PHYSIOLOGY OF HIGHER FUNCTION OF BRAIN

Integrative teaching bloc 16 Dr. Swanny, MSc

Objectives
Describe the functions of the different areas of the brain. Distinguish between different types of memory and describe the roles of different brain regions in memory. Describe the location of the hypothalamus and explain the significance of this region. Explain the role of the limbic system in the control of behavior and emotion.

Introduction
HIGHER FUNCTION OF BRAIN Neurobehavioral function. What is the part of brain? What is the function ? How is the mechanism ?

Neuronal part of brain

CEREBRAL CORTEX : the functional part of cerebral cortex a thin layer of neurons 2 to 5 mm in thickness covering the surface of all convolutions of cerebrum a total area of one quarter square meter contains about 100 billions neurons.

Function of cerebral cortex

1. Intellectual 2. Learning 3. Memory

Behavioral and motivational

The control of behavior is the function of ENTIRE nervous system wakefulness, sleep cycle. Brain control the level of activity. Motivational drives control of learning process, feeling of pleasure and punishment performed by basal regions of brain LIMBIC SYSTEM.

Behavioral State System: Emotion and Motivation

The link between emotions and physiological functions The amygdala is the center of emotion in the brain Stimulus to Cerebrumcreates perception, limbic creates emotion, cerebrum becomes aware of emotion while hypothalus stimulates multiple responses

Behavioral/Cognitive State : Motivation

Defined as internal signals that shape voluntary behavior (related to survival or emotions) Some states known as drives create increased arousal, goaloriented behavior, and disparate behavior to achieve the goal. Works with autonomic and endocrine responses to maintain homeostasis Motivated behaviors stop Satiety Pleasure is related to addictive behaviors which can be changed if given a different motivation.

Behavioral State System: Moods

Similar to emotions but longer-lasting- related to sense of being, not purely psychological, related to sense of well-being and proper neurotransmitter function Mood disorders Fourth leading cause of illness worldwide today Depression Sleep and appetite disturbances Alteration of mood and libido Antidepressant drugs alter synaptic transmission allow a neurotransmitter to remain at the synapse longer, change the receptor, or the amount of NT released.

Cognitive State: Learning and Memory

Learning has two broad types Associative links two stimuli or a stimulus to a behavior Nonassociative- change behavior due to repeated exposure Habituation do not respond to an irritant stimulus, filters out insignificant stimulus Sensitization- enhanced response to irritant stimulus, helps avoid harmful stimuli Memory has several types Short-term and long-term- combined by working memory, consolidation turns short-term into long term. Changes in synaptic connections are required Reflexive and declarative- requires unconscious (procedural) or conscious recall (infer, compare, evaluate). Declarative can become reflexive

Brain Function: Memory Processing

Brain Function: Language

Cerebral processing of spoken and visual language

Damage to Wernickes causes receptive aphasia- unable to understand spoken or visual information

Damage to Brocas area causes expressive aphasia- can understand information but cannot speak or write in proper order, are aware of mistakes

Functional Divisions - Cerebrum

primary sensory or motor areas

secondary sensory or motor areas

association cortex

Functional Divisions - Cerebrum

primary sensory areas

somatosensory cortex - postcentral gyrus visual cortex - occipital auditory cortex - temporal olfactory cortex - olfactory bulb gustatory - part of somatosensory

primary motor area - precentral gyrus

Cortical Areas

Neocortical Layers (I-VI)

Organization of nerve fibers within layer of cortex

1. 2. 3. 4. 5. 6. Molecular layer External granular layer Pyramidal cells layer Internal granular layer Large pyramidal cell layer Fusiform or polymorphic cells.

Granular/ stellate cell short axon, function as intracortical interneurons. Pyramidal and fusiform cells long nerve fibers give rise to almost all output fibers from cortex. They also give rise to most of large subcortical association fiber bundles that pass from one major part of brain to the other.

Function of fibers
Horizontal fibers extend between adjacent areas of cortex. Vertical fibers to and from cortex to lower areas of brain and to spinal cord or to distant regions of cerebral cortex through the long association bundles.

Sensory, association, and motor cortex

Layer IV vs. Layer V

Layer I, II and III perform most of the intracortical association functions. Layer IV incoming sensory signals terminate in this layer. Layer V, VI output signals leave cortex from neurons located in these layer. The very large fibers to brain stem and cord arises in layer V. The fibers to thalamus arises from neuron in layer VI.

Brain Function: complex processing and responses

Hemispheric Dominance (Lateralization)

90% of humans are right handed - left hemisphere is dominant for handedness many animal species also show handedness 98% of humans - comprehension of spoken and written word and motor control of speech is in the left hemisphere

Hemispheric Dominance - Human

left hemisphere (analytical) right hemisphere (creative)

speech spatial construction writing nonverbal ideation main language center simple language calculation comprehension

Hemispheric Dominance
hemispheric damage in the adult nearly permanent loss

damage in the child (up to age 3 yrs) results in functions being assumed to variable extents by the other hemisphere plasticity some hemispheric differences are present before birth, so anatomically predetermined
class demo

Memory
Encoding, sorting, storage, retrieval, and transfer of acquired verbal and nonverbal sensory experiences, concepts, and sensorimotor behavioral patterns. Memory is the substrate for all higher mental functions and the prerequisite for learning and adaptive behavior.

Memory & Learning

Learning: the process by which we and other animals acquire knowledge about the world. Memory: the retention or storage of that knowledge.

Alternate Definitions
Learning: the acquisition of an altered behavioral response due to an environmental stimulus. Memory: the process through which learned information is stored. Recall: the conscious or unconscious retrieval process through which this altered behavior is manifest.

Classification of Memory Forms

classified by how information is stored and recalled: explicit (declarative) memory

implicit (procedural) memory

Explicit/Declarative Memory
storage (& retrieval) of material that is available to the conscious mind "what" the world is about knowledge of people, places, and things that are available to the conscious mind involves evaluation, comparison, and inference can be recalled by a deliberate act of recollecting birth date, Social Security Number from single or multiple trials

Implicit/Procedural Memory
not available to the conscious mind involves skills and associations that are acquired and retrieved at an unconscious level "how" to do things motor or perceptual skills unavailable to conscious mind acquired slowly through repetition expressed primarily by improved performance signing your name or riding a bicycle

Implicit/Procedural Memory (cont.)

motor memory: physical acts learned through multiple repetitions to the point where conscious thought is not required for their performance other types emotions associated with a memory, etc.

Subdivisions of Human Memory

Time Domains of Memory

both explicit and implicit memories have short-term forms and long-term (nearly permanent) forms (more below) consolidation from short-term to long-term requires protein synthesis (and sleep!) recently acquired memories are more easily disrupted than older ones long-term memories gradually diminish with time, especially with disuse

Time Domains (3) of Memory

1. immediate memory lasts a few seconds, large capacity, all sensory modalities, awareness of environment 2. short-term memory - seconds to minutes; e.g. strings of digits; limited storage capacity, then either lost or transferred to more stable memory forms; rapid retrieval
working memory - form of short-term conscious memory used to carry out sequential actions toward a goal, i.e. searching for a lost object; not stored.

Time Domains of Memory

3. long-term memory - days, weeks, or a lifetime; requires transfer (consolidation) from short- term; depends on changes in synaptic strength or synapse numbers; vast capacity, rapid recall intermediate-term memory - name used by some to describe the memories that overlap short-term and long-term memory

Time Domains of Memory

Consolidation of memory from short-term to longterm:

hippocampus is required for memory consolidation

requires protein synthesis requires sleep REM and possibly SWS at least in animals

Simplified Model of Memory Processes During Learning

consolidation

Input

Short-term memory store

Long-term memory store

Output

Search and read out

Proposed Anatomic Correlates of Memory

explicit
immediate: prefrontal cortex and dorsal medial thalamus or primary & secondary sensory cortex short-term: hippocampus and temporal lobe, mammillary bodies, midline diencephalic structures long-term: diffuse throughout the cerebrum

Anatomic Correlates of Memory

implicit
motor: cerebellum, basal ganglia, secondary motor cortex

emotion-associated: amygdala

Mechanisms of Memory
immediate and short-term
reverberating circuits (minutes) altered electrical excitability changes in [Ca++] and altered ionic conductances due to neurotransmitters (minutes to hours) transient changes in receptors long-term potentiation (LTP) long-term depression (LTD)

Mechanisms of Memory
long-term
long-term potentiation (LTP) long-term depression (LTD) gene expression protein synthesis-mediated changes new dendritic spines replication and/or strengthening of synaptic contacts formation of new neuron-to-neuron contacts

Dendritic Spines: Young vs. Old Animals

Long-Term Potentiation (LTP)

strengthening the synaptic connections between activated neurons, especially in the hippocampus, cerebral cortex postsynaptic potential amplitudes are increased by tetanic stimulation of the presynaptic terminal (50 Hz, 1 sec) enhanced response can last for minutes to hours to days, perhaps longer can selectively enhance one input to a neuron without changing the strength of other inputs

Long-Term Potentiation

Long-Term Depression (LTD)

weakening of established synaptic connections between activated neurons "turning off" LTP results from reversing the biochemical pathways that produced LTP activated by low frequency activation of the same or different presynaptic terminal seen especially in cerebellum

Long-Term Depression

Ca++ Trigger of Both LTP & LTD

Memory Disorders
Amnesia (or pathological forgetting)
Anterograde amnesia Retrograde amnesia

Hyperthymestic syndrome

Memory Disorders
Anterograde amnesia - deficit in registration and storage of new recent or long-term memories Korsakoff syndrome (chronic alcoholics) damage to mammillary bodies & medial thalamus, confabulation Klver-Bucy syndrome bilateral lesion of hippocampal/temporal lobe; patient H.M. head trauma and/or impaired consciousness

Memory Disorders
Retrograde amnesia - deficit in ability to retrieve memories
head trauma impaired consciousness Alzheimer's disease electroconvulsive therapy Clinical amnesia cases typically show a mix of anterograde and retrograde amnesia

Memory Disorders
Hyperthymestic syndrome - deficit in ability to forget or suppress memories
Details of events going back 30 years Patient describes being consumed by the

"burden" of memories that were "nonstop, uncontrollable and totally exhausting." Normal IQ Two cases reported

Speech
Communication or expression of ideas or information through vocalization of standardized sounds (and/or words) with accepted associations

Speech In Humans - Left Hemisphere (98%)

Broca's area - frontal lobe, secondary motor cortex area for muscles involved in speech Wernicke's area tempero-parietal lobe, secondary auditory cortex Arcuate fasciculus - pathway from Wernicke's area to Broca's area

Language Areas of the Brain

Language Areas of the Brain

Speaking/Repeating a Heard Word

1. Primary auditory cortex 2. Wernicke's area 3. Arcuate fasciculus

4. Broca's area
5. Motor cortex

Speaking a Heard Word

Speaking a Written Word

1. Visual cortex 2. Angular gyrus

3. Wernicke's area
4. Arcuate fasciculus 5. Broca's area 6. Motor cortex

Speaking a Written Word

Speaking a Written Word

Cerebral Cortex: Outer layer of neurons (1mm thick)

Perception: hearing, vision, olfaction, muscles & viscera Reasoning, information integration Directing voluntary behavior

Lobes of Cerebral Cortex and Associated Integration

Frontal: voluntary movement, behavior, perception Parietal tactile sensory Occipital vision Temporal olfactory, auditory & gustatory

Cerebral Cortex: Outer layer of neurons (1mm thick) Perception: hearing, vision, olfaction, muscles & viscera Reasoning, information integration Directing voluntary behavior

Lobes of Cerebral Cortex and Associated Integration

Frontal: voluntary movement, behavior, perception Parietal tactile sensory Occipital vision Temporal olfactory, auditory & gustatory

HYPOTHALAMUS & LIMBIC SYSTEM

EMOTION
Emotion has been a notoriously difficult concept to define. Many psychologists argue that an emotion comprises three different elements: cognitive (thinking) component: an appraisal or judgment

feeling (subjective) component: what a person experiences privately

action (or, action tendency) component: either an action or, at least, a tendency to an action

Limbic System Functions

Brain Region
Cingulate Cortex Damage: reduced level of tension & anger Medial Frontal Cortex

Effect on Emotion

Inactivation = impaired ability to identify angry expressions (but not happy expressions)
Insula Activated by disgust + primary taste cortex Damage: fail to experience disgust or recognize other people's retching sound as meaning nausea or disgust

Limbic System Functions

RH more sensitive to emotional stimuli than the left hemisphere (LH). For example, Right amygdala: activated by laughing or crying Right temporal cortex: scanning faces for emotional expression increases activity RH damage: Difficulty interpreting facial expression indicating viewing pleasant or unpleasant scene LH damage: Higher than normal ability to interpret facial expression + greater than even chance to detect lying (60% vs. 50%) RH inactivation: facts, but not strong emotions, of past events remembered RH > LH activity: associated with shyness LH > RH activity: associated with outgoing & fun-loving personality

The Pleasure (Reward) Center

The nucleus accumbens is the engine of the reward response. And, in recent studies researchers determined that the reward pathway activates pain relief through the release of both opioids, a morphine-like drug produced by the body, and dopamine, a chemical messenger whose effects can be mimicked by amphetamine and cocaine, in this structure. The finding overturns the longheld assumption that the release of dopamine in the nucleus accumbens is associated only with positive experiences. Nociceptive (pain) stimuli depress mood and increase anxiety, irritability Antinociceptive (pain relief, analgesic) mechanisms elevate mood and decrease anxiety, irritability

Start (Approach, Repeat Behavior), Stop Signals, Pain and Pleasure

The reward pathway is a neural network in the middle of the brain that prompts good feelings in response to certain behaviors, such as relieving hunger, quenching thirst or having sex, and it thereby reinforces these evolutionarily important drives. However, the circuit also responds to drugs of abuse, such as heroin, cocaine, amphetamine and nicotine, which seem to hijack the circuitry, altering the behavior of its neurons.

Complex Pathways of Emotion and Motivation

Hypothalamus, limbic & cortex integration Emotions: pleasure, sexual arousal, anger & fear limited cognitive control "hard to turn off" Motivation: "drives", increase arousal coordinate goaloriented behavior Moods: Long term emotional states Depression, SSRI

Complex Pathways of Emotion and Motivation

Complex Pathways of Learning and Memory

Most Complex Pathways: Language and Personality

Language exchange complex information Wernike's area Broca's area Personality Genetic components Experiences Learning Memory Perceptions

References
1. Text book of medical physiology. Guyton & Hall. 2. Human Physiology Dee ungland Silverthorn 3. Neuronal control of mood, emotion and state of awareness. Dianna A. Johnson

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