Limbic System Lecture Notes PDF

Limbic System DOSYS-725 MedNeuro II Lecture 12 Wednesday Jan 29 @ 9am Tony Harper, Ph.D. 1 Lecture Objectives Know general locations of the major monoaminergic nuclei in the brainstem and their effect on behavior and mood Be able to draw out conn...

Limbic System DOSYS-725 MedNeuro II Lecture 12 Wednesday Jan 29 @ 9am Tony Harper, Ph.D. 1 Lecture Objectives Know general locations of the major monoaminergic nuclei in the brainstem and their effect on behavior and mood Be able to draw out connectivity of the grey matter centers and white matter tracts involved with the “Limbic Loop”, “Septal loop”, Papez Circuit and the Amygdala. Understand the symptoms and brain lesions involved with Amimia, Wernicke’s Syndrome, Korsakoff’s Syndrome, and Klüver-Bucy Syndrome Identify images of limbic system structures in photographs and myelin-stained cross sections. Have general sense of which structures are next to which other structures 2  Small Mammal Human Subpallium becomes striatum, globus pallidus, and friends Allocortex (“intratelencephalic” fibers not project outside telencephalon, less than 6 layers): Archicortex(3 layers, from medial pallium): Dentate Gyrus, Hippocampus Proper Paleocortex(3-5 layers, from lateral and ventral pallium): Primary Olfactory Cortex, parahippocampal gyrus Juxtallocortex(3-6layers):Cingulate Gyrus, Fasciolar Gyrus, Isthmus, Subiculum Neocortex(aka “Isocortex”, 6 layers, likely at least partly from dorsal pallium) most cerebral cortex, including entorhinal cortex 3  Sense of smell closely associated with “Limbic” emotion and memory Old name for limbic system was “Rhinencephalon” “Limbic” from French word for “border” because forms ring around diencephalon “Le Grande Lobe Limbique” as adapted from Broca’s original 1878 drawing of an otter’s brain. Broca’s “callosal gyrus” is now termed the cingulate gyrus 4 Grey Matter White Matter 5  Lots of Loops (and “C”s) Cyclic networks of excitation/inhibition can be exaggerated/abbreviated by later evolved brain structures - to produce more contingent/diverse behaviors Current concept of Limbic System is a group of forebrain structures that regulate mood and facilitate memory, planning, decision making, and other “higher functions” Limbic system made from many concentric “C” shaped structures, which form anatomical and “logical” loops C-shaped structures can usually be found in two different places when seen in cross sections Atlas of Functional Neuroanatomy Hendelman 2000 6  “Affects” (emotions) evolved at different times, for different purposes Defensive(aversive) and appetitive affects appeared in early vertebrates “Sub-social” Parental emotions appeared in early mammals, and independently in birds, dinosaurs, etc. Social emotions (guilt, jealousy) appeared later in mammals that live in large groups Many emotions likely started with individual adaptive function, then gained social and symbolic functions in group- living animals 7  Emotions Versus Reflexes Like reflexes, behaviors associated with emotions can be somatomotor or autonomic Emotions (unlike reflexes) usually outlast the duration of eliciting stimulus Emotional tearing seems to be a uniquely human Emotions make various types of behavior more or characteristic less likely, not specify single stereotyped response Like reflexes, emotions tend to take priority over other behaviors. And help set goals and motivations in animals capable of longer-term planning 8  Emotions VS “Higher Functions” Cortically derived motivations set goals, emotions orient relative to goals (limbic system sometimes called the “caring” system) Emotions also determine what is memorable and learnable, and allow organisms to alter behavior based on long past experiences and express individual characteristics Emotions(especially very intense or social emotions) are also strongly associated with the sense of smell, (e.g. smell of burning oil is a common trigger for PTSD in soldiers) Higher capacities for long term planning, simulation, and declarative memory are usually used to accomplish goals set by limbic system. Often when higher functions fail due to neurological deficits, individuals fall back on behaviors generated by limbic system 9  Sympathetic vs Parasympathetic : use- up versus accumulate metabolic reserves Different emotions are associated with autonomic responses, and may have appeared to allow finer control of neuroendocrine physiological state Weissman, D. G., & Mendes, W. B. (2021) 10 Categories of Emotion Many psychological books list “basic” or “universal” categories of emotion E.g. Plutchik’s “Wheel of Emotion” has 8 basic emotions with high and low intensity forms, and combinations of “neighboring” emotions 11  Simple vs Complex Emotions A List of some complex and culturally specific emotions Awumbuk The feeling of emptiness when visitors depart – Papua New Guinea Fago The pity felt for someone in need, which compels us to care for them, but is also haunted by a strong sense that one day we will lose them – Caroline Islands Gezelligheid Feeling of being snug in a warm and homely place surrounded by good friends (it's impossible to be gezelligheid alone) - Dutch The Expression of the Emotions in Man and Animals Charles Darwin’s 3rd Book Ilinx “a kind of voluptuous panic” - sociologist Roger Caillois Anthropoids are social primates with very mobile Kaukokaipu facial muscles (especially upper lip) The craving to visit a distant land - Finland Facial expressions corresponding to ~6 “basic Emotional expressions can be compared emotions” do seem to be universal across Malu cultures. E.g. infants born blind will still smile from using TheFacial Action feeling Coding of being System in flustered (FACS) the presence of pleasant stimuli. someone we hold in high esteem - Indonesia However, more complex emotions are generally harder for members of different cultures to express and understand Source: The Book of Human Emotions – Tiffany Watt Smith 12  Patient with volitional facial paresis on right side (Left corticobulbar lesion) Context Specific Facial Motor Deficits Emotional facial expression UMNs cell bodies are located in anterior cingulate gyrus and send their axons through the anterior limb of the internal capsule - not through corticobulbar tract Patient with emotional facial paresis(amimia) on right side Lesions of anterior limb of internal capsule can cause contralateral “emotional facial paresis” (amimia) 13 Moebius Syndrome LMN Inability to move facial muscles or rotate eyes laterally (which nerves involved??) Often associated with oromandibular/limb hypogenesis Some evidence of aberrant emotional autonomic responses (Nicolini et al 2019) Suggests at least part of emotional responses are learned through imitation Bianchi et al. 2009. Bilateral transplantation of gracilis muscle James-Lange Theory of Emotion: (re-innervated by masseteric n.) to provide lower facial mobility Limbic System primarily a motor system (no “primary sensory” area for emotions) Subjective experience of emotion is a byproduct of detecting own physiologic state, well after triggering motor expression of emotion Emotions are not entirely hard-wired, and are at least partly acquired through the imitation of others 14 Emotional Field Theory Many psychological descriptions of emotional state use “multidimensional scaling” to quantify “arousal”, “valiance”, and other variable aspects Describing as a point within a continuum is sometimes seen as more scientific because not have to arbitrarily “bin” mental states into predefined categories Quantitative variables are also more easily correlated with ways to record emotional state such as skin Wilhelm Wundt 1900s conductance, startle response 15 Lövheim, 2012 Cube of Emotions Dimensions defined based on specified “extreme” emotions Axes correlate well with activity of monoamine neurotransmitters in CNS 16  Better living through chemistry Groups of neurons in brainstem reticular formation form Diffuse Modulating Systems – each associated with one of three monoamine neurotransmitters (dopamine and norepinephrine are also catecholamines). Each system has only ~10-15,000 neurons but extremely long and widely distributed and branching axons Diffuse Modulating System neurotransmitters are used as broadcast signals. They are not just released at synapses, and use “volume transmission”- release of neurotransmitters directly into extracellular space and CSF Many of these nuclei are important for maintain normal sleep cycles and are part of the “Ascending Reticular Activating System” 17  Norepinephrine(NE) Serotonin(5HT, for “5-hydroxytryptamine”) Cell bodies of adrenergic neurons in brain located in Locus Raphe Nuclei throughout brainstem are locations of serotonergic Coeruleus neuron cell bodies NE disorders associated with anxiety, ADHD, PTSD, etc. 5HT disorders associated with depression, such as those treated with SSRIs Active during non-REM sleep 18  J. Milla Dopaminergic pathways rd Collections of neurons cell bodies which synthesize and project dopamine are primarily located in the midbrain. Typically, a one neuron pathway, projecting to forebrain. Major pathways include: oMesolimbic- Ventral tegmental area (VTA)à limbic structures (reward) oMesocortical- VTAà pre-frontal cortex (cognition) oMesostriatal (AKA nigrostriatal) - SNcà caudate/putamen oTuberoinfundibular- Hypothalamusà pituitary gland (prolactin release) Dopamine also produced in kidney and in arcuate nucleus of hypothalamus, where it is also sometimes called Neuroanatomy through Clinical Cases (2 ed ed), Blumenfeld, Fig. 14.10 (Right) https://brain.oit.duke.edu/lab04/lab04.html (Left) prolactin inhibiting hormone 19  Nucleus Accumbens Major Nucleus in Dopaminergic “Reward Pathway” Overabundance of mesolimbic dopamine is thought to be related to schizophrenia Nucleus accumbens is part of Ventral Striatum (along with olfactory tubercle) Excited by psychostimulants like amphetamine and Nucleus Accumbens cocaine (Cocaine and (part of ventral striatum) amphetamine block Accumbens = ‘reclined’ reuptake of DA) Atlas of Functional Neuroanatomy Hendelman 2000 20  Looks a lot like “direct Pathway” through The “Limbic Loop” basal ganglia Abusive drugs turn “adaptive loops” into “repetitive loops” Prefrontal Cortex Ventral Tegmental Area DA Nucleus Accumbens 5H T Raphe Nuclei Ventral Pallidum (and Substantia Nigra Pars Reticulata) Basolateral Nuclei of Amygdala Mediodorsal Nucleus of Thalamus 21  Septal Area and Nuclei *Septal Nuclei deep to cortex J. Millard 22 Basic Clinical Neuroscience (3rd ed.) Fig. 17-1 22  Also part of “reward pathway” Stimulation causes reinforcement of behaviors that evoked the stimulation Experiments show that mice Septal Region includes: will seek out artificial Septal Area (cortex) stimulation of the septal nuclei Paraterminal gyrus over food and other rewarding Subcallosal area Septal Nuclei stimuli 23 Basolateral Nuclei of Brainstem Reticular Brainstem and Spinal Amygdala Formation cord motor nuclei Fa sc Septal Nuclei ic u lu s le “Septal Loop” Retr nd St ria T h a Bu (o o fle M la m f a in ed br ul us) xu s re la ris Fo ia l ed M Hypothalamus Habenular Nuclei (part of diencephalon) 24  Fibers of MFB running through lateral hypothalamic nuclei Septal Nuclei Medial Forebrain Bundle Medial Forebrain Bundle Atlas of Functional Neuroanatomy Hendelman 2000 25  Are “goal oriented” (rewarding/aversive) sensory experiences the reason we have emotions? Is forebrain even needed for emotional responses? Phillip Bard experiments comparing behavior of cats with detached forebrain, with and without hypothalamus intact Cats with just hypothalamus and brainstem intact were capable of emotional expression (“sham rage”), some also showed fear response. However, these cats show anger or fear based on almost any stimulus, do not have ability to select and prioritize emotional responses based on current goals and past experience 26  Telencephalon has a larger, more interconnected, and faster firing populations of neurons compared to most parts of brainstem Limbic system is a group of forebrain structures which select/reject emotional behaviors on a moment-by-moment basis – much like how the basal ganglia select/reject potential voluntary motor behaviors Can think of limbic system as a group of forebrain structures fighting for control of the hypothalamus and lower centers on the brainstem and spinal cord 27  Lisa Loeb: Limbic Lobe: Very emotional, not technically a lobe Also called Fornicate Gyrus Septal area= paraterminal gyrus and subcallosal area Neuroanatomy in Clinical Context (9 th ed.), Haines D., Fig (2-26) 28  Limbic System Blue = Emotions Green = Memory SA –septal area A – amygdaloid nucleus NA – nucleus accumbens MB – mammillary bodies OC - orbitofrontal cortex BN – basal nucleus 29 Hippocampal formation is deep to the posterior part of parahippocampal gyrus 30  Corpus callosum (body) Fornix (body) Septum pellucidum Mammillary body Hippocampal formation Atlas of Human Anatomy (7 th ed.), Netter F., Plate 117 31 31  Fornix (body) Commissure of fornix * (hippocampal commissure) Fornix (column) Mamillary bodies Fornix Fornix (crura, wrap around ~Latin: pulvinar, under “For – Nicks” splenium of CC) Fornix begins from alveus (means “bed of a river”) and fimbria Amygdaloid body Hippocampus * There is also a group of precomissural fibers (not shown here) in the fornix that connect the hippocampus (CA3) to the septal American Singer-songwriter area Stevie Nicks Atlas of Human Anatomy (7 th ed.), Netter F., Plate 123 32  Corpus callosum (genu) Caudate nucleus (head) Hippocampus Fornix (body) Corpus callosum (splenium) Commissure of fornix Atlas of Human Anatomy (7 th ed.), Netter F., Plate 123 33 Hippocampal formation can be found in floor of the temporal horn(inferior horn) of the lateral ventricle 34 Hippocampus Caudate Nucleus Stria Terminalis Fornix Temporal horn of lateral ventricle 35  Geniculate Nuclei Diencephalon-Midbrain MGN LGN MGN LGN Lateral geniculate nucleus looks like “Napoleon’s Hat” in coronal section 36  Choroid Plexus in Continuous with Fasciolar Gyrus, lateral ventricle Indusium Griseum, Subcallosal Gyrus, and tenia tecta “dentate” because has “scalloped” margin, like “toothed” hinge of clam shell One of the few locations where new neurons formed as adult The hippocampal formation is critical for memory formation and learning. The hippocampal formation is composed of three primary parts: Ø Parvocellular: Dentate Gyrus Ø Magnocellular: Hippocampus Proper Subiculum = ‘support’ (cornu ammonis) Ø Subiculum Atlas of Functional Neuroanatomy Hendelman 2000 37  Hippocampus Hippocampus is a modified sulcus developmentally Neuroanatomy through Clinical Cases (2 ed ed), Blumenfeld, Fig 18.10 (left), Fig 18.7 (right) 38 Hippocampal Formation Medial Pallium, migrates inferior during development “Hippocampus” = seahorse CA = “Cornu Ammonis” CA1&2 is called Sommer’s Sector. Is particularly vulnerable to ischemia Bilateral lesion of hippocampus (such as drowning) can cause anterograde amnesia. J. Millard CA3 is vulnerable to high blood cortisol (why you Basic Clinical Neuroscience (3rd ed.) Fig. 17-2 can’t study after pounding 5 monsters) 39  Falcon feather Ancient Egyptian God Amun Hellenistic Egyptian god Ammon Structure of amino acid Temple of Amun, Siwa Oasis Sal Ammoniac (ammonium chloride) 40 Papez circuit Functions to consolidate memory and learning by transferring short term memory to long term memory. The hippocampus emits signals that rapidly reverberate through the circuit and are then stored permanently in areas of the cerebral cortex for long-term memory. Essential Neuroscience (4 th ed.), Seigel A., Fig. 24.3 41  High Yield Papez Circuit Use your Hippocampal Formation to Memorize Me! 42 Wernicke's Syndrome A thiamine(vitamin B1) deficiency, often associated with dry beriberi (and chronic alcoholism) Degeneration of mammillary bodies and mammillothalamic tract Carbohydrate metabolism consumes vitamin B1, alcohol also causes diaresis of B1 Wernicke's Encephalopathy COAT: C: Confusion O: Opthalmoplegia Wet beriberi – Dry beriberi – peripheral dilation, Demyelination of A: Ataxia chronic hypotension CNS/PNS from and edema thiamine deficiency T: Thyamine Deficiency (no inflammation) 43  Wernicke’s-> Korsakoff’s syndrome/ Korsakoff’s Psychosis / Wet Brain RACK: R: Retrograde Amnesia A: Anterograde Amnesia C: Confabulation K: Koraskoff’s If Wernicke’s encephalopathy is not successfully treated, symptoms may advance to a permanent Korsakoff syndrome Characterized by damage to the components of Papez circuit, including the mamillary bodies, ant. thalamic nucleus, dorsomedial thalamic nucleus, and the cingulate gyrus. Korsakoff Syndrome. Alzheimer’s Association. 2015. Web. 44 44  J. Milla rd 45 https://www.semanticscholar.org/paper/Neuroimaging-of-the-Wernicke-Korsakoff-syndrome.-Sullivan-Pfefferbaum/0363db283fb3be2d2098dfaacfd374ffb4d9edb3 45  Amygdala Means “almond” Corticomedial Nuclei (ventral-lateral pallium): Part of primary olfactory cortex, receives olfactory input from lateral stria Central Nuclei: Receive input from brainstem visceral nuclei and basolateral nuclei. Gives rise to stria terminalis Basolateral Nuclei:Associate stimuli with primary reinforcement value (inherently rewarding, noxious etc.) with stimuli that are originally neutral. Generates learned emotional responses (very big in humans) Amygdala is Anterior to Hippocampus and Temporal Horn of Lateral Ventricle (Important to remember to identify in coronal cross sections) 46  Amygdala Stria terminalis also has pre and post commissural fibers, like fornix Anterior Commissure Connections Most types of sensory modalities send projections to amygdala Projects directly to cortex without going through thalamus, to initiate immediate somatomotor and longer-term psychological responses Projections to/from hypothalamus (Ventral Amygodalofugal Pathway VAFP; Ventral Amygdalopetal Pathway VAPP) initiate visceral responses 47  Association Cortex Olfactory Bulb Amygdala Corticomedial Nuclei Central Nuclei Basolateral Nuclei Orbitofrontal Cortex S tria Te rm in ali Thalamus s (Mediodorsal Ventral Amygdalofugal Nucleus) Path (in substantia innominata/ anterior Same as part of Hypothalamus perforated substance) olfactory pathway 48 Green area shows cortex covering * Shows Amygdala in dissected location of amygdala temporal lobe 49 Klüver-Bucy syndrome Klüver-Bucy syndrome results from bilateral destruction of the amygdalae. It is very rare. Not related to actor Gary BusEy Villain “Renard” in James Bond World is Not Enough unrealistic portrayal of Klüver-Bucy syndrome Klüver-Bucy syndrome is characterized by the following signs: o Absence of fear response o Hypersexuality(no gender preference) o Overly attentive to all sensory stimuli o Docile Partial Klüver-Bucy syndrome follwing probable herpes simplex encephalitis, J of Neurology,Teramoto et al, 1979 50 Basic Clinical Neuroscience (3rd ed.) Fig. 17-5 51 Weiss et al, 2021 52  * = Amygdala Acc. Nucl. = Nucleus Accumbens Weiss et al, 2021 53 Hippocampus Amygdala Calcarine Sulcus (Calcar Avis) Putamen Anterior Commissure 54  * = Amygdala Acc. Nucl. = Nucleus Accumbens Monro = interventricular foramen Weiss et al, 2021 55  * = Amygdala Acc. Nucl. = Nucleus Accumbens Weiss et al, 2021 56 57