Abstract
BackgroundTranscranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure. ObjectivesIn this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. MethodsWe applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n = 22) and TBI participants (n = 34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure. ResultsWe find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region. ConclusionsOur results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation.
Highlights
Transcranial direct current stimulation is a powerful clinical and research tool that can improve cognition in healthy [1] and patient populations [2]
The brain network effects of TDCS are dependent on cognitive brain state in both healthy and traumatic brain injury (TBI) participants
An additional main effect of anodal Transcranial direct current stimulation (tDCS) in the absence of task was further activation of the posterior cingulate cortex (PCC), the precuneus, and the ventromedial prefrontal cortex, areas associated with the default mode network (DMN) (Fig. 2c)
Summary
Transcranial direct current stimulation (tDCS) is a powerful clinical and research tool that can improve cognition in healthy [1] and patient populations [2]. Variability in the efficacy of tDCS, owing to our insufficient understanding and control of sources of intra and interindividual variability, is a hurdle to its widespread clinical application [3] Participant factors, such as brain structure, and experimental factors, such as stimulation intensity, all influence tDCS's effects [3]. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. Objectives: In this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. Results: We find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. Conclusions: Our results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation
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