Summary neural networks- non invasive brain stimulation

Neural networks: non-invasive brain stimulation
INTRODUCTION
 Non-invasive brain stimulation (NIBS) techniques increasingly used for modulation of central nervous
system excitability in humans
- (non-invasive: not ‘inside’ the brain, but at the level of the scull)

 Fundamental Research: study fundamental aspects of human behavior
- Motor control, motor learning
- Cognition
- Memory
- ...
 Clinical Applications: induce neuromodulation facilitating neurorehabilitation
- Stroke
- Parkinson’s disease
- Depression
- Aging

CONTENT
 Transcranial Magnetic Stimulation (TMS)
 Transcranial direct current stimulation (tDCS)

 Evidence for application in stroke
 Evidence for application in Parkinson

 Transcranial alternating current stimulation (tACS)
 EEG-based Neurofeedback
 Transcutaneous electrical nerve stimulation (TENS)
- Vagal nerve stimulation (VNS)

HISTORY OF NIBS
 In 1959, Kolin et al. stimulated the nerves of frogs through alternating magnetic fields for the very first
time.
 Later in 1965, Bickford applied magnetic fields to stimulate the human peripheral
 nerve.
 In 1980, Merton and Morton (1980) electrically stimulated the motor cortex through the scalp using
transcranial electrical stimulation (TES).
- => TES became very useful for many purposes, but it was very painful…
- Stimuleren motor cortex= AP krijgen door stim. Corticospinale tract
 Later, in 1985, Barker et al. introduced transcranial magnetic stimulation (TMS) to stimulate the brain…
with no pain.
- also electrical field but with an magnetic field -> not detected by the pain sensors




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, Neural networks: non-invasive brain stimulation
TRANSCRANIAL MAGNETIC STIMULATION – TMS
 Non-invasive, focal stimulation of the brain
 Equipment
- Condensator
- Coil
 Primary electriccurrent in coil
- Induces magnetic field
- When coil is held over the brain
 => Magnetic field induces secondary electric current in underlying brain tissue
- Secondary = opposite direction!

 TMS over Primary motor contrex (M1)
- activation of corticospinal tract through stimulation of pyramidal cells in the primary motor cortex
- activation of α- motorneurons at the spinal tract
- measurable activity in the contralateral muscle (using electromyography)
- Motor evoked potential (MEP)

 Different types of TMS
- Single-pulse TMS
 Measurement of corticospinal excitability (MEPs)
- Repetitive TMS protocols (rTMS)
 Used to modify brain plasticity
- Basic mechanisms underlying rTMS-induced plasticity remain poorly understood
 Hoe kan TMS gebruikt maken van plasticiteit
- Suggested mechanisms for inducing plasticity
 At the level of the synaps
o Induction of long-term potentiation (LTP)
o Induction of long-term depression (LTD)
 (Non-synaptic)
o Cellular pathways by TMS

REPETITIVE TMS
 Different protocols
- Low-frequency rTMS (less than 1 stimulation/ sec) (< 1 Hz)
 => Inhibitory (decrease excitability through LTD)
o LTD+long term depression
- High-frequency rTMS (more than 5 stimulations/sec) (> 5 Hz)
 => Facilitatory (increase excitability through LTP)
o LTP= long term potentiation
- Continuous theta-burst stimulation (cTBS)
 Three pulses at 50 Hz every 200 ms for 20 – 40 seconds
o => Inhibitory (decrease excitability through LTD)
- Intermittent theta-burst stimulation (iTBS)
 Three pulses at 50 Hz every 200 ms for 2 seconds given at 10 sec intervals
o => Facilitatory (increase excitability through LTP)
 frequency=impact op richting
- Facilitatie
- Inhibatie




 Intervallen hebben ook invloed




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, Neural networks: non-invasive brain stimulation

1. FACILITATION – HIGH-FREQUENCY RTMS
 Synaptic mechanism
- Magnetic field simultaneously depolarizes the pre- and post-synaptic neurons.
- Induced action potentials in the presynaptic neuron result in the release of glutamate into the
synapse, whereas simultaneous depolarization of the post-synaptic dendrite by the stimulation
activates voltage-gated calcium channels and removes the magnesium block from the NMDA
receptor (receptor for glutamate) (N-methyl-D- aspartate) .
- This “cooperative” activation of the pre- and post-synaptic neurons promotes the accumulation
of AMPA receptors (α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid) on the post-synaptic
cell, resulting in an overall strengthening of the synapse and LTP-like effects.
- Of note!
 Shown IN VITRO (single-cell culture) of subcortical cells of the hippocampus
 Not known whether mechanism is similar for cortical neurons (which are more commonly
stimulated with rTMS at the scalp)
 Mechanism demonstrated for LTP Not known whether mechanism is the same for LTD

2. NON-SYNAPIC MECHANISMS FOR INDUCING PLASTICITY
 Biochemical : Regulation of gene and protein expression
- Brain-derived neurotrophic factor (BDNF)
 Belangrijke factor= trofic factor
 => potent trophic factor implicated in synaptic plasticity, neuronal survival, and regeneration
- Humans with genetic variants of BDNF respond differently to TMS protocols
- Human studies show up-regulation of BDNF in serum samples following high-intensity rTMS

 Role of rTMS-induced upregulation of BDNF?
- Promote plasticity
- Induce Neurogenesis
- Neuroprotection

 Main mechanisms

 details hiervan niet kennen! Wel het volgende:
- Promoting neuroplasticity, neuro survival -> inhibits neuronal cell death
 ↑ metabolische effecten
- Regulatie gene expression proteins




TRANSCRANIAL DIRECT CURRENT STIMULATION – TDCS
 tDCS is a transcranial electrical stimulation (tES) technique that involves the application of a weak direct
electrical current (e.g., 1–2 mA) through two or more electrodes placed on the scalp
 Gedetecteerd als kleine tinteling op huid/schedel
- Is niet onaangenaam
- Electrode kunnen eender waar geplaatst worden
 Magnetisch veld registreren
- LOW intensity/current!
- TMS: massive synchronized discharge of action potentials
- tDCS: electrical current is too weak to induce action potentials
 Modulation of membrane potential of neurons
 Steeds I tussen + &-




IN VITRO RODENT BRAIN TISSUE


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