Exam 3 Flashcards
(224 cards)
1
Q
Inputs that converge on LMNs
A
-Upper motor neurons (influenced by Basal ganglia and cerebellum)
—-Cortex (corticospinal tract)
—-Brainstem tracts:
——-Reticulospinal
——-Tectospinal
——-Vestibulospinal
- Spinal cord pattern generators
- Reflexes
*More upper motor neurons, CPG neurons and reflex connections than LMNs
—LMNs integrate all of these inputs at their dendrites to determine whether to fire an AP
—AP of LMN always triggers contraction of skeletal muscle
**All communicate via VA/VL of the thalamus
2
Q
Central Pattern Generators
A
- Networks of interneurons in the brainstem and SC that govern rhythmic, patterned movement
- Don’t involve tracts
- Humans rely on these for walking and breathing
- One part of network is inhibited, while the other is activated
*Higher areas tell CPGs to “start” or “stop” sequrences w/o having to command every single muscle involved
3
Q
Pyramidal System
A
-Set of motor neurons in the cortex that are critical for voluntary movement of the body
—Areas: primary motor cortex, premotor cortex, sensory areas
- Originate in cortical layer 5
- Axons comprise the cortical efferent component of the brainstem
4
Q
Cortical Efferent System
A
- Axons of the pyramidal system comprise it
1. Cell bodies- layer 5
2. Axons in the corona radiata
3. Axons in the internal capsule
4. Axons in the cerebral peduncles
5. Axons in the longitudinal fibers of the pons
6. Axons in the pyramids
7. 80% decussate, 20% don’t–> form lateral and ventral corticospinal tracts (respectively)
5
Q
Upper Motor Neuron Cell Groups in the Brainstem
A
*Tracts travel in the ventral white matter of the spinal cord
-The tectum
—At level of the superior colliculus
—Origin of the tectospinal tract–> head turning reflexes in response to auditory and visual stimuli
-The reticular system
—Form the medullary and pontine reticulospinal tract
—Control upright posture by altering the activity
—–Trunk and proximal limb muscles
-The vestibular nuclei
—Part of the vestibular compex serves as origin of the vestibulospinal tract
—Mediate righting movements
***In the event of damage to axons of the pyramids, distal muscle movement is impacted (fingers) but not gross movement
6
Q
Vestibular System
A
- Balance and spatial orientation
- Origin of the vestibulospinal tract
*Critical component of the motor system
*Inter-related to the cerebellum
-Inner ear structures–> tunnels carved into temporal bone, lined with membrane and filled with endolymph (K+ rich, important for hearing and balance)
—Transduces sound and percieves balance
- Projects into brainstem on CN 8
- Middle ear= ossicles
7
Q
Cerebellum
A
**Refines movement based on comparing motor plan with peripheral feedback
—Recieves info from vestibular nuclei and vestibular nerve, cortex, and body
- Integrates balance and other spatial information w/ body position
- Provides feedback to UMN in cortex about real or intended movements
- Movement planning
**Critical component of the motor system
**Inter-related to the vestibular system
****Like a backseat driver, tells cortex when it is making a mis-calculation, but cannot alter the motor plan itself
8
Q
Basal Ganglia
A
-Important for selection of motor plans and the inhibition of unwanted motor plans
**Critical component of the motor system
- Parts: Caudate, putamen, globus pallidus, subthalamic nucleus, substantia nigra
- Dorsal portions: circuits linking all of the cortex to UMN pools in regulation of voluntary movements (modulate beginning and end of movements)
- Ventral portions: Involved in limbic and behavioral loops w/ prefrontal cortex (modulate beginning and end of throughts/plans)
*Caudate+ Putamen= striatum–> involved in movement and behavioral disorders
9
Q
The Inner Ear- Vestibular Apparatus
A
- Has different parts for sensing different directions of force
1. Semicircular canals–> Angular acceleration of the head
—X, y, z direction
—Start and stop of motion
- Otolith Organs= urticle and saccul–> Gravity and linear acceleration
*Haircells transduce motion
10
Q
Otolith Organs
A
- Utricle and Saccule–> have hair cells anchored into a membrane with calcium carbonate crystals (Otoliths) on the surface
- Head movement causes the crystals to slide, bending hair cells and causing changes in membrane potential (interpreted as movement)
—Alters the activity of CN 8
-Detect static equilibrium-> gravity detectors, vertical and hortizontal acceleration (fire all the time, up or down when stimulus changes)
11
Q
Semicircular Canals
A
-In the macula of each canal is a region of hair cells
—One end of hair projects into a gel mass (cupola) that bends with endolymph movement, then springs back into position
—Hair cells bending as the cupola bends leads to either a depolarization or hyperpolarization
—Hair cells release NTM on sensory neurons of CN 8, so bending of the hair cells causes changes in the pattern of APs being sent to the CNS
**Because the cupula springs back into position right away, best at detecting changes in motion (acceleration)
12
Q
Vestibular Nuclei of the Brainstem
A
-Vestibular portion of CN 8 synapses here and the cerebellum
- Ascending projections from here to thalamus and cortex are responsible for perception of movement
- Feed into the MLF and initate eye movements in the direction opposite to the direction of head movement
- Descending MLF to the cervical spinal cord can direct head movements, and widespread connections of the vestibulospinal tract to the ventral horn trunk muscles can direct “righting” movements
13
Q
Pathways into the cerebellum
A
- Spinocerebellar Pathways
–Bring info about position of individual body partd
- Vestibulocerebellar pathways
–Bring info from vestibular organs about whole body position in space
- Corticopontocerebellar pathways
–Brings the cortical plan into the cerebellum
- Olivocerebellar pathways
–Brings info to the cerebellum as part of learned repetitive movements
14
Q
Pathways Out of the Cerebellum
A
-Main output from the cerebellum is via the Superior cerebellar peduncle
—Contralateral thalamus (VA/VL)
—Contralateral red nucleus
-Other outputs through other peduncles influence activity of vestibulospinal and reticulospinal pathways
15
Q
3 Zones of the Cerebellum
A
- Vestibulocerebellum–>Control of balance and eye movements; performing, monitoring, and error prediction for trunk and eyes
–Cortex area= vermis (medial)
–Deep nucleus= fastigal
- Spinocerebellum–>Performing, monitoring, and error prediction for the limbs
–Cortex area=Paravermis (Lateral to vermis)
–Deep nucleus= Interposed
- Pontocerebellum–> Motor planning and learning (cognition)
–Cortex area= Lateral hemispheres (most lateral)
–Deep nucleus= dentate
16
Q
Cortical regions of the Cerebellum and their associated nuclei
A
- Vermis–> fastigial nuclei
- Paravermis–> interposed nuclei
- Lateral hemisphere–> Dentate nuclei
*Neurons of the deep nuclei are output cells of the cerebellum
-Flocculus and nodule= flocculonodular lobe–> communicates with the vestibular pathways from the brainstem
17
Q
General Cerebellar Circuit
A
-All inputs to the cerebellum are excitatory
—Spinal input ipsilateral
—Vestibular input ipsilateral
—Olivary input contralateral
—Pontine input contralateral
- Output of the cerebellar cortex is inhibitory from purkinje cells to deep nucleus
- Output of cerebellum deep nuclei is excitatory to thalamus and red nucleus
–Contralateral via SCP
18
Q
Principal Cerebellar Efferents
A
- Limb and planning areas of cerebellum feed back to cortex
- Midline postural areas project to vestibular nuclei (thus, vestibulospinal tract centers) in the brainstem
19
Q
Organization of the Cerebellar Cortex
A
- 3 layers:
1. Granule cell layer (deep)
2. Purkinje cell layer
3. Molecular layer (superficial) - 5 cell types:
–Purkinje cell (projection cell) is the main cell in the cerebellar cortex; it projects to and inhibits cells in the corresponding deep nucleus
–Granular cells= projection cell
20
Q
Two major input fiber types in the cerebellar cortex
A
-Climbing fibers:
–Only come from the inferior olive
–Innervate the purkinje cells DIRECTLY by synapsing onto the cell body close to axon hillock
–One climbing fiber innervates only a few purkinje cells
-Mossy Fibers:
–Come from all other inputs
–Indirectly innervate purkinje cells via granule cells (project up to molecular layer)
–One mossy fiber activates hundreds of purkinje cells on their dendrites in the molecular layer
21
Q
The Cerebellum and Movement
A
- Ensures movements are smooth and allow you to learn and refine new motor sequences
- When the cortex plans a movement, it sends the plan to the cerebellum
—Cerebellum simulates the action, looks for where alterations need to be made, makes adjustments and resimulates, all B4 action commences
-Example: It takes less time to reach for something close then something far; athletic visualizstion exercises
**Sequence of activation in voluntary movements
- Corticopontocerebellar–> motor planning
- Dentatothalamocortical–> how movement is adjusted
- Corticospinal–> Motor output
- Olivocerebellar–> learning movement/relive it
22
Q
The Red Nucleus
A
-Origin of the descending motor pathway controlling flexion of big muscles of contralateral upper limb (Not digits)
—Rubrospinal tract= gross movements
- Influence of rubrospinal tract= minor in humans if corticospinal tracts are fxning
- Significant involvement in motor learning loops w/ inferior olivary nucleus
23
Q
Inferior Olivary Nucleus
A
-Works w red nucleus in a cerebellar loop
—Loop is associated w/ learning a repetitive motor activity
—Ex: swinging a golf club
24
Q
Motor Learning Loop
A
-Red nucleus–> inferior olivary nucleus–> cerebellum–climbing fibers–> deep nuclei of cerebellum— SCP–> contralateral red nucleus
25
Pathway of Activation of Movement Simplified
-Cerebellum influences upper motor neuron cell groups
---Corticospinal
---Reticulospinal
---Vestibulospinal
---Rubrospinal
- UMNs influence LMNs in brainstem or spinal cord
- LMNs synapse directly to skeletal muscle
\*Basal ganglia also have an indirect role in modulating motor activity, but do not directly influence LMNs
26
Relative Positions of the Caudate, Putamen, and Globus Pallidus
-Caudate and putamen separate as you move back along the lateral ventricle
---Become separated by the internal capsule during development
- Globus pallidus appears medial to the putamen
- Rostrally, the caudate and putamen lie together
---Work as a unit called the striatum
---The nucleus accumbens= the most ventral and anterior part of the striatum (disappears as we move more posteriorly)
27
Basal Ganglia Connections
1. Inputs from widespread cortex to the striatum
--Multimodal association cortex
--Motor and somatosensory cortex
--Visual association cortex and auditory association cortex
--Frontal lobe areas for eye movement
2. Striatum regulates activity in globus pallidus
--Striatum= input nucleus for the basal ganglia
3. Globus pallidus inhibits thalamus
4. Thalamus projects back to cortex frontal lobe
28
The Direct Pathway- Basal Ganglia circuitry
1. Cerebral cortex excites the striatum
2. The striatum inhibits the internus of the globus pallidus (GPi)
3. The GPi sends less inhibitoy messages to the thalamus
4. The thalamus can send more excitatory messages to the cortex--\> More movement
\*\*\*Overall, inhibition of the thalamus is turned down
\*\*Inhibitory neurotransmitter of globus pallidus= GABA
\*\*Corticothalamocortico-loops
29
The Indirect Pathway
1. Cortex excites the striatum
2. Striatum sends inhibitory message to the globus pallidus external (GPe)
3. GPe cannot fire, so it cannot send inhibitory messages to the subthalamic nucleus--\> STN fires more
4. STN sends excitatory messages to the GPi--\> GPi sends more inhibitory messages to the thalamus
5. Thalamus sends less excitatory messages to the cortex
\*\*Overall, indirect pathway will repress movements
30
Effects of the Subthalamic Nucleus on the corticothalamocortico-loop
- Uses glutamate as a NTM
- Increases the inhibitory drive on the thalamus by exciting the GPi
- Problems in the subthalamic nucleus--\> increase in overall activity in the circuit--\> hyperkinesa
\*\*Ballismus= people cannot control their limbs--\> flinging and jerking movements
\*\*OVERALL, STN turns movement down by activating GPi, turns down the thalamus
31
Influence of the Substantia Nigra
-Dopamine from the substantia nigra leads to an increase in thalamic activity through:
--Excitation of striatum to GPi (uses D1 receptors to inhibit GPi)
--Inhibition of striatum to GPe
---Inhibits output of the STN (D2 receptors inhibit the indirect pathway)
-Problems with the substantia nigra--\> decrease in thalamic drive on cortex--\> hypokinesa
32
Basal Ganglia, Movement, and the Cortex
1.When the striatum is at rest-\> the globus pallidus is tonically active-\> the VA/VL complex of the thalamus is inhibited--\>no excitation of the motor cortex
## Footnote
2. When the striatum is active--\> the globus pallidus is transiently inhibited--\> VA/VL of thalamus is disinhibited so other inputs can excite it--\> excitation of the motor cortex
33
Huntington's Chorea/Disease
-Autosomal dominant inherited disorder caused by degeneration of cells in the caudate nucleus and cerebral cortex
---Loss of indirect pathway--\> too much movement
-Symptoms commonly begin after child-bearing age and include a progressively developing chorea and dimentia
---Hyperkinesa
-Death w/in 15-20 years
\*Affected individuals--\> Large LVs
34
Parkinson's Disease
- Loss of substantia nigra dopaminergic input to the striatum
- Leads to hypokinesia and bradykinesia--\> too little movement and slowness of movement
---Difficulty initiating movement
-Parkinson's gait= rigid arms, slow shuffling steps
35
Basal Ganglia and the Selection of Movement
-Contribution of basal ganglia to movement:
--Direct pathway--\> releases an inhbitory "brake" on an intended movement
--Indirect pathway--\> maintains/applies an inhibitory "brake" on movements
---Neurons in a surroundregion of the GPi are driven by excitatory inputs from the subthalamic nucleus--\> supresses a broad set of competing motor programsthat would interfere with intended movement
-Overall, direct pathway disinhibits the thalamus, indirect pathway disinhibits the STN
36
Basal Ganglia Connections with the Cortex
- Basal ganglia regulates pools of UMNs from cortex
- Multiple loops--\> body movement loop, oculomotor loop, prefrontal loop, limbic loop
\*Caudate nuc +putamen= dorsal striatum
\*GPi+ SNr= Dorsal pallidum
37
Limbic System
- Collection of brain structures near the top of the brainstem, bordering the ventricles
- Involved in emotion and memory
38
Function of the Limbic System
- Emotional coordination and regulation
- Primitive memory system for sensory experiences
---Recognizing situations with high relevance to survivial and reproduction and regulating avoidance/approach, action/counteraction, in these situations
---Threat/opportunity tracking system
- Close relationship to olfactory system--\> smell evokes emotional memories
- Strong ties into associations areas of cerebral cortex
---Prefrontal cortex and posterior association cortex (parietal lobe)
---Behavioral regulation--\> impulsivity vs postponement of gratification
-Limbic areas usually inhibit other limbic areas
-----All limbic areas influence the hypothalamus
39
The Triune Brain
- 3 stages of evolutionary development of the brain
1. Reptilian (Brainstem)- reflexes and primitive survival functions
---Feeding, digestion
---Sexual development and reproduction
---Autonomic fxns
2. Paleomammalian (limbic system): emotion and memory
---Fear, anger, love, anxiety, aggression
---Remembering experiences that caused these to guide future actions
3. Neomammalian (Neocortex): Highest level functions
---Thought, reasoning, analysis, self-regulation
---Overcoming the motor plans dictated by the lower areas
40
Strengths of the Triune Brain
- Explains how areas of the reptilian brain are arranged into nuclei or reticular formations
- Many areas of the limbic system have a 3-layered structure
- Cortex does seem to produce concious sensation
41
Weaknesses of the Triune Brain
- Some fxns span more than one of the stages
- Circuits sub serving aspects of emotion and emotional regulation extend through all 3 areas
- Places mammals at the top of the "brain game"--\> however, evolution branches and is NOT linear
- Reptiles and birds have neocortical regions, they have just adopted a diff structural plan for it
42
Emotions
-Behavior-Emotions guide our plans for action
--Ex: fear leads us to take precautions
-Physiology-Cause changes to our bodies
--Ex: goosebumbs, sweating
-Feeling-Emotions are felt; often mapped on to the body's own somatosensory system
--Ex: The crushing feeling of heartbreak
\*\*We cannot decide our emotions, but we can deal with them and reason through them--\> emotional intelligence
43
Sensory Association Corticies
- Insula, parietal lobe
- Various different theories of emotions emphasize one aspect or the other
- Emotions and feelings may be tied to social communication, honest signals for each other to learn from that are difficult to fake
44
Limbic Areas
- Located around the top of the brainstem, and boarders the lateral and third ventricles
- Major limbic areas= hippocampal formation, amygdala, cingulate cortex
- Other structures can have limbic functions but are not entirely limbic
---Ex: hypothalamus
-Fiber tracts (white matter) interconnecting these areas
--Fornix, stria terminalis, stria medularis thalamicus, cingulum
-----Form C shape
----Part of the fornix makes up the foramen of monroe
45
The Limbic System in Relation to Ventricular System
- Hippocampus lies inferior and medial to the inferior horn of the lateral ventricle; connected to the basal forbrain nuclei and hypothalamus via the fornix
- Amygdala sits anterior and superior to the lateral/temporal horn of the LV
46
Responses Involve Different Combinations of Motor Output
- Volitional movement has more access to the somatic motor system
- Emotional expression system has more access to the autonomic NS and some parts of the somatic NS
\*Movement and expression systems are separated at their higher levels, but converge at lower levels
---We don't have concious control of our emotions, yet we can wrestle with how our emotions affect our actions
47
Hypothalamus and the Limbic System
- Limbic system regions are densely connected to the hypothalamus
- Cortex, Basal forebrain, amygdala, and hippocampus feed into the hypothalamus
- Hypothalamus sends output to pituitary, brainstem regulatory areas, and autonomic NS
\*Hypothalamus has subnulcei that mediate emotional behavior and the endocrine system--\> connections to brainstem and CN nuclei
48
Spatial Relationship Among Key Limbic System Components
- Ventral forebrain structures
- Hypothalamus and basal forebrain= centrally located
49
Neocortical Components of the Limbic System
-Orbitofrontal cortex--\> social and emotional decision making
---Flavors info from olfactory system
-Insular cortex--\> "feelings"- mapping of emotions onto the body
---When we experience emotions as feelings
50
Cortical Comonents of the Limbic System
- Parahippocampal gyrus-- memory
- Cingulate gyrus
----Anterior- motivation; other areas involved in emotional expression/ behavioral responses
-Medial Prefrontal Cortex- Involved in inhibiting learned emotional responses
---Emotional control/regulation
51
The Olfactory Pathway
1. Air-borne odors dissolve in fluid in nasal cavity
2. Dissolved chemicals open ion channels and depolarize the olfactory receptor neurons- leads to formation of APs encoding smell info
3. Nasal olfactory receptor neurons project through the cribiform plate (traveling via CN 1) synapse directly onto the olfactory bulb neurons
4. Olfactory bulb neuron's axons extend through olfactory tracts and into the brain
52
Olfactory Receptors Proteins
-Unique because:
---Found on neurons; cells for other senses are non-neuronal and pass the signal to neurons
---Life span= 60 days; long compared to other senses
---Regenerated throughout life through the division of basal stem cells
-We can detect over 1 trillion different odors using 400 receptors
---Combo of receptor activations determine smell
-Bipolar= part projects into fluid of nose, part synapses onto the glomerulus (where signals of 1st order olfactory receptor neurons pass to 2nd order in olfactory bulb mitral cells)
----Axons of mitral cells make up the olfactory tract
53
The Olfactory Bulb
- CNS tissue
- 2nd order neurons (Mitral cells) send axons back via olfactory tract
\*Smaller in humans than animals
-Neurons of the olfactory bulb (mitral cells) synapse directly into limbic areas of the cortex
---All other senses use thalamic nuclei , don't synapse directly
---Therefore, smell= 1st order sensory receptor--\> 2nd order in CNS--\> limbic system
54
Where do axons of the olfactory tract synapse?
1. Primitive (limbic) cortex; olfactory tubercle and the piriform cortex (anterior temporal lobe)
---Awareness of smell
---only sensory system w/ direct connection to the cortex
2. Medial dorsal nucleus of the thalamus--\> relays to orbitofrontal cortex in frontal lobe
---Concious discrimination of smell
----Comparison w/ memory bank--\> ID of smell
----No clear topography of good vs. bad smell
3. Hypothalamus and limbic areas via entorhinal cortex and hippocampus
---Memory and emotional components of smell
\*\*Extra: directly connects w/ amygdala body and parahippocampal gyrus
55
Two Forms of Long-term Memory
- Medial temporal lobe= critical in forming memory
1. Explicit (declarative)--\> Facts (semantic) + Events (episodic)
-----Medial temporal lobe, hippocampus
2. Implicit (Nondeclarative)
----Priming--\> Neocortex
----procedural (skills and habits)--\> Striatum
----associative learning (classical and operant conditioning)---\> Amygdala and cerebellum
----Nonassociative learning: habituation and sensitization--\> Reflex pathways
56
Stages of Memory Formation
1. Stimulus --perception--\> sensory memory\*\*---attention---\> short term memory\*\*---encoding---\> LTM\*\*
\*\*= Susceptible to forgetting
-Short term and long term memory can be retrieved
57
Hippocampal Fomation
- Made up of the hippocampus and parahippocampal gyrus
- Recieves input from most assocation areas of the brain
- Neocortical inputs to the hippocampus--\> get highly processed emotionally relevant sensory perceptions
---Cholingergic from basal forebrain via fornix
---Noradrenergic from locus ceruleus via median forebrain bundle
---Serotonergic from raphe via the median forebrain bundle
---Dopaminergic from the midbrain tegmentum via median forebrain bundle
\*\*NTMs help form declarative memory
58
Hippocampus and Memory
-Memory of concious facts (explicit memory, NOT motor memory)
---STM--consolidation--\> LTM
---Retrieval of LTM doesn't require the hippocampus
-----LTM stored in neocortical areas where sensation was first percieved
\*Patient HM: Hippocampus removed bilaterally--\> explicit memory harmed but not motor memory
59
Anterior-Posterior Differences in the Hippocampus
- Anterior: Active when viewing novel info
- Posterior: Active when viewing familiar material; LTM formation?
60
Hippocampal Formation and Navigation
- Interaction in 3D space
- L/R differences
---L= encoding language related information
---R= encoding spatial relationships
\*Cab driver study--\> Hippocampus= bigger after memorizing cab routes to become a cab driver
61
The Amygdala
- L and R; Lies at anterior end of the inferior horn of the LVs; deep to uncus
- Recieves input from sensory cortex, olfactory pathways and basal forebrain
---Sensory cortex info used to determine fearful vs nonfearful stimuli
----Direct connections from diff regions of thalamus
-Involved in generating fearful or agressive responses (link btwn fear and agression)
---Also active during feeding and reproduction
\*Lesions--\> docile animals w/ no fear
62
Outputs of the Amygdala
-Project to areas that are important for emotional expression
----Parabrachial nuclei and some cranial nerve nuclei (facial expression)
-Stria terminalis--\> connects amygdala to basal forebrain nuclei
---BNST-\> Keeps track of fearful stimuli, involved in anxiety
-Projects to pituitary and places of autonomic fxn (ex: vagus nerve)
----\> Stress hormones
63
The Fornix
-Bi-directional white matter tract that carries info btwn hippocampus and hypothalamus/basal forebrain areas
---Continuous w/ the hippocampus
- C-shaped
- Connects to septal area in basal forebrain, mamillary bodies of the hypothalamus, and nucleus accumbens
64
Basal Forebrain Nuclei
- Grey matter that includes: nucleus accumbens, septal nuclei, nucleus basalis of meynert
- Located anterior and lateral to hypothalamus; around anterior portion of basal ganglia
\*\*\*\*Nuc accumbens= part of basal ganglia and limbic system
-Nuc accumbens begins at olfactory tubercle (anterior boundary); in a coronal section joins the anterior putamen with the anterior caudate
65
The Nucleus Accumbens
-Nuc accumbens begins at olfactory tubercle (anterior boundary)
---Lies inferior to head of caudate and rostral and of the putamen
-Involved in pleasure pathways and substance abuse
---\> Electrical stimulation induces profound sense of well-being
-Recieves dopaminergic projections from the VTN
66
Septal Nucleus
- Involved in reward and reinforcement w/ nuc accumbens
- Stimulation--\> Sexual sensations
- Location- Ventral to septum pellucidim, near anterior commissure
---Connects w/ amygdala via stria terminalis
---Connects w/ Habenula via stria medullaris thalamicus (bidirectional)
---Connects w/ hippocampus via fornix
----Colinergic projections
67
Drug Dependency and the Nucleus Accumbens
- Most drugs of dependency act on the dopamine circuit to the nuc accumbens
- Nicotine causes VTN neurons to fire faster
- Opioids and ethanol block transmission from inhibitory neurons that influence VTN neurons
- Cocaine inhibits reuptake of dopamine
- Cannabinoids--\> euphoric sensation
68
Nucleus Basalis of Meynert
- Activated with new stimuli--\> Arousal, sustained attention
- Cholinergic projection from here to cortex is important for cognition
-----Loss= dementia
-Location- Base of forebrain inferior to anterior commissure
69
Types of Injury in the Nervous System
- Disease of the nervous system
- Metabolic disorders
- Local environmental disruptions
70
Diseases of the Nervous System
- Result of genetic and environmental interactions
- Symptoms are highly varied and depend on regions of the nervous system affected
Ex: Neurodegenerative, autoimmune
71
Metabolic Disorders
- Oftem results of systematic problems that affect neural (and non-neural) tissue
- Widespread damage by may affect vulnerable neurons
- Blood supply issues, chemical imbalances, vitamin deficiencies
- Ex: Diabetic neuropathy
72
Local Environmental Disruptions
- Focal damage or disruption caused by external forces acting on the nervous system
- Symtoms= highly varied and depend on the regions of the nervous system affected
- Can occur quickly or over time
Ex: axonal injury
73
Themes of Nervous System Injury
1. Due to convergence in motor systems, injury can lead to imbalances in activity in one circuit over another
---Ex: Pupil size, eye position
2.Because of divergence in processing, information has more than one way to get into the brain
---Ex: Concious vs reflex processing of vision; can mask symptoms of an injury
3. Evolution left us with parallel, redundant pathways
---Ex: Fine touch via. DCML vs Crude touch via Anterolateral Tract
4. Slow changes to the Nervous System are forgiving, rapid changes are less forgiving
---Ex: Chiari malformation vs Brian Herniation
5. Perception is different from sensory input and is cortex dependent
--Ex: touch on sholder; not aware of reflexes until they are percieved
74
Chiari Malformation
- Cerebellar tonsils are pulled through the foramen magnum slowly as the brain develops
- Nonfatal
75
Brain Herniation
- Rapid displacement of the brain through foramen magnum due to pressure difference
- Fatal due to brainstem compression
76
Structure of a Peripheral Nerve
- Epineurium= outer layer
- Perineurium= connective tissue around fasicles
- Endoneurium=Around axons and schwann cells
---Axons are myelinated/ensheated by schwann cells
-Blood vessels w/in nerves supply axons, glia, and connective tissue
\*Larger nerves have more fasicles and are myelinated; smaller=less fasicles and are ensheathed
\*Sensory vs motor axons look identical; but any one axon is either sensory OR motor, not both
77
Two Main Components of the PNS
-Sensory and motor neurons
---Bundled together in peripheral nerves with sympathetic postganglionic axons
---DRG cells- Sensory nerve endings at muscle, AP occurs at trigger point and heads toward CNS
---LMN- cell body in CNS, synapses to muscle and releases ACh for muscle contraction; trigger point near cell body
---Sympathetic post gang.- Pregang in CNS releases ACh on postgang; postgang releases norepi and epi onto smooth and cardiac muscle (BVs)
78
Peripheral Neuropathies
- Conditions that result when nerves that carry messages btwn the brain and SC from and the rest of the body are damaged or diseased
- Manifests probs in somatic sensory, somatic motor, and autonomic
----Depends on specific nerve and how it is injured
\*Damage affects nerves, not single axons--\> sensory and motor issues, not just one
79
Paresthesia
- Damage to peripheral sensory axons in a nerve that leads to altered sensation
- Sensory signs: tingling, burning, numbness (anesthesia)
80
Damage to peripheral sensory components in a nerve
1. Damage to cell body:
--Diseases that target sensory neurons
--Trauma to DRG (herniated disk, broken bone)
2. Damage to sensory axons from muscle
--Abnormal reflexes or no reflexes because sensory limb is absent
--Abnormal muscle fxn
3. Damage to sensory axons from skin
--Abnormal pain, touch, vibration, temperature, etc.
81
Damage to Peripheral Motor Axons
-Leads to motor unit failure
---Movement cannot occur because APs cannot reach muscle
---Motor unit= LMN and all the muscle fibers it innervates
82
Lower Motor Neuron Syndrome
- Signs resulting from LMN damage
1. Atrophy=wasting of muscles that aren't activating
---Normally, axons keep muscles alive w/ trophic factors
2. Paresis= Muscle weakness if some motor axons to muscle are damaged
3. Flaccid paralysis= If all motor axons to muscles are damaged
---Muscles cannot contract
4. Areflexia= loss of reflex activity in the muscle
\*Fasciculations and Fibrillations
83
How do we determine which muscle or skin area is affected by peripheral damage?
- Determined by which spinal nerve or peripheral branch is affected
- Effects of damage closer to SC are different than those closer to target
84
The Median Nerve of the Brachial Plexus
- Proximally (close to origin near sholder), a peripheral nerve contains many fasciles of axons
- Fasciles branch away from the parent nerve as it travels down the limb
- Nerve= smaller in diameter distally and only contains a few remaining fasicles
\*Therefore, damage that is more proximal leads to larger area affected and longer time for repair; distal damage= less area affected and less time for repair
85
Chromatolysis
- Reponse at cell body due to damage of an axon
- Characterized by fragmentation and dispersal of Nissl bodies and displacement of the nucleus
----Growth cone grows back out through nerve to re-innervate target
- Occurs in DRG if sensory, ventral horn if motor
- Nissl bodies= rough ER that make membrane-bound proteins
--Disperse throughout cell body, increase surface aea--\> need to create new proteins to create new axons
-Schwann cells and macrophages clear debris
86
Wallerian Degeneration
-Response of axon distal to injury
---Dissolving of axon disconnected from cell body
- Endoneurium remains intact
- Schwann cells abandon myelinating and differentiate into repair mode
----Help phagocytes clear debris
----Release trophic factors to help "stump" regrow
87
Guiding of Axon Regrowth in PNS
- Guided by the prescence of the remaining endoneurial/basal lamina tube
- Regeneration= 5 mm/day--\> quick
- Axonal sprout keeps schwann cells alive and keep dividing
--Growth cone extends distally along the surface of schwann cells
-----Once cone passes schwann cells, they revert back to myelinating schwann cells
88
Surgical Repair of Peripheral Nerves
- Via nerve suture
- Recovery of function is not guaranteed
- Better recovery when repaired immediately after injury; better recovery in younger people
- Surgeons re-align fascicles so motor and sensory match up
89
Nerve Compression Syndromes
- Impingement of nerves by neighboring structures
- If compressed long enough, damage may be permanent (LMN syndrome)
- Ex: Carpal tunnel syndrome= compression of median nerve entering wrist--\> atrophy of muscles at base of thumb
---Treatment= removing source of compression
-Ex: Ulnar nerve entrapment
---Muscles around the ulna become enflamed and compress the ulnar nerve--\> sensory problems in pinky and finger, motor problems in hand
90
Nerve Compression Proximally
- Problems at the vertebral column
- Spinal nerves exit the vertebral column via interverterbral foramina
- Intervertebral disks facililate movement of spine and absorption of stress--\> Herniation or slipped disk can lead to compression
- Osteophytes- Extra bone growth due to abnormal stress
91
Brachial Plexus
- Formed from ventral rami of C5-T1
- Innervates muscles and skin of the upper limbs
- Median nerve= one main nerve from arm to plexus
- Injury pattern= different when distal vs. proximal to plexus
----Skin innervated by damaged nerve= patchy areas of paresthesia; muscles innervated by that nerve will be weaker but not paralyzed
\*Damage distal to plexus= paralyzes individual muscles and patches of skin innervated by that nerve
\*Damage proximal to plexus= weakens any muscle this nerve contributes to, and denervates a dermatome
92
The Neural Tube
- Forms at the midline of an embryo
- Blocks of mesoderm (somites) form lateral to each side
- A muscle is formed from muscle cells from more than one somite
\*Segment of the neural tube= segment of the SC
--Each segment will innervate a patch of skin (dermatome) and muscle (myotome)
93
Dermatome
- A stripe of skin innervated by one pair of DRG cells, and thus one PAIR of spinal nerves
- Consequence of proximal injury= loss of dermatome
- Distal injury= loss of patch of dermatome, but not all of it
94
Damage to the Autonomic Nervous System
-Because sympathetic and parasympathetic axons take different routes to their targets, they can be damaged separately
----All about balance- when one is inhibited, the other will dominate
-Parasympathetic pregang.--\> travel CN 3,7,9 and 10 or in spinal nerves S 2,3 and 4
----Affect eyes, salivary glands, heart, bladder, and genitals
-Sympathetic= T1-L2
---Go from sympathetic chain ganglion b4 target
95
Damage to Parasympathetic Nerves
- Damage to CN nerves 3,7,9,10-- more than just parasympathetic probs
- Damage to pelvic splanchnic nerves- affect parasympathetic innervation to bladder, rectum, and erectile tissue
96
Damage in Sympathetic Nerves
-Sympathetic axons traveling to head innervate skin, blood vessels, and targets of the eye
--Affected if you damage top of symp chain
- Sympathetic axons travelling in splanchnic nerves regulate organ fxn
- Sympathetic axons travelling in peripheral nerves innervate skin and blood vessels
---If damaged: Probs with organ function; ex= increased gut motility
---If damaged: flushed, warm skin that won't become pale in the cold
\*Sympathetics provide tonic constructive tone that is lost with damage
97
Horner's Syndrome
-Presentation resulting from damage to sympathetic pathways to the head
---Compression in thorax or neck (top of symp chain)
-Damage on one side= effects seen on same sife
----Constricted pupil= loss of dialation
----Droopy eyelid= loss of innervation of smooth muscle in lid
----Flushed skin= loss of sympathetic vasoconstriction axons
----Lack of sweating= loss of sympathetic innervation of sweat glands
98
Diabetes
- Dysregulation of glucose levels in the body
- Characterized by high levels of glucose in the blood
- Type 1: inability to produce insulin
- Type 2: insulin receptors not sensitive to insulin
---Accomanied by other health probs such as heart disease, lipid probs, etc
\*Metabolic disorder that damages the PNS
99
Effects of Diabetes
- Vessel disease= affecting blood supply to nerves and ganglia
- Prolonged exposure to high glucose levels alters metabolism in neurons
---Nerve BVs are occulded-\> lack of oxygen
-Vessel disease can lead to neuropathy--\> tingling or burning sensation in distal muscles/ digits
---Eye= damage to retina--\> blindness
---Pressure ulcers that don't heal due to poor blood flow and damage to sensory neurons
100
Examples of Muscle Paralysis or Weakness That Leads to Imbalance of Acvitivity in a Body Area
1. Autonomics of eye
--Loss of sympathetics--\> pupil will constrict us parasymp=unopposed
--Loss of para--\> pupil dialates cuz symp= unopposed
2. Eye position
--Paralysis or paresis of LR--\> eye will deviate medially due to medial rectus muscle dominating (and vice versa)
3. Tongue Position
--Damage to CN XII on one side--\> oppisite side dominateds and tongue deviates to injured side
101
Glia's Role in CNS vs PNS regeneration
- Axonal regeneration= PNS not CNS
- In PNS- immune cells and schwann cells clear debris so new axon can grow; no inhibitory molecules present
- In CNS--\> no immune cells; oligodendrocytes express inhibitory molecules so axon cannot regrow
---Glial cells will create a glial scar at site of injury--\> axons cannot regrow
102
Sensory Pathways
1. Fine touch/vibration/concious proprioception= Dorsal Column Medial Lemniscus Pathway
1. DRG--\> gracile or cuneate nuc--crosses via internal arcuate fibers; creates ML--\>synapses in VPL of thal
2. Pain/Temperature/Crude Touch/Itch/Tickle= Anterolateral tract
1. DRG--\> dorsal horn--immediately crosses via anterolateral tract--\> synapses in the VPL of the thalamus
\*Both lead to concious recognition in the cortex/brainstem
103
Consequence of injury to sensory tracts of the spinal cord
-Complete SC injury= bilateral damage
----Bilateral loss of all sensation; affects any body area below level of injury
-Inury to only one side of SC
---Affects any body area with info entering the spinal cord below level of injury; loss of fine touch/vibration on same side, loss of pain on opposite side (both below lesion)
104
Branches of a DRG cell
-A DRG cell is an example of divergence in a sensory system
---Gets input from muscle spindle
-Branches=
---part of dorsal column pathway
---One synapses to clarkes nucleus (unconcious prop. via dorsospinocerebellar pathway)
---One branch to ventral horn--\> synapses to motor neurons for reflexes
105
What happens if you remove all UMNs that influence LMNs?
-Spinal cord central pattern generators and sensory neurons mediating reflexes have much more influence--\> more reflexes
106
Cortical Efferents= Corticobulbar Fibers and Corticospinal Tract
- Example of an UMN cell group
- Corticobulbar fibers= critical for voluntary movement of structures in head
----Jaw, facial expression muscles, tongue, voice box, swallowing
-Corticospinal tract= voluntary movement of distal limbs
---Digits!!
---Axons synapse directly on ventral horn motor neurons
107
Upper Motor Neuron Cell Groups of the Brainstem
-Rubrospinal tract-- Descending pathway controlling flexion of contralateral upper limb
---Flexors of proximal portions of arms
- Tectospinal tract- Descending pathway mediating head turning reflexes in response to auditory and visual stimuli
- Vestibulospinal Tract- Descending pathway mediating "righting" movements in response the changes of body position in space (trunk muscles)
- Reticulospinal tract- Exciting and inhibiting extensor muscles of trunk and limbs (gross movement)
108
Motor System Injury- LMNs vs UMNs
\*Different patterns of deficits depending on site of damage
-UMN- due to stroke, brainstem turmor
---Produces a set of similar symptoms
-LMN- flaccid paralysis, loss of refexes, atrophy of muscles
109
Damage to All Descending UMN pathways
- Ex: when SC is severed
- Voluntary paralysis
- Spasticity- Increased resistance to passive stretch (muscles contract more)
- Hyperreflexia of deep tendon reflexes
- NO muscle atrophy
- Loss of rapid independent finger movements and cortical drive to toe muscles (cuz loss of corticospinal tract if damage higher than lumbar)
- Babinski sign- extensor plantar reflex
- Ex: if severed at lumbar--\> no loss of finger movement, but Babinski sign present
110
Babinski Sign
- Extensor plantar reflex
- Lost at 1yo
- If a rigid object is raked across bottom of foot, normal people flex toward object
---If corticospinal tract is damaged, people flex away from object
111
The Two Main Pools of UMNs in the Brainstem and SC
- Spacially separated, so sometimes only one is lost in injury
- Rubrospinal, reticulospinal, vestibulospinal, and tectospinal are seperated from the lateral corticospinal tract (cortical efferents)
112
What happens if only the corticospinal tract is damaged?
- Partial upper motor neurons syndrome
- Loss of rapid independent finger movements
- Loss of cortical drive to toe muscles
- Babinski sign present
113
What happens if only the medullary reticulospinal tract is damaged?
- Partial upper motor neuron syndrome
- Spasticity
- Hyperreflexia of deep tendon reflexes
114
Spinal Cord Autonomic Pathway of Urination
- Urination is driven by local reflexes and descending controls
- In SC injury, damage may lead to failure to void complretely , urgency, and UTI
\*Micturition center- recieves projections that tell us that bladder is full
---Helps us voluntarily influence skeletal muscles so we can pee
---Turns down symp-- allows bladder to fill; increases tone so we don't pee ourselves
---Parasymps up-- decreases tone so we can pee and contract muscles
\*Damage= increase in reflexive drive
115
Spinal Cord Autonomic Pathway of Defecation
- Damage to axons in SC injury--\> problems w normal defecation
- Cortical drive to external anal sphincter muscle= voluntarily controlled
- Internal sphincter muscles controlled by autonomic and somatic NS
116
Injury resulting from SC damage is dependent on...
- Level of SC where injury occurs
- How much of the SC is injured--\> complete vs incomplete
---Complete--\> motor issues, sensory issues, and autonomic issues in all SC segments below the site of injury
\*The lower the spinal cord injury the better because fewer levels will be taken out
--Ex: if above C3= fatal cuz muscles of respiration can no longer fxn
117
Control of Voluntary Movements= Heirarchy of Multiple Pathways
- Planning-- Abstraction (ideation to move) and formulation (development of motor plan) involves the basal ganglia and association areas of the cerebral cortez
- Execution= UMNs of primary motor strip
- Movement= LMNs at specific muscles
- Guidance= comparing motor plan w/ actual plan via cerebellar loop
118
Diseases in the Basal Ganglia
- Controls initiation and cessation of movements in conjunction w/ motor and premotor cortex and the thalamus--\> motor probs= first sign of parkinson's disease
- Limbic/behavioral loops btwn the cortex and thalamus, as well as cog. loops--\> Effects of parkinson's later in the disease= decline in mental function and dementia
\*Loss of dopamine from SN
119
Hyperkinesias
- Motor alterations with basal ganglia lesion
- Spontaneous, involunatary movements of multiple forms
---Chorea= jerky movement
---Ballismus= flinging movement
---Athetosis= writing movement
\*Too much volitional movement
120
Hypokinesias
- Problems with initiating and executing movements
- Ex: Parkinsons
- Reduced expressive and automatic movements
- Impaired speed of initiation of movement
- Alterations in gait and posture
- Changes in muscle tone
121
Olivocerebellar Pathway
-Bring info about positon of body from muscle spindles, golgi tendon organs, joint receptors to the cerebellum
---Learned repetitive movements
122
Disorders of the Cerebellum
-Loss of motor coordination because cerebellum is not able to refine movement by comparing motor plan w/ peripheral feedback
123
Clinical signs of Cerebellar Lesions
- Loss of coordination of muscle during volitional acts
- Postural disturbances at rest (Vermis=trunk)
- Gait problems= damage to paravermis
- Intention tremors during volitional activity, slurred speech (lateral hemisphere damage)
- Loss of balance, wide gait= damage to flocculonodular lobe
124
Damage to Sensory Pathways in the Brainstem
-Damage to anterolateral and/or DCML
125
Motor Pathways Brainstem Injury
- Damage to cortical efferent pathway or UMN pathways in the tegmentum--\> partial or full UMN syndromes
- Injury to pyramids--\> takes out corticospinal tract--\> partial UMN syndrome
126
Injury to the Tegmentum (Brainstem injury)
- Damage to focal areas of the tegmentum give deficits specific to each level depending on CN nuclei at that level
- III= blown pupil, damage to parasymp
- V= motor nuc of 5, probs w/ muscles of mastication
- IX and X= speech and swallowing issues
- Lower brainstem lesions lead to issues in throat and mouth
127
Damage to Ascending Reticular Activating System
- Leaves a person unconcious
- Parts= columns of neurons in reticular formation of brainstem
---Recieves input from all sensory systems
---Broad excitatory influence over thalamus and cortex
\*Conciousness occurs in the neocortex
\*Brainstem keeps the lights on by releasing NTMs
128
Coma
- Low cerebral metabolism
- Profound or deep state of unconciousness
- Alive but unable to move or respond to environment
129
Persistent Vegetative State
- No cerebral metabolism
- Loss of thinking abilities and awareness of surroundings
- Retention of non-cognitive fxn and normal sleep patterns
- Key functions such as breathing and circulation remain intact
- Spontaneous movement may occur; eyes may occasionally open in response to external stimuli; occasional laugh, grimace, cry
- Do not speak, unable to respond to commands
\*Cortex= no longer fxnal
130
What occurs in the absence of cortical fxn?
- Movement may still occur due to brainstem pathways
- Ex: reflexes from auditory or visual stimuli
\*Cortical blindness= cortex cannot process visual info, but reflex connections in the brainstem are still intact
131
Why are some imaging modalities chosen over others?
- Some imaging techniques just show structure, others can determine fxn
- Different modalities afford different degrees of temporal and spatial resolution
132
EEG
- Electroencephalogram
- Real-time recording of cortical activity (activity at surface of brain)
- Safe
- Non-invasive- Scalp electrodes
- Limited in scope-- cannot measure activity in deeper brain structures/brainstem
- Measurement of summated post-synaptic potentials of pyramidal neurons that have similar spatial orientation and placement radial to scalp
\*\*NOT MEASURING APs
\*Has to be done in shielded environment
-People can move around while being recorded
133
What cortical input from subcortical regions can EEGs pick up?
- Projection pathway collaterals
- Thalamus
- Reticular formation
- Midbrain (mesencephalon)
134
Synaptic Potentials
- The different charges between body and dendrites due to ion flow
- Measured by EEG
135
Rhythmic Activity of the Cortex
\*Activity of pyramidal cells varys
\*Range from high frequency to low frequency
---HF- high activity, pyramidal cells aren't synched up
--LF- low activity, pyramidal cells synched up
- Gamma waves- cognitive functions (highest frequency)
- Beta waves- occur when alert of attentive, or in REM sleep; aroused
- Alpha waves- Major rhythm in normal, relaxed adults with eyes closed
\*Cortical activity decreases in vegetative state
- Theta waves- regular in children up to 13 yo and in sleep
- Delta waves- Dominant rhythm in infants and stages 3-4 of sleep (deep sleep, lowest frequency)
136
EEG and Sleep
- EEG used to determine stages in sleep
- Theta rhythms as we start to fall asleep, deeper and deeper till delta
- We start to wake up around 2 hrs--\> REM--\> Beta rhythms
---Sleep cycles shorten until we get more and more REM
-REM= paradoxical sleep- rapid eye movements, yet body is paralyzed
137
EMG
- Measures muscle tone
- Shows muscles are paralyzed during REM
138
EEG use in Polysomnography
-Looks for sleep apnea
---Obstructive apnea- airway is blocked, usually in throat
---Central apnea- problem resides in brainstem sleep centers
-------Aren't getting enough O2
-"Arousal" waves seen during sleep where person waves up
139
MEG
- Magnetoencephalograhy
- High-Resolution EEG
- Tiny magnetic field sensors (SQUIDS) detect magnetic effect of electrical currents within the cortex
- Noninvasive and functional
- Real-time--\> See activity in msec while subject performs activity
\*Better spatial res than EEG
140
Ultrasound
- Uses high-frequency sound waves that are reflected back in order to capture image
- Safe and inexpensive
- Common uses w/in NS:
---Babies before skull fuses
---Adult PNS
---Adult blood vessels supplying brain
\*Poor technique for imaging CNS because bone surrounding tissue absorbs and redirects waves
-Hard to read, but can be reconstructed using tech.
141
X-ray
-Specialized machine delivers small dose of radiation (1-10 mGy)
---Yearly background radiation= 2.4mGy
- Image captured compresses all structures into one 2D view
- Non-invasive unless contrast agent is used
\*Not good for resolving fine-tissue structures within the brain
Type of X-Ray= angiogram- X-ray used to view blood vessels with contrast agent
142
How to read an X-Ray
- X-ray beam doesn't pass through bones or teeth--\> show up as white
- Beam passes freely through air--\> black
- Everything else shows up as grey (inbetween the two extremes)
- Good at looking at bone, not CNS tissue
----Grey matter, white matter, and CSF all absorb about the same x-ray energy
143
CT/CAT Scan
- Computerized tomography
- Many 2D X-rays that form from a 3D (series of images!)
----Beam procided by rotating source
----Provides an x-ray image of multiple thin slices of tissue
-Very fast (minutes) w/ good spatial resolution
---Better than EEG
-Non-invasive procedure
---Can be done if metal in the body
144
Uses for CT
-Great for diagnosis in the ER
---Can detect blood in the brain
-Should be avoided in children if hemoarge, TBI, or stroke are not suspected pending neurological eval.
----Head CT= 56 mGy--\>lots of radiation!!!
145
How to read a CT
- Bone appears white
- Some contrast with tissue
- Lighest- bone\>grey matter\> white matter\> CSF\> air- Darkest
---Still difficult to reliably tell apart grey and white matter
- Can see some structures of brain but not super well
- 3D reconstructions improve spatial resolution (not super useful though)
146
MRI
- (nuclear) magnetic resonance imaging
- Magnets inside tube, hold protons in body in a certain orientation
---Diff protons in diff parts of the body have diff orientations and frequencies
------aka magnets and RF energy alter protons in water to make a signal
\*CT is the go-to, MRI only really used to clear up confusion
147
Advantages and Disadvantages of MRI
- A:No radiation-- can be repeated
- A:High resolution
- D: Use of magnets- patient cannot have any metal in them
- D: Takes a long time to perform, expensive
- D: People have problems holding still, claustrophobic
148
Reading an MRI
-Gives great differentiation of grey and white matter compared to CT
---Great res of CNS, even better with use of contrast agent
------Can see cortical ribbon, tracts
\*Increase quality of magnet in MRI, increases quality of MRI
-Allows us to see soft tissue abnormalities- Tumors,abscesses, etc
---Cannot be easily resolved by CT
149
Two Types of MRI Images
- T1-Highlights fat (light colored)
- T2- Highlights water (CSF= lightest)
\*WW2= Water is white on T2
150
Contrast Agents
- Chemicals injected into the blood before imaging
- Useful for seeing abnormal vasculature or for breakdown on BBB
- Can be down with CT and MRI
151
Diffusion Tensor Imaging
- MRI technique that creates an image of white matter tracts based on diffusion of water molecules whose direction of motion is limited by interactions w/ other tissue components
- For axons, water movement is limited by myelin sheath, so diffuses faster longitudinally
---Difference is detected and measured--\>Tractography
- Take 3D images- voxels- and knit picture together
- Can determine which brain structures are connected to each other and how strong that connection is (color codes what direction axons run)
\*Can show disruption of normal tissue that isn't seen in MRI--\>concussion, whiplash, shaken baby
152
Basics of Bloodflow in the Brain
-Total bloodflow in the brain is constant
---Brain, blood, CSF share fixed volume in skull
-----Changes with diseased states
-Different areas of the brain are active during different activities
---Blood flow changes in each area of brain depending on their activity
\*Therefore, total BF is constant, region BF is changing with activity
----Can be used for imaging, tracking O2 supply (functional imaging)
153
fMRI
- Functional MRI
- BOLD= blood oxygen level dependent activity
----BOLD signal comes 6 seconds after neuronal firing (poor temporal res)
-MRI procedure that measures changes in blood oxygenation as an indirect means of determining brain activity related to a task
----Oxyhemoglobin vs deoxyhemoglobin
\*Active parts of the brain-BVs will dilate and blood will flow there
\*Don't know which neurons are active
154
Subtraction Method
-Subtraction procedures allow visualization of just active areas in fMRI
---Subtract resting task from active state--\> just active areas
-Resting task= doesn't use brain area of interest
---Kind of subjective
155
PET scan
- Positron emission tomography
- Functional imaging
- SUPER BAD FOR U WE HATE IT
- Radioactive tracer is injected through the bloodstream
---Labeled glucose (FDG), concentrated in cells with high activity
---6-FDOPA=Shows areas activly releasing dopamine
---PITB binds to tau--\> shows up in alzhiemers disease
-Area of activity aligned with CT image levels
156
Concussion- Initial cascade of events
- Brain collides with skull, which can cause bruising, torn tissues, and swelling
- Abrupt release of NTMs
- Unchecked ion fluxes
- Na-K pump works overtime, increasing ATP and glucose use (neurons become hyperactive)
- When blood flow is diminished, leads to energy crisis for the brain(can lead to cell death and seizure)
157
Subsequent Events of a Concussion
- Axon stretching alters them long term
- Glial activation and inflammation
- Neuron death due to calcium accumulation
- Prolonged neurotransmitter alterations
---Memory problems
---Increased risk of another concussion
\*Mild concussion doesn't show up on MRI
158
Concussion Danger Signs in adults
-A dangerous bleed or blood clot may form in the brain in a person with a concussion and crowd the brain against the skull
---Headache (worsenes and doesn't go away)
---Weakness, numbness, or decreased coordination
---Repeated vomiting or nausea
-Slurred speech
159
When to go to the ER if concussed
- Look very drowsy/ cannot be awakened
- One pupil larger than the other
- Have convulsions or seizures
- Cannot recognize people or places
- Are getting more confused, restless, or agitated
- Have unusual behavior
- Lose conciousness
160
Danger signs of concussions in children
- Have any of the danger signs for adults listed
- Will not stop crying and cannot be consoled
- Will not nurse or eat
161
Seizure Disorders
- Sudden electrical disorder in the brain
- 10% of individuals w/ a TBI that require hospitalization
- Transient symptoms:
- Stiffening or shaking of body
- Unresponsiveness or staring
- Chewing, lip smaking, or fumbling movements
- Strange smell, sound, feeling, taste or visual images
- Sudden tiredness or dizziness
- Not able to speak or understand others
162
Brain tumors
-Another cause of seizures
- Come from 2 sources:
- --Brain glial celld
---Tumors in other parts of the body (ex: lung) that metastasized
-Affect O2 and nutrient supply avail to neurons, the extracellular environment around the neurons,and exert pressure on neurons
163
Herniation Patterns created by tumors, bleeds, and swelling
- Because skull has fixed volume, anything extra alters this balance
- Subfalcine- herniation of cortex under falx cerebri, across midline
- Uncal- Herniation under tentorium cerebelli to brainstem compartment
- Tonsillar: herniation through the forman magnum, compressing medulla
\*Detected by CT
164
Second Impact Syndrome
-Prevention of further damage is critical in management of concussion individual
----Cognitive rest, slowly introduce more and more activity
-If experience a 2nd blow to the head without fully recovering--\> massive swelling of brain that cuts off blood flow
165
CTE
-Chronic traumatic encephalopathy
----Long-term effect of impact injuries to the brain
- Memory loss, confusion, depression, agression, dementia
- Build up of tau protein w/in the brain & severe damage to axons
- No cure
166
Arterties
- Takeblood away from the heart
- Large arteries branch into smaller arteries
- Smaller arteries carry blood to organs
- Smaller arteries break into capillaries
- Oxygenated blood except pulmonary arteries
167
Veins
-Drain back to the heart from capillaries
---Deoxygenated except pulmonary veins
- Small veins branch into larger veins; larger veins carry blood to the heart
- In brain- small veins inside and outside surface drain back into large veins w/in dural sinus
\*Venous blood from brain drains from venous sinuses into the internal jugular vein
---Runs down the neck alongside the common carotid artery (returning blood to the heart)
168
Circulatory System
- 2 closed loops- systemic and pulmonary circulation
- Polmonary sends blood to the lungs to become oxygenated; pulmonary veins return oxygenated blood to heart
- Systemic arteries- deliver oxygenated blood to the body
---Largest artery= aorta; branches into smaller arteries that nourish organs like brain
169
Vessels visible on the surface of the brain
- Lie in the subarachnoid space
- Brain= part of systemic circuit
- Large and small vessels are visible (arteries and veins)
- Arteries= carry oxygen and nutrient-rich blood to neurions
- Veins= varry oxygen and nutrient-depleated blood away from the neurons (high in CO2)
----Towards the dural sinuses
-When arachnoid is removed, vessels ripped off with it
170
Anatomy of a Blood Vessel
- Arteries= rounder, thicker, and paler
- Veins= have valves to prevent backflow
- Inner layer= endothelium
- Middle layer= smooth layer
- Outer layer= connective tissue
\*Layers built with many layers of cells and collagen fibers (no exchange of materials btwn blood and tissues)
\*Cappilaries= exchange vessels
---One cell thick
---Allow for rapid movement of gas or solutes btwn blood and extracellular fluid of the tissues
171
Capillary Structure
\*Cappilaries= exchange vessels
---One cell thick
---Allow for rapid movement of gas or solutes btwn blood and extracellular fluid of the tissues
- "Leaky" due to space btwn endothelial cells
- Ex: capillary of endocrine gland
---Endothelial cells have poors within them to facilitate movement of hormones into blood
---Basal lamina= facilitates diffusion cuz meshwork of collagen surrounding cells
\*DIFFERENT IN BRAIN
172
Barriers protecting brain tissue
- Blood-brain barrier- exists btwn tissue of endothelial cells and tissue of the brain
- Blood-CSF- surrounds choroid plexus with ependymal cells
\*Very difficult to design drugs to get into the brain
---Must be lipid-soluble and small
173
Capillary Structure at the Blood Brain Barrier
- Least leaky capillaries in the body
- Endothelial cells joined together by tight junctions, limiting exchange w tissue
---Endosomes used to transfer things in and out
-Astrocytes extend processes toward BV/capillary walls, also making it difficult for things to get in
174
Astrocytes at the Blood Brain Barrier
- Enchances the blood brain barrier
- Surrounds the BBB with foot processes around basal lamina
- Also invovled in neuronal metabolism
---Break down glucose
175
Layers in the Blood Brain Barrier
1. Endothelial cells-innermost
---Tight junctions
---Basement membrane
2. Pericytes- important for neurovascular coupling (hemodynamic response that supplies active neurons with more blood, underlies the BOLD signal)
3. Astrocyte end-feet- outermost
176
What are the two sets of arteries that supply the brain?
1. Internal carotid arteries
---Arise from common carotid artery
---Ascend through the skull and supply the anterior brain
------Anterior circulation
2. Vertebral arteries
----Ascend through the spine and foramen magnum and supply the brainstem and posterior brain
-------Posterior circulation
---Arise fromsubclavian artery
177
Anterior Circulation
\*Posterior and anterior communicate at ventral surface of brain
-Consists of the internal carotid arteries
---Pair of two, split to form the anterior cerebral artery (supplies medial territory) and the middle cerebral artery
178
Posterior Circulation
- Also called the vertebro-basilar system
- A vertebral artery travels up each side of the spine, threaded through holes on sides of the vertebrae
---When they reach C1, turn medially and pass through the foramen magnum (injury at C1 impairs these vessels)
- R and L vertebral fuse at pontomedullary jxn to form single basilar artery
- Basilar artery ends at midbrain by splitting into L and R posterior cerebral arteries
- Supply brainstem, cerebellum, and spinal cord
- 3 sets of cerebellar arteries--\>ex: SCA
- Penetrating arteries to midbrain, pons, and medulla
- Each vertebral artery gives a branch to form the anterior spinal artery
\*Communicates with anterior circulation at ventral surface of brain
179
Circle of Willis
- L and R carotid artery circulations are connected via 1 anterior communicating artery
- The carotid (anterior) and vestebrobasilar (posterior) circulations are connected through paired posterior communicating arteries
- These connections make a circle on the base of the brain around the hypothalamus and the optic chiasm
----Provide backup incase blood flow is impaired
180
Arteries of the Circle of Willis
- Anterior communicating- usually present
- Anterior cerebral
- Middle cerebral
- Internal carotid
- Posterior communicating (usually small or absent)
- Posterior cerebral
- Basilar artery
\*Anterior perforated substance made by the lenticulostriate arteries
181
Middle cerebral artery
- Supplies most lateral side of frontal, parietal, and temporal lobes
- Supply head of caudate, putamen and globus pallidus, anterior limb of internal capsule , genu of internal capsule
---Around ears
182
Posterior Cerebral Artery
- Supplies inferior half of temporal lobe and occipital lobe
- Thalamus, posterior limb of internal capsule (sensory and motor fibers)
----Bottom back of cerebrum
183
What three main branches supply the cerebral cortex?
- Anterior cerebral artery (anterior circulation)
- Middle cerebral artery (anterior circulation)
- Posterior cerebral artery
184
Anterior Cerebral Artery
-Supplies medial aspect of frontal and parietal lobes
----Around interhemispheric fissure
- Orbitofrontal and ventromedial PFC
- Branches: Callosomarginal (above cingulate) and pericallosol arteries( above corpus callosum)
185
Lenticulostriates
- Supplies basal forebrain nuclei and basal ganglia
- Created the anterior perforated substance
- Originate from anterior and middle cerebral arteries
186
Motor and Sensory Homunculi and their relation to different cerebral arteries and stroke
- Strokes in different vessels produce different syndromes
- ACA=Effects movement in trunk, leg, and foot (motor)
---Genitals (sensory)
- MCA= Hand and face
- PCA= no motor symptoms, visual problems cuz occipital lobe
187
Functional Considerations- Anterior Cerebral Artery
- Medial part of the frontal and parietal lobes
- Cingulate gyrus, basal forebrain (limbic)--\> motivation, emotion
- Lower extremity (sensory and motor)
188
Functional Considerations- Middle Cerebral Artery
- Basal ganglia and anterior limb internal capsule--\> motor and limbic functions
- Lateral areas of the cortex:
---Speech
---Face and upper extremity (hands)--\> deficits in facial expression
---Auditory
\*80% of strokes involved MCA or its branches
189
Functional Considerations- Posterior Cerebral Artery
- Thalamus and posterior limb of internal capsule--\> sensory deficits,contralateral motor deficits
- Occipital lobe (vision)
- Inferior temporal lobe ("what" pathway)--\> deficits in object recognition
190
Angiography
- Imaging of blood suply to the brain-- can show blocked arteries
- A catheter is placed into the femoral artery
---Threaded up through the circulatory system to whereever u want
-------Injects contrast agent (barium or other heavy metal)
- Can be done w/ CT or MRI (higher res)
- Easy to see damage
191
The Internal Capsule
-The anterior limb of the internal capsule and adjacent basal ganglia are supplied by the lenticulostriate arteries
-
192
Distribution of perforating deep branches of the internal carotid, anterior, middle, and posterior cerebral arteries
-Middle cerebral artery= main supply to anterior limb of the internal capsule and basal ganglia (lenticulostriates)
- Posterior cerebral artery supplies posterior limb of the internal capsule and thalamus
- Genu of IC gets both
193
Blood supply to the spinal cord
-Ventral/anterior side is supplied by the singular anterior spinal artery
----Fusion of two arteries
---Supplies 2/3 of the spinal cord
-Dorsal/posterior side is supplied by two smaller posterior spinal arteries
---Near dorsal column
194
Great Cerebral Vein
- Brings blood from internal brains structures to straight sinus--\> back to heart
- Deeper veins drain directly toward confkeunce of sinuses trough it
195
Superficial Veins
- Drain through bridging veins into superior sagittal sinus, which flows toward confluence of sinuses then to internal jugular
- Located in subarachnoid space
196
Stoke Definition and its Key Requirements
- Neurological deficit of vascular origin
- Lasting clinical deficit-Lasts more than 6 hrs (doesn't improve)
- Vascular cause- interupption of blood flow to brain tissue
- Two types: Ischemic (clot) and hemoraggic (rupture of BV)
197
TIA
- Transient Ischemic Attack
- Signs of stroke last minutes, so don't meet formal definition
- "Warning stroke"--\> mostly likely will have a larger stroke in the future
198
Silent Strokes
-Strokes that occur in areas of the brain that give no direct clinical sign
----Non-eloquent, silent cortex areas (ex: multimodal areas)
------Other areas can compensate, no obvious sign of damage, or no way to test for damage in location
-Imaging reveals areas of prior brain death but patient never sought help
199
Atherosclerosis
- Formation of fatty inflammatory plaque material in the wall of blood vessels
- Major cause of heart disease--\> can lead to formation fo blood clots in brain, which reduce blood flow (ischemia)
- Caused by lifestyle factors, modified by genetics
---Type 2 diabetes, smoking, drug use, obesity/sedentary lifestyle, alcohol use, hypercholesterolemia, atrial fibrilatioins, high BP (hypertension)
200
Biggest Risk Factors for Stroke
-Atrial fibrillation- Heart problem generating small clots that pass into brain
---Atria values of heart flutter
--Leads to embolic stroke
--Treatment: blood thinners, filters to catch clots
-Hypertension
201
Hypertension
-Causes thickening of intracerebral vessels (to withstand extra pressure), narrowing them in diameter
\*Leads to less exchange of O2 and nutrients cuz less blood getting through
-Vessels fail in one of two ways:
---Occlude--\> ischemic stroke
---Rupture and bleed--\> Hemoraggic stroke
202
Ischemic Stroke
-Occurs when the lumen of the vessel is blocked
---Area of the brain is not recieving sufficient oxygen and glucose
-Thrombotic ischemia= blood vessel is occluded by a disease process
---Ex: atherosclerosis
-Embolic ischemic= clot or embolus becomes detached and travels in the bloodstream until it reaches a small diameter vessel in the brain
---Clot not from brain, came from somewhere else in body
\*80% of strokes (most common type)
203
Hemorrhagic Stroke
-Occurs when a vessel supplying the brain ruptures and there is bleeding around or inside the brain
---Intracerebral hemorrhage: If the bleed is within the substance of the brain, brainstem or cerebellum
---Subarchnoid hemorrhage: A bleed of an artery in the subarachnoid space
\*Most deadly--\> 4-times higher risk of death
204
Intracerebral Infarct
- Ischemic stroke
- Lenticulostriate vessel narrowed and did not deliver oxygen and nutrients to tissue
- "Lacunar infarct"- forms a little lake of fluid in dead area
- Motor symptoms related to basal ganglia and internal capsule damage
---Slowness of movement
---UMN syndrome (contralateral weakness or paralysis)
\*Can survive
205
Intracerebral Hemorrhage
- Lenticulostriate vessel ruptured and bled within brain
- Same symptoms, but acutely masked by others resulting from increased intracranial pressure, causing a dire medical emergency (inflates brain w/ blood)
- In the long-term, blood has cytotoxic effect (kills cells)
206
Intracranial Hemorrhages
\*NOT a stroke
-Vessels involveddo not supply the brain, but are within the cranial cavity and supply meningies and surround tissue
---Increase pressure on the brain, leading to stroke-like symptoms and potential death
-Classifications: epidural or subdural hemorrhage
\*SUBARACHNOID HEMORRAGE= A STROKE
207
Epidural Hemorrhage
-Not typically classified as a stroke
---Vessels involved don't supply brain tissue- they supply the dura
- Occurs following rupture of artery w/in dura
- Bleed occurs btwn dura and skull (epidural space)
----Aterial bleeds cause separation of dura from skull
-Clots in a confined area, and as hemorrhage grows, brain pressure increases and compressed brainstem--\> death
208
What is the most common site of injury that leads to an epidural hemorrhage?
-Skull fracture at fragile lateral skull region called the pterion
---Where 4 bones of the skull fuse together during infancy
-Under this region= the middle meningeal artery in the dura
---Tear of artery--\> hemorrhage
209
Increases of Intracranial Pressure- The Warning Signs
- Similar to warning signs of concussion
- Severe headache that gets worse and worse
- Compression in cortex presents as confusion, sensory/motor signs, cognitive impairment, disorientation
- Uncal herniation compresses oculomotor nerve
---Loss of oculomotor fxn gives "fixed and dialated pupil"
-----Unresponsive to light
210
Treating Increases in Intracranial Pressure
-Pharmaceutical agrents-- reduce pressure by making blood brain barrier more "leaky"
----Equalizes fluids
- Epidural hemorrhage may require formation of a burr-hole to relieve pressure
- Decompressive cranioscopy
---Remove parts of skull or drill holes to let pressure out
211
Subdural Hemorrhage
- Rupture of bridging veins-- drain cerebral veins into the superior sagittal sinus
- Dura is not fused to the arachoid, so blood distributes around brain in subdural space
- Bridging veins are stretched when there is greater separation btwn dura and arachnoid---present in young (brain still growing) and elderly (brain shrinking)
212
Comparison of epidural and subdural bleeds
-Epidural bleeds
---Result from tear in dural artery
---High pressure bleed
---Most likely to cause herniation
-Subdural bleeds
---Result from tear of bridging
---Low pressure bleed
---More likely to clot on its own
213
Subarachnoid Hemorrhage
-Rupture of a vessel within the subarachnoid space
---Vein or artery, but usually arteries
-Surface vessels surrounded by CSF, but not in communication w/ it
---When vessel ruptures, CSF and blood mix in subarachnoid space
214
Common cause of a subarachnoid hemorrhage
- Aneurysm= most common cause
- Weakening of the wall of a blood vessel
---Pressure inside the vessel causes wall of vessel to expand outward and fail
-Ruptured aneurysms in the vessels of the circle of Willis nleed into CSF of brain
--Ex: Berry aneurysm
215
Types of Hemorrhagic Strokes
1. Subarachnoid hemorrhage
---Vessels burst b4 reaching brain tissue
2. Intracerebral hemorrhage
---Artery bursts that has already reached brain tissue
- Sudden onset= worst headache of your life
- Slow onset= subclinical
216
Hemorrhagic Stroke- How to diagnose
- CT scan cuz can catch fresh blood
- Not good for acutely diagnosing ischemic strokes, but can guide treatment because can be seen in the longterm
217
What is the first thing you do to treat a hemorrhagic stroke?
-Stop the bleeding
---Pharmaceutical agents to enhance clotting
---Cauterize bleeding vessels
---Reinforce weakened arterial wall
---Done with either open skull surgery or with use of a catheter
---Catheter inserted into large vessels and go where bleed is occuring to block with coil or clip
218
Ischemia
- Due to diseased brain vessels
- Pattern of loss depends which vessel is impacted and the territory it covers
- Smaller diameter vessels branching from larger parent artery at 90 degrees from parent artery= especially at risk
- Ex: Blockage in lenticulostriate artery=damage to BG and internal capsule--\> sensory and motor loss (vol. paralysis)
- Ex 2: Blockage of MCA--\> Loss of motor in face and hands
219
FAST
- F-face
- A-arm
- S-speech
- T-time
- MCA= most common ischemic stroke that has FAST symptoms
220
Ischemia in Territory of Middle Cerebral Artery
- Due to occlusion of the internal carotid artery due to artherosclerosis
- 80% of ICA blood goes to MCA, so symptoms occur in MCA first
221
Vessel Blockage in the Brainstem
- Affects structures in zone of vessel distribution
- Ex: dorsolateral branch of pontine arteries
---Supply CN8 nucleus, CN 6 nucleus, CN 5--\> problems in these CNs
------Balance problems (CN 8)
------Lateral rectus damage (CN 6)
------Pain and temp in face (CN 5)
------Paralysis of muscles of facial expression on 1 side
222
Thalamic Pain Syndrome
- Due to damage of posterior cerebral artery
- Pain everywhere in body that does not improve with meds
223
Treatment for Ischemic Stroke
-Unclog the vessel
---Must be done carefully to avoid breaking the clot into pieces that could cause subsequent strokes
-Stent and vacuum-like devices
---Stent grabs clot and vacuum pulls it out
\*Restores blood flow
224
Why is time important to survival of a stroke?
- More time wasted= more tissue lost
- Tissue plasminogen activator (tPA)- administed in bloodstream to breakup clot
---Does more harm than good if wait too long (use within 2-3 hrs)
----Can't be used for hemorhaggic stroke cuz prevents clotting
