By Miss Rebecca Ong, Perron Institute & UWA, and Professor John Reynolds, University of Otago
A recent study expanded on the current understanding of non-invasive brain stimulation and its application in modulating various neural circuits and neurological processes across the brain.
The knowledge gained from this research could help optimise the application of non-invasive brain stimulation to promote neural plasticity in targeted regions of the brain that may be affected in neurological disorders.
Specifically, this preclinical study explored the effects of repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation currently approved by the TGA in Australia as a treatment for people with treatment-resistant depression.
It involves the delivery of a rapidly changing magnetic field which induces an electrical current in the underlying tissue, thereby stimulating cells within the targeted region.
Currently, a number of different rTMS protocols exist, with each thought to induce different effects on neural activity and neural plasticity in the brain.
Given its ability to non-invasively induce changes in the brain, several studies have looked into the potential of using rTMS in the treatment of neurological disorders where neural plasticity is impaired, for example in stroke and dementia.
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However, the molecular and cellular changes that occur following different rTMS protocols and how these effects may differ between brain regions is still unknown. By characterising within specific brain regions the different cellular processes that rTMS is able to modulate, it provides a greater evidence base to guide the selection and use of different rTMS protocols for the treatment of neurological conditions.
The method
In this study, the research team used two common protocols – intermittent theta burst stimulation and continuous theta burst stimulation. They revealed that rTMS targeted towards the primary motor cortex not only induced multiple neural plasticity mechanisms in the targeted cortical region, but also in several sub-cortical regions outside the direct stimulation site.
These rTMS-induced changes varied depending on the rTMS protocol that was applied to the brain and differed between each brain region, even down to individual cortical layers.
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It is well understood that rTMS is capable of altering processes relating to the strength of communication between neurons, better known as synaptic plasticity. However, increasing evidence has shown that rTMS can also affect other plasticity processes beyond the synapse.
For example, it may alter the neuron’s ability to generate action potentials, known as intrinsic plasticity, or may affect cells that produce and maintain myelin, the insulating fatty sheath around the axons of neurons, in the brain.
This research was the first to show that rTMS induces multiple neural plasticity mechanisms simultaneously across various regions of the brain but again varied depending on the stimulation protocol that was applied.
The results
The results of this study are exciting. Mapping out how various non-invasive brain stimulation protocols affect different regions of the brain provides a foundation to optimise TMS with a more targeted approach in both clinical and non-clinical applications.
It uncovers some of the specific effects that rTMS protocols can have on various neural circuity, and considered together with existing rTMS literature, provides new insights into the molecular mechanisms underlying the therapeutic effects of rTMS.
Key messages
- New research provides an understanding of how different brain regions respond to rTMS and which protocols may be best suited to target different neurological conditions
- Multiple neural plasticity mechanisms induced by rTMS were found to be specific to each layer of the cortex and sub-cortical structures
- By mapping what rTMS is changing in the brain and in which neural circuits, we have a clearer understanding of how to apply and interpret effects of rTMS.
Author competing interests – Miss Ong was directly involved in the study and Prof Reynolds provided critical input to the research.
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