Abstract
Non-invasive brain stimulation is a useful tool to probe brain function and provide therapeutic treatments in disease. When applied to the right posterior parietal cortex (PPC) of healthy participants, it is possible to temporarily shift spatial attention and mimic symptoms of spatial neglect. However, the field of brain stimulation is plagued by issues of high response variability. The aim of this study was to investigate baseline functional connectivity as a predictor of response to an inhibitory brain stimulation paradigm applied to the right PPC. In fourteen healthy adults (9 female, aged 24.8 ± 4.0 years) we applied continuous theta burst stimulation (cTBS) to suppress activity in the right PPC. Resting state functional connectivity was quantified by recording electroencephalography and assessing phase consistency. Spatial attention was assessed before and after cTBS with the Landmark Task. Finally, known determinants of response to brain stimulation were controlled for to enable robust investigation of the influence of resting state connectivity on cTBS response. We observed significant inter-individual variability in the behavioral response to cTBS with 53.8% of participants demonstrating the expected rightward shift in spatial attention. Baseline high beta connectivity between the right PPC, dorsomedial pre-motor region and left temporal-parietal region was strongly associated with cTBS response (R2 = 0.51). Regression analysis combining known cTBS determinants (age, sex, motor threshold, physical activity, stress) found connectivity between the right PPC and left temporal-parietal region was the only significant variable (p = 0.011). These results suggest baseline resting state functional connectivity is a strong predictor of a shift in spatial attention following cTBS. Findings from this study help further understand the mechanism by which cTBS modifies cortical function and could be used to improve the reliability of brain stimulation protocols.
Highlights
Transcranial magnetic stimulation (TMS) provides the ability to interact with neural tissue through the intact scalp (Rothwell et al, 1991)
Our results suggest a model of baseline functional connectivity in the high beta band comprising a seed electrode overlying the right posterior parietal cortex (PPC) and two clusters of electrodes approximating a dorsalmedial pre-motor region and the left temporal-parietal region was a strong determinant of behavioral change induced by continuous theta burst stimulation (cTBS)
In an exploratory investigation, we observed a trend suggesting that decrease in connectivity between the right PPC and the left temporal-parietal region following cTBS might be associated with a rightward shift in spatial bias, possibly suggesting this network has a role in behavioral change induced by cTBS to the PPC
Summary
Transcranial magnetic stimulation (TMS) provides the ability to interact with neural tissue through the intact scalp (Rothwell et al, 1991). Repetitive and patterned forms of TMS, such as theta burst stimulation, are thought to be capable of inducing behavioral and physiological aftereffects via mechanisms that resemble synaptic plasticity. Modulation of excitability by theta burst stimulation appears to be shortlasting (∼30–60 min), with aftereffects blocked by administration of the NMDA receptor antagonist Memantine (Huang et al, 2007). Dependency on the NMDA receptor suggests theta burst stimulation aftereffects likely involve changes at synaptic connections in the cortex. Given the relatively short time course of stimulation aftereffects, it appears that the neuroplastic response involves mechanisms similar to those responsible for early-phase long-term potentiation and long-term depression (Goldsworthy et al, 2014b)
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