Combining noninvasive brain stimulation and neuroimaging to study human brain biology

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There are theories about how the brain works. Those theories can be tested with tools that can change brain function and identify how that affects behaviours. Such tools are common in animal models (e.g., optogenetics), but there are no such tools for the human brain. Our long-term NSERC supported program entails developing such tools. A method that could test theories, noninvasively, on human causal brain-behaviour relationships would have a transformative impact in neuroscience. Transcranial current stimulation (tCS) combined with MRI can become such cardinal tool. Previous studies observed that tCS modulated human behaviours in vivo, whereas others found not effects. These inconsistencies reflect in large part the noninvasive quality of tCS. Indeed, tCS alone does not show how it influences the brain when it modulates behaviours. This is a fundamental step missing in tCS investigations: What does tCS modulate to, consequently, influence behaviours? The main goal of this 5-year program is to characterize how tDCS modulates human brain activity by conducting basic investigations concurrently combining tCS and MRI. Thanks to previous Discovery grants, we developed a method concurrently combining tCS with resting state MRI. This method can thus to test whether tCS can truly modulate brain activity, without confounding behavioural influence. We found that tCS over the dorsolateral prefrontal cortex of healthy adults during resting state functional MRI and MR spectroscopy strengthened connectivity in the frontoparietal network and elevated prefrontal NAA and striatal glutamate levels. Our studies provide evidence that tCS can impact human brain activity during stimulation. We also recently observed that brain morphometry, especially the volume, influences tCS-induced changes on neurotransmitter levels. Strikingly, there are scarce studies on how morphometry and tractography influence tCS effects on brain activity. Yet, morphometry and tractography are the main roads that the current travels through (and that we can assess in vivo in the human brain) to modulate brain activity and consequently behaviours. In this program, we propose to specifically test: 1. If sham tDCS is a good control condition, as one of the most used sham tDCS protocol has yet to be tested with MRI outcomes; 2. Intra-individual reliability of tDCS effects on resting state functional connectivity during and after stimulation and characterize the impact of brain anatomy (morphometry, tractography) on these effects; and 3.Intra-individual reliability of tDCS effects on neurotransmitter levels during and after stimulation and characterize the impact of brain anatomy (morphometry, tractography) on these effects. The development of concurrently combining tCS and MRI methods will contribute at providing tools that will reliably modulate specific brain networks. Such tools will have the quality to test human brain functions by establishing brain-behavioural causal relationships.