Neuromodulation in Autism: Basic Principles of Transcranial Magnetic Stimulation

In the past few blogs I started a discussion on neuromodulation, that is, the ability of certain techniques to change brainwaves in a positive manner. A review of the literature on neuromodulation indicates 3 different ways for changing brainwaves in a controlled manner. The most direct method is passing an electrical current through the brain.  If the current is high and able to induce a seizure, we call the technique electroconvulsive therapy (ECT). ECT has been used for major depression and schizophrenia but also for a few cases of self-injurious behaviors (SIB) associated with autism. If contrary to ECT the current is extremely low, we call the technique transcranial direct current stimulation (tDCS). I have serious doubts as to whether this technique even works and refer the reader to a previous blog for more information (http://bit.ly/1P8Brqx). I would recommend individuals with autism spectrum disorders to abstain from receiving tDCS therapy until more information becomes available. The second way of achieving neuromodulation is through the “induction” of electricity within the brain. The word induction may be difficult to understand at first, but in the next few paragraphs I will try to demystify the same. The third and last way for accomplishing neuromodulation encompasses a variety of techniques such as neurofeedback. We will cover these in future blogs.

In science the action of a force at a distance (i.e., without physical contact between the objects) is explained in terms of “fields”.  It is well known that particles of opposite charge attract one another while those having the same charge repel one another. This repulsion or attraction only happens over a certain distance. This region of influence is called a field, more specifically, an electrical field. The concept of fields has also been applied to metals and how they can attract or repel each other. A well know example of the latter is how magnets can attract iron-containing objects. This magnetic field is invisible to the human eye but can be visualized when we sprinkle a paper with iron shavings and put the same over a magnet (figure below).  In this particular example the iron shavings align themselves linearly in what scientists call flux lines. These flux lines always form closed loops and cannot cross each other. Furthermore, flux lines are used to measure the strength of a magnetic field. The greater the total number of lines or the higher their concentration over a given area (flux density) the stronger the magnetic field.

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Induction is the action or effect that a magnet or a magnetic field has over another object without any physical contact between them.  A special type of inductive phenomena is called electromagnetic induction and happens when a current is created in a conductor as it moves across a magnetic field.  This effect is called Faraday’s Law, simply meaning that any change in the magnetic environment of a conductor (e.g., a coil of wire) will cause a voltage to be “induced” in the same.

In transcranial magnetic stimulation (TMS) a high current flowing through a coil causes a transient expansion of a magnetic field.  The coil is closely apposed to the skull.  As the magnetic field cuts through cable-like projections called axons  an electrical current is induced. Those conductors (or axons in the case of the brain) at ninety degrees to the magnetic field will cut the maximum number of lines of force and will generate the greatest current. Similarly stated, axons and other projections that crisscross the width of the cerebral cortex will be more likely to be induced than those that travel tangential to the same or have very short lengths.

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Figure: In the cerebral cortex long axons crisscross the width of the cortex and provide a shower curtain of inhibition to the information processing units called minicolumns. This shower curtain of inhibition is presumably affected in autism. TMS is supposed to help rebuild the inhibitory tone of this shower curtain of inhibition.

In TMS a direct current is used to create an expanding magnetic field through a coiled wire. In most direct current (DC) circuits a steady state is reached after a fraction of second of turning on the power. During the transient time when the current is changing from zero to some finite value the magnetic field exerts its greatest effect on the stimulated anatomical elements. In TMS a varying DC is caused as a bank of capacitors discharge their energy. (Note: capacitors or condensers are electronic components that store electrical energy.) The small resistance through the coil ensures a rapid discharge but also dissipates a lot of heat/power. For high frequency discharges the coil may need to be cooled down to prevent it from melting.

The transient time before a direct current has been able to stabilize offers the greatest relative movement between targeted anatomical elements and the expanding magnetic field of the TMS device. What I find fascinating about this transient time is that the effects of the magnetic field do not follow some of the stated laws of physics (Ohm’s Law), that complex phenomena tend to compound the effects of the applied magnetic field (self-induction), and that effects can only be measured with highly sensitive equipment. For me it is highly intriguing that this brief laps of time when we know the least about the behavior of induction is when TMS has its greatest effect.

Induction is the basis by which TMS works. It also explains why high currents are used and why we wind the wire that creates the magnetic field. In effect, the total number of loops determines the inductance of a coil. The greater the number of loops the greater the expansion of the magnetic field and the more wires it is able to cut through.

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TMS is a simple device to use and understand.  The way it is presently used however is non-physiological. It aims to either have neurons fire or become depressed in their action.  It does not gently steers brainwaves in the desired direction but rather tugs on them forcefully to make them follow the direction desired by the clinician. My group was the first to use this technique in a clinical trial in autism and, thus far, have had more experience than all other groups around the world combined. We have reported significant positive effects with little in terms of side effects. Still we are looking for better and more physiological ways of achieving our therapeutic goals.  In autism, especially when using electrophysiological techniques, every step should be a baby step.

11 responses to “Neuromodulation in Autism: Basic Principles of Transcranial Magnetic Stimulation

  1. Intracranial excitation by several electrical/magnetic protocols are physically expected to reduce neuron volume differentials as first postulated in 1999. The recent gene-imaging and other combined imaging studies strongly suggest excitation induced regional brain volume/structural changes of multiple disorders.

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  2. As I may have stated before, it’s possible that non-neuronal cells, astrocytes and microglia, may be involved in autism. TMS would not be able to directly influence them since they don’t have action potentials. It might be possible for TMS to indirectly influence them in some way vis-a-vis interactions with neurons. If not, then I’m not sure how TMS could be of therapeutic value to autism if non-neuronal cells are involved.

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    • We will have to wait and see. It is never said anywhere TMS couldn’t be combined with some other therapy that is to be invented for microglia and astrocytes. But don’t look a gift horse in the mouth, TMS looks to be helpful in alleviating symptoms or at least improving social ability and executive function.

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  3. I agree totally with Jonathan and Hans. Any brain electrical source excitation, depending on where and when applied, and its intensity, will quite likely change nerve net event manifold timing/velocity, including all kinematic events such as action potentials. See (Newton, JR 1999) hypothesis, postulates, and illustrated mathematical invariants for bipolar disorders dyscoordination.

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    • We won a EUREKA award to initiate our investigation and since then the federal government has given nothing else. We have had to pay for the trials out of our own pockets. Pharmaceuticals have no interest in funding this, because they can’t get a patent or make money out of it. Shooting for a phase III trial without any resources is difficult, if not impossible.

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      • And the only non profit organizations like Spark and Autism Speaks wanna invest only in more gene sequencing. Damn.

        Keep going though. You have my faith.

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  4. I have said man times that research, specially with children, is all about taking baby steps. I wish that funding agencies would give a better priority to an intervention for ASD that focuses on its neuropathology and had little in terms of side effects. However their main priority appears to be the funding of molecular biology and animal models.

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  5. Hello Manuel,
    Your wife has written posts on autism too, but some of them seem to disagree with your hypotheses. Are there some disagreements you two have over autism?

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