Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the prefrontal cortex (PFC) has been widely applied in cognitive neurosciences and advocated as a therapeutic intervention, e.g. in major depressive disorder. Although several targets and protocols have been suggested, comparative studies of tDCS parameters, particularly electrode montages and their cortical targets, are still lacking. OBJECTIVE: This study investigated a priori hypotheses on specific effects of prefrontal-tDCS montages by using multimodal functional magnetic resonance imaging (fMRI) in healthy participants. METHODS: 28 healthy male participants underwent three common active-tDCS montages and sham tDCS in a pseudo-randomized order, comprising a total of 112 tDCS-fMRI sessions. Active tDCS was applied at 2 mA for 20 min. Before and after tDCS, a resting-state fMRI (RS fMRI) was recorded, followed by a task fMRI with a delayed-response working-memory (DWM) task for assessing cognitive control over emotionally negative or neutral distractors. RESULTS: After tDCS with a cathode-F3/anode-F4 montage, RS-fMRI connectivity decreased in a medial part of the left PFC. Also, after the same stimulation condition, regional brain activity during DWM retrieval decreased more in this area after negative than after neutral distraction, and responses to the DWM task were faster, independent of distractor type. CONCLUSION: The current study does not confirm our a priori hypotheses on direction and localization of polarity-dependent tDCS effects using common bipolar electrode montages over PFC regions, but it provides evidence for montage-specific effects on multimodal neurophysiological and behavioral outcome measures. Systematic research on the actual targets and the respective dose-response relationships of prefrontal tDCS is warranted.

Home Use, Remotely Supervised, and Remotely Controlled Transcranial Direct Current Stimulation: A Systematic Review of the Available Evidence.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is gaining growing importance in the treatment of neurological and psychiatric disorders and is currently investigated for home-based and remotely supervised applications. METHODS: Here, we systematically review the available evidence from a database search (PubMed, ICTRP, clinicaltrials.gov) from January 2000 to May 2017. RESULTS: We detected 22 original research papers, trial protocols or trial registrations dealing with tDCS as an add-on intervention to cognitive or physiotherapeutic intervention. Overall, study samples are small; many studies are single-blinded and focus on feasibility and safety. There are two guideline papers setting basic requirements for clinical trials. CONCLUSIONS: Further research needs to focus on home-based treatment from different viewpoints, that is, safety, technical monitoring, reproducibility of repeated applications, feasibility of combined interventions and systematic assessment of efficacy, and safety in large randomized controlled clinical trials (RCTs). However, remotely controlled and supervised tDCS for home use represents a promising approach for widespread use of noninvasive brain stimulation (NIBS) in clinical care.

Test-retest reliability of prefrontal transcranial Direct Current Stimulation (tDCS) effects on functional MRI connectivity in healthy subjects.

Transcranial Direct Current Stimulation (tDCS) of the prefrontal cortex (PFC) can be used for probing functional brain connectivity and meets general interest as novel therapeutic intervention in psychiatric and neurological disorders. Along with a more extensive use, it is important to understand the interplay between neural systems and stimulation protocols requiring basic methodological work. Here, we examined the test-retest (TRT) characteristics of tDCS-induced modulations in resting-state functional-connectivity MRI (RS fcMRI). Twenty healthy subjects received 20minutes of either active or sham tDCS of the dorsolateral PFC (2mA, anode over F3 and cathode over F4, international 10-20 system), preceded and ensued by a RS fcMRI (10minutes each). All subject underwent three tDCS sessions with one-week intervals in between. Effects of tDCS on RS fcMRI were determined at an individual as well as at a group level using both ROI-based and independent-component analyses (ICA). To evaluate the TRT reliability of individual active-tDCS and sham effects on RS fcMRI, voxel-wise intra-class correlation coefficients (ICC) of post-tDCS maps between testing sessions were calculated. For both approaches, results revealed low reliability of RS fcMRI after active tDCS (ICC(2,1) = -0.09 - 0.16). Reliability of RS fcMRI (baselines only) was low to moderate for ROI-derived (ICC(2,1) = 0.13 - 0.50) and low for ICA-derived connectivity (ICC(2,1) = 0.19 - 0.34). Thus, for ROI-based analyses, the distribution of voxel-wise ICC was shifted to lower TRT reliability after active, but not after sham tDCS, for which the distribution was similar to baseline. The intra-individual variation observed here resembles variability of tDCS effects in motor regions and may be one reason why in this study robust tDCS effects at a group level were missing. The data can be used for appropriately designing large scale studies investigating methodological issues such as sources of variability and localisation of tDCS effects.

Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects?

Transcranial current stimulation approaches include neurophysiologically distinct non-invasive brain stimulation techniques widely applied in basic, translational and clinical research: transcranial direct current stimulation (tDCS), oscillating transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). Prefrontal tDCS seems to be an especially promising tool for clinical practice. In order to effectively modulate relevant neural circuits, systematic research on prefrontal tDCS is needed that uses neuroimaging and neurophysiology measures to specifically target and adjust this method to physiological requirements. This review therefore analyses the various neuroimaging methods used in combination with prefrontal tDCS in healthy and psychiatric populations. First, we provide a systematic overview on applications, computational models and studies combining neuroimaging or neurophysiological measures with tDCS. Second, we categorise these studies in terms of their experimental designs and show that many studies do not vary the experimental conditions to the extent required to demonstrate specific relations between tDCS and its behavioural or neurophysiological effects. Finally, to support best-practice tDCS research we provide a methodological framework for orientation among experimental designs.

Autonomic cardiovascular regulation and cortical tone.

This study aimed to investigate interactions between tonic cortical arousal and features of autonomic cardiovascular regulation. In 50 healthy subjects, the power spectrum of the spontaneous EEG was obtained at resting state. Concurrently, respiratory sinus arrhythmia (RSA), baroreflex sensitivity (BRS) and R-wave to pulse interval (RPI) were recorded as indices of cardiovascular control. At the bivariate level, only a negative correlation between beta power recorded at frontal electrode positions and RPI was found. However, when common variance of BRS and RSA was controlled for in multiple regression analyses, a positive association between alpha power and RSA, and an inverse relationship with BRS, also arose. The findings concerning RPI and RSA are suggestive of a relationship between higher levels of cortical tone and increased sympathetic and reduced vagal cardiac influences. The inverse association between BRS and alpha activity may reflect bottom-up modulation of cortical arousal by baroreceptor afferents.

Interactions between autonomic cardiovascular regulation and cortical activity: a CNV study.

The study investigated interactions between autonomic cardiovascular regulation and cortical activity. In 54 healthy subjects, baroreflex sensitivity (BRS) and respiratory sinus arrhythmia (RSA) were assessed at resting conditions. As an EEG indicator of cortical excitability, the contingent negative variation (CNV) was induced using a constant foreperiod reaction time task. At bivariate level, only RSA showed a moderate positive correlation with the CNV recorded at frontal electrodes. However, when common variance of BRS and RSA was controlled for in multiple regression analysis, an inverse association between BRS and the frontal CNV also arose. The inverse association between BRS and the CNV is discussed as reflecting bottom-up modulation of cortical excitability by baroreceptor afferents. The positive correlation between RSA and the CNV may relate to the interplay between prefrontal processing and cardiac vagal tone.