Non-Invasive Neuromodulation of the Central Nervous System Opportunities and Challenges: Workshop Summary (2015) / Chapter Skim
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3 The Science and Technology of Non-Invasive Neuromodulation
3 The Science and Technology of Non-Invasive Neuromodulation
Pages 21-30
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The history of neuromodulation goes as far back as ancient times, when electric fish were used to treat pain, explained Mark Hallett, chief of the Human Motor Control Section at the National Institute of Neurological Disorders and Stroke (NINDS)
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NEUROSTIMULATION EFFECTS ON THE BRAIN Neurostimulation can alter brain function by creating a lesion or in some other way inducing an anatomical or functional change that will interrupt brain circuits or modulate oscillations within a circuit, said Hallett. In terms of non-invasive neuromodulation, most lesions are transient, although high-intensity focused ultrasound will create a more permanent lesion with longer lasting effects.
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For example, in order for TMS administered to the primary motor cortex to cause a muscle twitch, the polysynaptic neural response to the pulse must travel through the mid-brain and pons, cross the medulla, down the spinal cord, across a synapse to the alpha motor neuron, along that neuron down the limb and cross a neuromuscular junction, thus causing the muscle to contract. In other words, focal brain stimulation does not stay focal, but affects multiple areas of the brain (Fox et al., 2012b)
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. Roi Cohen Kadosh, Wellcome Research Career Development Fellow and university research lecturer at the University of Oxford, showed data from another study where learning effects persisted for 6 months following transcranial random noise stimulation (tRNS)
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The biggest advantage of animal models is found when large numbers of test animals are available, enabling systematic tweaking of protocols to identify the optimal dose, pattern and frequency of stimulation, etc. The molecular and electrophysiologic mechanisms are also accessible in isolated brain slices, which can be derived from experimental animals, and also (following brain surgery)
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The FDA scientists use modeling and simulation at both the macroscopic, or anatomical, level, and the microscopic, or neuronal, level, to assess the effects of various neurostimulation devices on the brain, said Leonardo Angelone, research biomedical engineer at CDRH. For example, to study the electric fields generated by a given source applied transcranially, they are using an anatomical model of the human head that was developed through an international collaboration.
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. Transcranial electrical stimulation includes both tDCS and tACS, which are among the most readily available and cheap neurostimulatory devices in use.
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O One uses multiple maagnetic coils to improvve magnetic field focaliity (NCT0 01431001)
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However, according to Jeffrey Elias, associate professor of neurological surgery and neurology and director of stereotactic and functional neurosurgery at the University of Virginia School of Medicine, there are some therapeutic frequencies that move through the skull better. Indeed, as far back as the 1950s, neuroscientists William and Frank Fry conceived the idea of focusing ultrasound beams deep inside the brain to treat movement disorders (Fry et al., 1958)
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In addition, laboratory models enable studies of mechanisms of action at a resolution not available in humans, such as assessing regional gene expression, changes in neurotransmitter receptor subtypes, and other molecular consequences of neurostimulation. For example, in vitro slice cultures enable scientists to assess the effect of different levels of stimulation on different cellular populations within different brain regions, providing access to molecular mechanisms such as plasticity in a simplified structure (Vlachos et al., 2012)
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