Limbic System; Memory & Amnesia

Medial Thalamic Cerebrovascular Accident (CVA) (aka stroke)

(eg to mediodorsal nuclei) Mediodorsal nuclei processes information from amygdala and passes it to frontal cortex - Disrupts limbic system connections Symptoms: - Transient diplopia - Lethargy - Hemiparesis - Memory loss

Anterograde vs retrograde amnesia

*Anterograde amnesia* - Inability to create and consolidate new memories due to brain damage, while long-term memories consolidated before the illness/injury remain intact *Retrograde amnesia* - Inability to recall memories acquired before onset of amnesia - Usually a temporal gradient with preservation of more remotely acquired memory Pathology: - Temporal lobe epilepsy, herpes simplex encephalitis, traumatic brain injury, cardiac arrest, PCA stroke

Classification of memory

*Semantic memory* refers to a portion of long-term memory that processes ideas and concepts that are not drawn from personal experience *Declarative memory* consists of facts and events that can be consciously recalled or "declared." Also known as explicit memory, it is based on the concept that this type of memory consists of information that can be explicitly stored and retrieved.

Limbic and Paralimbic anomalies associated with Neurodevelopmental and Acquired Disorders

- Autism spectrum - Schizophrenia - Bipolar disorder - Traumatic brain injury - ADHD - Temporal lobe epilepsy

Terms for lack of various memory systems

- Gnosis (Gr: knowledge) - Agnosia (Gr: lack of knowledge) - Visual agnosia (Gr: lack of visual knowledge) - Prosopagnosia (Gr: lack of face knowledge) - Auditory agnosia (Gr: lack of auditory knowledge) - Anosognosia (Gr: lack of self knowledge) - Astereognosis (Gr: lack of tactile knowledge) - Amnesia (Gr: lack of memory)

Limbic system cortex

- Neocortex comprises majority of cerebral cortex and comprises 6 layers - Allocortex is cortex with <6 layers (archicortex, paleocortex) - Allocortex includes the three-layered archicortex (meaning "first" or "original cortex") of the hippocampal formation, as well as paleocortex (meaning "old cortex"), which is found predominantly in the piriform cortex of the olfactory area

Diencephalic Amnesia - causes

1. *Alcoholic Korsakoff syndrome:* - Long-term alcoholism and malnutrition related to vitamin B1 deficiency - Causes damage to mammillary bodies & medial dorsal nucleus of thalamus - Progressive if alcohol intake and nutrition pattern are not modified - Confabulation prominent 2. Dorsomedial thalamic CVA

Stages of learning & memory

1. Encoding - Learning, registration 2. Consolidation - Synaptic/LTP - Systems 3. Recall/recognition

Components of limbic system

1. Hippocampus (hippocampal formation) - Consists of hippocampus, dentate gyrus, and subiculum 2. Amygdala 3. Parahippocampal gyrus 4. Multiple pathways to and from cortex and limbic structures

Memory systems

1. Motor/procedural memory - Motor skills 2. Sensory specific memory - Faces, sounds, tastes 3. Semantic memory - Words, objects, concepts. 4. Declarative memory - Specific facts, figures, dates related to events, people, temporal-spacial 5. Autobiographical memory - Personal episodic 6. Working memory - Brief, task-related memoranda

Basal forebrain

Comprised of several structures that lie on dorsal surface of forebrain - Interconnected with amygdala, hippocampus, hypothalamus - Reward processing - Implicated in addictions

Limbic Lobe (Medial temporal lobe)

Consists of: 1. Medial orbitofrontal region 2. Subcallosal gyrus 3. Cingulate gyrus 4. Retrosplenial gyrus 5. Parahippocampal gyrus 6. Temporal pole

Herpes simplex encephalitis

Infectious lesions cause: - Global amnesia - Anosomia - Blunting of emotions and motivations - Asymmetric encephalitis can cause partial amnesias/visuospacial deficits vs verbal (right-sided) HSV-1 encephalitis can also cause Klüver-Bucy syndrome - Bilateral amygdala lesions causing disinhibited behavior

Mesial Temporal Sclerosis aka hippocampal sclerosis

Lesion in hippocampal formation in temporal lobe involving marked neuronal loss and gliosis (nonspecific reactive change of glial cells in response to damage to the CNS), associated with childhood febrile seizures and later onset epilepsy - Associated with *temporal lobe epilepsy* - Sclerosis has characteristic hyper intensity on CT - May be *triggered by febrile seizures* as well as other precipitating injuries in infancy and childhood (eg head trauma or CNS infections). Latent period of up to several years between precipitant and onset of complex partial seizures Classic presentation: - Prolonged febrile seizures in infancy followed by development of medial temporal-onset complex partial seizures

Limbic and paralimbic cortices

Limbic cortex = paralimbic cortex = limbic association cortex - Forms a ring on the medial aspect of the brain consisting mainly of the cingulate gyrus and the parahippocampal gyrus - Hippocampal formation lies within ring - The paralimbic cortex lies close to, and is directly connected with, the structures of the limbic system. It provides a gradual transition from primary limbic regions to higher neocortical regions

Case reports of growing up without a hippocampus

Loss of: 1. Spacial memory - Cannot find way in familiar surroundings - Cannot find where they placed belongings 2. Temporal memory - Not oriented to date or time 3. Episodic memory - Cannot recall day's events 4. Independence - Cannot be left alone

Papez circuit

Medial limbic circuit - A neural circuit for the control of emotional expression - In 1937, James Papez proposed that the circuit connecting the hypothalamus to the limbic lobe was the basis for emotional experiences

Landmark case of amnesia

Patient HM underwent bilateral medial temporal lobectomy in order to control refractory epileptic seizures - Had severe anterograde amnesia with no other cognitive deficits

Transient global amnesia

Retrograde and anterograde memory loss symptoms come on suddenly and last for several hours, then clear - Precipitating factor(s) not clear - Episodes often occur in the setting of physical exertion or emotional stress - Possibly transient reduced blood flow, seizure activity or atypical migraine variant - Patients are typically amnestic of events more than a few minutes in the past - Often repeated questioning. Usually occurs once but may reoccur

Types of Amnesia - First Aid

Retrograde: - Inability to remember things occurring before a CNS insult Anterograde: - Inability to remember things occurring after a CNS insult

Basal forebrain amnesia

Rupture of anterior communicating artery aneurysm - "Source" amnesia: inability to remember where, when, or how previously learned information has been acquired, while retaining factual knowledge

Damage to medial temporal lobe

Short-term memory deficits reflect hemispheric specialization 1. *Left damage* - Causes loss of *verbal learning and new verbal memory retention* (partial amnesia) 2. *Right damage* - Causes loss of *visual (spatial, nonverbal) learning & new memory retention* (eg faces, locations, sounds, designs, objects) (partial amnesia) 3. *Bilateral damage* - Causes profound loss of learning & new memory retention - Clinical or global amnesia when both left and right are damaged

Hippocampal formation

Structure located deep within temporal lobe - Consists of *hippocampus proper, dentate gyrus, and subiculum* 1. Receives projections from *cortical association cortices* via: - Entorhinal cortex - Perforant pathway 2. Processes inputs in *dentate gyrus* and throughout *four fields* (CA1, CA2, CA3, CA4) - "Binding" of information - Information is sent here temporarily, but then sent outward for long-term storage 3. Circuitry gives rise to *fimbira-fornix*, major output pathways of hippocampal formation via *subiculum* - Pathways travel back to *association cortices and other limbic system structures* for consolidation and long-term storage

Limbic system

Structures unified by evolutionarily ancient origins, constituting a major part of the forebrain in many species - Components form a complex network - Interface between neocortical regions (higher sensory, motor, cognitive) and effector systems, allowing expression and experience of emotions through somatic, motor, endocrine, autonomic, and behavioral changes Functions divided into 4 basic categories: 1. Olfaction 2. Memory 3. Emotions & Drives 4. Homeostatic functions, including autonomic and neuroendocrine control (mnemonic HOME: homeostasis, olfaction, memory, emotions) or 5 F's: (also referred to in reference to hypothalamus) - Feeding - Fleeing - Fighting - Feeling - F**king

Wernicke-Korsakoff Syndrome

Syndrome associated with thiamine (B1) deficiency and excessive alcohol use - Classic triad of confusion, ophthalmoplegia, ataxia (Wernicke's encephalopathy) - Confabulation, personality change, permanent memory loss (anterograde and retrograde amnesia) (Korsakoff psychosis) - Damage to medial dorsal nucleus of thalamus & mamillary bodies - Can be precipitated by giving glucose without B1 to a B1-deficient patient (B1 involved in breakdown of glucose, specifically pyruvate dehydrogenase and alxha-ketoglutatare dehydrogenase) - Mneumonic: Wernicke problems come in a CAN of beer: Confusion, Ataxia, Nystagmus

Brain regions associated with specific memory systems

1. Motor/procedural memory (motor skills) - Motor/premotor cortex - Basal ganglia - Cerebellum 2. Sensory specific memory (faces, sounds, tastes) - Primary sensory and sensory association cortices 3. Semantic memory (words, objects, concepts) - Multimodal association cortices - Parietal lobe - Frontal lobe 4. Declarative memory (specific facts, figures, dates related to events, peoples, temporal-spacial) - Hippocampal & limbic system structures 5. Autobiographical memory (personal episodic) - Hippocampal & limbic system structures 6. Working memory (task-related memoranda) - Dorsolateral prefrontal cortex

Amygdala hypometabolism

Amygdala hypofunctioning can be caused by socioemotional deprivation and causes problems forming healthy personal attachments - Can occur in children who suffered severe socioemotional deprivation in orphanages - Developmental dysfunction of amygdala cortex circuits linked to the prominent social behavioral and emotional deficits in autism - More broadly linked to problems forming healthy personal attachments

Klüver-Bucy syndrome

Bilateral amygdala lesion causing disinhibited behavior: - Hyperphagia - Hypersexuality - Hyperorality - Hyperdocility - Associated with HSV-1 encephalitis

Amygdala

A limbic system interface between frontal cortex and lower structures - *Control of autonomic and visceral systems in hypothalamus and brainstem* - *Associates sensory stimuli* (faces, places, situations) *with emotional behavioral responses* (such as reward, fear) through modulation of hypothalamus & autonomic activation centers - Long term *"emotional memory"* localized in orbitofrontal cortex - Bilateral lesions associated with *Klüver-Bucy syndrome* - Developmental dysfunction associated with *problems forming healthy attachments (autism)* - Electrical stimulation causes arousal response, signs of fear or rage, emotional responses Interconnected with limbic system structures, 4 functionally distinct divisions: - Limbic - Striatal (one of the principal components of the basal ganglia, a group of nuclei that have a variety of functions but are best known for their role in facilitating voluntary movement) - Frontotemporal - Main and accessory olfactory

Triune brain theory

A model of the evolution of the vertebrate forebrain and behavior, proposed by the American physician and neuroscientist Paul D. MacLean