Basal Ganglia and Limbic System Flashcards
1
Q
Discuss the history of limbic lobe and how it was developed. What did limbic lobe consist of?
A
Limbic Lobe: described by Broca in 1874, as word ‘“limbic’” described the border or edge that formed between Diencepaholon and the more lateral Neocortex of the telencephalic hemispheres
-limbic lobe consists of a ring of cortex outside corpus callous, largely made up of subcallosal and cingulate gyro as well as parhippocampul gyrus
2
Q
What structures of the brain are seen in saggital view?
A
Forebrain (Telencephalon and Diencephalon), Midbrain (mesencephalon), Hindbrain (Metencephalon and myencephalon)
3
Q
Describe how James Papez, and his discovery of Papez circuit
A
James Papez- American physician who describes his anatomical model of emotion called Papez Circuit
-He hypothesized that hippocampus, cingulate gyrus, the hypothalamus, anterior thalamic nuclei and interconnections among these structures created a mechanism that would describe the functions of emotions
Papez believed that experience of emotion was determined by activity cingulate cortex, and less directly and other cortical areas.
(emotional expression thought to be governed by hypothalamus)
4
Q
Describe who Paul MacLean was and his Triune brain theory
A
Paul MacLean proposed that human brain was in reality 3 brains in one:
1) Reptilian complex
2) The limbic system
3) The Neocortex
5
Q
Describe the components of Triune theory and how it influenced behavior
A
Triune theory:
1) Reptilian Level
-Pavlovian/Adams
-Risk Thermostat
made of up brain stem and cerebellum, responsible for fight or flight response, Autopilot (each response for a stimulus)
2) Mammalian Brain:(CHIMP level) limbic system was responsible for emotions, memories and habits formed by humans ; corresponded to Decisions or “gut feel” that people have. It described one’s perception of things
3) The Human Brain: made up Neocortex portion of brain that contributed to language, abstract thought, imagination, consciousness. It also correlated to how one reasons or rationalizes, or one’s persona
These different brains described how one anyalzed physiological behavior and how there is a balacne between taking risks, being rewarded, having accidents and how one perceives risks
6
Q
What were cellular structures that were considered a part of limbic cortex for All vs Most or Some authors?
A
There is no universal on total list of structures that are included in limbic system.
-All authors include limbic cortex (cingulate and parahippocampal gyri), the Hippocampal Formation, the Amygdala, and the Septal area.
-most include the hypothalamus, part of midbrain reticular formation and olfactory areas
-Some authors include thalamic and neocortical regions
7
Q
What part of brain is responsible for control of movement?
A
Basal Nuclei
8
Q
Describe the different roles in Cingulate gyrus, Hippocampus and Amygdala that are apart of limbic system
A
Limbic System:
-Cingulate gyrus: role in EMOTION
-Hippocampus: Learning and Memory
-Amygdala: Emotion and Memory
9
Q
What are the three anatomical planes of the body?
A
Anatomical planes;
-Coronal (frontal) will separate Anterior(front) and Posterior (back) parts of the body
-Saggital (longitudinal; vertical) : separates the left and right sides of the body
-Transverse plane (axial; horizontal) separates upper(superior; dorsal) and lower (inferior; ventral) halves of the body
10
Q
Describe the structure of Amygdala and its role in Limbic system
A
Amydala: two almond shaped neural clusters that are components of limbic system, linked to emotion and fear.
(play important role in behavior: fear, agreeableness, rage)
11
Q
What occurs in the Basolateral amygdala and where is it located in brain?
A
Basolateral amygdala:
-basaloateral nuclear group receives higher-order sensory information from association areas in the frontal, temporal and insular cortex
-axons run back from amygdala to association regions of the cortex, suggesting that activity in amygdala may **modulate sensory information processing in association cortex **
-basolateral amygdala is also connected via stria terminals and amydalofugal pathway, to ventral striatum and thalamus
12
Q
Where is Corticomedial amygdala and what is its role?
A
Corticomedial amydala
-the corticomedial nuclear group of the amygdala is located close to the Olfactory Cortex, and is interconnected with it and also the Olfactory Bulb
-Connections also run via the stria terminals and amygdalofugal pathway, to and from the brain stem and hypothalamus
13
Q
Describe the major functions of the Amydala
A
Functions:
-because of the interconnections with sensory association cortex and hypothalamus, its suggested that Amydala plays an important role in establishing associations between sensory inputs and various affective states*
-The amygdala appears to participate in regulating endocrine activity, sexual behavior, food and water intake possibly by modulating hypothalamic activity
14
Q
Describe the two broad functional divisions of Limbic system
A
The Broad functional Divisions of Limbic system:
Rostral limbic system: amygdala, septum, orbitofrontal cortex, anterior insula and anterior cingulate
-Important for EMOTION
Caudal system: Hippocampus, posterior parahippocampal cortex and posterior cingulate
-Important for MEMORY and Visual-spatial functions
15
Q
What happens to people who have gotten lobotomies?
A
People with lobotomies, have experienced issue with rostral limbic system, that leads to many psychotic disorder (bipolar disorder)
16
Q
Differentiate between the Limbic Lobe vs Limbic System and include the cellular structures that are a part of each
A
Limbic Lobe (cortical areas of limbic system)
-Parahippocampal gyrus, hippocampus, orbitalforntal, cingulate gyrus and insula
Limbic System (Limbic Lobe + Nuclei and connection);
-include all structures from limbic lobe, AND Nuclei (amygdala, septal nuclei, mammillary body, anterial thalamus connection) and Fornix (median forebrain bundle, stria terminals, and Mamillothalamic tract)
17
Q
What are all of the different structures of limbic system and what are their functions?
A
Limbic system:
-Hypothalamus, pituitary, amygdala, and hippocampus all deal with BASIC drives, emotions, and memory
-Hippocampus–> Memory processing
-Amydala–> Agression (fight) and Fear (flight)
-hypothalamus–>Hunger, thirst, body temperature, pleasure; regulates pituitary gland (hormones)
18
Q
Describe how structures of limbic system are connected and how sensory information is transferred.
A
The major structures of limbic system are interconnected with each other and with other components of nervous system. Sensory information from cingulate, orbital and temporal cortices, and amygdala is transmitted to entorhinal cortex of parahippocampal gyrus and then to hippocampal formation
19
Q
What are the comments of the limbic system?
A
Components of Limbic system:
-Olfactory pathways,
Anterior perforated substance
pyriform lobe
Septal area
Amygdaloid body
Limbic cortex
Hippocampal formation
-Elements of diencephalon
Bundles of ions connecting above region
20
Q
Describe how information is transferred in the Function circuit between hippocampal formation , thalamus, cerebral cortex and hypothalamus
A
After traversing the intrinsic circuitry of Hippocampal formation, information is projected through the fornix, either to the Anterior Thalamus, which in turn projects to limbic cortex, or to Septal Area and Hypothalamus
-The Septal area and Hypothalamus also provide feedback to hippocampal formation through fornix
The mammillary bodies of hypothalamus project to anterior thalamus
Finally, the hypothalamus and septal area project to the brainstem and spinal cord
(other function circuits are between amygdala, hypothalamus and prefrontal and temporal cortices)
21
Q
What are the three major Amygdala pathways?
A
1) Ventral Amdydalofugal pathway
-Nucleus Accumbens septi
(ventral striatum), global pallidus (ventral pallidum), anterior olfactory nucleus, orbital cingulate cortex, prefrontal cortex, septal area and hypothalamus )
2) Stria Terminalis (septal area, hypothalamus (lateral/ventral nucleus) , habenula, and contralateral amygdala)
3) Direct connections from Amygdala
-Hippocampus, Entorhinal cortex, dorsomedial thalamus and brain stem
22
Q
What is the major role of basal Ganglia and why is important?
A
Basal Ganglia: controls voluntary movement and is involved in all motor disorders (like Parkinson’s disease)
23
Q
How is the Limbic system associated with Olfaction?
A
Olfaction
-The limbic structures are closely related to olfactory cortex
-Amygdala is involved in emotional response to smell Entorhinal cortex, is concerned with olfactory memories.
(sense of smell is crucial to survival)
you are able to form direct connections that don’t require memory processing when it comes to olfaction
(Olfactory receptors–> Axons of Olfactory neurons–> Olfactory bulb (mitral and Tufted) –> Perform Cortex (Primary olfactory cortex) –> Amydala
24
Q
What structures in brain contribute to appetite and eating behaviors?
A
Appetite and Eating Behaviors:
Amygdala plays a role in food choice and emotional modulation of food intake
-The lateral nucleus of the hypothalamus is the center for control of feeding
Whereas, the ventromedial nucleus functions as SATIETY center
25
What causes emotional responses like fear? Which structures in the brain are involved? How can fear be diminished or activated?
Fear responses are produced by the stimulation of Hypothalamus and Amygdala
-Amygdala Destruction abolishes fear and its autonomic and endocrine responses
-Amydala is also involved in fear learning
-imaging studies have shown that viewing fearful faces activates the left amygdala.
26
What can induce rage and placidity? How can placidity turn into rage?
-The Destruction of the Ventromedial Hypothalamic Nuclei and septal nuclei in animals may induce Rage.
-Bilateral destruction of the amygdala results in Placidity (calm or peacefulness)
-However, when the Ventromedian nucleus is destroyed after the destruction of the amygdala, the placidity generated is converted to rage.
27
Describe the different autonomic and endocrine responses to emotion. What happens when limbic system or hypothalamus is stimulated?
limbic stimulation causes changes in respiration and blood pressure
-The stimulation of the cingulate gyrus and hypothalamus can elicit autonomic responses
Hypothalamic autonomic responses are mediated by cortical and limbic structures processing drives and emotions
28
Which structures of the brain will be stimulated when fear and rage responses occur? What is the Fight or Flight Response?
The fear and rage responses mediated by the limbic system cause stimulation of the hypothalamus, especially lateral areas and produce diffuse sympathetic discharge.
-The massive sympathetic discharge, during stress is called the "Fight or Flight" response
29
How does CRH (corticotropin releasing hormone) become released and what is its role?
Stress via cortical and limbic connections causes the release of corticotropin-releasing hormone (CRH) from the paraventricular nuclei of hypothalamus.
CRH release mediates endocrine and immune responses
30
Explain how sensory information is transferred through different areas of the brain and causes autonomic and endocrine responses
Sensory stimuli--> Cortex--> Limbic system (attaches emotion) --> hypothalamus --> activate autonomic, somatic, immune and endocrine responses.
31
Explain how emotions influences memory and which brain structures are involved. Which structure is crucial for long-term memory storage? How does Anxiety affect memories?
Emotion has a powerful influence on learning and memory
-Amygdala, prefrontal cortex, and medial temporal lobe is involved in consolidation, and retrieval of emotional memories
-Amygdala, prefrontal cortex and hippocampus are also involved in the acquisition, extinction and recovery of fears to cues and contexts
-Hippocampus is critical for long-term, declarative memory storage
(with anxiety, reduce ability to learn or consolidate memories)
32
What is the Medial Temporal Lobe Memory System? What role does it play?
Medial Temporal Lobe Memory System:
includes the hippocampus and adjacent cortex, the parahippocampal regions (PHG) and the entorhinal and perirhinal regions
involved in storage of NEW Memories
33
What is the role of Diencephalic Memory System? What occurs if there is a disfunction in this system?
Diencephalic Memory System:
Consists of the hypothalamus, mammillary body, and the dorsomedial nucleus of thalamus
-Important for the storage of RECENT memory
- A dysfunction of this circuit results in KORSAKOFF'S Syndrome (caused by a deficiency of thiamine, vitamin B1; not made in our bodies)
(This deficiency in thiamine can cause anterograde or retrograde amnesia (associated with alcoholics, since Vitamin B1 is required for metabolism of alcohol) )
34
What is social cognition?
Social Cognition: thought processes involved in understanding and dealing with other people
-limbic structures involved are the cingulate gyrus and amygdala
35
Describe the brain's shortcut to emotions, including an example
The brain's shortcut for emotions:
short cut enables instant fear response
Ex: seeing a snake and running away from it. The speed of response. we do not need to process visual input of snake and go through all processes. We go straight from visually seeing snake to fight or flight response (running or "freezing") Sympathetic activation occurs.
Also, how people respond to dogs, if they have been attacked before, due to association of fear formed with dogs, (PTSD) which is hard to overcome it. It is hard to rewire, needs therapy, retraining and relearning .
36
Explain the different ways that amygdala stimulation produces emotional behaviors through subcortical pathways.
The Lateral hypothalamus--> Sympathetic Activation (due to amygdala stimulation) --> may cause tachycardia, galvanic skin response, paleness, pupil dilation, blood pressure elevation
-Dorsal motor n of vagus and Nucleus ambiguous can affect parasympathetic activation (due to amygdala stimulation) which may lead to ulcers, urination, defecation and bradycardia
-The Parabrachial nucleus can lead to increased respiration and causes panting, and respiratory distress.
-The ventral tegmental area, locus ceruleus, Doral lateral segmental neuron can affect activation of dopamine, norepinephrine and acetlycholine causing behavioral and EEG arousal, increased vigilance.
-The N. Reticularis pontis and caudalis can cause increased reflexes (due to amygdala) and lead to increased startle
-The Central grey can cause cessation of behavior (due to amygdala stimulation) leading to freezing, conflict test, CER, or social interaction
-Trigeminal, facial motor nerves can cause mouth open, jaw movements (amygdala stimulation) and lead to facial expressions of fear
-paraventricular nerves (hypothalamus) can cause ACTH release (amygdala stimulation) and lead to corticosteroid release ("stress response")
37
What are functions of the Amygdala?
Functions of the Amygdala:
-Behavioral awareness areas
-Project into the limbic system (one's current status in relation to both surroundings and thoughts)
-Make the person behavioral response appropriate for each occasion
-relate environmental stimulus to coordinated behavioral autonomic and endocrine responses seen in species-preservation
-Responses include:
feeding and drinking
-Fighting behavior
-mating and maternal care
-responses to physical or emotional stresses
38
Who was Charles Whitman and why was he significant
Charles Witman (August 1st, 1966) was married and had a dog. During last few months, he wrote a note on August 1st, about him hearing voices for him to do certain things. He talked to a psychiatrist and no psychiatric conditions were detected. That same day, Charles killed his wife (with a knife) and went to his mother and killed her as well. He also went to public place and started shooting people.
-his pathology showed that something was haunting Charles and he was being forced to do this.
He had a pathological condition (astrocytoma; brain tumor on his amygdala) that led him to do this. He had this tumor going on for a year.
-This brought the attention to the amygdala, the function and importance of it
39
Who was Phineas Gage? How did his behavior change before vs after incident
Phones Gage (September 13, 1948)
-he was working on railroad and had an accident, where rod went through his frontal cortex. After reconstruction of brain he had a lot of damage, lost Vision in one eye, and entire prefrontal cortex was lesioned, and had major sprouting due to inflammation and trauma he went through.
He changed his behavior after accident, from being very nice, and hardworking to rage, violence
Hence our prefrontal cortex can change our behavior or our personality.
Before accident: capable, efficient, best freeman and well balanced mind
After accident: extravagant, anti-social, liar, grossly profane
He died 12 years later
40
What is the Kluver Bucy syndrome? How does this affect behavior in animals? What can help those with this syndrome?
Kluver -Bucy Syndrome: odd behavior that appears in cats, and also occurs in humans that are addicted to pornography
- Cats become sexually very active, hyper sexual, orally fixated and compulsive behavior when you REMOVE the amygdala in animals.
-Preoperation (before removal of amygdala)
-cat will be aggressive and raging
-Postoperation (after removal): Docile, orally fixated, increased sexual and compulsive behaviors)
41
What are the features that occur with Kluver Bucy syndrome in Humans?
Kluver Bucy Syndrome in Humans:
- caused by Severe temporal lobe damage (also seen in humans addicted to pornography)
may occur with people who had tumors, surgery, trauma
Symptoms:
-Visual Agnosia- the inability to identify the face of a familiar person or object
-Apathy/placidity
-Hyperorality
-Disturbance in sexual function (hyper sexuality)
-Dementia, aphasia, amnesia
-
42
What are the roles of Anterior Cingulate Gyri and Subcallosal gyri? What happens if the gyri are destroyed?
The Anterior Cingulate gyri and Subcallosal Gyri: are portions of the limbic cortex that communicate between the prefrontal cortex and cerebral cortex and the subcortical limbic structures.
-Destruction of these gyri bilaterally releases the rage centers of the septum and hypothalamus from prefrontal inhibitory influence
-Animals can become viscous and Violent and much more subject to fits of rage than normally.
43
What are the different Roles of prefrontal cortex?
Roles of the Prefrontal Cortex:
-Higher levels of the cortex are also crucial for CONSCIOUS AWARENESS of emotional feelings
-Higher levels of the cortex, particularly the prefrontal and limbic association areas, are important in conscious learned control of innate behavioral patterns
-Prefrontal cortex formulates plans and guides behavior, SUPPRESSING amygdala-induced responses that may be inappropriate for the situation at hand.
(prefrontal cortex has inhibitory repose on amygdala response to rage)
44
Which brain structures modulate emotion?
Hypothalamus, Limbic system, limbic cortex, amygdala and brainstem
45
What are the functions of the Hypothalamus ?
Hypothalamus:
-Nueral structure lying below (hypo) the thalamus; directs several maintenance activities:
-eating
-drinking
-body temperature
-helps govern the endocrine system via the pituitary gland
-linked to emotion
46
what other brain structures is the hypothalamus connected?
Hypothalamus is also connected to Lamina terminals, ventral thalamus, internal capsule and third ventricle
47
Discuss the afferent connections present in brain
Afferent connections :
-The hypothalamus receives visceral (including taste) through spinal cord and brain stem
-Afferents from nucleus of tractors solitarus to hypothalamus carry taste sensation
-somatic afferents reach through collaterals of major ascending tract
-Afferents from olfactory pathway and limbic system (anterior perforated substance, septal nuclei, amygdaloid complex, hippocampus, pyriform cortex)
48
How are animal models used to describe how behavior is generated?
Animal model: rats are very smart, and used for conditioning experiment
triune brain: reptilian, limbic and human brain; you need to decide how much risk you are willing to to take to get reward
rat must balance how much fear it must go through (on electrified grid) to press lever and receive stimulation that induces well being or pleasure or perhaps psychotic drugs.
49
Which brain structures are apart of reward circuit?
Reward circuit involve the hippocampus, amygdala, nucleus accumbent, prefrontal cortex, ventral pallidum, ventral segmental area
Ventral segmental area- reward system
when fear and rage occurs, you need a reward system (way of recovering and a prize to help overcome emotion)
-Glutamate (excitatory amino acid) , GABA and Dopamine are always involved.
GABA-aminobutryic acid always need to stop excitation in the brain
50
What is known about Ablation(lesion) studies in Cats? How this affect their behavior?
Ablation (lesion) Studies in Cats :
-We can sever an area of brain (like entire cortex)
-If we remove Cerebral hemispheres: it leads to rage in cats
-If we remove hemispheres and Hypothalmaus: we do not have rage (instead have plasticity)
-hence we need balance between certain connections of brain with others.
51
What can be observed in stimulation studies in cats?
Stimulation studies in cats:
Lateral hypothalamic stimulation: causes rage and attack in kids
-in other areas, cats are defensive and have fear
52
Describe all of the different hormones that are secreted by hypothalamus, and their functions.
Hypothalamic function:
1) Thyrotropin releasing hormone (TRH; produced by Parvocellular neurosecretory neurons): stimulate the thyroid-stimulating hormone (TSH) release from anterior pituitary
-TRH also stimulates prolactin release from anterior pituitary
2) Dopamine (DA; produced by dopamine neurons of arcuate nucleus) INHIBIT prolactin release from anterior pituitary.
3) growth-hormone releasing hormone: (GHRH; produced by neuroendocrine neurons of arcuate nucleus) Stimulate the growth hormone (GH) release from anterior pituitary
4) Somatostatin (SS; growth hormone inhibiting hormone) produced by neuronecrince cells of periventricular nucleus; SS inhibits growth hormone relate from anterior pituitary and inhibits TSH release from anterior pituitary
5) Gonadotropin releasing hormone (GnRH; produced by neuroendocrine cells of paretic area) stimulate the follicle stimulating hormone (FSH) release from anterior pituitary and stimulate the Lutenizing hormone (LH) release from anterior pituitary
6) Corticotropin releasing hormone (CRH) produced by parvocellular neurosecrteory neurons stimulate the adrenocorticotropic hormone (ACTH) release from anterior pituitary
7) Oxytocin (responsible for delivery of babies) is produced by magnocellular neurosecretory cells and causes uterine contraction and Lactation (letdown reflex)
8) Vasopressin (antidiuretic hormone): produced by magnocellular neurosecretory cells causes increase in permeability to water of the cells of distal tubule and collecting duct in the kidney and thus allows water reabsorption and excretion of concentrated urine
53
What is Hypothalamic Pituitary Axis? What happens if this Axis is out of control?
Hypothalamic Pituitary Axis: Describes How Hypothalamus (corticoreleasing hormone) will stimulate the Anterior pituitary (produces Adrenocorticotropic hormone) to affect the Adrenal cortex (that produces cortisol)
However, if this Axis (cycle) is out of control, this can cause rage, violent behavior or even neurodegeneration in a person)
-(this effect was noticeable in one who had MRI, and had Cushing's syndrome)
54
Explain what happens when there is damage to mammillary bodies?
Damages to Mamillary bodies:
-Due to THIAMINE deficiency (Vitamin B1) is implied in pathogenesis of Wernicke-Korsakoff Syndrome (more severe than Korsakoff)
-Symptoms include impaired memory, also called ANTEROGRADE AMNESIA (no ability to form New memories)
-Lesions of the medial dorsal and anterior nuclei of thalami and lesions of the mammillary bodies are commonly involved in amnesic syndromes in humans
55
Describe the structure of the Hippocampus and its components
Hippocampus
-In cross section resembles "sea horse"
- Is the inferomedial structure of the parahippocampal formation
-Hippocampus is divided into several zones of pyramidal cells: CA1-CA4 fields
-Trilaminate structure
-Molecular
-Pyramidal
-Polymorphic
The most sensitive area in the brain for ischemic events in hippocampus is CA1
-Stretches in a "C" shape formation over the corpus callous
(hippocampus relevant in short term memory, acquisition of memory, learning, consolidate memories and transfer information to adrenal cortex)
56
Describe the cytoarchitecture of human vs rodent, including where the hippocampus can be seen. What are the two interlocking cell fields?
Cytoarchitecture:
-In Humans: the hippocampus can be seen in saggital view
while in rodents: the hippocampus is seen in coronal section
Two interlocking cell fields :
-Dentate gyrus
-hippocampus
57
Describe the structure and function of the Dentate gyrus
Dentate Gyrus
-Lies between fimbria of hippocampus and parahippocampal gyrus
-Toothed/beaded surface
-Consists of three layers of neurons:
-Molecular Granular- most prominent, contains granule cells, principle excitatory neurons of dentate gyrus, Polymorphic
-The major input- perforant pathway form layer II of the entorhinal cortex
The perforant pathway- medial perforant path; lateral perforant path
Function: formation of memories play a role in depression
58
What other pathologies can malfunction or damage of hippocampus cause?
Damage or malfunction of hippocampus can trigger seizures (focal, or ones that spread all around brain) , or cause depression
59
What happens to hippocampus when one with severe depression is not treated?
if severe depression is not treated, the hippocampus will SHRINK (due to cell death in those areas; apoptosis) that can be observed in MRI.
60
Explain differences seen in hippocampus and Entorhinal cortex with normal brain vs brain of someone with Alzheimer's disease
Normal Brain: Cerebral cortex, hippocampus and entorhinal cortex are all normal size
Alzheimer's disease (or any progressive form of Dementia): the Ventricles will become severely ENLARGED (due to atrophy; loss of brain matter) , extreme SHRINKAGE of Hippocampus and Shrinkage of Cerebral cortex
61
which parts of brain are affected when one has seizures?
Hippocampus and temporal lobe are brain structures involved in seizures.
Temporal lobe epilepsy: can be focal and spread throughout brain (lead to fatal form of epilepsy)
62
What are the Limbic Clinical Syndromes?
Hypolimbic (reduction in limbic system function)
-Depression
-Apathy
-Amnesia (hippocampus)
-Kluver-Bucy Syndrome (Amygdala)
-Anxiety/Panic
-Psychosis
-Narcolepsy
Hyperlimbic (increase in Limbic function)
-Mania
-OCD
-ADHD
-Limbic Epilepsy
-Limbic encephalitis
-Rage (from Hypothalamus and Amygdala dysfunction) due to trauma or tumors
63
Describe the brain structure involved in sleep and Dreams.
PET and fMRI have shown that the LIMBIC SYSTEM is one of the most active brain areas during Dreaming
-The limbic system probably interweaves unconscious primal emotions with our conscious cognitive thoughts and perceptions and thereby ties together emotions and memory during REM sleep to form content of dreams
64
Describe the parts of the hypothalamus that control the sleep-wake cycle, and how it works.
The suprachiasmitc Nucleus of Hypothalamus is the circadian rhythm generator controlling the sleep-wake cycle
-The Ventrolateral Preoptic Nucleus (VLPO) of the hypothalamus sends projections to the Histaminergic tuberomamillary nucleus (TMN), the serotonergic dorsal and medial raphe nucleus and the noradenergic locus coeruleus.
(LHA are orexin-releasing (active during arousal) ; VLPO is sleep promoting; RAPHE, TMN LC are arousal-promoting)
65
What are the functions of VLPO and LHA (lateral hypothalamic area) and how do they contribute to sleep regulation?
The VLPO (ventral lateral pre optic nucleus) via its inhibition of the Major arousal mechanisms, functions as a "sleep switch" promoting sleep
-The VLPO by its DISINHIBITION of the PPT-LDT also promotes REM sleep
-The Lateral Hypothalamic area (LHA) contains orexinergic neurons that promote wakefulness
**The OREXINERGIC neurons inhibit the sleep-promoting VLPO and the REM sleep-promoting neurons in PPT-LDT**
66
Which structure in the brain are Sleep promoting vs Arousal promoting? Discuss the neurotransmitters that are also involved
Arousal promoting: LC, RAPHE, TMN all inhibit VLPO function and promote arousal
-SLEEP promoting: VLPO; has direct INHIBITORY connections to all arousal promoting nuclei
Sleep promoting like VLPO: have GABA that is most active during sleep (since GABA will inhibit )
-Arousal promoting like LC has Norepinephrine most active during arousal; RAPHE has serotonin most active and TMN has histamine most active during arousal
-Orexin-releasing LHA; has orexin (neurotransmitter) that is most active during arousal
67
What is Narcolepsy? What causes it?
Narcolepsy: A disorder due to a malfunction of the sleep/wake cycle regulating system in the brain, caused by Lack of an important chemical in the part of the brain responsible for controlling sleep
68
What are the characteristics of Narcolepsy?
Characteristics of Narcolepsy:
-Daytime sleepiness
-Cataplexy (sudden muscle weakness that occurs when one is awake)
-Sleep paralysis
-Instantaneous REM sleep
-Hypnagogic Hallucinations (hallucinations that occur as you fall asleep)
69
What is the incidence of Narcolepsy in America? how many are aware?
1 in 2000 (or 250,000) Americans have Narcolepsy
-While less than 50,000 are ware of their own disease
70
Describe the stages of Normal/Sleep Wake Cycle
Normal Sleep/Wake Cycle
-Sleep is not merely passive
-Normal sleep occurs with a distinct cycle of stages:
1) Waking state
2) 4 stages of Non-REM (Slow wave)
3) REM sleep
71
What are the characteristics of REM sleep?
REM Sleep
-Rapid Eye Movements
-Neocortex activation is similar to waking state
-Makes up 20% of sleep duration
-Occurs 70-90 minutes into sleep
-Muscular paralysis
72
Describe what occurs in Narcoleptic Sleep cycles
Narcoleptic Sleep Cycles:
Onset of sleep= less than 10 minutes
Poor nocturnal sleep contributes to feelings of sleepiness in the morning
REM sleep= less than 20 minutes
Quick onset of REM sleep causes inadequate rest, other mental problems
-Hallucinations and nightmares (often causes them to have insomnia, since circadian rhythm is affected)
-
73
Discuss how Narcolepsy affects REM sleep
REM sleep and Narcolepsy
-Loss of muscle control resembles a neurological protective of REM sleep
-Hypnagogic hallucinations, illusions similar to dreams
-Sleep paralysis where after falling to or waking from sleep, a person finds that they cannot move
74
Describe the Canine Model for Narcolepsy and what was found inside the dog brain
Canine Model for Narcolepsy (in brain of dog):
Found axonal Degeneration in:
-Amygdala
-Basal Forebrain
-entopenucular Nucleus
-Medial Septal region
They also found that Narcolepsy was caused by a mutation in:
-Orexin peptide gene
-Involved with sleep and wake cycles
-Hypocretin Receptor 2 Gene (Hctr2)
-Involved with excitatory system
75
What is the role of Hypocretin?
Role of hypocretins:
-Modulate neurons involved with REM sleep
-Help the interaction between the aminergic and cholinergic systems
-May produce Wakefulness and depress REM sleep
-Stimulation of hypocretin receptor 2 gene
76
Describe how different brain structures work normally vs in Narcoleptics
Neurological correlates
-Dorsolateral Pons and Medulla:
Normal: Suppresses muscle tone during REM
Narcoleptics: causes cataplexy (muscle weakness or paralysis while awake)
-Amygdala
Normal: aids perception of emotional responses
Narcoleptics: Activates brain stem's motor inhibitory system causing cataplexy through strong emotional triggers
-Hypothalamus
Normal: regulates the excitatory system
Narcoleptic: Possess a reduction in Hypocretin and thus causes a decrease in Heart activation, which results in sleepiness.
77
What are some cures or forms of treatment that can be sued for Narcolepsy
Narcoleptic Cures:
There is NO cure for narcolepsy
-However, there are some drugs that help with many of the symptoms
-Amphetamines- help with day time sleepiness
-Antidepressants- help with suppressing REM, cataplexy, paralysis, and hallucination
-Hypocretin- helped cure dogs of cataplexy
78
Describe how changes in the limbic system can lead to Dementia
Dementia (group of conditions characterized by impairment of at least two or more functions; such as memory or judgement )
- **Degenerative Changes in limbic system likely have a role in neurodegenerative diseases, particularly Pick's disease (FTD) and Alzheimer's disease
-Marked Atrophy is found in the limbic system, most notably the dentate gyrus, and hippocampus.
79
Discuss how different brain structures are affected in Alzheimer's Disease
In Alzheimer's disease, senile plaques and neurofibrillary tangles are dispersed throughout the cerebral cortex and basal ganglia
-But the hippocampus and amygdala are often severely involved; may be the result of a failure of the anterior cingulate and hippocampus to modulate the activity of amygdala
-A fear circuitry, involving the amygdala, prefrontal and anterior cingulate has been described.
80
What are the changes observed in limbic system in someone who has Schizophrenia? How are other brain structures affected?
Schizophrenia:
-Studies have shown REDUCED limbic volumes. Distortion of cortical neurons, decreased size of hippocampus, reduced number of GABAergic cells in the cingulate and anterior thalamus with glutamatergic excitoxicity.
(imbalance of GABA and glutamate)
Biological finding: when comparing twins (one who was normal, other was schizophrenic)
-Enlarged ventricles (spaces) in the brain and or decreased volume in frontal and temporal lobes
-Indicates deterioration or atrophy of brain tissue
-Supportive evidence: CT scan and MRI studies
(many symptoms associated with psychosis: see reduction of cerebellum, enlargement of 4th ventricle, and atrophy of brain in MRI)
81
Explain the changes in limbic system that are seen with Affective Disorders
Affective Disorders:
Studies have shown variation in volumes of the frontal lobes, basal ganglia, amygdala and hippocampus
-Functional studies have revealed decreased prefrontal and anterior cingulate activity. Recently, researchers have posited that affective and cognitive symptomatology represents dysfunction within a network- the anterior limbic network; which includes prefrontal regions and subcortical structures such as thalamus, striatum and amygdala
-The dysfunction of this system (anterior limbic network) is suggested in bipolar disorder, but its role in depression is unclear.
82
Which brain structures are affected in those with ADHD?
ADHD (attention deficit Hyperactive Disorder)
-The ENLARGED hippocampus represent a compensatory response to the presence of disturbances in the perception of time, temporal processing and stimulus-seeking associated with ADHD
-Disrupted connections between amygdala and orbitofrontal cortex may contribute to behavioral disinhibition
(imbalance of excitatory vs inhibitory neurotransmitters)
83
How are brain structures affected Kluver-Bucy Syndrome? What are the causes?
Kluver-Bucy Syndrome:
Bilateral destruction of the amygdaloid body and inferior temporal cortex, characterized by visual agnosia (visual impariemtn) , placidity, hyperorality, and hyper sexuality.
Caused by cerebral trauma; infections including herpes and other encephalitides; Alzheimer's disease and other dementias; Niemann-Pick disease and cerebrovascular disease
84
what occurs in brain structures during Korsakoff's Psychosis? How does this affect memory?
Korsakoff's Psychosis (amnesic disorder due to vitamin b1 deficiency ; memory impairment)
-Damage to mammillary bodies, dorsomedial nucleus of thalamus and hypothalamus (diencephalic memory circuit)
- Chronic prominent impairment of recent and remote memory (events in past; LTM)
-Immediate recall is usually preserved
-Confabulation may babe marked but is not invariably present
(confabulation: creation of false or erroneous memories without intent deceive)
-if this condition is severe, and chronic, can result in irreversible impairment
85
Which brain structures are affected in those with Autism?
Autism
-Disproportionate impairment in specific aspects of social cognition
-Limbic structures involved--> Cingulate gyrus and amygdala, which mediate cognitive and affective processing
-The basolateral circuit integral for social cognition is disrupted in autism spectrum disorders.
86
What is the most common epilepsy in adults? What causes it and which brain structures are affected by Epilepsy?
Epilepsy
-TEMPORAL Lobe epilepsy is the Most COMMON epilepsy in adults
-It is most often caused by hippocampal sclerosis
-Hippocampal sclerosis with involvement of amygdala and parahippocampal gyrus--> medial temporal sclerosis (MTS; scarring in deep part of temporal lobe)
-The frequency and widespread distribution of cerebral abnormalities suggest that MTS is NOT limited to the medial temporal lobe but instead, represents a limbic system disorder.
87
What occurs in limbic encephalitis? Which brain structures are involved ?
Limbic encephalitis:
-A paraneoplastic syndrome reported with carcinoma of the lung, breast and some other primaries (mostly seen in metastisized cancer, that has reached brain)
-Manifests as encephalitis that primarily involves the hippocampus, amygdala, cingulate gyrus, insulation and orbital-frontal cortex
Afflicted patients develop subacute onset of memory loss, dementia, involuntary movements and ataxia (poor muscle control)
(limbic encephalitis will also have personal behavioral changes, sleep wake/cycle changes and personality changes)
88
What is the role of Reticular Formation? Where is it located in the brain and what is its role?
in Brain stem: Reticular formation
-reticular formation is part of brainstem web
-has 100+ cell groups
-Controls Sleepwalk rhythm, Arousal and attention
89
Describe the structure of the Reticular Formation ?
Reticular Formation (RF)
-The Reticular Formation is formed of large number of neurons present through entire brainstem, it extends upward to the level of thalamus and downward to be continuous with interneurons of spinal cord.
90
What are the respiratory control centers in brain stem? What structures are involved in these centers?
Respiratory control (breathing) centers in brain stem:
-Pons Respiratory centers:
Pneumotaxic center
Apneustic center
Pre-Botzinger complex
-Medullary Respiratory Center
-Dorsal respiratory group
-Ventral respiratory group
91
What are the Afferent projections of the Reticular formation?
The Reticular Formation:
Afferent projections
-All sensory pathways (general or special sensations)
-cerebral cortex
-cerebellum
-Basal ganglia (corpus striatum)
-Vestibular nuclei, visual pathway
-Thalamus, Subthalamus, and Hypothalamic Nuclei
92
What are the Efferent projections of the Reticular formation?
Efferent projections of The Reticular Formation:
(go to motor control)
-Reticulobulbar and reticulospinal tracts
-descending pathway to sympathetic and parasympathetic outflow of ANS (autonomic nervous system)
-cerebellum
-Basal ganglia (corpus striatum)
-Thalamus, Subthalamus and Hypothalamic nuclei
93
What are the connections of Reticular Formation?
Afferent connections of Reticular formation
cerebellum cortex, spinal cord (pathway for touch, pain, temperature, kinesthetic sensation) , sensory pathways (optic pathway, auditory, olfactory and taste pathway)
Efferent connection of Reticular formation:
-cortex, cerebellum, Thalamus, hypothalamus and subthalmaus, spinal cord and Red nucleus, substantial Nigra, tectum
94
What are the major function of Reticular Formation?
Reticular formation Functions
1) control of skeletal muscles
2) control of somatic and visceral sensations
3) control of autonomic nervous system
4) Influence the biological clock
5) The reticular activating system
6) control of endocrine nervous system
95
How does Reticular Formation influence sleep? Differentiate between sleep and coma
RF and Sleep
-Sleep is defined as a changed state of consciousness from which the person can be aroused by sensory or other stimuli. it is facilitated by reducing sensory input and fatigue
Coma is unconsciousness from which the person CANNOT be aroused
**DAMAGE to RF (reticular formation) causes persistent unconsciousness and even coma ***
96
Where is the Basal Ganglia located and what is its primary role
Basal ganglia located in front of thalamus, and controls voluntary movement
97
Discuss the components, function and circuitry of basal ganglia
Basal Ganglia
Components of basal ganglia: putamen, caudate nucleus, globes pallidus (lateral and medial parts; in cerebrum) , Thalamus, subthalamic nucleus (in diencephalon) , substantia Nigra (midbrain)
Functions: control voluntary movement
Functional circuitry of basal ganglia (ex: direct and indirect pathways, transmitters)
-Circuitry involved in movement disorders discussed (Parkinson's disease; more than 90% cells in substantial nigra are depleted)
98
What brain structure drives our voluntary movement?
Substantia Nigra
99
What is the Substantia nigra components? How are they divided?
substantial nigra: two parts: P.c and p.r
- tiny area rich in dopamininc cell bodies, that contain putamen, cortex, global pallidus and thalamus
Throughout balance of intertwined interactions, we have ability to understand, freeze or function
one core separated by two; one is filled with compacted dopaminergic cell bodies, and gabaergic one (inhibitory input)
100
Which brain structures are involved in movement?
basal ganglia, thalamus, cerebellum and motor neurons, intermotorneurons and spinal cord.
101
Where is the thalamus located in the brain? What are its roles?
Thalamus: The brain's sensory switchboard, located on top of the brainstem
-It directs messages to the sensory receiving areas in the cortex, and transmits replies to the cerebellum and medulla
(there are multiple nuclei in the thalamus)
102
What are the major nuclei of thalamus?
Nuclei of Thalamus:
-It is subdivided into the following major nuclear groups on basis of their rostrocaudal and mediolateral location within thalamus;
-Anterior
-Medial
-Lateral
-Intralaminar and reticular
-Midline
-Posterior
103
What are the Neural structures involved in the control of movement?
Neural structures involved in control of movement:
Descending systems (upper motor neurons)
-Motor cortex (planning, initiating, and directing voluntary movements)
-Brainstem centers (basic movements and postural control)
-Basal Ganglia (gating proper initiation of movement)
-Cerebellum (sensory motor coordination)
-Spinal cord and Brains stem circuits (include local circuit neurons, motor neuron pools, sensory inputs and Skeletal muscles)
104
Which view of brain is basal ganglia able to be seen
In coronal and saggital view of cats, you can see basal ganglia
105
Which structure in brain are connected to basal ganglia?
Basal ganglia is intertwined with caudate and Putamen. It also close to amygdala and temporal lobe
106
Describe the convergence loop in Basal ganglia. How does cell number change?
The Basal ganglia have convergence loop that are made up of large dendritic trees of striatum output neurons (aka as medium spiny neurons). These medium spiny neurons are only formed in basal ganglia
The large dendritic trees and cell number DECREASES as you go from Cortex (highest)--> To striatum (30,000)--> GPe (global pallidus exterior; 100)--> Gpi/SNr (global pallidum interior/ substantial nigra; 1) which is lowest
107
What are the major basal ganglia loops?
Basal Ganglia loops:
-Motor loop: which start in primary motor, premotor, and supplementary motor cortex and then reach Motor, premotor, somatosensory cortex --> Putamen--> Lateral globus pallidus, internal segment--> Ventral lateral and ventral anterior nuclei
-Prefrontal (Associative) loop: start in Dorsolateral prefrontal cortex--> Anterior caudate--> globus pallidus, internal segment; substantia nigra pars reticulata--> mediodorsal and ventral anterior nuclei
-Limbic loop: start in anterior cingulate, orbital frontal cortex and reach Amygdala, hippocampus, orbitofrontal, and anterior cingulate, temporal cortex--> Ventral striatum--> Ventral pallidum--> Mediodorsal nucleus
108
What occurs in the direct pathway of the Basal ganglia? What brain structures are involved?
REVIEW
Direct Pathway (Basal Ganglia): facilities movement
-pathway driven by substantial nigra
-Cortex undergoes excitation (glutamate) to activate striatum which will INHIBIT globus pallidus interior (Gpi) and substantial nigra (Gpi/SNr)
-Striatum
-Inihbiton of Gpi/SNr (by GABA) will cause Disinhibition of VA/VL (of thalamus) and cause so you facilitate movement (excite cortex)
(global pallidus exterior and interior are tonically active)
109
What occurs in the indirect pathway of Basal ganglia?
REVIEW.
Indirect Pathway (basal ganglia): INHIBITS movement
-Cortex will undergo excitation (glutamate) which will activate striatum. The striatum will inhibit globus pallidus exterior and lead to Disinhibition of globus pallidus exterior
The disinhibition will lead to excitation (glutamate) of GPi (globus pallidus interior) /SNr (substantial Niagra) that will also inhibit VA/VL (of thalamus; inhibit through GABA)
110
What determines Motor behavior?
Motor behavior is determined by the balance between direct and indirect striatal outputs
111
What are Hypokinetic and Hyperkinetic disorders?
Hypokinetic disorders: insufficient Direct pathway output; Excess indirect pathway output
Hyperkinetic disorders: Excess DIRECT pathway output and Insufficient indirect pathway output
112
What clinical features are seen in Hypokinetic Disorders? Provide examples of diseases that fall under this category of Hypokinetic disorders
Hypokinetic Disorders: are diseases where patients have Slowness of voluntary movement (bradykinesia) and muscle rigidity (Stifness), or in general, diminished and slowed automatic movements (such as eye blinking or arm swing when walking)
The most common of these disorders is PARKINSON'S Disease (PD). But other degenerative disorders include : Progressive Supranucelar Palsy (PSP) ; multiple system atrophy (MSA) and corticobasal ganglionic degeneration
-hypokinetic disorders also occur because of Stroke or medications
(Side note: antipsychotic medications target dopamine (as an atagonist; but also causes hyperkinesia)
113
Describe the pathophysiology of Parkinson's disease. Which celebrities are known to have Parkinson's disease?
Pathoyphysiology of Parkinson's disease:
Primary: Loss of nigrostritatal DA (dopamine) projection
Celebrities with Parkinson's disease: Michael J. Fox, Muhammad Ali, Pope John Paul, Janet Reno, and Katherine Hepburn
114
What are the Diagnostic features of Parkinson's disease?
Diagnostic Features
Four Cardinal Signs (TRAP)
-Tremor (at rest)
-Rigidity
-Akinesian(no movement) and Bradykinesia (slow movement)
-Postural instability
(these four signs were used to diagnose one with Parkinson's disease)
115
Discuss the difference in human midbrain structure of normal person vs one with Parkinson's disease
Normal Human Midbrain : all structures of brain are in place; including substantial nigra
-Parkinson's disease: substantial Nigra is missing.
116
What characterizes hyperkinetic disorders? List these disorders and their causes
Hyperkinetic disorders: Chromatic syndromes
1) Huntington's chorea; Cause: Genetic (autosomal Dominant)
2) Dystonia; Cause: Genetic or idiopathic (disease with no cause)
3) Tardive dyskinesia; Cause: Chronic neuroleptic use (dopmainergic antagonist)
4) DOPA-induced dyskinesia; Cause: Parkinson's therapy
(L-DOPA is a precursor of dopamine develops sensitization of receptors and causes dyskinesia)
5) Hemiballismus (abnormal movement of eyes) ; Cause: Unilateral vascular accident, typically subthalamic nucleus
117
Describe The clinical features of Tourette's syndrome and what most patients have in addition to this syndrome. What kind of disorder is Tourette's syndrome?
Tourette's syndrome; one of Hyperkinetic disorders (choreatic syndrome)
-Tourette's syndrome: characterized by repetitive involuntary movements. Precise etiology unknown. May be inherited in 80% of cases.
Support for developmental disorder of synaptic neurotransmission involving cortical-subcortical circuitry.
(Tourette's syndrome can come with motor pathology and limbic pathology (ex: mania, depression)
-Approximatelty 90% of patients have comorbid condition:
-ADHD
-Obsessive compulsive symptoms/disorder
-learning difficulties/Learning disorder
-Anxiety disorders, including phobias
-Mood disorders (depression, dysthymia)
-Sleep disturbance
-Oppositional defiant disorder
-Executive dysfunction
self-injurious behaviors (may be tics)
-Link between comorbid conditions unknown.
118
What are four major comorbidities that can occur with Tourette's syndrome?
TS (Tourette's syndrome) course with comorbidites:
-Obesssive compulsive behavior
-Vocal tics (simple --> complex) ; people may say vulgar, absence things that are against their will
-Motor tics (rostral--> caudal progression)
-Attention-deficit-hyperactivity disorder
119
what are the different choreactic symptoms that can occur?
Choreactic symptoms:
-involuntary (unwanted) movements
-Chorea (dance-like)
-Athetosis (changeable or writhing movements)
-Dystonia (torsion spasm)
120
Describe the pathophysiology that occurs with Huntington's disease
Pathophysiology of Huntington's disease:
-Atrophy of striatum
-Loss of striatal GABAergic neurons
Nuerophtalogical sequence:
1st: Loss of striatal GABA/enkephalin/D2-R neurons (INDIRECT pathway)
2nd: Loss of striatal GABA/dynorphin/D1-R neurons (direct pathway)
121
Differentiate between the brain in normal person vs one with Huntington's Disease
Normal brain: normal shape of ventricles and brain
Huntington's Disease brain: complete eradiaction of basal ganglia, great volume loss
122
Discuss the Etiology (cause) of Huntington's disease
Etiology of Huntington's Disease:
-Caused by Huntington Mutation
-Mutation near 5' end contains >>> CAG repeats
-produces protein with excess glutamines near NH2 terminus
Why cell death? (seen in brain cells)
-Not certain yet
(there are treatments like antisense and CRISPR editing, gene sequencing for improving symptoms of gene therapy
123
Discuss the cognitive abnormalities, psychiatric changes and later effects that occurs with Huntington's disease
Huntington's disease; Hyperkinetic disorder
Cognitive abnormalities:
-Executive function (complex tasks)
-Recent and remote memory (Poor retrieval)
Psychiatric changes
-Depression
-Psychosis
Later Decline
-immobility
-Weight loss
-Death within 10-25 years (often from pneumonia)
