Function of limbic system and the cerebral cortex

1
Function of limbic system and the cerebral cortex

• Prof. Romana Šlamberová, MD PhD
• Department of Normal, Pathological and Clinical
  Physiology

2
Limbic system

• from Latin limbus, means "border" or "belt
• Main parts
• Hippocampus
• Amygdala
• anterior thalamic nuclei
• limbic cortex
• Function
• Emotion
• Behavior
• Long-term memory
• Olfaction

3
History

• in 1878 - French physician Paul Broca first
  called this part of the brain le grand lobe
  limbique
• in 1937 - American physician James Papez
  described his anatomical model of emotion, the
  Papez circuit.
• in 1952 - American physician Paul D. MacLean
  expanded these ideas to include additional
  structures in a more dispersed "limbic system"

4
Limbic system - basic parts

• Amygdala - emotions (reward, fear, social
  functions)
• Hippocampus cognition (long-term memories, map
  navigation, spatial memory)
• Parahippocampal gyrus cognition (spatial
  memory)
• Cingulate gyrus - autonomic functions (heart
  rate, blood pressure) and cognition (attentional
  processing)
• Fornix - carries signals from the hippocampus to
  the mammillary bodies and septal nuclei
• Hypothalamus - autonomic functions (hormones,
  blood pressure, heart rate, hunger, thirst,
  sexual arousal, sleep/wake cycle)
• Thalamus - The "relay station" to the cerebral
  cortex

5
Limbic system additional parts

• Mammillary body - cognition (formation of memory)
  
• Pituitary gland regulating homeostasis
  (hormones)
• Dentate gyrus cognition (new memories) and
  emotions (happiness)
• Entorhinal cortex and piriform cortex - sensation
  (smell input in the olfactory system)
• Olfactory bulb - sensation (olfactory sensory
  input)
• Nucleus accumbens - reward, pleasure, and
  addiction
• Orbitofrontal cortex - decision making

6
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.

7
Amygdala (1)

• 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

8
Amygdala (2)

• 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

9
Emotions

• Emotions can be differentiated
• Feelings are best understood as a subjective
  representation of emotions
• Moods are diffuse affective states that generally
  last for much longer durations than feelings and
  are also usually less intense than feelings
• Affect is an encompassing term, used to describe
  the topics of emotion, feelings, and moods
  together
• A distinction can be made between emotional
  episodes and emotional dispositions.
• Emotions can be measured by multidimensional
  scaling.
• The emotional experiences are divided into two
  dimensions known as
• valences (how negative or positive the experience
  was)
• arousal (extent of reaction to stimuli)

10
Bipolar disorder

• Bipolar affective disorder, manic-depressive
  disorder, or manic depression) is a mental
  illness typically classified as a mood disorder
• Characterized by episodes of an elevated or
  agitated mood known as mania, usually alternating
  with episodes of depression
• About 3 of people, a proportion consistent for
  both men and women and across racial and ethnic
  groups
• Causes - both genetic and environmental risk
  factors are believed to play a role
• Treatment
• Psychotherapy
• Medication
• lithium, effective in treating acute manic
  episodes, preventing relapses, reduces the risk
  of suicide
• anticonvulsants (carbamazepin, sodium valproate,
  lamotrigine)
• Antipsychotic medications only for short-term
  treatment of bipolar manic episodes
• Benzodiazepines may be used in addition to other
  medications until mood stabilizing become
  effective

11
Emotions and memory

• Emotion can have a powerful impact on memory.
• The most vivid autobiographical memories tend to
  be of emotional events.
• The activity of emotionally enhanced memory
  retention can be linked to human evolution.
• The process of learning became genetically
  embedded in humans and all animal species in what
  is known as flight or fight instinct.
• Emotionally arousing stimuli can lead to
  retrograde amnesia for preceding events and
  anterograde amnesia for subsequent events.

12
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).

13
History

• In 1564 - the anatomist Giulio Cesare Aranzi -
  first used the term hippocampus (connected with
  the sense of smell)
• Around 1900 - the Russian neurophysiologist
  Vladimir Bekhterev - the role of the hippocampus
  in memory
• the 1950s - HM (patient) (Henry Gustav Molaison
  (19262008) - 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.

14
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
• profound difficulties in forming new memories
  (anterograde amnesia)
• also affects access to memories prior to the
  damage (retrograde amnesia)
• Damage to the hippocampus does not affect the
  ability to learn new skills (playing a musical
  instrument)

15
LTP Long-term potentiation

• 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
• LTP was first observed by Terje Lømo in 1966 in
  the Oslo, Norway who studied the hippocampus of
  rabits for short-term memory.
• electrical stimulation to a fiber of the
  perforant pathway caused an excitatory
  postsynaptic potential (EPSP) in a cell of the
  dentate gyrus

16
Basic hippocampal circuit

• The alveus - most superficial layer - contains
  axons from pyramidal neurons
• Stratum oriens - cell bodies of inhibitory basket
  cells
• Stratum pyramidale - cell bodies of the pyramidal
  neurons
• Stratum lucidum - mossy fibers from DG granule
  cells
• Stratum lacunosum - Schaffer collateral fibers
  and perforant path
• Stratum moleculare synaps between perforant
  path fibers and dendrites of pyramidal cells
• The hippocampal sulcus or fissure - cell-free
  region that separates CA1 from DG

17
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.

18
Memory disorders

• Amnesia - loss of memory
• caused by brain damage, disease, or psychological
  trauma
• two main types of amnesia retrograde amnesia and
  anterograde amnesia
• Hyperthymesia - condition of possessing an
  extremely detailed autobiographical memory
• reason is not known
• Alzheimer's disease - the most common form of
  dementia
• Cause genetic in 1-5
• Cholinergic hypothesis - reduced synthesis of the
  neurotransmitter acetylcholine
• Amyloid hypothesis - extracellular beta-amyloid
  (Aß) deposits
• Tau hypothesis - tau protein abnormalities
  initiate the disease cascade
• Korsakoff's syndrome - a neurological disorder
  caused by a lack of thiamine (vitamin B1) in the
  brain
• Cause - chronic alcohol abuse and/or severe
  malnutrition
• Symptoms retrograde and anterograde amnesia,
  confabulation, apathy

19
The Hypothalamus (1)

• A division of the diencephalon
• It sub serves 3 major systems
• AUTONOMIC NERVOUS SYSTEM
• ENDOCRINE SYSTEM
• LIMBIC SYSTEM
• 11 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
• Its destruction results in hyperthermia
• PARAVENTRICULAR NUCLEUS
• Synthesizes ADH- and thus regulates water balance
• Releases oxytocin
• Projects directly to autonomic nuclei of brain
  stem and all spinal cord levels

20
The Hypothalamus (2)

• 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 (in Wernickes Encephalopathy patients)
  are associated with thiamine deficiency and
  alcoholicism
• POSTERIOR HYPOTHALAMIC NUCLEUS
• Plays a role in thermoregulation
• Lesion results in poikilothermia

21
Hypothalamic nuclei
22
Function of the hypothalamus

• AUTONOMIC
• Stimulation of the ANTERIOR HYPOTHALAMUS
  excitatory effect on parasympathetic system
• Stimulation of POSTERIOR HYPOTHALAMUS excitatory
  effect of sympathetic system
• 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

23
Cerebral cortex

• In humans - 24 mm (0.080.16 inches) thick
• neocortex (isocortex) - phylogenetically most
  recent part of the cerebral cortex (older part
  hippocampus archicortex)
• Layers from outside (pial surface) to inside
  (white matter)
• molecular layer I - apical dendrites,
  horizontally-oriented axons, glial cells
• external granular layer II - small pyramidal
  neurons and stellate neurons
• external pyramidal layer III - small and
  medium-size pyramidal neurons, non-pyramidal
  neurons with vertically-oriented intracortical
  axons (main cortico-cortico efferents)
• internal granular layer IV - stellate and
  pyramidal neurons (main thalamo-cortical
  afferents)
• internal pyramidal layer V - large pyramidal
  neurons (Betz cells in the primary motor cortex)
• multiform layer VI - small spindle-like pyramidal
  and multiform neurons (efferents to thalamus)

24
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)

25
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,
  spatial frequencies 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.

The dorsal stream (green) and ventral stream
(purple) are shown. They originate from primary
visual cortex.
26
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)

27
Association auditory cortex

• Broca's area (pars opercularis and pars
  triangularis of the inferior frontal gyrus) BA
  44, 45
• responsible for speech production
• Brocas (motor) aphasia understands, but
  problems with fluent speaking
• Wernicke's area (where the temporal lobe meets
  the parietal lobe) posterior part of BA 22
• responsible for understanding
• Wernickes (receptive, sensory) aphasia can
  speak, but does not understand
• In the left hemisphere (in most people
  specialized for language skills)

28
Somatosensory cortex

• The postcentral gyrus - the sense of touch
• Primary somatosensory cortex - BA 3, 1 and 2
• Secondary somatosensory cortex BA 5, 7
• Lesions
• Agraphesthesia - disorder of directional
  cutaneous kinesthesia (writing on skin)
• Astereognosia (tactile agnosia) - impaired
  ability to recognize or identify objects by
  touch alone
• Loss of vibration, proprioception, fine touch
• Hemineglect - ignoring the contralesional side of
  their body (no shaving, no make-up)
• It could also reduce nociception, thermoception
  and crude touch (but these are more in insular
  cortex and cingulate gyrus).

29
Somatosensory homunculus
30
Motor areas

• 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.
• Involved in
• planning actions (basal ganglia)
• refining movements (cerebellum)

31
Motor homunculus
32
Motor tracts

• The corticospinal tract originates from pyramidal
  cells in layer V of the cerebral cortex.
• 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

33
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

34
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

35
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.

36
Damage of the 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.

37
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

38
Prefrontal cortex