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Limbic system Limbic system from Latin limbus, means "border" or "belt„ Functions: emotion, behavior, long-term memory, olfaction Cortical region cingular orbitofrontal insular medial prefrontal Subcortical region insula anterior thalamic nuclei septal area nucleus accumbens hippocampus, amygdala mammilary body Papez circuit the major pathways of the limbic system - involved in the cortical control of emotion, plays a role in storing memory Papez discovered the circuit after injecting rabies virus into a cat's hippocampus and monitoring its progression through the brain. (Associative cortex) – cingulate cortexentorhinal cortex – hippocampus – fornix hypothalamus MB – anterior thalamus – cingulate cortex Hippocampus From Greek hippos = horse, kampos = sea monster) • part of the telencephalon (forebrain) • located inside the medial temporal lobe of the cerebral cortex • The strongest connections of the hippocampus are with the entorhinal cortex (EC). Information flows into and through the hippocampus by three principal pathways 1. the perforant pathway from the entorhinal cortex to granule cells of the dentate gyrus; 2. the mossy fiber pathway from the granule cell of the dentate gyrus to the pyramidal cells of the CA3 region of the hippocampus; and 3. the Schaffer collateral pathway from the CA3 region of the hippocampus to the CA1 region of the hippocampus. Function • storing and processing spatial information (London's taxi drivers – larger hippocampus) • important role in the formation of new memories about experienced events (episodic or autobiographical memory) • Damage to the hippocampus does not affect the ability to learn new skills (playing a musical instrument) Place cells Patient H.M. the 1950s - HM (patient) (Henry Gustav Molaison (1926–2008) - memory-impaired patient In 1953 – William Scoville (surgeon at Hartford Hospital) removed two-thirds of his hippocampus, parahippocampal gyrus, and amygdala (for diagnosed focal epilepsy in medial temporal lobes) After the surgery - severe anterograde amnesia (he could not commit new events to long-term memory). His ability to form long-term procedural memories was intact - he could learn new motor skills, despite not being able to remember learning them. Long Term LTPPotentiation (LTP) • long-lasting improvement in communication between two neurons that results from stimulating them simultaneously • one of the major cellular mechanisms that underlies learning and memory • electrical stimulation to a fiber of the perforant pathway caused an excitatory postsynaptic potential (EPSP) in a cell of the dentate gyrus Parahippocampal gyrus • a grey matter cortical region of the brain that surrounds the hippocampus • important role in memory encoding and retrieval • The anterior part of the gyrus includes the perirhinal and entorhinal cortices Grid cells Amygdala • from Greek = Almond • primary role in the processing and memory of emotional reactions • related to many psychological disorders (social phobia, autism, bipolar disorder) • Nuclei: – basolateral complex (lateral, basal, accessory basal nuclei) – centromedial nucleus – cortical nucleus Amygdala • Connections to: – hypothalamus - important activation of the sympathetic nervous system – thalamic reticular nucleus increased reflexes – nuclei of the trigeminal nerve and facial nerve - facial expressions of fear – ventral tegmental area, locus coeruleus, and laterodorsal tegmental nucleus - activation of DA, NE and E • Inputs from: – from the olfactory bulb and olfactory cortex to the cortical nucleus - sense of smell and pheromone-processing. – from the sensory systems to the lateral amygdalae Associative cortex – cingular cortex – hippocampus – hypothalamus – thalamus – cingular cortex center for identification of danger Role of amygdala Rage Fear Immediate reaction on threat Sensory cortex „Long route“ 30 – 40 ms „Short route“ Senory thalamus Emotional stimulus 12 ms Amygdala Emotional reaction Conditioned fear (emotional learning) memory is stored in amygdala nuclei Medina et al. 2002 Syndrom Klüver-Bucy Bilateral ablation of anterior temporal lobes (including amygdala) (1939) • Hyperorality • Loss of fear • Decreased aggression • Changed alimentary behavior • Hypersexuality • Curiosity about everything, forgets rapidly VTA - located in the mesencephalic part of the brain stem There are dopamine-secreting neurons whose axons end in the nucleus accumbens (mesolimbic dopaminergic pathway) – reward Reduction of D2 receptors- reward deficiency syndrome Reward centre Meso-cortico-limbic dopaminergic system : Olds and Milner. Intracranial selfstimulation (1954) José Delgado 1965 Septal region anteriorly to the thalamus this area is associated with different kinds of pleasant sensations, mainly those related to sexual experiences Generator of theta rhythm Septal nuclei provide essential interconnections between various parts of the limbic system Hypothalamus NTS: from the vagus (blood pressure and gut distension) circumventricular organs: lack a blood-brain barrier (osmolarity, toxins) amygdala, hippocampus, olfactory cortex Limbic system A division of the diencephalon Reticular formation: from the spinal cord (skin temperature) H Retina: from retinohypothalamic tract to SCN (photoperiod) Endocrine system Autonomic nervous system Hypothalamus 12 important nuclei: • MEDIAL PREOPTIC NUCLEUS – Regulates the release of gonadotropic hormones from the Adenohypophysis • SUPRACHIASMIC NUCLEUS – Receives input directly form the retina. – Plays a role in regulating circadian rhythm • ANTERIOR NUCLEUS – Important in temperature regulation – Stimulates PNS – It’s destruction results in hyperthermia • PARAVENTRICULAR NUCLEUS – Synthesizes ADH- and thus regulates water balance – Releases oxytocin – Synthesizes CRH - stress • SUPRAOPTIC NUCLEUS – Synthesizes ADH- and thus regulates water balance – Releases oxytocin • DORSOMEDIAL NUCLEUS – When stimulated in animals, causes savage behavior! • VENTROMEDIAL NUCLEUS – Is the satiety center- this means that once it is stimulates, it inhibits the urge to eat • LATERAL HYPOTHALAMIC NUCLEUS – Induces eating • ARCUATE (INFUNDIBULAR) NUCLEUS – Contains neurons that produce factors that stimulate or inhibit action of hypothalamus – Contains neurons that produce Dopamine • MAMILLARY NUCLEUS – Lesions (Korsakoff syndrome) are associated with thiamine deficiency and alcoholism – anterograde amnesia • POSTERIOR HYPOTHALAMIC NUCLEUS – Plays a role in thermoregulation – Lesion results in poikilothermia • VENTROLATERAL PREOPTIC NUCLEUS (VLPO) - regulation of sleep and wakefulness Hypothalamus - functions • AUTONOMIC – Stimulation of the ANTERIOR HYPOTHALAMUS: excitatory effect on parasympathetic system (trophotropic) – Stimulation of POSTERIOR HYPOTHALAMUS: excitatory effect of sympathetic system (ergotropic) • THERMOREGULATION – Stimulation of ANTERIOR HYPOTHALAMUS: regulates and maintains temperature – Stimulation of POSTERIOR HYPOTHAMUS: produces and conserves heat • WATER BALANCE – Paraventricular (Supraoptic) nuclei synthesize ADH and control kidney water excretion • FOOD INTAKE – Stimulation of VENTROMEDIAL NUCLEUS inhibits the urge to eat – Stimulation of LATERAL HYPOTHALAMIC NUCLEUS induces the urge to eat Cerebral cortex • • • Left and right hemisphere Lobes- frontal, parietal, occipital, temporal Sulci et gyri Phylogenetically older – allocortex (10 %) – does not receive thalamic input paleocortex (parahippocampal gyrus, olfactory cortex archicortex (hippocampal formation: hippocampus, dentate gyrus) 3-4 • layers Phylogenetically younger - neocortex (90%) – 6 layers Lamina molecularis Input from nonspecific thalamus Lamina granularis externa Lamina pyramidalis externa Interhemispheric connection Lamina granularis interna Input from specific thalamus Lamina pyramidalis interna Betz cells (to brain stem and spinal cord) Lamina multiformis (to thalamus) Output fibers Associative connections Surface 0.25 m2 Thickness 2 – 5 mm Columnar organisation Column – functional unite visual cortex Brodman's areas Motor cortex Sensory cortex Associative cortex Primary Secondary Tertiary Sensory areas • Primary sensory areas receive sensory inputs from the thalamus • In general, the two hemispheres receive information from the contralateral side of the body. Topographic maps - the organization of sensory maps in the cortex correspond with the sensing organs the primary visual cortex - retinotopic map the primary auditory cortex - tonotopic map the primary somatosensory cortex - somatotopic map (homunculus) Somatosensory cortex • The postcentral gyrus - the sense of touch • Primary somatosensory cortex - BA 3, 1 and 2 • Secondary somatosensory cortex – BA 5, 7 Lesions: Loss of vibration, proprioception, fine touch It could also reduce nociception, thermoception and crude touch (but these are more in insular cortex and cingulate gyrus). Agraphesthesia - disorder of directional cutaneous kinesthesia (writing on skin) Astereognosia (tactile agnosia) - impaired ability to recognize or identify objects by touch alone Hemineglect - ignoring the contra-lesional side of their body (no shaving, no make-up) Motor cortex • The primary motor cortex (M1) - the posterior portion of the frontal lobe. • Precentral gyrus = BA 4 • M1 contains large neurons known as Betz cells (pyramidal cells in layer V) - long axons to alpha motoneurons in the spinal cord. • Supplementary motor area • • BA 6 - on the medial face of the hemisphere, just in front of primary motor cortex (premotor cortex) Function: – planning of motor actions – bimanual control – In contrast to M1 - actions that are under internal control (performance of a sequence of movements from memory) – involved in retrieving the sequence of movements • The corticospinal (pyramidal) tract – About half of its fibres arise from the primary motor cortex. – Other contributions come from: • supplementary motor area • premotor cortex • somatosensory cortex • parietal lobe • cingulate gyrus Visual cortex • Located and around the calcarine fissure in the occipital lobe. • Anatomically - Brodmann area BA 17 • 6 layers - Layer 4, which receives most visual input from the lateral geniculate nucleus • Primary visual cortex – V1 (visual orientations and colors) • Extrastriate visual cortical areas – V2, V3, V4, V5 – BA 18, 19 (attention, working memory, and reward expectation) • Function: – The dorsal stream ("Where Pathway" or "How Pathway„) motion, object locations, control of the eyes and arms – The ventral stream ("What Pathway„) - form recognition and object representation, storage of long-term memory. Auditory cortex • Anatomically – BA 41, 42 • Inputs from the medial geniculate nucleus of the thalamus. • Function: – Primary auditory cortex in the superior temporal lobe -sensation of basic characteristics of sound (pitch and rhythm) – Additional areas - in the frontal and parietal lobes processing of acoustic signals (distinguished between speech, music, noise) Association auditory cortex Broca's area (pars opercularis and pars triangularis of the inferior frontal gyrus) BA 44, 45 – responsible for speech production – Broca’s (motor) aphasia – understands, but problems with fluent speaking In the left hemisphere Wernicke's area (where the temporal lobe meets the parietal lobe) posterior part of BA 22 – responsible for understanding – Wernicke’s (receptive, sensory) aphasia – can speak, but does not understand • In the left hemisphere (in most people specialized for language skills) In the left hemisphere (95%) Association areas Parieto-occipito-temporal: integration of visual, auditory and somatosensory modalities continuous analysis of spatial coordinates of all parts of the body area for language comprehension (Wernicke's sensory speech center) understanding of written text (gyrus angularis) Unilateral neglect Association areas Frontal lobe • Reaches full maturity around age 25 – increased myelin in the frontal lobe white matter of young adults compared to that of teens – A typical onset of schizophrenia in early adult years correlates with poorly myelinated (inefficient) connections between cells in the fore-brain. • The frontal lobe contains most of the dopamine-sensitive neurons in the cerebral cortex. • Functions (involved in higher mental functions): – to recognize future consequences resulting from current actions – to choose between good and bad actions – override and suppress unacceptable social responses – determine similarities and differences between things or events Phineas Gage 1848 Damage of frontal lobes • Impaired mental flexibility and spontaneity, but IQ is not reduced. • Talking may increase or decrease dramatically. • Increase of risk taking behavior. • Socialization can diminish or increase. • Orbital frontal lobe damage can result in perverse sexual habits. • Diminished creativity and problem solving skills. • Frequent distractions. Prefrontal cortex • the anterior part of the frontal lobes • defined by the presence of an internal granular layer IV (in contrast to the agranular premotor cortex) • Parts: – – – – – – orbitofrontal (OFC) and ventromedial areas (vm-PFC) dorsolateral prefrontal cortex (dl-PFC) anterior and ventral cingulate cortex ventrolateral cortex (vl-PFC) medial prefrontal cortex (m-PFC) anterior prefrontal cortex (a-PFC). • Function: – – – – planning complex cognitive behaviors personality expression decision making moderating correct social behavior Psychosurgery • In the early 20th century - Portuguese neurologist Egas Moniz developed a medical treatment for mental illness • Damage of the pathways connecting the frontal lobe and the limbic system • Frontal lobotomy successfully reduced distress, but suppressed emotions, volition and personality. Association areas Two brains • Left hemisphere analytic rational verbal • Right hemisphere synthetic intuitive non-verbal