are more sensitive to decline with age?
Prefrontal functions
Memory as mediated by the hippocampus and other medial temporal lobe areas also decline (but not as sensitive)
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What are prefrontal functions that decline with age?
Working memory
Attending to significant events
Reasoning ability
Planning
Guiding goal-directed behavior
Executive function
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What are some things that individuals with diminished prefrontal functions (due to aging/AD) have difficulty with?
Altering daily routine
Learning new strategies
Managing medications
Keeping track of finances and paying bills
Scheduling/keeping appointments
Being efficient at home activities like cooking, cleaning
Interacting socially
Working with their immediate environment
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What are some tests of medial temporal lobe (MTL) function?
Mostly recall tests - word recall after dealy/picture recognition after delay
fMRI with specific tasks - showing decreased activity in hippocampus
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When do we see deficits in top-down suppression of irrelevant information?
In normal aging
Associated with working memory impairment
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What are large mushroom spines?
Spines that have strong AMPAR-mediated currents that contribute to strong, **stable** synaptic circuits
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What are thin spines?
NMDAR-dominated, **highly plastic** can expand and stabilize or retract
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What are the memory spines?
Large mushroom spines
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What are the learning spines?
Small thin spines
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What types of spines and connections are AMPAR-mediated currents associated with/
Mushroom - strong, stable circuits
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What types of spines and connections are NMDAR-dominated currents associated with?
Long thin spines - plastic learning spines
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What occurs on a cellular/molecular level in age-related cognitive decline?
Loss of thin spines - age-related loss of structural plasticity
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What types of spines are lost in age-related cognitive decline?
Long thin spines that are associated with learning
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What is a potential therapeutic target for the preservation of thin spines?
Estrogen receptors are present - estrogen may be protective
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What changes are seen in the hippocampus with aging?
No synapse loss or shift in size of total axospinous synapses
Changes in numbers of perforated synapses and multi-synaptic boutons - degree correlated with cognitive decline
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What are some identifiable pathological changes seen in most elderly individuals?
Cortical atrophy
Enlarged ventricles and cerebral cortical sulci
Cell loss
Amyloid plaques
Neurofibrillary tangles
Lewy bodies, etc
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Does the level of neurological decline correlate with brain pathology?
Not necessarily
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What defines Mild Cognitive Impairment/Mild Neurocognitive Disorder?
Impaired cognition in one or more domains and to a lesser degree than in dementia
**Do not** interfere with capacity for independence in everyday activities
(may be prodromal state of dementia) - most develop
1/3 improve
