Treatment of depression with transcranial direct current stimulation (tDCS): A Review

Major Depression Disorder (MDD) is usually accompanied by alterations of cortical activity and excitability, especially in prefrontal areas. These are reflections of a dysfunction in a distributed cortico-subcortical, bihemispheric network. Therefore it is reasonable to hypothesize that altering this pathological state with techniques of brain stimulation may offer a therapeutic target. Besides repetitive transcranial magnetic stimulation, tonic stimulation with weak direct currents (tDCS) modulates cortical excitability for hours after the end of stimulation, thus, it is a promising non-invasive therapeutic option. Early studies from the 1960s suggested some efficacy of DC stimulation to reduce symptoms in depression, but mixed results and development of psychotropic drugs resulted in an early abandonment of this technique. In the last years tDCS protocols have been optimized. Application of the newly developed stimulation protocols in patients with major depression has shown promise in few pilot studies. Further studies are needed to identify the optimal parameters of stimulation and the clinical and patient characteristics that may condition response to tDCS.     

Limited impact of homeostatic plasticity on motor learning in humans

Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a de-stabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e. high previous activity enhances the threshold for synaptic strengthening and vice versa. However, the relevance of metaplasticity for actual learning processes has not been tested so far. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, and a reaction time task (RTT) by transcranial direct current stimulation (tDCS). If homeostatic rules apply, excitability-diminishing cathodal tDCS should improve subsequent motor learning, especially if combined with the partial NMDA receptor-agonist d-cycloserine, which selectively enhances efficacy of active receptors, while excitability-enhancing anodal tDCS should reduce it. Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has a limited influence on implicit sequential motor learning.     

Effects of Different Electrical Brain Stimulation Protocols on Subcomponents of Motor Skill Learning

BackgroundNoninvasive electrical brain stimulation (NEBS) with transcranial direct current (tDCS) or random noise stimulation (tRNS) applied to the primary motor cortex (M1) can augment motor learning.ObjectiveWe tested whether different types of stimulation alter particular aspects of learning a tracing task over three consecutive days, namely skill acquisition (online/within session effects) or consolidation (offline/between session effects).MethodsMotor training on a tracing task over three consecutive days was combined with different types and montages of stimulation (tDCS, tRNS).ResultsUnilateral M1 stimulation using tRNS as well as unilateral and bilateral M1 tDCS all enhanced motor skill learning compared to sham stimulation. In all groups, this appeared to be driven by online effects without an additional offline effect. Unilateral tDCS resulted in large skill gains immediately following the onset of stimulation, while tRNS exerted more gradual effects. Control stimulation of the right temporal lobe did not enhance skill learning relative to sham.ConclusionsThe mechanisms of action of tDCS and tRNS are likely different. Hence, the time course of skill improvement within sessions could point to specific and temporally distinct interactions with the physiological process of motor skill learning. Exploring the parameters of NEBS on different tasks and in patients with brain injury will allow us to maximize the benefits of NEBS for neurorehabilitation.     

Transcranial direct current stimulation of prefrontal cortex: An auditory event-related potential study in schizophrenia

Cognitive impairment is one of the most significant factors determining the long-term rehabilitation prospects of schizophrenia patients. Cognitive training has been shown to be beneficial; however, effect sizes of cognitive remediation remain relatively low. Anodal transcranial direct current stimulation (tDCS) increases cortical excitability along with larger N1 auditory event-related potentials (ERPs), thus providing a non-invasive physiological mechanism that is potentially capable of facilitating cognitive training of schizophrenia patients. The current study investigated the effects of left-prefrontal anodal tDCS on auditory discrimination performance and N1, Mismatch Negativity (MMN), and P3b ERPs, which have been linked to cognitive and global function deficits in schizophrenia. We compared 20 min of 2 mA tDCS versus sham stimulation in 14 schizophrenia patients by employing a randomised crossover design. Patients performed equally well in a go/no-go auditory discrimination task when compared to healthy subjects but presented with significantly smaller N1, MMN and P3b amplitudes, which did not change with tDCS. Auditory discrimination performance and reaction times also remained unaffected by tDCS. Our findings suggest that a single application of tDCS has no acute effects on ERPs and associated auditory information processing in schizophrenia patients.     

Cognitive processes in the development of TOL performance

Components of executive function continue to develop through adolescence. There is limited knowledge of how these cognitive components impact complex cognitive function requiring their integration. This study examines the development of response planning, a complex cognitive function, and the contributions of selected cognitive processes, including speed of processing, response inhibition, and working memory to its development. We tested 100 healthy 8-30 year old individuals with a computerized version to the Tower of London (TOL) task and cognitive oculomotor tests including the visually guided saccade, oculomotor delayed response, and antisaccade tasks. Speed of processing, response inhibition, working memory, and TOL performance all demonstrated maturation in adolescence. While all processes were correlated with the development of TOL performance, antisaccade performance showed the strongest association indicating an important role for response inhibition in planning. These results indicate that the development of converging cognitive processes in adolescence, including response inhibition and working memory, support response planning and may serve as a model for the development of performance in other complex problem solving tasks.     

Mitigating Cutaneous Sensation Differences During tDCS: Comparing Sham Versus Low Intensity Control Conditions

BackgroundCutaneous sensations at electrode sites during the administration of direct current brain stimulation may inadvertently influence participants' subjective experience and task performance.ObjectiveThe present study evaluated the utility of a methodological variation that substitutes sham administration with very low intensity (0.5 mA) current delivery.MethodsWe used a 4 × 1 high-definition ring electrode transcranial direct current (HD-tDCS) system to target the left dorsolateral prefrontal cortex (Brodmann's Area 9). Four stimulation conditions were compared in a repeated-measures design: sham 2.0 mA and 0.5 mA intensity, versus active 2.0 mA and 0.5 mA intensity. During stimulation participants performed a cognitive interference task that activates the cingulo-frontal-parietal network, and periodically provided perceived sensation ratings.ResultsWe demonstrate that a relatively low intensity control condition attenuates otherwise large differences in perceived sensation between active and sham conditions. Critically, behavioral task differences maintained between the two active conditions.ConclusionA low intensity control stimulation condition may prove a viable methodological alternative to conventional sham techniques used in repeated-measures designs, though important limitations are discussed.     

Targeting repetitive transcranial magnetic stimulation in depression: do we really know what we are stimulating and how best to do it?

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an established treatment for patients with depression who have not achieved optimal outcomes with one or more trials of antidepressant medication. It is an effective antidepressant treatment but there remains considerable scope for improving clinical outcomes. One method to potentially enhance the efficacy of rTMS is through the improvement of methods of stimulation localization.ObjectiveThe purpose of this paper is to review the literature pertaining to rTMS localization methods and approaches relevant to the treatment of major depressive disorder (MDD) and provide specific opinions on the state of the art in regards to targeting of rTMS treatment in depression.MethodsA targeted review of the literature on rTMS targeting in depression.ResultsThere is emerging evidence that optimal rTMS treatment outcomes are likely to be achieved with stimulation at a relatively anterior stimulation site in the left dorsolateral prefrontal cortex (DLPFC). However, some lines of research suggest that there may be two effective stimulation sites: one quite posterior, and one more anterior, in the DLPFC. The ‘Beam F3’ method provides reasonable localization to the anterior stimulation site and the posterior stimulation site corresponds to that typically used in studies using the ‘5 cm method’. Neuro-navigational methods are generally most likely to consistently ensure placement of the TMS coil such that it results in stimulation of a selected cortical site. fMRI – connectivity based approaches to targeting specific circuits in the DLPFC are intellectually attractive but it may not be possible to demonstrate differential effectiveness of these over the methods most commonly been used in clinical practice.ConclusionsThere is an emerging literature helping to improve our understanding of the optimal methods for targeting rTMS treatment for depression. However, we lack substantive prospective clinical trials demonstrating improved clinical outcomes with these techniques.     

Bilateral decrease in ventrolateral prefrontal cortex activation during motor response inhibition in mania

Mania has been frequently associated with impaired inhibitory control. The present study aimed to identify brain functional abnormalities specifically related to motor response inhibition in mania by using event-related fMRI in combination with a Go/NoGo task designed to control for extraneous cognitive processes involved in task performance. Sixteen manic patients and 16 healthy subjects, group-matched for age and sex, were imaged while performing a warned equiprobable Go/NoGo task during event-related fMRI. Between-group differences in brain activation associated with motor response inhibition were assessed using analyses of covariance. Although no significant between-group differences in task performance accuracy were observed, patients showed significantly longer response times on Go trials. After controlling for covariates, the only brain region that differentiated the two groups during motor response inhibition was the ventrolateral prefrontal cortex (VLPFC), where activation was significantly decreased in both the right and left hemispheres in manic patients. Our data suggest that response inhibition in mania is associated with a lack of engagement of the bilateral VLPFC, which is known to play a primary role in the suppression of irrelevant responses. This result might give clues to understanding the pathophysiology of dishinhibition and impulsivity that characterize mania.     

A study of the effectiveness of high-frequency left prefrontal cortex transcranial magnetic stimulation in major depression in patients who have not responded to right-sided stimulation

The objective of this study was to explore the response rate to high-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) in patients who had failed to respond to right-sided low-frequency stimulation, and to investigate whether there was differential efficacy between stimulation at 5 or 10 Hz. Data from two randomized controlled trials were pooled. In both studies a group of patients were randomized to receive either 5- or 10-Hz left prefrontal rTMS after failing to respond to right-sided stimulation. These patients received blinded 5- or 10-Hz stimulation (but without a sham control) for a period of up to 4 weeks and outcomes were compared. There was a small but significant overall response to left-sided rTMS but no difference in response between the 5- and 10-Hz treatment conditions. There appears to be a significant but modest likelihood of response to left-sided TMS in patients who fail right-sided stimulation, but there is no difference in efficacy between 5- and 10-Hz stimulation.     

Evidence for a Role of the Right Dorsolateral Prefrontal Cortex in Controlling Stimulus-response Integration: A Transcranial Direct Current Stimulation (tDCS) Study

BackgroundActing coherently upon stimuli requires some kind of integration of stimulus and response features across various distinct cortical feature maps (one aspect of the binding problem). Although the process of feature binding proper seems rather automatic, recent studies revealed that the management of stimulus-response bindings is less efficient in populations with impaired cognitive-control processes.ObjectiveHere, we investigated whether the cognitive control of stimulus-response feature bindings (“event files”) in healthy participants is affected by non-invasive brain stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC)—a main component of the cognitive-control network.MethodIn different sessions, participants received anodal, cathodal, or sham tDCS (2 mA, 20 min) while performing an audio-visual event-file task assessing the creation and retrieval of stimulus–stimulus and stimulus-response feature bindings. The general findings from this task indicate that performance suffers when some, but not all of the features are repeated (the so-called partial repetition cost).ResultsStimulation over the right, but not the left DLPFC reduced control of stimulus-response bindings and produced outcome patterns similar to those previously observed in autistic children, people with lower fluid intelligence, and older adults.ConclusionsThis finding provides empirical support for a role of the right DLPFC in feature-binding management, which might consist in preventing the stimulus-induced activation of previously created, but now task-irrelevant, episodic bindings. From a methodological perspective, the finding may suggest that tDCS could be used as a temporary, reversible “brain lesion” generator in healthy subjects, enabling experimental investigation of how the brain works.     

Prefrontal hypoactivation during cognitive control in early abstinent methamphetamine-dependent subjects

Individuals who abuse methamphetamine (MA) perform at levels below those of healthy controls on tests that require cognitive control. As cognitive control deficits may influence the success of treatment for addiction, we sought to help clarify the neural correlates of this deficit. MA-dependent (n = 10, abstinent 4–7 days) and control subjects (n = 18) performed a color-word Stroop task, which requires cognitive control, during functional MRI (fMRI). The task included a condition in which participants were required to respond to one stimulus dimension while ignoring another conflicting dimension, and another condition without conflict. We compared the groups on performance and neural activation in the two conditions. MA-dependent subjects made more errors and responded more slowly than controls. Controlling for response times in the incongruent condition, voxel-wise mixed effects analyses (whole-brain corrected) demonstrated that MA-dependent subjects had less activation than control subjects in the right inferior frontal gyrus, supplementary motor cortex/anterior cingulate gyrus and the anterior insular cortex during the incongruent condition only. MA-dependent subjects did not exhibit greater activation in any brain region in either of the Stroop conditions. These preliminary findings suggest that hypofunction in cortical areas that are important for executive function underlies cognitive control deficits associated with MA dependence.