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Electrical Stimulation of the Brain (ESB)

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Neural targets for ESB

the results of ESB totally depend on what is being targeted...

 

 

Topography of brain and phrenology of mind

Sticking electrodes just anywhere into the brain matter isn't going to produce great results. Targeting specific functionally relevant areas of the brain is essential to achieving the desired effect, preferably with previous experiments in animals.

Currently the number of possible targets for ESB are determined by two things: knowledge of the functional anatomy, and the accuracy of electrode insertion. Lets look at each of these more closely to see what is involved, and what the future holds.


Functional anatomy

Anatomists have mapped out brain structures using every available means of differentiating tissues from each other. At the grossest level the lobes, gyri and fibre tracts can be separated. Under a microscope further differentiation is possible, noting where cell phenotypes change, or using stains to mark otherwise identical cells.
Further one can deduce pathways by looking for expression of characteristic molecules, for instance enzymes involved in catacholamine synthesis. With the dawn of transgenics it is also becoming possible to find individual genes within groups of cells, and to track the expression of these genes. One can use existing, naturally occuring genes as markers, or introduce one's own, such as green-flourescent protein.

Using a variety of techniques, including electrical stimulation, ablation, transgenics and neuro-imaging one can extrapolate the functional aspects of discrete anatomical regions. The first line of testing is usually quite gross, making changes to large areas and checking for effects on behaviour. When studying specific processes like Parkinson's or addiction one can use experimental models to give a benchmark against which interventions in the brain can be measured.

Existing knowedge of pharmacology can lend insight for electrical stimulation. Major behaviouarlly relevant pathways in the brain have been deduced; such as the dopaminergic seeking pathways connecting ventral tegmental area, nucleus accumbens, hypothalamus and neo-cortex. With this foundation one can immediately begin working with such pathways, stimulating them at each point and observing behavoiural effects.

Ultimately to uncover the functional relevance of brain structures requires intense and continuous refinement, using every technique available, in a host of different experimental paradigms. As is becoming clear, brain areas thought to be exclusively for, say, vision also have other functions when tested in a sensitive enough manner.
[Rushworth et al, 2002]

As work into these areas becomes ever more refined, and new techniques are used to understand the functional relevance of anatomy, more and more possible targets for ESB will become available.


Electrode insertion

Today the target for stimulation is determined using many techniques, each refining the target zone for electrode insertion. MRI scans are used to acquire images of the patient's brain, which is then referred to a stereotactic atlas. Using the patient's images with the map one can generate co-ordinates in proportion to landmarks, such as the ventricular dimensions or anterior-posterior commissural distance. These coordinates can then be used when the patient's head is mounted in place, allowing surgery accurate to around 1mm.

Macro-stimulation can be applied during surgery to test for the desired behavioral effects. This behavoiural reference will allow fine tuning of the eletrode's placement within the designated region. Some electrode implants are being developed which automatically adjust and seek out the ideal point of stimulation.

Microelectrodes can also be introduced to record from the area, testing how stimulation is spreading to surrounding tissues. This is often desirable when a checking the site with a behavoural reference isn't possible. However adding further elctrodes is associated with greater risk of infection, longer operating times and more intrusive damage to the brain. Thus it is best kept as a backup fro when the other techniques are unable to do it alone.
[Rodriguez-Oroz et al,2004]


Looking for new targets

Generally new targets for ESB are found by applying electrical stimulation to an area, chosen because of some previous insight, with a degree of exhaustive trial and error. If a target is found to elicit some effect consistenly between animals in some disease model, then it can begin to be investigated in humans.

A gamma knife is able to destory tissue deep within the body by focusing many fine beams of radiation into a fine point. In some cases surgery with a Gamma knife produces comparable effects to deep brain stimulation in the same area. Stimulation profiles which cause inhibition of local neurons have thus been described as causing 'funcitonal ablation' or 'functional deafferentation'.

Interestingly this bombardment with electromagnetic radiation has some ESB like effects, causing a flux of charge at the centre point. However the destructive nature of a gamma knife means it is only useful for damaging tissue, as least in it's current form. Perhaps the use of electromagnetic waves will become another way to affect electrical signallling in the nervous system.
[Schwartz,1998]

Listed below are stimulation sites used commonly in research and clinical therapy:

Site

effects

used for

 

 

 

Medial forebrain bundle

reward

reinforcing behaviour

Sub-thalamic nucleus

alterations in motor tone

movement disorders

Globus pallidus interna

motor tone

movement disorders

Vagus nerve

autonomic regualtion

reducing seizures in epilepsy

motor cortex

control of musculature

controlling external limbs

sensory cortex

sensation from body

triggering false sensation

pre-motor cortex

planning movements

predicting desired movement

peri-aqueductal grey

spinal gating

aversive stimuli, drug testing

 

 

 

[Jung,2001]

 

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Electrical Stimulation of the Brain (ESB)

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