A pinboard by
Aron Hill

PhD Student, Monash University


Impairments in cognition such as attention, memory and problem solving, frequently accompany a range of psychiatric and neurological disorders and have been strongly linked to dysfunctional activity within a number of brain networks. Often, the degree of cognitive dysfunction in these disorders is severe, leading to significant functional disability and remaining largely unresponsive to conventional drug-based therapies.

Transcranial direct current stimulation (tDCS) is a safe, painless and non-invasive technique in which weak electric currents are passed into the brain via electrodes placed on the scalp. Current evidence indicates a capacity for tDCS to transiently enhance cognitive function through alterations in cortical plasticity – the brain’s ability to respond and adapt to change. Nevertheless, a clear understanding of the specific biological alterations that take place in the brain following tDCS still remains elusive. Therefore, my research aims to to utilise a novel neuroimaging approach combining electroencephalography (EEG) – a measure of a person’s brain waves, with transcranial magnetic stimulation (TMS), a technique for activating cells in certain regions of the brain, to explore the specific neurobiological changes that transpire following tDCS applied over brain regions important for cognition.

Through a series of three independent studies, I was able to use co-registered TMS-EEG to record and quantify the brain’s responses to tDCS applied over two separate regions essential for cognition – the prefrontal cortex and parietal cortex. Overall, tDCS was seen to induced robust plasticity-related changes within the brain, which continued for up to 30 minutes after the end of the stimulation period.

These initial findings provide some of the first evidence that tDCS can induce ongoing plasticity-related changes in brain activity across regions important for cognition. These findings have important implications both for understanding how the brain respondes to electrical stimulation, as well as for developing more efficacious future stimulation protocols aimed at enhancing cognitive function.


Cognitive Training and Noninvasive Brain Stimulation for Cognition in Parkinson's Disease: A Meta-analysis.

Abstract: Many people with Parkinson's disease (PD) experience cognitive decline. It is not known whether cognitive training or noninvasive brain stimulation are effective at alleviating cognitive deficits in PD.To examine cognitive training and non-invasive brain stimulation interventions for cognition in PD.An extensive search was conducted of published and unpublished studies in online databases. Studies were selected if they were controlled trials examining standard (not individualized) or tailored (individualized) cognitive training, repetitive transcranial magnetic stimulation (rTMS), or transcranial direct current stimulation (tDCS) in PD, with outcomes measured by standardized neuropsychological tests.Fourteen controlled trials met inclusion criteria. For executive function, the pooled effect size (Hedges' g) for cognitive training (standard and tailored combined) was small ( g = 0.42) but statistically significant (95% CI 0.15-0.68). The pooled effect for standard cognitive training (alone) was medium ( g = 0.51) and significant (95% CI 0.16-0.85). For attention/working memory, small pooled effect sizes were found when combining standard and tailored cognitive training ( g = 0.23; 95% CI 0.02-0.44) and for standard cognitive training alone ( g = 0.29; 95% CI 0.04-0.53), both significant. For memory, small but significant pooled effect sizes were also found when combining standard and tailored cognitive training and for standard cognitive training alone.The results suggest that standard and tailored cognitive training may improve executive function, attention/working memory, and memory in PD. Future studies must adopt randomized controlled trial designs to explore the therapeutic potential of these interventions.

Pub.: 07 Jun '17, Pinned: 12 Aug '17

Transcranial direct current stimulation can enhance working memory in Huntington's disease.

Abstract: Transcranial direct current stimulation (tDCS) combined with a cognitive task can enhance targeted aspects of cognitive functioning in clinical populations. The movement disorder Huntington's disease (HD) is associated with progressive cognitive impairment. Deficits in working memory (WM) can be apparent early in the disease and impact functional capacity. We investigated whether tDCS combined with cognitive training could improve WM in patients with HD, and if baseline clinical or cognitive measures may predict efficacy. Twenty participants with HD completed this crossover trial, undergoing 1.5mA anodal tDCS over left dorsolateral prefrontal cortex and sham stimulation on separate visits. Participants and assessor were blinded to condition order, which was randomised across participants. All participants completed baseline clinical and cognitive assessments. Pre- and post-stimulation tasks included digit reordering, computerised n-back tests and a Stroop task. During 15min of tDCS/sham stimulation, participants practiced 1- and 2-back WM tasks. Participants exhibited an increase in WM span on the digit re-ordering span task from pre- to post-stimulation after tDCS, but not after sham stimulation. Gains in WM were positively related to motor symptom ratings and negatively associated with verbal fluency scores. Patients with more severe motor symptoms showed greatest improvement, suggesting that motor symptom ratings may help identify patients who are most likely to benefit from tDCS.Dorsolateral prefrontal tDCS appears well tolerated in HD and enhances WM span compared to sham stimulation. Our findings strongly encourage further investigation of the extent to which tDCS combined with cognitive training could enhance everyday function in HD. ClinicalTrials.gov; NCT02216474 Brain stimulation in Movement Disorders; https://clinicaltrials.gov/ct2/show/NCT02216474.

Pub.: 10 Apr '17, Pinned: 12 Aug '17

Frontoparietal neurostimulation modulates working memory training benefits and oscillatory synchronization.

Abstract: There is considerable interest in maintaining working memory (WM) because it is essential to accomplish most cognitive tasks, and it is correlated with fluid intelligence and ecologically valid measures of daily living. Toward this end, WM training protocols aim to improve WM capacity and extend improvements to unpracticed domains, yet success is limited. One emerging approach is to couple WM training with transcranial direct current stimulation (tDCS). This pairing of WM training with tDCS in longitudinal designs promotes behavioral improvement and evidence of transfer of performance gains to untrained WM tasks. However, the mechanism(s) underlying tDCS-linked training benefits remain unclear. Our goal was to gain purchase on this question by recording high-density EEG before and after a weeklong WM training + tDCS study. Participants completed four sessions of frontoparietal tDCS (active anodal or sham) during which they performed a visuospatial WM change detection task. Participants who received active anodal tDCS demonstrated significant improvement on the WM task, unlike those who received sham stimulation. Importantly, this pattern was mirrored by neural correlates in spectral and phase synchrony analyses of the HD-EEG data. Notably, the behavioral interaction was echoed by interactions in frontal-posterior alpha band power, and theta and low alpha oscillations. These findings indicate that one mechanism by which paired tDCS + WM training operates is to enhance cortical efficiency and connectivity in task-relevant networks.

Pub.: 16 May '17, Pinned: 12 Aug '17

Low-Intensity Transcranial Current Stimulation in Psychiatry.

Abstract: Neurostimulation is rapidly emerging as an important treatment modality for psychiatric disorders. One of the fastest-growing and least-regulated approaches to noninvasive therapeutic stimulation involves the application of weak electrical currents. Widespread enthusiasm for low-intensity transcranial electrical current stimulation (tCS) is reflected by the recent surge in direct-to-consumer device marketing, do-it-yourself enthusiasm, and an escalating number of clinical trials. In the wake of this rapid growth, clinicians may lack sufficient information about tCS to inform their clinical practices. Interpretation of tCS clinical trial data is aided by familiarity with basic neurophysiological principles, potential mechanisms of action of tCS, and the complicated regulatory history governing tCS devices. A growing literature includes randomized controlled trials of tCS for major depression, schizophrenia, cognitive disorders, and substance use disorders. The relative ease of use and abundant access to tCS may represent a broad-reaching and important advance for future mental health care. Evidence supports application of one type of tCS, transcranial direct current stimulation (tDCS), for major depression. However, tDCS devices do not have regulatory approval for treating medical disorders, evidence is largely inconclusive for other therapeutic areas, and their use is associated with some physical and psychiatric risks. One unexpected finding to arise from this review is that the use of cranial electrotherapy stimulation devices-the only category of tCS devices cleared for use in psychiatric disorders-is supported by low-quality evidence.

Pub.: 25 Feb '17, Pinned: 12 Aug '17

Working Memory Capacity Differentially Influences Responses to tDCS and HD-tDCS in a Retro-Cue task

Abstract: There is growing interest in non-invasive brain stimulation techniques. A drawback is that the relationship between stimulation and cognitive outcomes for various tasks are unknown. Transcranial direct current stimulation (tDCS) provides diffuse current spread, whereas high-definition tDCS (HD-tDCS) provides more targeted current. The direction of behavioral effects after tDCS can be difficult to predict in cognitive realms such as attention and working memory (WM). Previously, we showed that in low and high WM capacity groups tDCS modulates performance in nearly equal and opposite directions on a change detection task, with improvement for the high capacity participants alone. Here, we used the retro-cue paradigm to test attentional shifting among items in WM to investigate whether WM capacity (WMC) predicted different behavioral consequences during anodal tDCS or HD-tDCS to posterior parietal cortex (PPC). In two experiments, with 24 participants each, we used different stimulus categories (colored circles, letters) and stimulation sites (right, left PPC). The results showed a significant (Experiment 1) or trending (Experiment 2) WMC x stimulation interaction. Compared to tDCS, after HD-tDCS the retro-cueing benefit was significantly greater for the low WMC group but numerically worse for the high WMC group. These data highlight the importance of considering group differences when using non-invasive neurostimulation techniques.

Pub.: 28 Jun '16, Pinned: 12 Aug '17

ncesEnhanced Working Memory Performance via Transcranial Direct Current Stimulation: The Possibility of Near and Far Transfer

Abstract: Although working memory (WM) training programs consistently result in improvement on the trained task, benefit is typically short-lived and extends only to tasks very similar to the trained task (i.e., near transfer). It is possible that pairing repeated performance of a WM task with brain stimulation encourages plasticity in brain networks involved in WM task performance, thereby improving the training benefit. In the current study, transcranial direct current stimulation (tDCS) was paired with performance of a WM task (n-back). In Experiment 1, participants performed a spatial location-monitoring n-back during stimulation, while Experiment 2 used a verbal identity-monitoring n-back. In each experiment, participants received either active (2.0 mA) or sham (0.1 mA) stimulation with the anode placed over either the right or the left dorsolateral prefrontal cortex (DLPFC) and the cathode placed extracephalically. In Experiment 1, only participants receiving active stimulation with the anode placed over the right DLPFC showed marginal improvement on the trained spatial n-back, which did not extend to a near transfer (verbal n-back) or far transfer task (a matrix-reasoning task designed to measure fluid intelligence). In Experiment 2, both left and right anode placements led to improvement, and right DLPFC stimulation resulted in numerical (though not sham-adjusted) improvement on the near transfer (spatial n-back) and far transfer (fluid intelligence) task. Results suggest that WM training paired with brain stimulation may result in cognitive enhancement that transfers to performance on other tasks, depending on the combination of training task and tDCS parameters used.

Pub.: 15 Oct '16, Pinned: 12 Aug '17

Boosting Cognition: Effects of Multiple Session Transcranial Direct Current Stimulation on Working Memory.

Abstract: Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent studies combining multiple sessions of anodal tDCS over lDLPFC with verbal WM training did not observe additional benefits of tDCS in subsequent stimulation sessions nor transfer of benefits to novel WM tasks posttraining. Using an enhanced stimulation protocol as well as a design that included a baseline measure each day, the current study aimed to further investigate the effects of multiple sessions of tDCS on WM. Specifically, we investigated the effects of three subsequent days of stimulation with anodal (20 min, 1 mA) versus sham tDCS (1 min, 1 mA) over lDLPFC (with a right supraorbital reference) paired with a challenging verbal WM task. WM performance was measured with a verbal WM updating task (the letter n-back) in the stimulation sessions and several WM transfer tasks (different letter set n-back, spatial n-back, operation span) before and 2 days after stimulation. Anodal tDCS over lDLPFC enhanced WM performance in the first stimulation session, an effect that remained visible 24 hr later. However, no further gains of anodal tDCS were observed in the second and third stimulation sessions, nor did benefits transfer to other WM tasks at the group level. Yet, interestingly, post hoc individual difference analyses revealed that in the anodal stimulation group the extent of change in WM performance on the first day of stimulation predicted pre to post changes on both the verbal and the spatial transfer task. Notably, this relationship was not observed in the sham group. Performance of two individuals worsened during anodal stimulation and on the transfer tasks. Together, these findings suggest that repeated anodal tDCS over lDLPFC combined with a challenging WM task may be an effective method to enhance domain-independent WM functioning in some individuals, but not others, or can even impair WM. They thus call for a thorough investigation into individual differences in tDCS respondence as well as further research into the design of multisession tDCS protocols that may be optimal for boosting cognition across a wide range of individuals.

Pub.: 30 Nov '16, Pinned: 12 Aug '17

Modulation of frontal effective connectivity during speech

Abstract: Noninvasive neurostimulation methods such as transcranial direct current stimulation (tDCS) can elicit long-lasting, polarity-dependent changes in neocortical excitability. In a previous concurrent tDCS-fMRI study of overt picture naming, we reported significant behavioural and regionally specific neural facilitation effects in left inferior frontal cortex (IFC) with anodal tDCS applied to left frontal cortex (Holland et al., 2011). Although distributed connectivity effects of anodal tDCS have been modelled at rest, the mechanism by which ‘on-line’ tDCS may modulate neuronal connectivity during a task-state remains unclear. Here, we used Dynamic Causal Modelling (DCM) to determine: (i) how neural connectivity within the frontal speech network is modulated during anodal tDCS; and, (ii) how individual variability in behavioural response to anodal tDCS relates to changes in effective connectivity strength. Results showed that compared to sham, anodal tDCS elicited stronger feedback from inferior frontal sulcus (IFS) to ventral premotor (VPM) accompanied by weaker self-connections within VPM, consistent with processes of neuronal adaptation. During anodal tDCS individual variability in the feedforward connection strength from IFS to VPM positively correlated with the degree of facilitation in naming behaviour. These results provide an essential step towards understanding the mechanism of ‘online’ tDCS paired with a cognitive task. They also identify left IFS as a ‘top-down’ hub and driver for speech change.

Pub.: 26 Jan '16, Pinned: 12 Aug '17

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

Abstract: To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation.

Pub.: 05 Jun '17, Pinned: 12 Aug '17

Analysing concurrent transcranial magnetic stimulation and electroencephalographic data: a review and introduction to the open-source TESA software

Abstract: The concurrent use of transcranial magnetic stimulation with electroencephalography (TMS–EEG) is growing in popularity as a method for assessing various cortical properties such as excitability, oscillations and connectivity. However, this combination of methods is technically challenging, resulting in artifacts both during recording and following typical EEG analysis methods, which can distort the underlying neural signal. In this article, we review the causes of artifacts in EEG recordings resulting from TMS, as well as artifacts introduced during analysis (e.g. as the result of filtering over high-frequency, large amplitude artifacts). We then discuss methods for removing artifacts, and ways of designing pipelines to minimise analysis-related artifacts. Finally, we introduce the TMS–EEG signal analyser (TESA), an open-source extension for EEGLAB, which includes functions that are specific for TMS–EEG analysis, such as removing and interpolating the TMS pulse artifact, removing and minimising TMS-evoked muscle activity, and analysing TMS-evoked potentials. The aims of TESA are to provide users with easy access to current TMS–EEG analysis methods and to encourage direct comparisons of these methods and pipelines. It is hoped that providing open-source functions will aid in both improving and standardising analysis across the field of TMS–EEG research.

Pub.: 20 Oct '16, Pinned: 12 Aug '17

Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis ☆

Abstract: Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity-dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCS-induced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p < 0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p < 0.05). Local graph measures showed a tDCS-induced polarity-specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner.

Pub.: 04 Jun '16, Pinned: 28 Jul '17

A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters.

Abstract: Research into the effects of transcranial direct current stimulation of the dorsolateral prefrontal cortex on cognitive functioning is increasing rapidly. However, methodological heterogeneity in prefrontal tDCS research is also increasing, particularly in technical stimulation parameters that might influence tDCS effects.To systematically examine the influence of technical stimulation parameters on DLPFC-tDCS effects.We performed a systematic review and meta-analysis of tDCS studies targeting the DLPFC published from the first data available to February 2016. Only single-session, sham-controlled, within-subject studies reporting the effects of tDCS on cognition in healthy controls and neuropsychiatric patients were included.Evaluation of 61 studies showed that after single-session a-tDCS, but not c-tDCS, participants responded faster and more accurately on cognitive tasks. Sub-analyses specified that following a-tDCS, healthy subjects responded faster, while neuropsychiatric patients responded more accurately. Importantly, different stimulation parameters affected a-tDCS effects, but not c-tDCS effects, on accuracy in healthy samples vs.increased current density and density charge resulted in improved accuracy in healthy samples, most prominently in females; for neuropsychiatric patients, task performance during a-tDCS resulted in stronger increases in accuracy rates compared to task performance following a-tDCS.Healthy participants respond faster, but not more accurate on cognitive tasks after a-tDCS. However, increasing the current density and/or charge might be able to enhance response accuracy, particularly in females. In contrast, online task performance leads to greater increases in response accuracy than offline task performance in neuropsychiatric patients. Possible implications and practical recommendations are discussed.

Pub.: 11 May '16, Pinned: 28 Jul '17

Transcranial direct current stimulation changes resting state functional connectivity: A large-scale brain network modeling study

Abstract: Transcranial direct current stimulation (tDCS) is a noninvasive technique for affecting brain dynamics with promising application in the clinical therapy of neurological and psychiatric disorders such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Resting state dynamics increasingly play a role in the assessment of connectivity-based pathologies such as Alzheimer's and schizophrenia. We systematically applied tDCS in a large-scale network model of 74 cerebral areas, investigating the spatiotemporal changes in dynamic states as a function of structural connectivity changes. Structural connectivity was defined by the human connectome. The main findings of this study are fourfold: Firstly, we found a tDCS-induced increase in functional connectivity among cerebral areas and among EEG sensors, where the latter reproduced empirical findings of other researchers. Secondly, the analysis of the network dynamics suggested synchronization to be the main mechanism of the observed effects. Thirdly, we found that tDCS sharpens and shifts the frequency distribution of scalp EEG sensors slightly towards higher frequencies. Fourthly, new dynamic states emerged through interacting areas in the network compared to the dynamics of an isolated area. The findings propose synchronization as a key mechanism underlying the changes in the spatiotemporal pattern formation due to tDCS. Our work supports the notion that noninvasive brain stimulation is able to bias brain dynamics by affecting the competitive interplay of functional subnetworks.

Pub.: 13 Feb '16, Pinned: 28 Jul '17

Transcranial direct current stimulation of superior medial frontal cortex disrupts response selection during proactive response inhibition

Abstract: Cognitive control is a vital executive process that is involved in selecting, generating, and maintaining appropriate, goal-directed behaviour. One operation that draws heavily on this resource is the mapping of sensory information to appropriate motor responses (i.e., response selection). Recently, a transcranial direct current stimulation (tDCS) study demonstrated that the left posterior lateral prefrontal cortex (pLPFC) is casually involved in response selection and response selection training. Correlational brain imaging evidence has also implicated the superior medial frontal cortex (SMFC) in response selection, and there is causal evidence that this brain region is involved in the proactive modulation of response tendencies when occasional stopping is required (response inhibition). However, to date there is only limited causal evidence that implicates the SMFC in response selection. Here, we investigated the role of SMFC in response selection, response selection training (Experiment 1) and response selection when occasional response inhibition is anticipated (Experiments 2 and 3) by employing anodal, cathodal, and sham tDCS. Cathodal stimulation of the SMFC modulated response selection by increasing reaction times in the context of proactive response inhibition. Our results suggest a context dependent role of the SMFC in response selection and hint that task set can influence the interaction between the brain and behaviour.

Pub.: 24 Oct '16, Pinned: 28 Jul '17

Transcranial direct-current stimulation modulates offline visual oscillatory activity: A magnetoencephalography study

Abstract: Transcranial direct-current stimulation (tDCS) is a noninvasive neuromodulatory method that involves delivering low amplitude, direct current to specific regions of the brain. While a wealth of literature shows changes in behavior and cognition following tDCS administration, the underlying neuronal mechanisms remain largely unknown. Neuroimaging studies have generally used fMRI and shown only limited consensus to date, while the few electrophysiological studies have reported mostly null or counterintuitive findings. The goal of the current investigation was to quantify tDCS-induced alterations in the oscillatory dynamics of visual processing. To this end, we performed either active or sham tDCS using an occipital-frontal electrode configuration, and then recorded magnetoencephalography (MEG) offline during a visual entrainment task. Significant oscillatory responses were imaged in the time-frequency domain using beamforming, and the effects of tDCS on absolute and relative power were assessed. The results indicated significantly increased basal alpha levels in the occipital cortex following anodal tDCS, as well as reduced occipital synchronization at the second harmonic of the stimulus-flicker frequency relative to sham stimulation. In addition, we found reduced power in brain regions near the cathode (e.g., right inferior frontal gyrus) following active tDCS, which was absent in the sham group. Taken together, these results suggest that anodal tDCS of the occipital cortices differentially modulates spontaneous and induced activity, and may interfere with the entrainment of neuronal populations by a visual-flicker stimulus. These findings also demonstrate the importance of electrode configuration on whole-brain dynamics, and highlight the deceptively complicated nature of tDCS in the context of neurophysiology.

Pub.: 07 Dec '16, Pinned: 28 Jul '17

Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning

Abstract: Publication date: Available online 28 December 2016 Source:Brain Stimulation Author(s): Natasza D. Orlov, Derek K. Tracy, Daniel Joyce, Shinal Patel, Joanna Rodzinka-Pasko, Hayley Dolan, John Hodsoll, Tracy Collier, John Rothwell, Sukhwinder S. Shergill Background Schizophrenia is characterized by prominent cognitive deficits, impacting on memory and learning; these are strongly associated with the prefrontal cortex. Objective/hypothesis To combine two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia. Methods A double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task, indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions. Results 24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14–1.21; p = 0.044) and at day-56 (b = 0.71, 0.16–1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43–0.77; p = 0.058) was found. Conclusions This is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia.

Pub.: 03 Jan '17, Pinned: 28 Jul '17

Multifocal tDCS targeting the resting state motor network increases cortical excitability beyond traditional tDCS targeting unilateral motor cortex.

Abstract: Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether the effects of brain stimulation can be enhanced by simultaneously targeting a region and its network, identified with resting state functional connectivity MRI. Fifteen healthy participants received two types of transcranial direct current stimulation (tDCS): a traditional two-electrode montage targeting a single brain region (left primary motor cortex [M1]) and a novel eight-electrode montage targeting this region and its associated resting state network. As a control, 8 participants also received multifocal tDCS mismatched to this network. Network-targeted tDCS more than doubled the increase in left M1 excitability over time compared to traditional tDCS and the multifocal control. Modeling studies suggest these results are unlikely to be due to tDCS effects on left M1 itself, however it is impossible to completely exclude this possibility. It also remains unclear whether multifocal tDCS targeting a network selectively modulates this network and which regions within the network are most responsible for observed effects. Despite these limitations, network-targeted tDCS appears to be a promising approach for enhancing tDCS effects beyond traditional stimulation targeting a single brain region. Future work is needed to test whether these results extend to other resting state networks and enhance behavioral or therapeutic effects.

Pub.: 03 Jun '17, Pinned: 28 Jul '17

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016

Abstract: This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose–response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3–13 A/m2) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations.

Pub.: 15 Jun '16, Pinned: 28 Jul '17

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Abstract: Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m(2) that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Pub.: 16 Jul '17, Pinned: 28 Jul '17