Lecture 3: Epilepsy and Neuroplasticity

epilepsy

-a chronic medical condition produced by temporary changes in the electrical function of the brain, causing seizures which affect awareness, movement or sensation

-affects 0.5-1% of the population

features of epilepsy

-idiopathic disease

-wide range of symptoms

-symptoms depend on:

• type of epilepsy

• areas of the brain affected

types of epilepsy

• partial epilepsy

  -simple partial seizures

  -complex partial seizures

• generalised epilepsy

  -grand mal seizures

  -petit mal seizures

simple partial seizures (partial epilepsy)

-localised to specific areas of the brain

-localised effects are usually sensory and/or motor

Jacksonian March (simple partial seizures)

-localised jerking beginning in right hand and progressing to clonic movements of entire arm

-this progression up the arm is produced by epileptiform activity in the motor cortex that controls the arm

complex partial seizures (partial seizures)

-localised to specific areas of the brain

-effects are complex and diverse

-also called focal onset impaired awareness seizures

-associated with apparently ordered/co-ordinated, but inappropriate motor behaviour

-localisation in temporal lobe

features of complex partial seizures (partial seizures)

-inappropriate motor behaviour:

• running, chewing, buttoning

-impaired consciousness

-lasts a few minutes

-often no memory of the episode

auras (partial seizures)

-symptoms that precede partial seizures

-abnormal sensations:

• sense of fear

• rising feeling in abdomen

• strange tastes or odours

• visual sensations

-due to early abnormal electrical activity originating from seizure focus → earliest manifestation of partial seizure

petit mal seizures (generalised epilepsy)

-can involve entire brain

-person is briefly absent, disrupted consciousness

-brain is disrupted by seizure activity

-more common in children and often disappears with age

-widely undiagnosed

grand mal seizures (generalised epilepsy)

-involve entire brain

-patient may lose consciousness, fall to ground

• tonic phase → rigidly extend all limbs

• clonic phase → jerks in all extremeties

partial seizures can generalise to generalised seizures

-specific and small part of the brain can be the source of the seizure activity

-may be the case for localised brain damage or following an infection or presence of a tumour

-seizure activity spreads via axons and white matter pathways

-can travel across the hemispheres via the corpus callosum

-can spread across the thalamus → a big relay station of nuclei that spreads messages across the brain

EEG to measure seizure activity

-shows an extensive synchronisation of firing across a large number of neurons

-’spike and wave’ at 3Hz associated with petit mal generalised seizures

-can also be seen via invasive measures

EEG data

-look at signal over time

-look at frequency components → how fast the waveforms are oscillating

animal models of epilepsy

-infusions of excitatory agents into the cortex can induce seizures in animal models

-recreates epileptic activity → a seizure that spreads

-useful for investigating treatment possibilities

pharmacological treatments of epilepsy

-drugs that target GABA or Na+ channels

-drugs often look/act like GABA or increase the amount of GABA available

-GABA is inhibitory and makes other neurons less likely to fire

-seeks to dampen down the excessive neural firing

surgical treatments of epilepsy

-surgery to remove problematic brain areas that cause seizures and do not serve their proper function

-use of deep brain stimulation to interrupt problematic brain activity and calm the excessive activity

neuroplasticity

-changes to brain structure, connectivity and function over time in response to changing environment

-both external and internal environment changes

• internal → cells around the neuron, chemicals around the neuron that strengthen or weaken pathways

• external → new environments, learning a new skill

three key principles of neuroplasticity

1. neurodegeneration

2. neural regeneration

3. neural reorganisation

neurodegeneration

-up to 100 billion neurons in the adult brain

-this tends to remain relatively stable over time

-number of connections changes dramatically → pruned to the most effective and fast networks

grey matter (neurodegeneration)

-grey matter volume declines with age (cell bodies)

-due to reduction in connections and in numbers of other support cells

white matter (neurodegeneration)

-white matter volume increases for a while as the connections get better insulated with myelin

-connection to/from frontal cortex amongst the last to become fully myelinated

damage to individual neurons (neurodegeneration)

• anterograde transneuronal degeneration

• retrograde transneural degeneration

• trans-neuronal degeneration

-neurodegeneration can result from a disruption to the homeostatic environment within and surrounding the neuron

neuronal death (neurodegeneration)

-disruption of normal neurotransmitter function

-loss of fuel supply e.g., oxygen, glucose

-attack from infections, toxins or our own immune system

-faulty genetic signalling

-physical injury

necrosis (neuronal death)

-death due to cellular ill health

-unmanaged

-bits of cell float around and damage health of other cells

apoptosis (neuronal death)

-cellular self destructive option

-adaptive, managed

-cell destroys itself if is signalled it is not needed or has bad health

neural regeneration

-clear capacity for regrowth/regeneration in the PNS

-more complex/difficult in the CNS

central nervous system

-made up of brain and spinal chord

peripheral nervous system

-made up of everything outside of skull and spine

-two divisions:

• somatic nervous system → interacts with external environment

• autonomic nervous system → regulates body’s internal environment

neural regeneration after degeneration

-whether there will be any regeneration depends on the tissue environment

neural regeneration if cause of degeneration has been resolved

-presence of Schwann cells appears critical for regeneration of PNS neurons

-distance to the target is also a key factor

-regrowth is not always helpful → wiring can get messed up if the Schwann cells are not able to guide it properly

implications for spinal cord injury (neural regeneration)

-part of CNS

-target of spinal cord axons is usually quite distant → harder for Schwann cells to access

-regeneration potential for seriously injured spinal cord neurons is therefore much reduced

-peripheral nerve targets stand a much better chance

stability and adaptability (neural regeneration)

-in CNS thoughts, skills and learning needs to be stable due to it being biologically expensive to relearn things

-PNS is less stable due to relearning movements, healing injuries and the body is growing all the time, so prefer higher levels of adaptability over stability

-so different pressures on CNS and PNS regarding regeneration

treatments for peripheral nerve injury (neural regeneration)

-strategies tend to focus on guiding regrowth and enhancing the tissue environment

brain mapping (neural reorganisation)

-the brain is full of maps

-damage, training and experience can reconfigure these maps

-representations in the brain for specific areas are complex and overlapping → good for neural re-organisation following damage

-few motor commands require isolated activation of a single muscle or small group of muscles

neural reorganisation

-in response to loss of peripheral input, reorganisation involves intact/connected areas expanding to take over tissue that receives no input

-based on changes in:

• connectivity

• strengthening of previous partially overlapping connections

• new connections

-continuous competition for space amongst neural circuits and maps