PYB102 Lecture Notes PDF

**PYB102 Lecture** [Week 1 ] Neuroanatomical terms and conventions - Tracts (bundles of axons in the CNS (white matter)) vs nerves (bundles of axons in the PNS) - Nuclei (groups of neuron cell bodies in the CNS (grey matter)) vs ganglia (groups of neuron cell bodies in PNS) - Plan...

**PYB102 Lecture** [Week 1 ] Neuroanatomical terms and conventions - Tracts (bundles of axons in the CNS (white matter)) vs nerves (bundles of axons in the PNS) - Nuclei (groups of neuron cell bodies in the CNS (grey matter)) vs ganglia (groups of neuron cell bodies in PNS) - Planes of view -- sagittal, coronal, horizontal Planes of view -- physically or imaging cutting or slicing of brain to visualise key brain structures in different planes. Horizontal plane (parallel slice from normal brain orientation) Sagittal (slice from front of forehead to back) -- when sagittal view right down the middle, it can be called "mid sagittal view" (mid sagittal view would appear frequent as it provides the most visual access to whole range of brain structures). -- aka medial view. Coronal plane (coronal = crown) -- great for visualising different structures **within** the brain. (Top left) All slices are sagittal sections as it is all in the same orientation -- middle cut is the medial view. (Top right) No matter where the level of the horizontal cut might be, they are all horizontal view. (Bottom left) coronal view. (Bottom right) To visualise structures associated with spinal cord and brain stem, there will slices of spinal cord -- which is call cross-section. Neuroanatomical direction - Neuroanatomical directions are relative to an imaginary line. - Neuroaxis (imaginary line) -- go from front of the brain to very end of spinal cord. - Human's neuroanatomical directions in relative to neuroaxis are different in the brain compared the spinal cord. Dorsal - (spinal cord) direction towards the back -\> (brain) direction towards the top of the brain. Ventral -- (spinal cord) direction towards belly -\> (brain) direction down towards the bottom. Anterior (rostral) -- (brain) direction towards the front -\> (spinal cord) direction towards the top of spinal cord. Posterior (caudal) -- (brain) direction towards the back -\> (spinal cord) direction towards the bottom part of spinal cord. Divisions of Brain - Forebrain often subdivided into telencephalon and the diencephalon. - Telencephalon contains structures such as cerebral cortex, limbic system, and basal ganglia. - Diencephalon contains thalamus and hypothalamus. - Midbrain is the location of two pairs of colliculi- the superior colliculi and inferior colliculi. - Hindbrain contains medulla, pons, cerebellum, and reticular formation. Cross section of developing neutral tube - Ectoderm is where our nervous system develops from. - Begin by outer layer (neural plate) thickening and then developing a groove called the neural groove. - The two edges of the neural groove than eventually come together and form a completely enclosed tubed called neural tube. - As it developed, the edge pieces of outside layer of the embryo come together, sitting adjacent to the neural tube, form a neural crest. - Neural tube will grow to form CNS. - Neural crests will develop into PNS. Developing neural tube begins to form discrete enlargement or vesicles. These embryonic vesicles will develop into the major region of the brain: the forebrain, midbrain, hindbrain. - Forebrain undergoes most kind of massive amount of development, while midbrain is less so, and hindbrain undergoes medium amount of development. - Additionally, forebrain will continually be developing in the postnatal period. Midsagittal view of the brain - (Dorsal view) There is a big groove that runs from front to back (Longitudinal fissure) -- if cut the brain along the longitudinal fissure, its like cutting down a bread that have already been sliced (nothing happens). - However, at some point, it would hit Corpus callosum (hard body) -- the region is densely packed with white matter tracts. Important functions of hindbrain regions Medulla - Contains circuits of neurons that control functions vital for surviving such as heart rate, blood pressure, and respiration. Pons - Includes a bridge of fibres connected brainstem with cerebellum. Pons also contains several clusters of nuclei. One of the clusters that run through the cs is reticular formation which has an influence on our level of consciousness and alertness. Cerebellum - Large structure located behind the brain step. Iti is official to co-ordinating of movement and to balance. (cerebellum -\> movement -\> smooth, make movement coordinated, voluntary movement). - Cerebellum is not organised in contralateral way, its organised in ipsilateral way (left side of cerebellum coordinates the movement on the left side of the and vice versa). Reticular Formation [Week 2] Ventral surface of medulla Decussation - Pyramidal tracts/ axons of nerve cells travel from top surface of brain cross over at the base of medulla. - They then travel down opposite side of spinal cord (cells originated from Primary Motor cortex -\> responsible for controlling movements). - Cells from left side of motor cortex/ left hemisphere travel down brain, then decussate at medulla and travel down opposite (right) side of spinal cord and innovate muscles on opposite (right) side of body. - Contralateral arrangement of brain -\> The arrangement whereby the motor cortex of each cerebral hemisphere is mainly responsible for control of movements of the contralateral (opposite) side of the body. Midbrain - Better visualised from mid-sagittal view - Superior (anterior) colliculi -\> relay visual information and are important for visual attention. \*Kind of monitoring visual field and are involved in orienting visual attention to something exciting\* - Inferior (posterior) colliculi -\> relay auditory information and are important for auditory attention. \*E.g., might hear name somewhere and help orient auditory - Thalamus -\> sits beneath the corpus callosum -\> breaks down into 2 lobes -\> there is a pathway which joint the two lobes together which is called Masa Intermedia (Interthalamic adhesion) - Thalamus function: relay station through which all sensory information (except smell) must pass to get to cerebral cortex -\> filters and begins to organise sensory input. - Hypothalamus -\> position at centre and beneath the thalamus -\> small area of brain tissue (size of a pea) - Hypothalamus function: regulation of range of biological processes such as hunger and thirst, controls autonomic nervous system and is involved with regulation of body temp. - Hypothalamus also controls pituitary gland (attached by stalk to base of hypothalamus) - Pituitary releases hormones into body and controls other glands. Forebrain (Telencephalon: Basal Ganglia, Limbic system, Cerebral cortex) Basal ganglia: group of structures crucial for planning and producing movement. - Basal ganglia are group of brain structures that are thought to be particularly implicated in Parkinson's disease - There two important structures: hippocampus and amygdala - Hippocampus function: plays role in memory, particularly in consolidation of new memories (learning). - Amygdala function: serves vital role in processing emotional info, particularly the learning of fear response - Bump or bulge on cortex is called gyrus (plural word -\> gyri) and a groove is called sulcus (plural word -\> sulci) - Longitudinal fissure: Big deep sulcus that runs between two cerebral hemispheres - Lateral fissure (Sylvian fissure): Begins near the basal forebrain and extends to the lateral surface of the brain separating the frontal and parietal lobes superiorly from the temporal lobe inferiorly   - Located at the back - Includes primary visual cortex - Concerned with many aspects of vision - Located behind central sulcus - Concerned with perception of stimuli related to touch, pressure, temperature and pain Temporal lobes - Located below lateral fissure - Concerned with perception and recognition of auditory stimuli and memory. Frontal lobes - Located in front of central sulcus - Concerned with reasoning, planning, parts of speech and movement (motor cortex), emotions, and problem-solving ---------------------------------- ------------------------------------------------------------------------------- **Cortical Area** **Important Functions** **Prefrontal Cortex** Problem solving, Emotion, Complex Thought, 'Higher Order' Cognitive Functions **Primary Motor Cortex** Initiation of voluntary movement **Motor Association Cortex** Co-ordination of complex movement **Primary Somatosensory Cortex** Receives tactile information from the body **Sensory Association Area** Processing of multisensory information **Visual Cortex** Detection of simple visual stimuli **Visual Association Area** Complex processing of visual information **Auditory Cortex** Detection of sound quality (loudness, tone) **Auditory Association Area** Complex processing of auditory information **Wernicke's Area** Comprehension of language **Broca's Area** Speech production ---------------------------------- ------------------------------------------------------------------------------- Primary somatosensory cortex Primary motor cortex [Week 3] Corpus callosum The cerebral hemispheres - Two important concepts: - Lateralisation (specialisation) -- idea that one hemisphere of the brain is specialised to perform particular tasks - Contralateral arrangement - e.g. left cerebral hemisphere is receiving sensory input from the right side of the body -- pyramidal decussation How visual system experiences contralateral arrangement - Diagram demonstrates how visual information from left visual field (in both eyes) is projected to right hemisphere of brain - Information from right visual field is projected to left hemisphere Split-brain experiments - Patients with serve epilepsy had bundle of neuron fibres that allow two hemispheres to communicate (corpus callosum) severed. - Clever experimental paradigm (split-brain experiment) was used with these patients to investigate lateralisation of cerebral hemisphere Brain support systems: Cerebral Ventricles - Inside brain is a series of chambers filled with cerebrospinal fluid (CSF) -- these cavities form what is known as ventricular system - The CSF circulating through ventricular system has at least two main functions: - One is mechanical shock absorber -- floating in CSF, the brain is protected from sudden movement that would otherwise cause contact with inside of skull - Second is as medium for exchange of materials -- including nutrients, between blood vessels and brain tissue Brain support systems: Vascular system - Although accounts for only 2% of weight of average human body -- brain consumes more than 20% of body's energy -\> however, brain has very little reserve of basic metabolic fuels such as oxygen and glucose, and thus it depends critically on its blood supply provide to them - Because of tight junctions between cells that form their walls, brain capillaries found elsewhere in body - Blood-brain barrier is a protective mechanism that may evolved to help protect brain from infections and blood-borne toxins -- also makes delivery of drugs to brain more difficult Brain support systems: the Meninges - Protective sheaths around brain and spinal cord are referred to as meninges - Meninges consist of three layers: - Dura mater (closest to skull) - Arachnoid membrane - Pia mater (closest to cerebral cortex) - Between pia mater and arachnoid membrane is a gap called subarachnoid space -\> space is filled with CSF  Divisions of CNS: Spinal cord - Principal function -- distribute motor connections to muscles and glands and to collect somatosensory information - Spinal cord is protected by vertebral column and passes through a hole in each of vertebrae - Spinal cord is only two-thirds of length of vertebral column -- the rest of space is filled b mass of spinal nerves composing cauda equina  Divisions of PNS: Somatic Nervous System Spinal nerves - Each spinal nerve consists of fusion of two distinct branches, called roots -- spinal nerves begin at junction of dorsal and ventral roots of spinal cord - Nerves leave vertebral column and travel to muscles or sensory receptors they innervate - Afferent axons travel toward CNS conveying sensory information - Efferent axons travel way from CNS conveying motor commands to muscles and glands Cranial nerves - Twelves pairs of cranial nerves are attached to ventral surface of brain -- most nerves serve sensory and motor functions of the head and neck region - The tenth, vagus nerve, regulates functions of organs in thoracic and abdominal cavities Divisions of PNS: Autonomic nervous system - Is concerned with regulation of smooth muscle (e.g. skin, blood vessels, walls of gut), cardiac muscle, and glands - ANS consists of two anatomically separate systems: sympathetic division and parasympathetic division Sympathetic division (fight and flight) - Most involved in activities associated with expenditure of energy from reserves stored in body Parasympathetic division (rest and digest) - Supports activities that are involved with increases in body's supply of stored energy  [Week 4] Cells in human nervous system - Neurons -\> basic functional units of nervous system - Take in information from other neurons (reception) -\> integrate those signals (conduction) -\> pass signals to other neurons (transmission) - Glial cells nourish, protect, and physically support neurons and are though to be particularly critical in brain development - One type of glial cell, oligodendrocyte, covers axons of neurons with myelin, substance critical to effective functioning of the brain Parts of neurons - Dendrites -\> function principally to receive messages from other neurons -\> transmit information they receive to soma - Soma (cell body) contains mechanisms that control metabolism and maintenance of cell -\> also collates 'messages' from other neurons - Axon carries 'messages' away from soma towards cells with which neuron communicates; messages are called action potentials - Terminal buttons -\> located at the end of the 'twigs 'that branch off the ends of axons; they secrete neurotransmitters which affect activity of other cells with which neuron communicates - Myelin insulates some axons to promote efficient transmission of action potential -- serves to increases speed of propagation of action potential along axon Cell Membrane - Made up of lipid bilayer -- two layers of fatty molecules -- within which many types of specialised proteins 'float' - Cell membrane: - Lipid bilayer: two layers of fat (lipid) molecules - Embedded protein molecules - Proteins form pores or channels that control movement of material into and out of call  - Cell membranes separate two different chemicals solutions - Those solution interact vis pores or channels - Typically, these are protein molecules with a central passage - At rest, pores are usually closed - To prevent interchange of inside (intracellular) and outside (extracellular) materials Neuron 'at rest' Resting membrane potential - Resting membrane (RMP) derives from difference in chemical composition inside and outside of cell at rest - Result of relative concentrations of potassium ions (K+), chloride ions (Cl-), negatively charged protein ions, and sodium ions (Na+) - The RMP is approximately equal to -70mV (-50 mV to -80mV) Measuring RMP Action potential - Is a brief reversal in resting charge of neuron -- triggered by an exchange of ions across the neuron membrane - Is created when neuron membrane is sufficiently depolarised (i.e. resting potential moves towards 0 mV) -- when depolarisation reaches threshold of about -55 mV -\> neuron will fire action potential -- if neuron does not reach critical threshold level, then no action potentials are fire - If threshold level is reached -- action potential of fixed sixed will always fire -- for any given neuron, size of action potential is always the same - Therefore, neuron either does not reach threshold or full action potential is fired Movements of sodium and potassium ions during action potential Speed of propagation of Action Potential - Speed of propagation of action potential is determined by: - Diameter of axon (bigger = faster) - Presence or absences of myelin sheath Myelin sheath - Electric insulator - Prevents ion flow across - Current can only flow across membrane at breaks in myelin sheath (called Nodes of Ranvier) - Sodium channels are concentrated in Nodes of Ranvier - Action potential can only be generated in these gaps - 'Jumping' of action potential from break to break massively increases speed - Non-myelinated axons are much slower as action potential is generated repeatedly along the axon Synaptic transmission - Neurons do not touch one another; they are separated by small space known as synaptic cleft (or synaptic gap.... Or synapse) - When an action potential reaches terminal buttons, it causes the release of specialised chemicals (neurotransmitters) that travel across synaptic cleft and are received by dendrites of other neurons Release of neurotransmitters from a terminal button - Stage 1 - before action potential has arrived, neurotransmitters are stored in vesicles within terminal button  - Stage 2 - action potential triggers release of neurotransmitters into synaptic cleft \- Stage 3 -- neurotransmitters diffuse across synaptic cleft. Some of them will attach to receptor molecules in post synaptic membrane and activate them -- thus either inhibiting or enabling postsynaptic neuron to generate action potential  Neurotransmitter types - Neurotransmitter is a generic word used for chemical substances that carry signals across synaptic cleft -\> they bind to receptors on postsynaptic neuron - Receptors are specialised protein moles -\> they are binding of neurotransmitters to receptors causes ion channels to open, which changes membrane potential at that location, thus affecting probability that neuron will fire an action potential - If neurotransmitter binds with receptor and depolarises membrane -- excitatory and increases likelihood that receiving neuron will fire action potential - In contrast -- if neurotransmitter's binding hyperpolarises membrane -\> it is inhibitory and makes receiving neuron less likely to fire action potential Terminating synaptic transmission: removal of neurotransmitters from synaptic cleft - Reuptake -- whole neurotransmitter molecule is taken back into axon terminal that released it - Diffusion -- neurotransmitter drifts away, out of synaptic cleft where it can no longer act on a receptor - Deactivation/ degradation specific enzyme changes structure of neurotransmitter so it is not recognised by receptor -- e.g. acetylcholinesterase is enzyme that breaks acetylcholine into choline and acetate [Week 5: Attention and memory I ] Basic processes of memory - Three basic processes are needed for any successful act of remembering: - Encoding = transform sensory stimuli into a form that can be placed in memory - Storage = effectively retraining information for later use - Retrieval = locating the item and using it (e.g., recall vs recognition )  Encoding Role of attention in encoding - Cherry's (1953) "cocktail party phenomenon" - How do we concentrate on one conversation only? - Attention = 'Filter'(Broadbent, 1958) - Assumptions: - Stimuli processed in parallel - One stimulus allowed through filter while remains buffered - Filter prevents overload in system Models of selective attention - Amount/type of attention determines quality of encoding - 'Dept' of processing is also influential - Maintenance rehearsal: \*Rote repetition of information, without transformation into a deeper more meaningful code - Elaborative rehearsal: \*Meaningful processing of information Craik & Tulving (1975) Word -\> hat - Superficial: written in upper case? No - Phonological: Does it rhyme with mat? Yes - Semantic (deep): Does it fit into this sentence? The man put on his..... Yes - Recognition task: old or new - Best learning in semantic condition Other means of enriching encoding - Elaborative rehearsal: thinking about the material while trying to memorise -- i.e., what the poem is about - Visual imagery: concrete objects recalled better than abstract items - Self -- referent encoding applying information processed to own self Storage - Memory storage 1. Senory register storage system that registers (and briefly holds) information from the senses a. Iconic memory -- related to visual system - Duration: \ - This is called a whole-report task - He found that no matter how many letters he presented, the participants could not recall more than 4.5 letters on average The partial-report task - Sperling (1960) asked whether this limit of 4.5 letters reflected the amount participants could see or the amount they recall - He tried to answer this by lowering the memory load of the task - This partial-report task went as follows: - Participants viewed the matrix of letters for a brief time - After the letter disappeared, the participants were presented with a sound to tell them which row to recall (partial position report task) - The participants reported only what they remembered from the probed row - Sperling (1960) argued that the proportion of letters recalled from a given row must reflect the proportion of letters seen in the whole display - This is reasonable because the participants did not know which row would be probed while the letters were visible - Sperling (1960) found that participants could recall about 75% of the letters in any row - Thus, Sperling (1960) extrapolated that the participants must have 'seen' 9 of the 12 letters in the display Partial category report - In one of his experiments, Sperling (1960) presented matrices containing an equal number of both consonants and digits and used two auditory probes to tell participants to report either the letters or the digits - Unlike his earlier experiments where the probe identified which row (position) to report, Sperling (1960) did not observe a partial report superiority effect when he used this partial category report task - This suggests that the contents of the icon are not yet "recognised" -- that the icon is just a "raw visual image" 2. Short term memory (STM): intermediate storage system that briefly holds information prior to consolidation - How large is STM? How long does it last? Consider the memory span/ digit studies: - \~ 20 seconds duration - Measure recall for varying length digit lists: 7 ± 2 (score can be inflate) Chunking: units of [subjective] organisation - For example: - Phone numbers 3485 9235 - Student numbers - Credit cards 4567 2773 3737 4854 A traditional view - Duration can exceed 20s: rehearsal - Without rehearsal information is lost -\ decay - Information also lost through interference [\[CHART\]]{.chart}Is STM one unitary system - Dual-task technique: one concurrent memory task (e.g., digits), combined with a task dependent on STM (e.g. reasoning) - Increase in latency: only 35% - Error rate constant - Pattern cannot be accounted for by assuming unitary STM - Inference: digit span set by subcomponent of STM, with other components still available to process information Working memory Working memory key components - Phonological (articulatory) loop/buffer: - Responsible for manipulation of speech-based information - Visuospatial sketchpad: - Responsible for setting up and manipulating visual & spatial images - Central executive: - Attentional system which supervises and controls the two 'slave' systems 3. Long term Memory (LTM): storage system that retains information for a long period of term - Large capacity - Long duration - Different types of LTM Retrieval Free recall - [\[CHART\]]{.chart} Serial position effect [\[CHART\]]{.chart} U-shaped curve - Some general effects - Primacy effect: memory best for things learned first - Recency effect: memory also good for things learned last (but mostly this is STM contribution to the task) - Context: memory is better when you are in the context you learned the material in - Internal state: memory is better when your internal state is the same as at the time of learning [Week 6: Memory II ] Conceptualising memory Memory by time - Multiple-trace hypothesis of memory classifies memory by duration: - Iconic memories -\> briefest - Short-term (STM) -\> longer than iconic but shorter than lang-term - Long-term (LTM -\> most enduring form of memory -- last for days or years Another way of conceptualising memory Memory by type (i) - Nondeclarative (procedural) memory: things you know that you can show by doing (e.g., grammar, or motor skills, or problem -- solving) - Declarative memory: things you know that you can tell others (e.g., facts and events) - Sematic memory -- generalised memory -- general knowledge - (e.g. date) - Episodic memory -- autobiographical -- what is the graphical nature of memory (e.g. who was at the birthday party) Memory by type (ii) - Nondeclarative or procedural memory is shown by performance rather than by conscious recollection - Memory without conscious awareness -\> implicit memory - Memory with conscious awareness -\> explicit memory (conscious memory) Brain structures involved in learning and memory - Knowledge of brain structures involved in learning and memory has to a large extent come from the study of neuropsychological patients with brain damage-produced amnesia - Important to review some critical case studies and implication of understanding of neuroanatomical bases of memory Henery Gustav Molasion (H.M.) - Born February 26^th^ 1926, died December 2^nd^ 2008 - Seizures began at age 10 - From age 16-27, had \~10 partial seizures a day, 1 generalised seizure a week - Seizures not controlled by antiepileptic medications - EEG showed abnormalities in central temporal lobes - At the age 27, bilateral medial temporal lobectomy was performed H.M. - Involved removal of medial portions of both temporal lobes including most of hippocampus, amygdala, and adjacent context (rhinal cortex) - Following the surgery: - Preserved perceptual and motor abilities - Preserved STM - Some retrograde amnesia - Severer anterograde amnesia - Seizure reduced & cognitive function improved Kind of amnesia - Anterograde amnesia = loss of memory **after** injury event - Retrograde amnesia = loss of memory **prior** to injury event  Formal assessment of HM's amnesia - Digit span + 1 test - Showed HM's inability to form new long-term memories for verbal information - Block tapping memory span test - Showed that his inability to form new memories was not just restricted to verbal information - Mirror drawing test - Despite not remembering the test, HM's performance improved - Incomplete pictures test - Despite no, HM's performance improved H.M asked to draw floor plan of the house \*He moved to the house after the surgery \* (a) drew during living in the house \* (b) drew 3 years after moving out of the house Case studies are all very well but... - First reports of HM's case in 1950's triggered massive effort to develop an animal model of his disorder so that it could be subjected to experimental analysis. - In its early years, this effort was a dismal failure; lesions of medial temporal lobe structures did not produce severe anterograde amnesia in rats, monkeys, or other nonhuman species Why was it so difficult to create an animal model of HM's amnesia - In retrospect -- there were probably two reasons for initial difficulty in developing animal model of medial temporal lobe amnesia - First -\> it was not initially apparent that HM's anterograde amnesia was specific to declarative (explicit) long term memories - Secondly -\> it was incorrectly assumed that amnesic effects of medial temporal lobe damage were largely, if not entirely, attribute to hippocampal damage. Most efforts to develop animal models focussed on hippocampal lesions Delayed non-matching-to-sample task - Important advance was development of method for testing declarative memory in sample task - Development of this task for monkeys also provided means of testing assumption that amnesia resulting from medial temporal lobe damage is entirely consequence of hippocampal damage What do these studies tell us? - Reviewers of this research have generally reached these conclusions - Bilateral surgical removal of perirhinal cortex consistently produces severe and permanent deficits in performance on delayed non-matching-to-sample-test and other tests of object recognition - In contrast, bilateral surgical removal of hippocampus produces either moderate deficits or none at all, and; - Bilateral destruction of amygdala has no effect on object recognition Hippocampus - Memory formation and consolidation -\> hippocampus still plays role in forming memories and reorganising them over time - Temporary storage: plays temporary role in memory storage, with damage typically impairing recent but not remote memories - Spatial representation: involved in representing spatial information and navigation - Memory retrieval: works with cortex to support LTM storage, with its role gradually declining as memories become more stable in cortex Synaptic mechanisms of learning and memory - There are many hypotheses as to neural mechanism of learning and memory - Tend to focus on - Structural changes at synapses - Physiological changes at synapses Structural changes at synapse may include: - Formation of new synapses - Rearrangement of synapses - Neurogenesis Physiology changes at synapses may include: - Long-term potentiation (LTP) - Stable and enduring increase in effectiveness of synapses LTP - Repeated firing of a synapse lowers the threshold of that synapse to fire - Time 1 (before any changes happens) - Pre-synaptic neuron fires at normal rate - Post-synaptic neuron fires at a certain strength in response - Time 2 (the cause of the change) - Pre-synaptic neuron fires a lot, causing post-synaptic neuron to fire a lot - Time 3 (after the change) - Pre-synaptic neuron fires at normal rate - Post-synaptic neuron now fires more strongly than it did at Time 1 Mechanism of LTP - LTP has been studied most extensively at synapses at which the NMDA receptor is prominent - The NMDA receptor = receptor for glutamate -- the main excitatory neurotransmitter of the brain - NMDA receptor has special property -- it does not respond maximally unless two events occur simultaneously: - Glutamate must bind to it, and; - Postsynaptic neuron must already be partially depolarised - Dual requirement stems from the fact that calcium channels that are associated with NMDA receptors allow only small numbers of calcium ions enter unless neuron already depolarised when glutamate binds to receptor - It is influx of calcium ions that triggers action potentials and cascade of events in post-synaptic neuron that induces LTP  [Week 8: Variation in consciousness ] Common measures used to detect physiological changes during sleep Electroencephalography (EEG) - Uses electrodes placed on scalp to detect and measure patterns of electrical activity emanating from brain - EEG electrode amplifies electric potentials occurring in many thousands of brain cells  EEG signal - Image shows one second of EEG signal from a signal electrode placed on the scalp EEG during wakefulness and NREM sleep EEG during different sleep stages (& REM)  Sleep stage variations in EEG, EOG and EMG - Lack of muscle activity in REM sleep - EEG in REM sleep is similar to EEG while awake (accordingly, REM sleep is often known as 'paradoxical sleep' Sequence of sleep stages on a typical night  Age-related changes in total amount of daily sleep and percentage of REM  Comparison of generalised physiological changes between REM and NREM **Physiological process** **During NREM** **During REM** --------------------------- ---------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------- Brain activity Decreases from wakefulness Increases in motor and sensory areas, while other areas similar to NREM Heart rate Slows from wakefulness Increases and varies from NREM Blood pressure Decreases from wakefulness Increase (up to 30%) and varies from NREM Blood flow to brain Does not change from wakefulness in most regions Increases from 50 -200% from NREM -- depending on brain region Respiration Decreases from wakefulness Increases and varies from NREM, coughing suppressed Body temperature Is regulated at lower set point than wakefulness (i.e. shivering will not start until a lower-than-normal temp is reached) Is not regulated; no shivering or sweating; temperature drifts toward that of local environment Average total sleep requirements for various species (hours/day) Brain regions important for circadian rhythm and REM sleep Circadian sleep cycle - Sleep-wake cycle is intrinsically linked to circadian rhythm - Circadian rhythm is predominantly entrained by light-dark transitions - At the neuronal level circadian rhythm is controlled by suprachiasmatic nucleus (SCN) - SCN, a small strucute in hypothalamus - Entrainment by light-dark cycle via retinohypothalamic tract - Sectioning optic nerves prevents light-dark regulation of circadian rhythms by not sectioning of optic tract The retinohypothalamic pathway Some neural system involved in sleep - Basal forebrain region in ventral frontal lobe may be responsible for inducing SWS - Reticular formation in brain stem may be responsible for activating/waking brain from sleep - Regions of pons are important for triggering REM sleep and muscle atonia associated with REM sleep stage - Hypothalamic system may be important in regulating transitions between activation of other neural sleep system Functions of sleep - Restoration and recovery of bodily systems - Energy conservation - Memory consolidation - Protection from predation - Brain development Sleep disorders - Insomnia - Sleep apnoea - Somnambulism - Night terrors - REM sleep behaviour disorder - Narcolepsy Theories of dreaming - Freud (early 1900's): dream as wish fulfilment - Cartwright (early 1900's): problem-solving view - Hobson and McCarley (1970's to late 1990's): activation-synthesis model [Week 9: Emotion and stress ] Feeling emotional?? - Emotion vs mood - Traditional/basic emotions approach would suggest that there are certain number of emotions -- however, there isn't a great deal of agreement on this - Most frequently used number is 6: surprise, anger, fear, sadness, disgust, and happiness (Ekman,1999) James-Lange theory  Canon's criticism of James-Lange theory of emotion 1. Autonomic responses are relatively slow (i.e., - we experience or 'feel' emotion before physiological changes have occurred) 2. Cutting nerves from viscera has no effect on emotions in rats 3. Many different emotional states are linked to same visceral responses 4. Injecting adrenaline/ epinephrine (as can be released during a 'normal' emotional state) does not induce feeling of an emotion Canon-Bard theory Schachter-Singer two-factor theory [\ ] Schachter and Singer's experiment 1. Experimenters advertised for participants to have a 'multivitamin' injection, under the pretence that they were testing for side-effects 2. Participants actually injected with either adrenalin or placebo (inert salt solution) 3. Those given adrenalin were told to expect one of the following: a. Exactly what adrenalin does to the body b. That they would get itchy eyeballs c. Nothing 4. Those given placebo were told nothing 5. Then the participants waited with confederate the experimenter who either: a. Acted the fool and attempted to be quite humorous (euphoric situation) b. Acted really rude and asked participant to fill in an anger provoking questionnaire 6. Results: - Group 3a reported "It's as if I'm happy/angry, but it's the effect of injection" - Group 3b reported being very happy or very angry depending on the situation - Group 3C reported feeling quite happy or quite angry - Group 4 (placebo group) reported feeling a bit happy (not as much as 3C), or quite angry [\ ] Summaries of important emotion theories  The major structures of limbic system  Limitations of traditional/ basic emotions approach - Lack of agreement on how many emotions - Lack of specific physiology for each emotion - Difficulty localising these in the brain Stress - Refers to a challenge to person's capacity to adapt to inner and outer demands - Stressful experiences typically produce physiological and emotional arousal - Stressful experiences typically elicit and behavioural efforts to cope with stress Stress as psychobiological process - Stress can be both psychobiological and physiological components and consequences - Understanding the physiological components of stress requires us to consider both nervous and endocrine (hormonal) systems PNS: Autonomic nervous system - Concerned with regulation of smooth muscle (e.g., skin, blood vessels, wall of gut), cardiac muscle and glands - Consists of two anatomically separate systems: sympathetic and parasympathetic division Sympathetic division - Most involved in activities associated with expenditure of energy from reserves stored in body Parasympathetic division - Supports activities that are involved with increases in body supply of stored energy Glands of Endocrine system  Acronym: - HPA: [H]ypothalamic-[p]ituitary-[a]drenal - CRF: [C]orticotropin [r]eleasing [f]actor - ACTH: [A]dreno[c]ortico[t]ropic [h]ormone  [Week 10: Language] Aphasia - Broad term used to clinically describe language disorders - Prefix "a" means without and prefix "dys" suggests impairment - Term "dysphasia" is rarely used Languages have similar basic - Phonemes -- smallest unit of sound that makes a difference to meaning - Morphemes -- smallest unit of language that has meaning - Semantics -- meanings of words or sentences - Syntax -- how words are combined to conduct phrases and sentences - Grammar -- all of the rules for usage of a language Some signs aphasia: - Paraphasia -- substitution for a word by a sound, an incorrect word, or an unintended word - Neologism -- entirely novel word - Nonfluent speech -- talking with considerable effort Many patients with aphasia may also show other impairments: - Agraphia/ dysgraphia -- inability to write/ impairment of writing - Alexia/ dyslexia -- inability to read/ impairment of reading Classic aphasiology approach (understanding language disorders)  Foundation of Knowledge: - Classica approach provides foundational understanding of how language functions and how it can be disrupted by brain injuries - Historical perspective is crucial for appreciating evolution of theories and practices Clinical (diagnostic) relevance: - Many contemporary assessment and treatment techniques are built upon the principles of established by classic aphasiology Critical thinking: - Studying classic approaches encourages critical thinking and deeper understanding of complexities of language disorders - Allows you to critically evaluate new theories and methods in context of this knowledge Historical antecedents of the Wernicke -- 'Geschwind' Model Paul Broca (1861) - Post-mortem reports of two patients with impaired language function - Patient Leborgne, a.k.a "Tan" (named after one of his few utterances) - Right hemisphere and loss of speech - Comprehension okay - Lesions in lower region on left frontal lobe - Broca's area - Ignored other damages (long history of epilepsy) Carl (Karl) Wernicke (1874) - Reported two patients with profound deficits in comprehension and fluent, incomprehensible speech - Lesion found in posterior part of the superior temporal gyrus in left hemisphere - Posterior to primary auditory cortex Lichtheim's House - Lichtheim (1885) proposed disconnection model of aphasia - A = 'auditory'-- auditory word form area - M = 'motor' -- spoken word from area - B = 'concept' area Wernicke -- 'Geschwind' Model of language - In 1972, Norman Geschwind reignited discussion of Wernicke's and Lichtheim's conceptualisations and this resulted in what is now commonly known as the Wernicke -- Geschwind model - Approach also often referred to as disconnection model, to emphasise symptoms of language impairment following loss of connections among brain regions in network - Important to understand contributions of the this historically important model to our understanding od neuroanatomical basis of language Broca's aphasia - Also known as "production aphasia", "non-fluent aphasia", "expressive aphasia" or "motor aphasia" - *Generally* results from injury in vicinity of Broca's area, which is posterior part of inferior frontal convolution in left hemisphere (i.e., left inferior frontal lesion) - Broca's area lies just anterior to portion of motor cortex that controls the muscles involved in speech production, including those in throat, tongue, jaw and lips - Damage to this region is thought to result in destruction of memory traces of movements required of produce speech Broca's aphasia: symptoms (i) - Disturbance of language characterised by slow, effortful, and deliberate speech - Telegraphic speech -- i.e., simple grammatical structure (e.g., using nouns in singular forms) - For example, when asked what s/he is doing, a patient with Broca's aphasia might reply, "make dinner" or "eat dinner" - Difficulty finding and producing appropriate phoneme or word - May result in anomia (complete inability to come up with desired word), or paraphasia (distorted productions) - Phonemic paraphasias -\> individual cannot come up with desired phoneme but instead substitutes a phoneme that has some similarity to desired sound (e.g., pill for spill) - Significant disruptions in prosody -- i.e., intonation, emphasis, and emotional tone of spoken language - Reduced verbal fluency - Perseveration -- i.e., repetitive production of same utterance, even when it does not fit their intended meaning - Automatic speech may be preserved (e.g., greetings; short, common expressions; and swear words) - Hemiplegia is common -- i.e., partial paralysis of one some of body (usually right, because lesion often extends to nearby motor cortex in left hemisphere - Insight intact - Language comprehension is largely intact - However, patients have good comprehension for nouns and verbs, they have difficulty comprehending small function wors (e.g., preposition comprehending pronouns) and inflected endings - They may be confused by problems like these: - That's my aunt brother. Would that be a man or a woman? Or - The lion was killed by tiger. Which animal died? Broca's aphasia: example (Goodglass, 1976) Doctor: Why did you come to the hospital? Client: Ah... Monday... ah dad and Paul... and Dad...hospital. Two... ah doctors... and ah... thirty minutes... and yes... ah hospital. And er Wednesday... nine o'clock... doctors. Two doctors... and ah... teeth. Yeah... fine. Wernicke's aphasia - Also known as "fluent aphasia" - *Generally* results from injury in vicinity of Wernicke's area in left superior temporal cortex posterior to primary auditory cortex - This region has been suggested as locus of memory for constituent sounds of speech and is thought to mediate linking of auditory representations of words with their meaning Wernicke's aphasia: symptoms - Severely impaired ability to comprehend speech (others' and own) - Fluent, grammatical speech production without effort or distress - Speech retains information pattern, rhythm, and pronunciation of normal speech - Jargon-like words make their speech difficult to interpret - Includes paraphasias: - Semantic paraphasias -- individual makes an error that has a semantic similarity to desired word (e.g., look for show) - Neologism -- i.e., distortion of two or more sounds within word or inventions of novel words (e.g., zailfops) is also frequent - Circumlocutory speech -- i.e., the patient often talks around topic or word in way that may makes them difficult to understand (e.g., man who sweeps and cleans up for cleaner) - Impaired ability to repeat words and sentences - Unlike individuals with Broca's aphasia, ppl with Wernicke's aphasia do not display partial paralysis - Intact understanding of facial expression; facilitates communication - Often poor insight into language difficulties Wernicke's aphasia: example (Martin, 2003) Therapist: What did you have (to eat)? PH: Today I haven't touched a/maiwa/d/David. He had beastly tomorrow. Therapist: Was the food good? PH:Yes, it was fine. Conduction aphasia: symptoms - Normal speech comprehension and production - Deficits in repetition of non-meaningful words and words sequences - Usually preserved ability to repeat colloquialisms and stock phrases - Damasio and Damasio (1980) -\> patient with conduction aphasia were found to have damage to association fibres of inferior parietal lobe, which normally connects Wernicke's and Broca's areas - Geschwind (1965) has suggested that: - When individual with conduction aphasia hears a word (e.g., 'bicycle), they produce mental representation of that object - Information concerning this image is sent from visual association cortex to Broca's area (thus bypassing damaged arcuate fasciculus) in order to initiate the movements necessary to produce the sounds that constitute word - However, if perception of non-word fails to produce visual image, patient is unable to reproduce the word Conduction aphasia: example (Carlson, 1986) Doctor: Bicycle. Patient: Bicycle. Doctor: Hippopotamus. Patient: Hippopotamus. Doctor: Blaynge. Patient: I didn't get it. Doctor: Up and down. Patient: Up and down. Doctor: Yellow, big, south. Patient: Yellen... Can't get it. Current status of Wernicke-Geschwind Model and Aphasia - Empirical evidence supports two elements - Important roles played by Broca's and Wernicke's - Many aphasics have damage in these areas - Anterior damage somewhat more associated with expressive deficits and posterior with receptive - No support for more specific predictions - Damage limited to identified areas has little lasting effect on language - Brain damage in other aeras can produce aphasia - Pure aphasias (expressive OR receptive) rare [Week 11: Higher order cognition ] What are Executive functions? - Skills that are heavily associated with frontal lobe One conceptualisation - Ability to over-ride automatic behaviour in order to deal with novel (new) situations (inhibitory control) - Ability to switch flexibly between tasks (cognitive flexibility) - Ability to carry out task while holding in mind other goals (working memory) Another conceptualisation: - Volition - Goal/intention formulation, motivation (initiation), awareness of self & environment - Planning - Conceptualise change, think abstractly, ability to conceive of alternative solutions and male choices, impulse control, sustained attention, memory - Purposive action - Initiate, maintain attention, switch and stop sequences of complex behaviour (non-routine) Other conceptualisation (Norman & Shalice, 1985) - Executive functions required when: - Planning and decision making needed - Error correction or troubleshooting required - Non-automatic or novel responses to be made - Dangerous or technically complicated - Need to overcome habit or temptation Hot executive functions - How do we use them in real life (trigger emotion responses, include social aspects) Cold executive functions - How executive functions would perform in an ideal condition Importantn regions of frontal lobes - Primary motor cortex - Non-primary motor cortex - Premotor cortex and supplementary motor area - Prefrontal motor cortex Frontal lobe - Frontal lobes are richly connected with other cortical and subcortical regions of brain - Thus, we should not consider functions attributed to frontal circuits o regions to be solely localised or mediated by specific circuit or region Prefrontal cortex - Prefrontal cortex can be 'divided' in many ways - One common subdivision of prefrontal cortex is into three 'regions': - Dorsolateral prefrontal cortex - Orbitiofrontal cortex - Mediofrontal cortex (most of the time people don't only damaged this area by itself) The dorsolateral prefrontal cortex (DLPFC) - DLPFC and its circuitry is involved in higher cognitive operations - This circuit is often labelled the 'executive' circuit, however its important to recognise that executive functioning is also implicated in mediation of emotional, motivational and social behaviour - Deficits following damage to DLPFC may include: - Working memory - Planning, task-setting, and problem solving - Sequencing - Selective and sustained attention - Perseveration -- "getting stuck" - Inhibition - Cognitive flexibility Neuropsychological measures sensitive to dorsolateral frontal damage - F-A-S test (individuals may repeat items or get stuck) -- design to test verbal fluency -\> how easily and efficiently can you name items - Digit span backwards, backwards 7's, N-Back (working memory) - Tower of Hanoi/ Tower of London (task-setting/planning, sequencing, problem solving) - Stroop (inhibition) - Wisconsin card sort (cognitive flexibility) Tower of London Wisconsin Card Sort Stroop The orbitofrontal lobe (OFC) - OFC and its circuitry is involved in mediation of emotional and social response - Responsible for executive processing of emotional stimuli - Deficits following damage to OFC may include: - Emotional lability - Diminished social insight - Socially inappropriate behaviour, esp. conversational skills - Difficulties with changing reinforcements - Lack of sensitivity to future outcomes, both outcomes, both positive and negative - Lack of empathy Neuropsychological measures sensitive OFC damage - Family/caregiver reports of social behaviour, empathy, aggression - F-A-S test (individuals may give socially inappropriate answers) - Bechara's gambling task The mediofrontal cortex (MFC) - This prefrontal region is believed to support number of overlapping functions, including; - Response monitoring (control and monitoring action) - Error detection - Motivation or drive behaviour - Deficits following damage to mediofrontal cortex may include: - Apathy - Akinesia - Difficulties with emotion: flat affect - Diminished verbal output Neuropsychological measures sensitive to mediofrontal damage - Family/caregiver reports (apathy) - Questionnaires, scales measuring motivation - Reaction time (individuals with damage to this region may be slower on speeded task) [Week 12: Brain injury ] Acquired Brain Injury (ABI) - Acquired brain injury (ABI) is used to describe all types of brain injury occur after birth - ABI general definition: Injury to the brain that results in deterioration of cognitive, physical or behavioural functioning - Brain injury ≠ intellectual disability - People with ABI often retain their 'intellectual' abilities but may have difficulty controlling, coordinating and communicating their thoughts and actions - ABI is often called invisible disability - no outward physical signs of disability, effects such as fatigue, lack of initiation, anger, mood swings and egocentricity may be seen as simply as personality defects by family members, health professionals and government policy makers 'External' Causes of ABI - Traumatic brain injury (TBI) - Motor vehicle and other traffic accidents - Falls - Assault - Sports related - Work-related or industrial accidents - Poisoning - Inhalation of organic solvents - Metabolic disturbance (e.g, diabetic coma) - Alcohol and drug abuse - Infections and diseases - HIV/AIDS - Bacterial (e.g., meningitis and brain abscesses) - Viral (e.g., herpes simplex) - Parasitic (e.g., cerebral malaria) - Encephalitis (inflammation of CNS due to infection) 'Internal' causes of ABI - Strokes/Cerebrovascular Accident - Tumours - Hypoxia/ anoxia (e.g., near drowning) -- reduce or completely eliminate oxygen in brain - Secondary effects of TBI - Haemorrhage of haematoma - Intercranial pressure - Oedema or brain swelling ' - Post-traumatic epilepsy Progressive conditions which can lead to ABI - Alzheimer's diseases (and other dementia type conditions) - Parkinson's disease - Multiple sclerosis - Korsakoff's syndrome - Creutzfeldt-Jakob's disease Traumatic Brain Injury - Pathomechanism of brain injury is typically shearing, stretching and tearing at neuron level - Cascading responses -- disruption to blood flow - Broadly, we think of two primary classifications: - Penetrating head injury (object coming from outside into the brain) - Closed head injury (impact of force) Closed head injury - closed head injury may have many different causes, but common to all is that the brain undergoes either marked acceleration, deceleration, or both - The bat impacts skull is coup injury (damage to frontal lobe) then resulting force will cause the brain to move back and cause countercoup (occipital lobes also damaged ). - Twisting and shearing of brain stem neurons - May affect levels of arousal, respiration rate, consciousness -- may result in in coma  - Bony ridges and protrusions on internal surface - This means when we have acceleration or deceleration forces, there are particular part of the brain that are highly vulnerable (temporal and frontal lobes) Closed head injury - Contusions - Damage to cerebral circulatory system, resulting in internal bleeding and haematoma (bruise/ clotted blood) - Concussion - Disturbance of consciousness but no evidence of structural damage (e.g., no contusion) - Lack of evident structural damage does not mean concussion is benign (e.g., CTE) Some possible consequences of traumatic brain injury - Physical effects - Fatigue - Headaches - Dizziness - Paralysis - Chronic pain Cognitive effects - Memory problems - Poor concentration - Slowed responses - Lack of insight - Poor planning and problem - Inflexibility - Impulsivity Emotional and behavioural effects - Lack of initiative and motivation - Irritability - Socially inappropriate behaviour - Depression - Emotional lability Stroke (CVA) Two broad types: - Ischaemic (disruption of blood flow to the brain tissue through blockage process) - e.g. thrombosis or embolism - Haemorrhagic (disruption of blood flow to brain tissue through bleeding process)-- e.g., rupturing an aneurysm  Aneurysm (A) -- area of weekend blood vessel wall: - Can occur at any parts of the body - Most of the time might not be the problem -- sometimes it can be because unerupted aneurysm might end up being quite large and might put pressure on different parts of brain tissue - May have no impact unless it ruptures -\> causing haemorrhagic \*In short, it's a typical mechanism through which haemorrhagic stroke might occur\* Thrombus (blood clot): - Buildup within blood vessel of a clotted area on the interior surface of the vessel Embolism (fatty plaque or blood clot) - Fatty plaque of bad cholesterol that's built up on internal lining \* Classification of severity - Glasgow coma scale -- GSC (lower GSC = more severity) - Loss of consciousness -- LOC (duration which a person loss consciousness) - Post-traumatic amnesia -- PTA \*best prognostic measure\* (period of essentially confusion, disruptive memory functioning after brain injury) Role of clinical neuropsychologist - Not generally involved in the initial weeks/months following injury - Role to assesses the extent of persisting symptoms, both cognitive and behavioural, and infer their impact on functioning - Educate clients and families strategies about expected recovery and management - Design and implement strategies to assist clients to utilise strengths and to compensate for deficits