Paulo S. Boggio

Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory

Previous studies have claimed that weak transcranial direct current stimulation (tDCS) induces persisting excitability changes in the human motor cortex that can be more pronounced than cortical modulation induced by transcranial magnetic stimulation, but there are no studies that have evaluated the effects of tDCS on working memory. Our aim was to determine whether anodal transcranial direct current stimulation, which enhances brain cortical excitability and activity, would modify performance in a sequential-letter working memory task when administered to the dorsolateral prefrontal cortex (DLPFC). Fifteen subjects underwent a three-back working memory task based on letters. This task was performed during sham and anodal stimulation applied over the left DLPFC. Moreover seven of these subjects performed the same task, but with inverse polarity (cathodal stimulation of the left DLPFC) and anodal stimulation of the primary motor cortex (M1). Our results indicate that only anodal stimulation of the left prefrontal cortex, but not cathodal stimulation of left DLPFC or anodal stimulation of M1, increases the accuracy of the task performance when compared to sham stimulation of the same area. This accuracy enhancement during active stimulation cannot be accounted for by slowed responses, as response times were not changed by stimulation. Our results indicate that left prefrontal anodal stimulation leads to an enhancement of working memory performance. Furthermore, this effect depends on the stimulation polarity and is specific to the site of stimulation. This result may be helpful to develop future interventions aiming at clinical benefits.

Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions

BACKGROUNDnTranscranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them.nnnMETHODSnWe convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research.nnnMAIN FINDINGS/DISCUSSIONnWe reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.

A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury

Abstract Past evidence has shown that motor cortical stimulation with invasive and non‐invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non‐invasive brain stimulation – transcranial direct current stimulation (tDCS) – on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2 mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.

A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients

The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation (rTMS) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke. Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected hand after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS.

Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease

OBJECTIVESnCognitive impairment is a common feature in Parkinsons disease (PD) and is an important predictor of quality of life. Past studies showed that some aspects of cognition, such as working memory, can be enhanced following dopaminergic therapy and transcranial magnetic stimulation. The aim of our study was to investigate whether another form of noninvasive brain stimulation, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability, is associated with a change in a working memory task performance in PD patients.nnnMETHODSnWe studied 18 patients (12 men and 6 women) with idiopathic PD. The patients performed a three-back working memory task during active anodal tDCS of the left dorsolateral prefrontal cortex (LDLPFC), anodal tDCS of the primary motor cortex (M1) or sham tDCS. In addition, patients underwent two different types of stimulation with different intensities: 1 and 2 mA.nnnRESULTSnThe results of this study show a significant improvement in working memory as indexed by task accuracy, after active anodal tDCS of the LDLPFC with 2 mA. The other conditions of stimulation: sham tDCS, anodal tDCS of LDLPFC with 1 mA or anodal tDCS of M1 did not result in a significant task performance change.nnnCONCLUSIONntDCS may exert a beneficial effect on working memory in PD patients that depends on the intensity and site of stimulation. This effect might be explained by the local increase in the excitability of the dorsolateral prefrontal cortex.

Noninvasive Cortical Stimulation With Transcranial Direct Current Stimulation in Parkinson's Disease

Electrical stimulation of deep brain structures, such as globus pallidus and subthalamic nucleus, is widely accepted as a therapeutic tool for patients with Parkinsons disease (PD). Cortical stimulation either with epidural implanted electrodes or repetitive transcranial magnetic stimulation can be associated with motor function enhancement in PD. We aimed to study the effects of another noninvasive technique of cortical brain stimulation, transcranial direct current stimulation (tDCS), on motor function and motor‐evoked potential (MEP) characteristics of PD patients. We tested tDCS using different electrode montages [anodal stimulation of primary motor cortex (M1), cathodal stimulation of M1, anodal stimulation of dorsolateral prefrontal cortex (DLPFC), and sham‐stimulation] and evaluated the effects on motor function—as indexed by Unified Parkinsons Disease Rating Scale (UPDRS), simple reaction time (sRT) and Purdue Pegboard test—and on corticospinal motor excitability (MEP characteristics). All experiments were performed in a double‐blinded manner. Anodal stimulation of M1 was associated with a significant improvement of motor function compared to sham‐stimulation in the UPDRS (P < 0.001) and sRT (P = 0.019). This effect was not observed for cathodal stimulation of M1 or anodal stimulation of DLPFC. Furthermore, whereas anodal stimulation of M1 significantly increased MEP amplitude and area, cathodal stimulation of M1 significantly decreased them. There was a trend toward a significant correlation between motor function improvement after M1 anodal–tDCS and MEP area increase. These results confirm and extend the notion that cortical brain stimulation might improve motor function in patients with PD.

Enhancement of non-dominant hand motor function by anodal transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is a non-invasive powerful method to modulate brain activity. It can enhance motor learning and working memory in healthy subjects. To investigate the effects of anodal tDCS (1 mA, 20 min) of the dominant and non-dominant primary motor cortex (M1) on hand motor performance in healthy right-handed volunteers, healthy subjects underwent one session of both sham and active anodal stimulation of the non-dominant or dominant primary motor cortex. A blinded rater assessed motor function using the Jebsen Taylor Hand Function Test. For the non-dominant hand, active tDCS was able to improve motor function significantly-there was a significant interaction between time and condition of stimulation (p = 0.003). Post hoc tests showed a significant enhancement of JTT performance after 1 mA anodal tDCS of M1 (mean improvement of 9.41%, p = 0.0004), but not after sham tDCS (mean improvement of 1.3%, p = 0.84). For the dominant hand, however, neither active nor sham tDCS resulted in a significant change in motor performance. Our findings show that anodal tDCS of the non-dominant primary motor cortex results in motor function enhancement and thus confirm and extend the notion that tDCS can change behavior. We speculate that the under-use of the non-dominant hand with its associated consequences in cortical plasticity might be one of the reasons to explain motor performance enhancement in the non-dominant hand only.

Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation

Modulation of activity in the left temporoparietal area (LTA) by 10u2003Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10‐Hz rTMS of LTA, 10‐Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non‐parametric analysis of variance showed a significant main effect of type of stimulation (Pu2003=u20030.002) and post hoc tests showed that 10‐Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high‐frequency rTMS.

Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers.

Background and purpose:u2002 We aimed to evaluate whether transcranial direct current stimulation (tDCS) is effective in modulating sensory and pain perception thresholds in healthy subjects as to further explore mechanisms of tDCS in pain relief.

A randomized clinical trial of repetitive transcranial magnetic stimulation in patients with refractory epilepsy.

To study the antiepileptic effects of rTMS in patients with refractory epilepsy and malformations of cortical development in a randomized, double‐blind, sham‐controlled trial.