Neuro physiology 🧠 Flashcards
What is the McGurk effect?
What can we hear?
Range of human hearing
20Hz-
What is the function of the middle ear?
Acoustic impedance match
Between air and fluid filled inner ear
Amplifies the movement and so makes the sound louder
Because
Ratio area TM: stapes 14:1
Lever action of ossicles
Total gain is 20-35 db
200fold increase in transfer of energy
What is the loss of energy transferring from air to fluid?
97%
What is the role of the muscles of the middle ear
Protect inner ear from acoustic trauma
Stiffens ossciular chain
Stapedius stimulated acoustically
Reflex arc- 3 or 4 neurones
Tensir tympani
What is the role of the eustacian tube
Ventilation of the middle ear space
Drainage of secretions
Grommits
What are the cochlear fluids?
Endlolymph- High K+
Perilymph- Like ECF and CSF Na+ rich
Gradients maintained by Na, K-ATPase
and NKCC1 CIC-K chlorine channels
Ion channel abnormalities- deafness
Pressure wave in cochlear
Moves basilar membrane
What does the organ of corti do
basilar membrane moves
inner hair cells move and move tectorial membrane
Inner hair cells- mechanical transduction
Outer hair cells- fine tuning (stiffens the basilar membrrane so hair cells either side don’t move and so the sound is sharpened
Stereocillia move
Rapid response required
Mechanically gated K+ channels opened causing depolarisation
frequency
Amplitude intensity
What does the brainstem do for hearing
Localisation of sound
Interaural time differences
What are neurons
- Specialised for electrical signalling
- Inputs via dendrites
- Action potentials propagate along the
axon from the axon hillock - Mainly formed during development
What are neurons stained with?
- Tissue sections can be stained with
histological stains - e.g. H&E:
- Haemotoxylin, stains nucleic acids
blue - Eosin – stains proteins red
Neuronal communication
- Neurons communicate via synapses - 2 types
- Chemical – majority – via neurotransmitters (glutamate, GABA, dopamine, serotonin,
etc.) - Electrical – less abundant – via direct flow of ions
- enable synchronized electrical activity, e.g brainstem (breathing) and hypothalamus (hormone secretion)
Describe chemical synaptic transmission
- Axon potential depolarises synaptic
terminal membrane - Opening of voltage-gated calcium
channels leads to calcium influx - Calcium influx triggers
neurotransmitter release
Electrical synapse structire
Electron dense material on both sides
rings called connecins
gap junctions
Excitatory synapses
Concentrated on dendritic spines
What is neural plasticity?
-changes in neuronal/synaptic structure and function in response to neural activity
-basis of learning and memory
Describe spines
- Spines are dynamic structures – number, size, composition
- Spine remodelling linked to neural activity
- Relevant to disease – e.g. schizophrenia & Alzheimer’s - ↓spine density
Describe neuronal heterogeneity
Neurons differ in their:
* Size
* Morphology
* Neurotransmitter content
* Electrical properties
* E.g. neocortex (right)
Examples of neuronal heterogeneity
- Betz cells = upper motor neurons –
large, excitatory (glutamatergic,) long
projections, pyramidal cells - Vulnerable in MND
- Medium spiny neurons = striatal
interneurons – small, inhibitory
(GABAergic) - Vulnerable in Huntington’s disease
Describe arborisation of axons and dendrites
Cortical projection neuron
Cerebellar Purkinje cell
What are oligodendrocytes?
- Myelinating cells of the CNS
- Unique to vertebrates
- Myelin insulates axon segments,
enables rapid nerve conduction - Myelin sheath segments interrupted by
nodes of Ranvier – saltatory conduction - Provide metabolic support for axons
Describe myelin sheath
- Formed by wrapping of axons by
oligodendrocyte processes
(membranes) - Highly compacted – 70% lipid, 30%
protein - Myelin specific proteins, e.g. myelin
basic protein (MBP) can be used as
“markers
Describe microglia
- Resident immune cells of the CNS
- Originate from yolk sac progenitors
that migrate into the CNS - “Resting” state, highly ramified, motile
processes survey environment (2-3
µm/min) - Upon activation (e.g. by ATP), retract
processes, become “amoeboid” &
motile - Proliferate at sites of injury -
phagocytic
Not like the other types- more like macrophages
What are the functions of microglia?
- Immune surveillance
- Phagocytosis – debris/microbes
- Synaptic plasticity – pruning of spine
- “bad” (M1) and “good” (M2) microglia
What are astrocytes?
- “Star-like cells”
- Most numerous glial
cells in the CNS - Highly heterogeneous –
not all star-shaped - Common “marker” glial
fibrillary acidic protein
(GFAP)
Contribute to the blood-brain barrier
Describe how astrocytes contribute to blood brain barrier
Processes of astrocytes wrap around capillaries
What are the functions of astrocytes?
- Structural - define brain micro-architecture
- Envelope synapses – “tripartite synapse” – buffer K+, glutamate, etc
- Metabolic support – e.g. Glutamate-Glutamine shuttle
- Neurovascular coupling – changes in cerebral blood flow in response to neural
activity - Proliferate in disease = gliosis or astrocytosis
What are some specialised astrocytes?
- Radial glia –important for brain development
- Bergmann glia (cerebellum) - green
- Müller cells (retina)
CNS terminology
- Abundance of neuronal cell bodies in nuclei
- Axons gathered into tracts
- Tracts that cross midline = commissures
- Grey matter abundant in neural cell bodies & processes – neuropil contains few cell
bodies - White matter contains abundance of myelinated tracts & commissures
PNS terminology
- Cell bodies & supporting cells located
in ganglia – e.g. dorsal root ganglia
(DRGs) - Axons bundled into nerves
- Many PNS axons are enveloped by
Schwann cells (myelinating cells
of the PNS – neural crest derived c.f.
oligodendrocytes, derived from CNSresident neural progenitors)
Describe the blood brain barrier
- Dyes injected into blood penetrate
most tissues, but not the brain - Dyes injected into CSF – brain stains →
specialised blood-brain barrier - Formed by endothelial cell tight junctions, basement membrane (few
fenestrations), astrocyte end feet &
pericytes (contractile, aid blood flow) - Sensitive to inflammation,
hypertension, trauma, ischaemia - Problem for drug delivery!
Describe ependymal cells
- Epithelial-like, line ventricles & central
canal of spinal cord - Functions - CSF production, flow &
absorption - Ciliated – facilitates flow
- Allow solute exchange between
nervous tissue & CSF
Describe the choroid plexus
- Frond-like projections in ventricles
- Formed from modified ependymal cells - villi form
around network of capillaries
→ highly vascularised with a large surface area - Main site CSF production by plasma filtration driven
by solute secretion - Gap junctions between ependymal cells form bloodCSF barrier
What are 3 different levels of defence and the part of the CNS activated?
Learned threat- cortex and limbic system
Loom- Sensorimotor midbrain
Pain- spinal cord
Describe dualism
“There are two kinds of foundation: mental and body”
“The mental cannot exist outside of the body; and the body cannot think”
“Thus: mental events cause physical events and vice-versa
Critiques of dualism 1
What is this “non physical” substance which is not brain?
How can an “immaterial” mind cause anything in a “material” body and vice versa
Theory leads to explanations involving another being - soul, animal spirits, deity?
Lack of scientific evidence for this
Critiques of dualism 2
What about “inexplicable” symptoms? Or where “biological reductionism” does not explain symptoms?
“functional, conversion, psychosomatic, medically unexplained, persistent physical symptoms, overlay, psychogenic, hysterical, manipulative, factitious, Munchausen’s ”
How do we reflect the importance of the fact that the individual is part of a range of larger (social /political /cultural) systems?
What is the impact of environment /society is critical in our perception of self and our wellbeing
How do we think about dualism when the WHO defines health in positivist terms as:
“a state of complete physical, mental and social well-being” or
“the capacity, relative to potential and aspirations, for living fully in the social environment” (Tarlov)
Why does dualistic thinking persist?
Familiar: 300 years of medical experience
Economics: private enterprise (Big Pharma?) rely on this paradigm
Power: health is traditionally the business of doctors (or is it – currently being challenged)
Convenience: ability to design experiments to test
NB not only biological reductionism, can also have social reductionism (e.g postnatal depression is not “valid” as the experiences can be understood as the adaptation to a significant environmental change??)
Advantages of classification in health/ ill health
Facilitate reporting and inform public health issues such as allocation of resources
Facilitate meaningful communication and debate between patients, professionals, organisations and legislators
Promote a feeling of being understood (“we’ve seen this before – your problems are not unique”)
Provide a framework for research
Offer evidence for treatment options and some information about natural history and prognosis
Problems with using classification systems and diagnosis?
Improved scientific understanding makes a mockery of previous attempts to classify (e.g. phrenology)
Categorisation means defining thresholds which are arbitrary
depression / dysthymia / fed up
obese / well built / chubby / slender
Categorisation can lead to stigma and prejudice
Economy of thought may lead to oversimplification, reductionism and ultimately inhumane action
Role of emotion
Motivator for learning
Means of best obtaining rewards/ avoiding punishment
- Stimulus-reinforcer associations
- Instrumental (action-outcome) learning
Movement and emotion
Ability to act s
Basic theory
-Biologically privileged emotion automatically triggered by oblects and events
-Hard-wired circuits
-Variability: cultural
Appraisal
- Meaningful interpretation of an object or a situation by an individual
- Action readimess
- May be automatic
Psychological constructionist
Psychial compounds of basic ingredients (affect and ideational component)
Same ingredients involved in other mental states
Internal state subject of meanig analysis
Baysian model
Neuroanatomy of emotion
-limbus
-described by broca
- emotion result of network of sirect and trans synaptic connections-#
- no single limbic system
network of connections
Appraisal: Orbitofrontal cortex
-Appraisal - input: ventral cortical streams (identity)
0 Medial- reward- activation: subjective to pleasantness
Lateral- punishment/ non reward- negative reward prediction error- expectation of punishment
Mesolimbic pathway
Appraisal amygdala
- Older brain overshadowed by OFC
- conditions responses to stimuli predicting harm
- facial expression recognition
- Little involved in subjective emotional experience
- slower response in verbal? learning tasks
Reactivity: cingulate cortex
Action- outcome learning
Anterior- outcome- subgenual reward signals from ofc
Supracallosal punishment/ non reward from lateral ofc
posterior- action- input from parietal lobes (spatial/ action related info
output hippocampus
mid output to premotor area
Reactivity: hypothalamus and insula
Modulated by: OFC via anteroventral insula and subgenual cingulate cortex, amygdala- hypothalamus and periaqueductal grey
feedback from autonomic output not needed for emotional behaviour/ feelings
What layer of the embryo gives rise to the nervous system?
Ectoderm
What happens in the 4th week to the ectoderm and what will it become
Ectoderm thickens in midline to form the neural plate- neural tube and then eventually spinal canal
Step 1 of
Notochord forms from mesoderm cells soon after gastrulation is complete
Signals from the notochord cause inward folding of the ectoderm at the neural plate
Ends of neural plate fuse and disconnect to form an autonomous neural tube
What are the presumptive neural crest cells and where are they?
Stem cells
Lateral to the neural groove lie presumptive neural crest cells
in ectoderm form- melanocytes, schwann cells and neurons
in mesoderm- osteoblasts, adipocytes and chondrocytes
Main things that the neural crest cells form
Sensory dorsal root ganglia of spinal cord and V/VII/IX/X
Schwann cells
Adrenal medulla
Bony skull
Meninges
What are some abnormalities of the spinal cord?
The neural tube usually closes at the end of 4th embryonic week
Failure to close cephalic region – anencephaly
Failure to close spinal region – spina bifida
Collectively called – neural tube defects
What is hydrocephalus?
Accumulation of CSF with increased intracranial pressure
Can cause macrocephaly in children (therefore always scan increasing head size)
Obstructive (non-communicating): e.g. tumour, haemorrhage.
Non-obstructive (communicating): e.g. increased CSF production
Describe the cerebrospinal fluid circulation
CSF circulates through the subarachnoid spaces and through the ventricles
CSF cushions the brain and helps circulate metabolites
Around 120 mLs
Produced as filtrate of blood at choroid plexuses in ventricules
Absorbed via arachnoid granulations in superior sagittal sinus
Brain structures in week 4
Prosencephalon-cerebral hemispheres and thalamic structures
Mesencephalon – midbrain
Rhombencephalon – medulla, pons and cerebellum
What are the areas of the brain in week 6
Telencephalon
Diencephalon
Mesencephalon
fourth ventricle
rhombencephalon
cortex is thin in development but complicated layered structure in adults
What are microcephaly and macrocephaly?
Microcephaly – reduced head circumference
Macrocephaly – increased head circumference
Give a brief overview of the neuron
Basic cellular unit of the nervous system
Huge range - specialised for different functions
All have same basic components
Approximately 100 billion (109) neurons in the ‘average’ brain
But, 0.15 quadrillion (1015) connections between them (synapses)
Basic components of a neuron
Dendrites
Cell body/soma
Axon
Presynaptic terminals
Neuron types
Multipolar neuron
Bipolar neuron
Pseudo-unipolar neuron
Unipolar-neuron
What is axonal transmission?
Transmission of information from location A to location B
What is synaptic transmission?
Integration/processing of information and transmission between neurons
What is the charge inside a neuron at rest?
Negative
Describe the semi-permeability of neuronal cells
Some substances which are electrically charged (+ve or –ve) cross readily – potassium (K+) and chloride (Cl-)
Some cross with difficulty – sodium (Na+)
Some not at all – large organic proteins (-ve charge)
WHat is a force determining the distribution of charged ions?
Diffusion – the force driving molecules to move to areas of lower concentration
What is the force determining the distribution of CHARGED ions?
electrostatic attraction/repulsion
Electrostatic pressure - ions (like magnets) move according to charge – Like ions repel and unlike attract
Ions:
A- (anions - protein)
Na+ (sodium ions)
+ (potassium ions)
Cl- (chlorine ions)
Ion distribution in neurons at rest
A- (anions - protein) - restricted to inside of cell
Na+ (sodium ions) - mostly outside neuron
K+ (potassium ions) - mostly inside neuron
Cl- (chlorine ions) - mostly outside neuron
Forces determining sodium and potassium conc.
Active process to transport Na+ ions out of neuron & K+ in
Three Na+ for every two K+
Require energy supplied by ATP
Describe final resting potential
Result is NA+ high concentration outside but with both forces pushing in
Membrane and pump resists Na+ inward movement
K+ & Cl- can move backward and forward across membrane so reach steady state determined by opposing forces of diffusion and electrostatic pressure
Some sodium leaks back in but is expelled by the pump
Describe an action potential
Neuron fires – a sudden pulse where the negative resting potential is temporarily reversed
Transmits information i.e. the message [digitally / all or none / 0 or 1]
What are the events within the action potential?
Depolarization & threshold
Reversal of membrane potential
Repolarisation to resting potential
Refractory period
Describe the action of neurotransmitters
The membrane potential remains in this resting ‘stable’ state until something disturbs the balance:Membrane permeability changes
Neurotransmitters initiate such changes at the dendrites of neurons
Describe the process of changing action potential in the neuron
Neurotransmitters activate receptors on dendrites / soma
Receptors open ion channels
Ions cross plasma membrane, changing the membrane potential
The potential changes spread through the cell
If the potential changes felt at the axon hillock are positive (+mV), and large enough, an action potential is triggered
WHat does whether an action potential is reached
The voltage of the potential spread thru the cell
What do excitatory neurotransmitters do?
Excitatory neurotransmitters depolarise the cell membrane
increases probability of an action potential being elicited
cause an Excitatory Post Synaptic Potential (EPSP)
What do inhibitory neurotransmitters do
Inhibitory neurotransmitters hyperpolarise the cell membrane
decreases probability of an action potential being elicited
cause an Inhibitory Post Synaptic Potential (IPSP)
When will an action potential occur?
An action potential will be elicited if the membrane potential is depolarised beyond the threshold of excitation
What is passive conduction?
Voltage changes spread away (decrementally) from point of origin (Passive Conduction).
Whether AP is generated depends on what reaches the axon hillock.
Spatial summation
Inhibitory post synaptic potential
Temporal summation
Excitatory post synaptic potential
Describe the action potential
EPSPs begin to depolarise cell membrane
Threshold ~ -60mV
When reached Na+ channels open (Na+ rushes in) and polarity reverses to +30 inside
Membrane potential reverses with the inside going positive
…at which point voltage-gated Na+ channels close and K+ channels open (K+ rushes out)
…which restores resting membrane potential
Describe the self perpetuating nature of the action potential
The voltage changes are caused by the opening or closing of ion channels
In the cell membrane there are channels which are opened by voltage changes…thus
voltage changes control the ion channels which control the voltage changes……….
The action potential is therefore self perpetuating
Initiation and propagation of the action potential
Receptors- (neurotransmitter activated ion channels)
Summation
Voltage activated ion channels open
What does myelination do?
Speeds up axonal conduction
Allows the conduction of current as it means it can jump from nodes of ranvie
Unmyelinated neuron
Signal loss due to lack of insulation –could be overcome by continual opening of next ion channel
But SLOW due to time to activate each channel.
Mainly short axon interneurons
Myelinated neuron
Saltatory Conduction
Decremental conduction between nodes (but ‘re-boosted’ each time)
But very fast along axon.
Most CNS neurons.
How does a synapse work
action potential triggers opening of voltage gated Ca+ channels to open
This causes the vesicles in presynaptic terminal release neurotransmitter into the synapse
Why synapse
allows for modulation of signal
charge spread
charge slowed
What happens to the neurotransmitter after it has crossed the synapse?
Would remain active in synapse if it wasn’t for:
Enzymatic Degradation
Reuptake
Acetylcholinesterase is the name of the enzyme that breaks down the neurotransmitter acetylcholine
What afre bottom up and top down processing
Bottom up processing- sensation
Top down processing- perception
What is sensation
A mental process resulting from immediate external stimulation of a sense organ
Touch, smell, taste, sight hearing
WHat is perception
The ability to become aware of something or understand something following sensory stimulation
Tactile, olfactory, gustatory, visual, auditory
What is perceptual set?
Psychological factors that determine how you perceive your environment
What determines how we perceive things?
Context, culture, expectations, mood & motivation
what is gestalt theory
Proximity, common fate, continuity, similarity, closure, common region, symmetry
What is illusion?
An instance of a wrong or misinterpreted perception of
a sensory experience
Realise quickly
What is a hallucination?
Experiences involving the
apparent perception of
something not present
Cannot shake it quickly like illusion
What areas of the brain with most activity in hallucinations?
Visual and auditory cortices
What causes hallucinations
Drugs, delerium, sleep deprivation, psychiatric illness
Psychiatric conditions that cause hallucinations
SCHIZOPHRENIA
DEPRESSION WITH PSYCHOSIS
BIPOLAR AFFECTIVE DISORDER
SCHIZOAFFECTIVE DISORDER
DRUG INDUCED PSYCHOSIS
ACUTE TRANSIENT PSYCHOSIS
Bio-psychosocial model of care for hallucinatory disorders
Medication
Psychologists
Social networks
What are the categories of mental illness/conditions?
The organic illnesses
The dependency states – alcohol; drugs
The mood disorders
The anxiety states
The psychoses
The behavioural disorders
Neurodiversity
Childhood disorders
Personality disorders
What are the organic illness types?
Dementias
Delerium
What are the types of dementia?
Alzheimer’s
Rx - Acetylcholine esterase inhibitors
Rx - Glutamate blockade
Vascular dementia
Subcortical
Stoke related
Multi-infarct
Lewy body
Frontotemporal
What are some causes of delerium?
B12 and Folate deficiency
Cushing’s disease
Thyrotoxic storm
Wilson’s disease
And many more physical illnesses
Give an overview of the types of drugs used in dependency states
Drugs: Key examples
Heroin
Cocaine
Marijuana
Alcohol
Give an example of physical dependency
What are the mood disorders?
Depressive illness (Unipolar)
Mania (Unipolar)
Bipolar (Manic-depression)
Cyclothymia
Low mood (adjustment disorders, burnout, life setting)
What are some key examples of the anxiety states?
Generalised anxiety disorder
Panic attacks
OCD
Derealisation-depersonalisation
What are the psychoses?
Schizophrenia
Acute and transient psychosis
Monosymptomatic delusion
Post-natal (Puerperal) psychosis
Drug induced psychosis
What are the behavioural disorders?
Sleep
Sex
Eating
Habits
What us the bed nucleus involved in?
Anxiety
Gender identity
Appetite
Dampens startle response
Social recognition
Parental bonding
Give some examples of neurodiversity
The developmental ‘disorders’
Autistic spectrum
ADHD
Learning disability
What is involved in the default mode network?
Medial PFC
Posterior CC
Angular gyrus
Precuneus
What are some psychiatric conditions related to childhood?
Separation anxiety
General anxiety states
School refusal
Other behavioural problems
Sexual, psychological and physical abuse
What are some examples of personality disorders?
Many recognised types
Two key examples
Borderline PD
Dissocial PD
What is eustress (good stress)?
Positive stress which is beneficial and motivating; typically, the experience of striving for a goal which is within reach
What is distress (bad stress)?
Negative stress which is damaging and harmful. Typically occurs when a challenge (or threat) is not resolved by coping or (rapid) adaptation.
The type of stressor is less important than how it is experienced ie negative (threat) or positive (challenge), whether it is experienced physically and/or psychologically and how long it goes on.
What are stresses?
Stresses are physical and psychological. Different neuronal networks are involved but these are connected.
What are stress responses?
Stress responses are often characterised as either physiological or psychological (mind). But these overlap and both are mediated via the brain.
What are physical stressors?
(processed in brainstem & hypothalamus: reflexive)
Insults or injuries that produce direct physiological effects eg damage of body tissue and/or bodily threat (eg pain, haemorrhage or inflammation).
What is psychological stress?
(Involving PFC, amygdala and hippocampus)
Stimuli that are perceived as excessively demanding or threatening, often involving anticipation.
What are the 3 phases of stress response?
Alarm, adaptation, exhaustion
Alarm
Threat identified; body’s response is state of alarm (fight or flight)
Adaptation
Body engages defensive countermeasures
Exhaustion
Body runs out of defences and resources are depleted
General adaptation syndrome
Stress as “non-specific response of the body to any demand for change”.
Selye (1907-1982) found that different insults caused the same disease (eg heart attacks, stroke, kidney disease and rheumatoid arthritis).
Early evidence of neuroendocrine mechanisms and role of HPA axis.
Homeostasis
Maintaining internal environment necessary for cell functioning
Allostasis
How complex systems adapt (eg via HPA axis) to changing environments by changing set-points (“adaptation through change”).
Allostatic load
refers to cumulative exposure to stressors (and cost to the body of allostasis), which if unrelieved leads to systems ‘wearing out’.
What happens if there is continued attempts to restore balance?
Continued attempts to restore balance have long-term effects on physiological systems, including structural changes (eg to the CNS).
What is acute stress?
Brief response to a novel but short-lived situation experienced by the body as a danger. Conscious perception of threat is not always involved.
The acute stress response (‘fight or flight’) is healthy & adaptive and necessary for survival.
What is chronic stress?
Arises from repeated or continued exposure to threatening or dangerous situations, especially those that cannot be controlled. More likely than acute stress response to involve appraisal and conscious perception.
What are some of the examples of chronic stressors?
- Physical illness, disability & pain
- Physical or sexual abuse
- Poverty including poor housing, hunger, cold or damp, debt
- Unemployment
- Bullying or discrimination
- Caregiving
Describe the importance of individual differences
Individual differences are important, including differences in perception of threat & control and physiological differences in the timing and duration of the stress response
What are the 5 elements of the human stress response?
Biochemical
Physiological
Behavioural
Cognitive
Emotional
Key facts about stress responses
Stress responses are generic and not stressor-specific.
Stress responses mediated via autonomic nervous system (ANS) and the hypothalamo-pituitary (HPA) axis.
These responses lead to changes that influence future responses to stress, also reflecting brain plasticity.
Describe the sympathomedullary pathway
hypothalamus activates adrenal medulla ->
Adrenal medulla releases adrenaline and noradrenaline into the bloodstream ->
Body prepares for fight or flight, adrenaline and noradrenaline reinfordes bthe pattern e.g increased hr and bp ->
Energy
Pituitary adrenal system
Chemicals released in the blood in stress
Steroids especially glucocorticoids (cortisol)
Catecholamines (adrenaline & noradrenaline)
The so-called sympathetic nervous system (SNS) ‘fight-or-flight’ chemicals
Inflammation and the immune response
are important & complex, mediated and modified by adrenaline and cortisol. Effects can be pro- and anti-inflammatory, and GCCs also have direct effects on the CNS.
Balance between immune activation & autoimmunity disrupted in chronic stress response (NB reduced vaccination response)
Immunosenescence?
Immune response in acute stress
Immune suppression (anti-inflammatory)
Chronic stress immune response
Partial immune suppression + low-grade chronic inflammatory response, possibly through epigenetic effects on gene expression
What are some fast psychological stress responses?
Breathing more rapid to increase oxygen
Blood flow increases up to 400%, directed to heart & muscles
Increased heart rate & blood pressure
Muscles tense
Glucose released, insulin levels fall: boost energy to muscles
Red blood cells discharged from the spleen
Mouth becomes dry & digestion is inhibited
Sweating
Cytotoxic & surveillance WBCs go where injury & inflammation may occur i.e. bone marrow, skin, lymph nodes
Physical (somatic) effects of chronic stress
Headache
Chest pain
Stomach ache
Musculoskeletal pain
Low energy
Loss of libido
Colds & infections
Cold hands & feet
Clenched jaw & grinding teeth
Behavioural responses to stress
- Easily startled & hypervigilant
Change in appetite – both directions
Weight gain (obesity) or weight loss
Procrastinating and avoiding responsibilities
Increased use of alcohol, drugs & smoking
Nail biting, fidgeting and pacing
Sleep disturbances especially insomnia
Withdrawal
Cognitive responses to stress
- Constant worrying
- Racing thoughts
- Forgetfulness and disorganisation
- Inability to focus
- Poor judgement
- Being pessimistic or seeing only the negative side
- Altered learning
Emotional responses to stress
- Depression & sadness
- Tearfulness
- Mood swings
- Irritability
- Restlessness
- Aggression
- Low self-esteem and worthlessness
- Boredom & apathy
- Feeling overwhelmed
- Rumination, anticipation & avoidance
Unhealthy stress responses
Anticipatory reaction
Lack of recovery- stress decreases at normal rate but doesn’t fully stop
Lack of habituation response continues for a while but does decrease
Lack of habituation and recovery- response doesn’t decrease and doesn’t go away
How does stress affect us?
Ppl vary
Different parts of the brain mediate responses to different types of stressor (but amygdala and hippocampus are key).
Context, appraisal, vulnerability and learning (past experience) modify perception of threat and hence the stress response. People exposed to adversity in early life are more sensitive to stress later on.
Stress mechanisms alter affect (mood, anxiety levels). This is likely to mediate the effects of stress on other bodily systems including through behaviours (eg alcohol, diet etc).
Link between stress and illness
Stress is related to a host of illnesses, esp of cardiovascular and GI systems, ie those with strong ANS connections.
Stress exacerbates physical illnesses and slows recovery and increases susceptibility to infection.
Strong evidence of association between depression and mortality following an MI.
Evidence of causal association between stress and physical illness is still limited, though note emerging evidence that chronic stress increases ‘immune ageing’.
Exposure to stress (trauma)
Possible links between stress and various illnesses
- Cancer: stress linked to survival rather than incidence
- Cardiovascular disease: high blood pressure, abnormal heart rhythms, MI and stroke
- Obesity & eating disorders
- Infertility, recurrent miscarriage & menstrual problems
- Rheumatoid arthritis
- Skin & hair problems eg acne, psoriasis, eczema
- Gastrointestinal problems: inflammatory bowel disease, irritable bowel syndrome.
- Medically unexplained symptoms (MUS)
- Infectious diseases especially covid-19
PTSD symptoms
- Vivid flashbacks & nightmares
- Intrusive thoughts and images
- Sweating
- Nausea
- Trembling
- Hypervigilance & increased startle response
- Agoraphobia
- Insomnia
- Irritability
- Impaired concentration
Ways to manage stress
- Shiatsu, T’ai Chi, Yoga
- Mindfulness
- Meditation
- Exercise
- Sleep hygiene
- Friends and family
- Healthy diet
- Exposure to natural environments
- Aromatherapy
- Cognitive Behavioural Therapy
What is evolutionary psychiatry?
Ask questions about why natural selection has left us vulnerable to developing mental disorders
Four areas of biology
Ontogeny
mechanism
phylogeny
adaptive significance
Why did natural selection leave us vulnerable to disease?
Mismatch- body unable to cope with modern environment
Infection- bacteria and viruses evolve faster than us
Constraints- some things evolution can’t do
Trade off- everything has advantages and disadvantages
Reproduction- ns maximises reproduction not health
Defensive responses- responses such as pain and anxiety are useful in the face of threats
Smoke detector principle
Want alarm system to go off if there is an actual fire- benefits
So false alarms happen to err on the side of caution
5 fundamental processes of synaptic transmission
Manufacture – intracellular biochemical processes
Storage – vesicles
Release – by action potential
Interact with post-synaptic receptors – diffusion across the synapse
Inactivation – break down or re-uptake
Fast neurotransmitters
– short lasting effects
Acetylcholine (ACh)
Glutamate (GLU)
Gamma-aminobutyric acid (GABA)
Neuromodulators
slower timescale
Dopamine (DA)
Noradrenalin (NA) (norepenephrine)
Serotonin (5HT) (5-hydroxytryptamine)
Problems for drug design
A region of the brain engaged in a particular function uses several neurotransmission systems e.g. basal ganglia
Glutamate
GABA
Dopamine
Acetylcholine
Substance P
Enkephalin
Regions of the brain engaged in different functions use the same neurotransmission systems
Glutamate
GABA
Acetylcholine
Serotonin
Dopamine/Noradrenalin
How do hallucinogenic drugs work?
Hallucinogenic drugs include LSD, Magic Mushrooms, Ketamine
They mimic serotonin, and can activate numerous different serotonin receptor subtypes
But the hallucinogenic effect itself appears to be specifically related to the way they target the serotonin ‘2a’ receptor (5-HT2a)
Types of motor control
- Involuntary: eye movements, facial expressions, jaw, tongue, postural muscles throughout trunk, hand and fingers, diaphragm, cardiac, intercostals (around lungs), digestive tract……
- Goal-directed: conscious, explicit, controlled.
- Habit: unconscious, implicit, automatic
- Voluntary: running, walking, talking playing guitar etc.,……
Key concepts in the sensorimotor system
Motor control governed by lower and upper motor neurons.
The lower motor neuron begins (has its cell body) in brainstem or spinal cord and projects to the muscle
The upper motor neurons originate in higher centres and project down to meet the lower motor neurons
Key facts about muscles
Muscles can only contract or relax (i.e. stop contracting)
The activation of muscle fibres is all or none
So how do we achieve such a range of movements and forces ??
Antagonistic arrangement – combined co-ordinated action
Recruitment of muscle fibres – fast/slow twitch, small and large motor units (see later)
INdividual differences in muscles
The number of muscle fibres varies across individuals, but changes little with either time or training – appears to be genetically determined
Muscle size (+ strength) is more about cross sectional area of individual fibres and different proportions of the different types of fibre (see later)
How do muscles contract?
A skeletal muscle is attached to the bone by the tendon
A skeletal muscle comprises several muscle fasciculi (group of muscle fibres)
A muscle fasciculus comprises several muscle fibres (= muscle cells)
A muscle fibre is constituted of several myofibrils
Myofibrils contain protein filaments: Actin and Myosin myofilaments
When the muscle fibre is depolarised actin and myosin slide against each other which produce muscle contraction
Describe rigor mortis
The release of acetylcholine causes a cascade of events resulting in the release of packets of calcium from inside the muscle cell (fibre)
This causes the myosin head to change shape, enabling it to bind with the actin filament
ATP (provides energy for cells) is required to break the bond between the myosin head and the actin filament
ATP is produced by oxidative metabolism, which stops upon death
So the muscle become contracted and remain that way until enzymes begin to disrupt the actin/myosin
What is the motor unit?
Single alpha () motor neuron + all the muscle fibres it innervates – Different motor neurones innervate different numbers of muscle fibres – fewer fibres means greater movement resolution - those innervating finger tips and tongue
Key facts about the motor unit
The motor unit is the final common pathway for motor control
Activation of an alpha motor neuron depolarises and causes contraction of all muscle fibres in that unit (all or none)
Muscle fibres innervated by each unit are the same type of fibre and often distributed through the muscle to provide evenly distributed force (and may help reduce effect of damage)
More motor units fire – more fibres contract – more power
Control of muscle force
Average number of muscle fibres innervated by single motor neuron (a motor unit) varies according to two functional requirements for that muscle:
1. Level of control
2. Strength
Typically a range of motor units in a muscle, some with few, some with many fibres.
Size principle
Units are recruited in order of size (smallest first)
Fine control typically required at lower forces
Try playing the violin with weights attached to your arms!!
What are the 3 types of muscle fibres?
Slow
Fast fatigue resistant
Fast fatigable
What is the motor pool?
All the lower motor neurons that innervate single muscle
The motor pool contains both the alpha and gamma motor neurons (see later)
Motor pools are often arranged in a rod like shape within the ventral horn of the spinal column
Describe innervation of the muscles
Cell bodies in the ventral horn: activated by:
Sensory information from muscle
Descending information from brain
Sensing in muscles
Muscles can be contracted or relaxed to provide movement, but a good control system (the CNS) needs to know two things:
how much tension is on the muscle- golgi tendon organs sense tension
what is the length (stretch) of the muscle- muscle spindles sense stretch
Describe golgi tendon organs- muscle tension (force)
The GTO is within the tendon (where the muscle joins to bone)
Mostly, it sends ascending sensory information to the brain via the spinal cord about how much force there is in the muscle
Critical for proprioception
Under conditions of extreme tension, it is possible that GTOs act to inhibit muscle fibres (via a circuit in the spinal cord) to prevent damage
Muscle spindles- muscle strength (stretch)
Muscle spindles sense the length of muscles, i.e. the amount of stretch
This information forms a key part of reflex circuits…….
Extrafusal muscle fibres
Ones that do stuff
Intrafusal muscle fibres
Sensory neuron connected so it can sense stretch
Complex reflexes in quadrapeds
Quadrupeds will walk on treadmill if weight supported if spinal cord damaged at thoracic level
Will change to appropriate patterns of limb movement as treadmill speed is altered
Complex reflex system responding to nothing more than stretch of muscle spindles!!
Withdrawal reflex?
Reciprocal Innervation
Principle described by Sherrington (also called Sherrington’s Law of reciprocal innervation)
Reciprocal innervation of antagonistic muscles explains why the contraction of one muscle induces the relaxation of the other
Permits the execution of smooth movements
Brainstem importance
Pathways and nuclei within the brainstem (and midbrain) connect sensory input to motor output in quite direct ways, providing an evolutionarily ancient but still very important control system. E.g balance and speech
Motor cortex overview
Primary motor cortex exerts quite direct, top down control over muscular activity, with as few as one synapse (in the spine) between a cortical neuron and innervation of muscle cells
Describe descending projections from cortical motor areas
Motor command originates in motor cortex pyramidal cells (in layer 5-6, grey matter).
These are the upper motor neurons.
Pyramidal cell axons project directly or indirectly (e.g. via brainstem) to spinal cord, where they synapse with lower motor neurons.
The axons of these upper motor (pyramidal) neurons form the pyramidal tract
Most cortical projections innervate contralateral motor units
Basal ganglia- inhibitory
Cerebellum- excitatory
Describe the homunculus
Homunculus is a reasonable representation, but an oversimplification: damage to a single finger area doesn’t mean loss of voluntary control of that finger.
Representations are more complex and overlapping
After all, few motor commands require isolated activation of a single motor unit
What is the dorsolateral tracts?
In spinal white matter
Innervate contralateral side of one segment of spinal cord
Sometimes project directly to alpha motor neuron
Project to distal muscles, e.g. fingers
Ventromedial tract
Direct route
Diffuse innervation projecting to both sides and multiple segments of spinal cord
Project to proximal muscles of trunk and limbs
Give an overview of the basal ganglia through the lens of the motor system
A group of structures beneath the cortex that act as a ‘gate-keeper’ for control of the motor system (muscles)
- The basal ganglia are a group of nuclei lying deep within cerebral hemispheres
- Widely studied (including here at Sheffield)
- Role in motor control not fully understood- inhibitory
- Basal ganglia dysfunction implicated in many disorders
What happens in the basal ganglia?
Receives excitatory input from many areas of cortex (Glutamate)
Output goes back to cortex via the thalamus
Output is mainly inhibitory (GABA)
Complex internal connectivity involving 5 principle nuclei
What are the 5 principle nuclei of the basal ganglia?
What is the selection problem?
Multiple command systems
Spatially distributed
Processing in parallel
All act through final common motor path
[Cannot do more then one thing (well) at a time]
How do you resolve the competition?
work out how to word slide 24
dopamine drives disinhibitory effect
Give an overview of the cerebellum
The cerebellum is a large brain structure that acts as a ‘parallel processor’, enabling smooth, co-ordinated movements. It may also be very important in a range of cognitive tasks
Like basal ganglia, no direct projection to the lower motor neurons – instead modulate activity of upper motor neurons
Describe some key facts about the neurons and weight of cerebellum
Contains approx half total number of CNS neurons
Just 10% of total brain weight
Projects to almost all upper motor neurons
What inputs into the cerebellum?
Cerebral cortex via pons
Vestibular system
spinal cord
What is the output of the cerebellum
Via thalamus to motor cortex
See slide 30
Cerebellar function
-It knows what the current motor command is
-It knows about actual body position and movement
-It projects back to motor cortex
Computes motor error and adjusts cortical motor commands accordingly
What are some debating thoughts about what the cerebellum does?
Not just motor control, but motor learning too, in collaboration with basal ganglia and cortical circuits.
Functional brain imaging studies have demonstrated that the cerebellum is involved in a wide variety of non-motor tasks
How to bypass lower motor neurons?
Record brain activity
Decode
Specify desired movement sequence
Move limbs
Phototransduction
What are the 3 types of vision?
Emmetropia- normal vision
Myopia- short sightedness as refractive power is too high
Hypermetropia- long sightedness as refractive power is too low
Hypermetropia
Underpowered to focus near objects on the retina
May be due to:
Corneal curvature too shallow
Lens not flexible enough
Axial length of eyeball too short
Posterior segment
Vitreous humour
Avascular viscoestalic gel
Hyaluronic acid (GAG)
Collagen
Adnexae (things near the eye)
Lids- protect the globe
Anterior skin
Eye lashes
Melbomian glands
Orbicularis oculi
Tarsal plate
Tarsal conjunctiva
Levator palpebrae superioris and sympathetic muscle
Conjunctiva- palpebral (tarsal) vs bulbar (ocular)
Limbal stem cells
Conjunctival fornix
Mucous membranes (goblet cells)
Lymphoid cells ( protective)
Tear film
Lids
Anterior skin
Eye lashes
Melbomian glands
Orbicularis oculi
Tarsal plate
Tarsal conjunctiva
Levator palpebrae superioris and sympathetic muscle
Conjunctiva
palpebral (tarsal) vs bulbar (ocular)
Limbal stem cells
Conjunctival fornix
Mucous membranes (goblet cells)
Lymphoid cells ( protective)
Tear film
3 layers- anterior lipid, middle aqueous, posterior mucous
Protective
Nutrition for cornea
Arterial supply of the eye
- Internal carotid a. -> Ophthalmic a.
- Branches of the ophthalmic a. (ocular group):
- central retinal a.
- Posterior ciliary a. -> long and short
- muscular a. -> anterior ciliary a.
- Branches of the ophthalmic artery (orbital group:
- lacrimal a.
- several other branches supply the face and lids - External carotid a. -> facial a. -> angular a.
Allodynia
Pain due to a stimulus that does not normally provoke pain.
Dysesthesia
An unpleasant abnormal sensation, whether spontaneous or evoked.
Hyperalgesia
Increased pain from a stimulus that normally provokes pain.
Hypoalgesia
Diminished pain in response to a normally painful stimulus.
Pain pathway
Peripheral receptor
1st order neuron
2nd order neuron
3rd order neuron
peripheral receptor
to detect the relevant stimulus
1st order neuron
- from the periphery to the ipsilateral spinal cord
2nd order neuron
which crosses to the contralateral cord and ascends to the thalamus, the system’s integrative ‘relay station’
3rd order neuron
rom thalamus to midbrain and higher cortical centers
Function of nociceptors
Transduction
Physical stimulus action potential
Most are poly-modal (thermal / chemical / mechanical)
Describe primary afferent neurons
Nociceptors are the free nerve endings of primary afferent neurons
AΔ fibres
C fibres
found in any area of the body that can sense pain either externally or internally
External: skin / cornea / mucosa
Internal: viscera / joints / muscles / connective tissue
The cell bodies of these neurons reside in either
Dorsal root ganglion (body)
Trigeminal ganglion (face / head / neck)
Dorsal root ganglion
Present on the dorsal root (sensory)
Composed of cell bodies of nerve fibres that are sensory (afferent)
First order neurons
Pseudo-unipolar neurons
Can be the source of pain pathology
Trigeminal ganglion is the equivalent for the face / head
A- alpha nerve fibers
Info carried- proprioception
Myelin sheath?- yes
Diameter(micrometers)-13- 20
Conduction (m/s)- 80-120
A- beta nerve fibres
Info carried- touch
Myelin sheath?- yes
Diameter (micrometers)- 6-12
Conduction- 35-90
A- delta nerve fibre
Info carried- pain (mechanical and thermal)
Myelin sheath?- yes
Diameter 1-5
Conduction 5-40
C
Describe doral horn
On the posterior aspect of the SC the grey matter forms two horns called the dorsal horns. (the ones at the front are called the ventral horns)
Contains distal nerve endings from primary afferents, cell bodies of second order neurones as well as a complex network of other nerves such as excitatory and inhibitory interneurons (and projection neurones) that transmit somatosensory info from the SC to the brain
1952 Rexed subdivided the grey matter of the SC into 10 laminae. Lamina 1 5/6 correspond to the DH. Some of these rexed laminae have special names e.g. lamina II (2) is called substantia gelatinosa
Aδ primary afferents synapse directly withsecondary afferentsthat will eventually carry the pain signal to the thalamus.
C fibres do not synapse directly with secondary afferents, but connect instead withinterneuronsthat carry the signal on to secondary afferents in laminae I or V. These interneurons are important in modulation of the pain signal
Visceral input differs in that fewer primary afferents activate a larger number of second order neurons, resulting in poorer localisation of pain. Visceral afferents also converge with somatic inputs, which may account for the phenomenon of referred pain
Spinothalamic tract
Sensory pathway that carries pain, temperature and crude touch information from the body
2nd order neurons
Originate in the spinal cord (substantia gelatinosa and nucleus proprius)
Axons decussate at / few levels above the site of entry / spinal segment
Cross the midline in the anterior commissure
Then form the anterolateral tract
lateral STT (pain & temperature) and
anterior STT (crude touch)
Terminate in the thalamus
(ventral posterior lateral nucleus)
Ascending tracts
Doral columns- fine touch, proprioception, vibration)
Lateral spinothalamic tract- pain and tgemperature
Ventral spinothalamic tract- light touch
Describe the thalamus
Midline, paired symmetrical structure in the brain
Approx 6 X 3 cms long
All sensations (except olfactory) relay / pass through
Multiple nuclei
VPL
Medial group
Reciprocal connections to all parts of the cortex
Insula
severity of pain and addiction
Amygdala
emotional processing of pain
Cingulate cortex
Emotional formation around pain
Periaqueductal gray
Grey matter located around the cerebral aqueduct
Receives input from cortical and sub-cortical areas
Projects onto neurons in the dorsal horn
Modulate afferent noxious transmission
Neurons bear opioid receptors
Pathways also include noradrenergic and serotonergic neurones
Stimulus of the PAG can result in profound analgesia
Bio-psycho-social model of pain
Pain affects all areas which then affects the pain
Yellow flags
Beliefs and emotional response
pain behaviours- being told something about how you should cope with pain affects how you will cope with it and its duration
Blue flags
Pain perception and relationship between work and health
Black flags
System or contextual obstacles
e.g ongoing lawsuit
Gate control theory
This schematic has drawn a gate to illustrate what inhibitory interneurons would do functionally
What you have to know about Melzack and Walls gate control theory is that it is the concept that onwards transmission of a nociceptive signal depends on the balance between inhibitory and excitatory inputs at points of integration along the path from transduction to perception.
Drugs used in pain management
NSAID’S
Paracetamol
Opioids
LA’s
⍺2 agonists
NMDA receptor antagonists
TCA’s
gabapentinoids
SNRI’s
Define pain
Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.
Nociplastic pain
Pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors, or evidence for disease or lesion of the somatosensory system causing the pain.
Neuropathic pain
Pain caused by a lesion or disease of the somatosensory nervous system
Nociceptive pain
Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors.
Acute vs chronic pain
Acute- physiological- Pain < 12 weeks duration
Chronic- pathological- Continuous pain lasting > 12 weeks
Pain that persist beyond the tissue healing time
classified into cancer and non-cancer pain
Nociceptive pain pathways
Transduction in the periphery, through transmission to the dorsal horn of the spinal cord, then on to the brain
What is nociception?
Describes the neural processes involved in producing the sensation of pain
What is the purpose of persisting pain?
Later,persisting painencourages us to immobilize the injured area, giving damaged tissue the best chance to heal.
What is the purpose of immediate pain?
Immediate painwarns of imminent tissue damage withdraw from the source of injury
What is depression
-Low mood, anhedonia, low energy
-“Biological” symptoms
◦ Poor sleep
◦ Poor appetite
◦ Reduced libido
◦ Poor concentration
-“Cognitive” symptoms
◦ Worthlessness (poor self esteem)
◦ Guilt
◦ Hopelessness
◦ Suicidal thought
Describe how the Hypothalamus Pituitary Adrenal axis changes in depression
- Increased CRH
- Enlarged adrenals and pituitary
- Reduced –ve feedback
- Reduced GR expression in the brain
◦ “Glucocorticoid resistance”
Describe the HPA axis
Hypothalamus –(CRH- corticotropin releasing hormone)—-> Anterior pituitary —(ACTH- adrenocorticotropic hormone)—> Adrenal cortex —(CORT)—-> Negative feedback to the hypothalamus
Role of early adversity and parenting effect on depression
History of childhood maltreatment (with or
without current MDD) -> ↑ACTH release in
response to stress
Offspring of “high licking” lab rats show high
GR expression (higher ACTH suppression)
◦ Even if swapped at birth
◦ Or even if brushed
by a research assistant!
◦ Blocked by 5HT antagonists
◦ Possibly oxytocin mediated
Social rank effects on HPA function
Subordinate monkeys have:
◦ Heavier adrenal glands.
◦ Increased cortisol in hair
◦ Reduced dexamethasone suppression
How does stress affect the brain?
Findings suggest that steroids are:
◦ Neurotoxic
◦ Cause neuro-vulnerability
◦ Affect dendrite formation
◦ Reduces neurogenesis
◦ Cause changes to the EEG.
Particularly affects the frontal lobes and
hippocampus.
Impact on stress on different parts of the frontal lobes
Medial PFC
◦ Evaluating emotional state
◦ Social cognition
◦ Less volume loss
Dorsolateral PFC
◦ Working memory
◦ Problem solving
◦ Large volume loss
Impact of depression on the hippocampus
Reduced in size in MDD
◦ Up to 20% volume loss
A dose related effect
◦ Correlated with number of,
and length of previous episodes.
Associates with learning based cognitive
deficits.
Much of the volume loss is irreversible
◦ Is depression a neurodegenerative disease?
What is neurogenesis
Grow axons
and dendrites,
and integrate
into existing
networks
6% of the total
dendate gyrus
population a
month!
How does stress regulate neurogenesis
Restraint and shock stress
causes reduced neurogenesis.
Particularly when learned
helplessness is induced.
‘Social dominance stress’
reduces the number of
surviving new cells (same
rate)
How does stress affect dendrites
Mediated by reduced neurotrophins
Eg. Brain derived neurotrophic factor (BDNF)
Link between Brain Derived Neurotrophic Factor and depression
Stress -> ↓BDNF (animals).
◦ Reversed with antidepressants
Low BDNF in unmedicated depressives
◦ Normal to high in medicated patients
The lowest levels in post-mortems of
successful suicide victims
How do antidepressants work?
- Original observations about their
pharmacology ->
◦ “The monoamine theory of depression” - The answer is “by affecting gene expression”
- Antidepressants increase GR expression
◦ (regulating HPA activity) - Antidepressants increase neurogenesis
They increase BDNF synthesis.
◦ ∴ improve connectivity and increase
number of synapses.
What is the function of the default mode network?
It’s what comes on when there’s nothing to
do (“resting state”)
- The brain’s ‘screen saver’
- Daydreaming, internal ‘flow’ of
consciousness.
- Autobiographical details
◦ The self’s place in time and space
◦ Projecting to other places in time and space
- Self reference
◦ Referring to traits or states
◦ Emotional and moral reasoning
- Thinking about others
◦ Theory of mind
◦ Social judgements/evaluations
DMN in depression
- Depressed people find it hard to
appropriately switch off their DMN in
response to a task.1 - We already knew depressed people
excessively ruminate. - Dinner party with a deadline.
Relationship between the DMN and LSD
- Carhart Harris used modern functional
scanning techniques on people in the acute
psychedelic state. - Positive symptoms -> ?surely increased
activity - Reduced activity in the DMN
- Reduced alpha power in PCC
5 pillars of wellbeing
- Physical activity
- Connect with others
- Learn something new
- Practice mindfulness
- Acts of generosity
Differences between the somatic and autonomic nervous system
S:Conscious- A: unconscious
S: no synapse after CNS - A: fibres synapse at a ganglion after the CNS
S: SkM, stimulatory - A: SmM and CM stimulatory and inhibitory
Parasympathetic
Cranial nerves to head, thorax + abdm
Sacral outflow to pelvic organs
The vagus nerve to thorax and abdm
Sympathetic
Cranial nerves to eye
The sympathetic chain
Other ganglia
Post ganglionic fibres
Where are the ganglion in the autonomic nerves?
In the middle of the motor neuron
Before it is myelinated after it is not
Usually uses acetyl choline or NE at the neuromuscular junction
Functions of the autonomic nervous system
Thermoregulation, Exercise, Digestion, Competition, Sexual Function, Fight/flight
Sympathetic stimulation
Heart rate and force of contraction increases
Blood vessel constriction
Bronchodilation]
Decreased motility in gut
Sphincter contraction
Decreased secretion in gut
Male ejaculation
Parasympathetic stimulation
Heart rate and force of contraction decrease
Blood vessels can dilate
Bronchoconstriction
Increased gut motility
Sphincter relaxation
Increased secretions in gut
Sympathetic chain running alongside spinal cord
parasymp acetyl choline
symp adrenaline/noradrenaline
Rami communicantes
Which cranial nerves have parasympathetic fibres?
Oculomotor III
Facial nerve VII
Glossopharyngeal nerve IX
Vagus nerve X
Main neurotransmitter in enteric nervous system
Serotonin
Nicotinic receptos
Muscarinic receptors
Only in parasympathetic
Adrenergic receptors
Only in sympathetic
Subtypes of noradrenaline
Alpha- alpha 1, alpha 2
Beta- beta 1,2,3
ANS inputs carotid receptors
Carotid body in carotid bifurcation
Baroreceptors for BP
Chemoreceptors for O2
Afferents to the brainstem
Affect output of brainstem
ANS inputs- ventricle receptor
Volume in ventricle
Diving response
Acute primary A.N.S disorders
Pan-dysautonomia with neurological features
Chronic primary A.N.S. disorders
Pure autonomic failure
Multiple system atrophy (Shy-Drager syndrome)
Autonomic failure with Parkinson’s disease
Secondary A.N.S. disorders- metabolic diseases
Diabetes mellitus
Chronic renal failure
Chronic liver disease
Alcohol induced
Secondary ANS disorders
Inflammatory- Guillian-Barré syndrome
Infections- Bacterial: tetanus
Parasitic: Chagas’ disease
Viral: HIV
Neoplasmia- Brain tumours, especially of third ventricle or posterior fossa
Cardiovascular disorders of the ANS
Postural hypoternsion
Supine hypertension
Liability of BP
Paroxysmal hypertension
Tachycardia
Bradycardia
Fainting
Sexual disorders of the ANS
Erectile failure
Ejaculatory failure
Retrograde ejaculation
Priapism
Sudomotor disorders
Hypo/anhidrosis
Hyperhidrosis
Gustatory sweating
hypothermia
Hyperpyrexia
Ailementary disorders
Gastric stasis
Dumping syndrome
Constipation
Diarrhoea
Disorders of the eyes
Pupillary abnormalities
Ptosis
Alachryma
How can you measure the ANS cardiovascularly?
HR and BP- preferably beat by beat
-> can do it using the radial artery
Tilt test
Baro-reflex testing- By Phenylephrine test
Non cardiovascular ANS measurement
Pupillometry
Sweat measurement
Skin blood flow, thermoregulation
Gastric acid secretion
Sexual function
Outline fMRI
- BOLD contrast reflects blood flow changes
secondary to neuronal activation - Simple or complex tasks compared with a
“rest” state - Statistical analysis of significant changes in
BOLD contrast demonstrates areas of
“activation” which are overlaid on anatomical
images
Outline auditory fMRI
- Study the auditory pathway
both in cortical & subcortical
structures - 3T
-HIGH Resolution 2x2x2 mm3
-HIGH SENSE factor 2.5
-“Silent gap” scanning
-Binaural auditory stimulation
Define pain
An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage
Important factors in understanding pain in the moment
Body/nervous system
Attention
Expectation
Past experience (incl. trauma)
Thoughts/words
Senses
Emotions
Feedback/response
What is DIM and SIM
DIM- Danger
SIM- Safety
Key features of long term pain
- Sensitisation
- catastrophic thinking - not only more likely to experience pain, but more likely to have an acute pain become chronic
- situation where sustaining an injury would have high levels of consequence
- more general psychological states of threat (e.g. abuse)
What is sensitisation?
- Neurons that fire together
(path through the woods)
(playing the pain song) - Nervous system
- “Smudging” etc.
Acute pain
A warning – (generally) helpful and protects you from further physical damage
Can usually be explained and treated
E.g. toothache, sprained ankle, broken bone
Others tend to understand and offer sympathy
Temporary - you can carry on as normal afterwards
Chronic pain
Typically serves no useful warning purpose – a ‘nuisance’
Medical investigations may not provide a diagnosis or an explanation
Treatment is aimed at relieving pain, not curing it
Others might not understand
Ongoing and often has a negative and widespread effect on life
What can chronic pain affect?
Ability to work
Activities (e.g. social and daily activities)
Satisfaction and enjoyment from activities
Contact with others
Relationships with family and friends
Self confidence
Sleeping patterns
Poor concentration
Mood
Sense of self -‘Not the person I used to be’
pre-occupation with pain
Uncertainty about the cause of pain and the future
What are the 3 Ps
- Pacing
- Prioritising
- Planning
What is pacing?
Limiting the time spent on an activity to prevent marked increases in pain, and keeping to a regular amount of activity to prevent the problems of too much rest.
Planning activity rather than just doing things according to how you feel.
Taking frequent short breaks, breaking tasks or activities down to smaller tasks and changing position regularly.
What is planning?
Involves thinking about when and how activities are going to be done.
Make sure that difficult activities are spread out
Balance essential with non-essential activities
Taking regular breaks
What is prioritising?
Means making (difficult) choices about what is done
Try to balance what needs to be done with what is pleasurable or interesting.
Why can learning to relax be helpful?
When we know something is going to hurt the natural and automatic response is for our muscles to tense up in anticipation to protect ourselves Pain leads to muscle tension
Egs: something being thrown at us, injections
Muscle tension can make the experience of pain worse
Effects of prolonged muscle tension
cause aches, discomfort and tiredness
cause simple movements, e.g. walking or getting out of a chair, to become stiff and slow
become normal - maybe physically tense without being aware of it
What can relaxation do?
Be beneficial to a person’s general health
Help to change their experience of pain
Help to manage pain and feel more in control
Be a useful means of distraction
Be helpful in dealing with stress
Distraction
Pain is a powerful signal which gets your attention, but we can influence that attention
Awareness of pain is affected by mental activity
Distraction is a very valuable and practical approach to managing pain
Tips for managing flare ups
Help patients Plan for flare ups
Remember the ‘box of tools’
Advise patients to talk to others about flare ups and how best they can help
Advise patients to focus on getting through the short period of time during a flare up.
Review medication use during and after a flare up.
What are the different circuits in the basal ganglia?
-Motor circuit
-Limbic circuit
-Oculomotor circuit
Motor disorders related to the basal ganglia
Parkinson’s Disease
Huntington’s Disease
Dystonia
Gilles de la Tourette syndrome
What are some psychiatric disorders related to the basal ganglia?
Obsessive compulsive disorder
Attention Deficit Hyperactivity Disorder (ADHD)
What are some diseases secondary to damage of the basal ganglia?
Cerebral Palsy
Wilson Disease
Key points of parkinsons disease
Increased muscle tone
Reduced movements
Not enough dopamine
Key points of huntington’s disease
-Decreased muscle tone
-Overshooting movements
-Too much dopamine
How to synthesise dopamine?
-Tyrosine- amino acid
-L-DOPA
-Dopamine
Key findings in the brain of someone with Parkinson’s
loss of dopaminergic receptors in the substantia nigra
Presence of lewy bodies
What is the area of cell loss in Huntington’s disease?
Striatum
Pathway of
What is the dopamine antagonist in the brain?
GABA- produced in striatum
WHere is dopamine produced?
Substantia nigra
What happens biochemically in parkinsons?
Loss of substantia nigra means decreased dopamine and so more GABA and less movement
What happens biochemically in Huntington’s?
Loss of striatum means loss of GABA so more dopamine and more movement
Key features of Parkinson’s disease
Brady/Akinesia
Problems with doing up buttons, keyboard etc
Writing smaller
Walking deteriorated: Small steps, dragging one foot etc
Tremor
At rest
May be on one side only
Rigidity
Pain
Problems with turning in bed
Drug treatment of Parkinson’s disease
Drugs mostly aim at correction of dopamine deficit
But:
More and more cells die
The drugs work shorter and shorter
The longer on treatment, the more likely are the patients to develop side effects, in particular dyskinesias
Outline deep brain stimulation to treat Parkinson’s
Functional lesioning of the subthalamic
Nucleus leads to dramatic improvement of PD
It deactivates the break (subthalamic nucleus)
Key clinical features of Huntington’s disease
Chorea
Dementia/psychiatric illness
Personality change
Clinical genetics of Huntington’s disease
Autosomal dominant
Fully penetrant
Trinucleotide repeat expansion
Trinucleotide repeat expansion
