Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive-emotional training for treatment-resistant depression

Transcranial direct current stimulation (tDCS), a form of non‐invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive‐emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment‐resistant depression took part in this open‐label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting‐state and task‐related EEG during a 3‐back working memory task were acquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting‐state power spectral density (frontal theta and alpha asymmetry), time–frequency power (alpha event‐related desynchronisation and theta event‐related synchronisation) or event‐related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near‐transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham‐controlled group may be necessary to identify the neurophysiological effects of the intervention

Behavioural and neurophysiological differences in working memory function of depressed patients and healthy controls

Objective: Major depressive disorder (MDD) is associated with deficits in working memory. Several cognitive subprocesses interact to produce working memory, including attention, encoding, maintenenace and manipulation. We sought to clarify the contribution of functional deficits in these subprocesses in MDD by varying cognitive load during a working memory task. Methods: 41 depressed participants and 41 age- and gender-matched healthy controls performed the n-back working memory task at three levels of difficulty (0-, 1-, and 2-back) in a pregistered study. We assessed response times, accuracy, and event-related electroencephalography (EEG), including P2 and P3 amplitudes, and frontal theta power (4-8 Hz). Results: MDD participants had prolonged response times and more positive P3 amplitudes relative to controls. Working memory accuracy, P2 amplitudes and frontal theta event-related synchronisation did not differ between groups at any level of task difficulty. Conclusions: Depression is associated with generalized psychomotor slowing of working memory processes, as well as compensatory hyperactivity in frontal regions.Significance: These findings provide insights into MDD working memory deficits, indicating that depressed individuals dedicate greater levels of cortical processing and cognitive resources to achieve comparable workig memory performance to controls.</p

Effects of High-Definition Transcranial Direct Current Stimulation (HD-tDCS) of the Intraparietal Sulcus and Dorsolateral Prefrontal Cortex on Working Memory and Divided Attention

Objective: There is a need to elucidate the underlying neural mechanisms subserving working memory and divided attention functioning. Recent neuroimaging studies provide evidence for anatomical co-localization of both functions. In the present study we used a functional intervention, whereby we applied a novel type of focalised, non-invasive brain stimulation, High-Definition transcranial Direct Current Stimulation (HD-tDCS), to the regions subserving these processes, the left intraparietal sulcus (IPS) and left dorsolateral prefrontal cortex (LDLPFC). Our aim was therefore to modulate activity in these regions using HD-tDCS and thereby assess their relevance for working memory, divided attention and their shared sub-processes.Method: 78 participants were evenly randomized to one of three conditions in a single blind, parallel group study design. Anodal or sham HD-tDCS was applied to either the left IPS or LDLPFC while participants completed a verbal working memory task, a divided attention task, and two tasks measuring subcomponents of working memory (updating and maintenance).Results: Focalised stimulation of the IPS and LDLPFC did not significantly modulate performance compared to sham stimulation. However, moderate effect sizes were obtained for at least one HD-tDCS condition relative to sham for all tasks, warranting further research into the functional importance of the IPS in subserving these abilities.Conclusions: The current results may be useful for informing future tDCS studies for modulating working memory and divided attention functioning

Behavioural and neurophysiological differences in working memory function of depressed patients and healthy controls

OBJECTIVE: Major depressive disorder (MDD) is associated with deficits in working memory. Several cognitive subprocesses interact to produce working memory, including attention, encoding, maintenance and manipulation. We sought to clarify the contribution of functional deficits in these subprocesses in MDD by varying cognitive load during a working memory task. METHODS: 41 depressed participants and 41 age and gender-matched healthy controls performed the n-back working memory task at three levels of difficulty (0-, 1-, and 2-back) in a pregistered study. We assessed response times, accuracy, and event-related electroencephalography (EEG), including P2 and P3 amplitudes, and frontal theta power (4-8 Hz). RESULTS: MDD participants had prolonged response times and more positive frontal P3 amplitudes (i.e., Fz) relative to controls, mainly in the most difficult 2-back condition. Working memory accuracy, P2 amplitudes and frontal theta event-related synchronisation did not differ between groups at any level of task difficulty. CONCLUSIONS: Depression is associated with generalized psychomotor slowing of working memory processes, and may involve compensatory hyperactivity in frontal and parietal regions. SIGNIFICANCE: These findings provide insights into MDD working memory deficits, indicating that depressed individuals dedicate greater levels of cortical processing and cognitive resources to achieve comparable working memory performance to controls

TMS-EEG Collaboration

The TMS-EEG Collaboration (TEC) seeks to address the challenges identified in the field of concurrent TMS and EEG research and drive multi-site collaborative efforts to improve our understanding of the brain

Master sheet V7.xlsx.gsheet

Database containing all studies using repeated sessions of tDCS spaced at least a day apar

Developing transcranial direct current stimulation as a neuromodulatory tool: critical considerations on dose, prefrontal stimulation, and safety

Transcranial direct current stimulation (tDCS) is a mild form of non-invasive brain stimulation, which involves the use of a weak electric current passed between electrodes placed on the scalp to modulate brain activity. It is an emerging technique that shows promise for the treatment of a variety of neuropsychiatric disorders, including depression. However, several critical gaps in knowledge remain, including the safety of repeated sessions of tDCS delivered over a course of treatment, optimal parameters of use, and identification of simple physiological markers of response to stimulation. The overarching aim of this thesis is to address these gaps and aid in the development of tDCS as a neuromodulatory tool and clinical intervention. This was addressed through studies in healthy participants and through a systematic review and meta-analysis of the existing tDCS safety literature.Study 1 examined whether repeated sessions of tDCS increase the likelihood of adverse events using a meta-analytic approach. Results from this study suggest that repeated sessions do not increase risk of side effects, lending further support in favour of the safety profile of tDCS. Study 2 assessed the dose-response curve of tDCS in healthy participants for enhancement of working memory. Findings suggest that none of the current intensities examined significantly improved cognitive performance. However, neurophysiological outcome measures revealed significant effects of stimulation, with the largest effect size obtained using 1mA stimulation intensity.Study 3 explored the use of a physiological biomarker of autonomic activity, heart rate variability, to objectively measure the neuromodulatory effects of tDCS on cortical activity following a single session of prefrontal stimulation. Results showed that parasympathetic activity increased during and immediately following tDCS, providing evidence that prefrontal cortex functioning is indeed modulated by tDCS, and can be assessed using a simple measure collected from heart rate data. In summary, the studies presented in this thesis contribute to the growing development of tDCS as a neuromodulatory and clinical tool

Transcranial Direct Current Stimulation Modulates Working Memory Maintenance Processes in Healthy Individuals

BACKGROUND: The effects of transcranial direct current stimulation (tDCS) at the pFC are often investigated using cognitive paradigms, particularly working memory tasks. However, the neural basis for the neuromodulatory cognitive effects of tDCS, including which subprocesses are affected by stimulation, is not completely understood. AIMS: We investigated the effects of tDCS on working memory task-related spectral activity during and after tDCS to gain better insights into the neurophysiological changes associated with stimulation. METHODS: We reanalyzed data from 100 healthy participants grouped by allocation to receive either sham (0 mA, 0.016 mA, and 0.034 mA) or active (1 mA or 2 mA) stimulation during a 3-back task. EEG data were used to analyze event-related spectral power in frequency bands associated with working memory performance. RESULTS: Frontal theta event-related synchronization (ERS) was significantly reduced post-tDCS in the active group. Participants receiving active tDCS had slower RTs following tDCS compared with sham, suggesting interference with practice effects associated with task repetition. Theta ERS was not significantly correlated with RTs or accuracy. CONCLUSIONS: tDCS reduced frontal theta ERS poststimulation, suggesting a selective disruption to working memory cognitive control and maintenance processes. These findings suggest that tDCS selectively affects specific subprocesses during working memory, which may explain heterogenous behavioral effects

Combined effect of prefrontal transcranial direct current stimulation and a working memory task on heart rate variability.

Prefrontal cortex activity has been associated with changes to heart rate variability (HRV) via mediation of the cortico-subcortical pathways that regulate the parasympathetic and sympathetic branches of the autonomic nervous system. Changes in HRV due to altered prefrontal cortex functioning can be predicted using the neurovisceral integration model, which suggests that prefrontal hyperactivity increases parasympathetic tone and decreases contributions from the sympathetic nervous system. Working memory (WM) tasks and transcranial direct current stimulation (tDCS) have been used independently to modulate brain activity demonstrating changes to HRV in agreement with the model. We investigated the combined effects of prefrontal tDCS and a WM task on HRV. Bifrontal tDCS was administered for 15 minutes at 2mA to 20 participants in a sham controlled, single-blind study using parallel groups. A WM task was completed by participants at three time points; pre-, during-, and post-tDCS, with resting state data collected at similar times. Frequency-domain HRV was computed for high frequency (HF; 0.15-0.4Hz) and low frequency (LF; 0.04-0.15Hz) power reflecting parasympathetic and sympathetic branch activity, respectively. Response time on the WM task, but not accuracy, improved from baseline to during-tDCS and post-tDCS with sham, but not active, stimulation. HF-HRV was significantly increased in the active tDCS group compared to sham, lasting beyond cessation of stimulation. Additionally, HF-HRV showed a task-related reduction in power during performance on the WM task. Changes in LF-HRV were moderately inversely correlated (r > 0.4) with changes in WM accuracy during and following tDCS compared to baseline levels. Stimulation of the prefrontal cortex resulted in changes to the parasympathetic branch of the nervous system in agreement with a linearly additive interpretation of effects. Sympathetic activity was not directly altered by tDCS, but was correlated with changes in WM performance. This suggests that the parasympathetic and sympathetic branches respond differentially due to similar, but distinct neural pathways. Given the ease of HRV data collection, studies of prefrontal tDCS would benefit from collection of this data as it provides unique insight into tDCS effects resulting from propagation through brain networks