Alberto Priori

Transcranial direct current stimulation: State of the art 2008

Effects of weak electrical currents on brain and neuronal function were first described decades ago. Recently, DC polarization of the brain was reintroduced as a noninvasive technique to alter cortical activity in humans. Beyond this, transcranial direct current stimulation (tDCS) of different cortical areas has been shown, in various studies, to result in modifications of perceptual, cognitive, and behavioral functions. Moreover, preliminary data suggest that it can induce beneficial effects in brain disorders. Brain stimulation with weak direct currents is a promising tool in human neuroscience and neurobehavioral research. To facilitate and standardize future tDCS studies, we offer this overview of the state of the art for tDCS.

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

BACKGROUND Transcranial 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. METHODS We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION We 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.

Brain polarization in humans: a reappraisal of an old tool for prolonged non-invasive modulation of brain excitability

Direct current (DC) is very effective in modulating spontaneous neuronal firing. The history of electrophysiology starts with the discovery of the biological effects of DC and as early as two centuries ago scalp DC was used to treat mental disorder. Psychophysiological investigations suggested a possible effect of scalp DC in humans. More recently several studies assessed, with motor potentials evoked by transcranial brain stimulation, the motor-cortical excitability changes induced by scalp DC. Even weak DCs pass through the scalp and influence human brain activity. DCs delivered at relatively strong intensities (1 mA) and for long periods (10 min or so), not only influence (either increase or decrease) brain excitability during their application in normal subjects, but induce persistent changes in excitability after their offset that, at least in the motor cortex, can last for almost 1 h. Scalp DC might represent a non-invasive simple and valuable potential treatment for psychiatric and neurologic diseases with changes in brain excitability or focally abnormal (increased or decreased) function.

Efficacy of repetitive transcranial magnetic stimulation/transcranial direct current stimulation in cognitive neurorehabilitation

Cognitive deficits are a common consequence of neurologic disease, in particular, of traumatic brain injury, stroke, and neurodegenerative disorders, and there is evidence that specific cognitive training may be effective in cognitive rehabilitation. Several investigations emphasize the fact that interacting with cortical activity, by means of cortical stimulation, can positively affect the short-term cognitive performance and improve the rehabilitation potential of neurologic patients. In this respect, preliminary evidence suggests that cortical stimulation may play a role in treating aphasia, unilateral neglect, and other cognitive disorders. Several possible mechanisms can account for the effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) on cognitive performance. They all reflect the potential of these methods to improve the subjects ability to relearn or to acquire new strategies for carrying out behavioral tasks. The responsible mechanisms remain unclear but they are most likely related to the activation of impeded pathways or inhibition of maladaptive responses. Modifications of the brain activity may assist relearning by facilitating local activity or by suppressing interfering activity from other brain areas. Notwithstanding the promise of these preliminary findings, to date no systematic application of these methods to neurorehabilitation research has been reported. Considering the potential benefit of these interventions, further studies taking into consideration large patient populations, long treatment periods, or the combination of different rehabilitation strategies are needed. Brain stimulation is indeed an exciting opportunity in the field of cognitive neurorehabilitation, which is clearly in need of further research.

Repetitive transcranial magnetic stimulation or transcranial direct current stimulation

In recent years two techniques have become available to stimulate the human brain noninvasively through the scalp: repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Prolonged application of either method (eg, several hundred TMS pulses [rTMS] or several minutes of tDCS) leads to changes in excitability of the cortex that outlast the period of stimulation. Because of this, besides the implications for experimental neuroscientists, there is increasing interest in the potential for applying either method as a therapy in neurology, psychiatry, rehabilitation, and pain. Given that both techniques lead to the same final result, this article discusses in theory several issues that can help an investigator to decide whether rTMS or tDCS would be more suitable for the scope of the planned work.

Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinsons disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimers disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.

Multifocal motor neuropathy: current concepts and controversies.

Multifocal motor neuropathy (MMN) is now a well‐defined purely motor multineuropathy characterized by the presence of multifocal partial motor conduction blocks (CB), frequent association with anti‐GM1 IgM antibodies, and usually a good response to high‐dose intravenous immunoglobulin (IVIg) therapy. However, several issues remain to be clarified in the diagnosis, pathogenesis, and therapy of this condition including its nosological position and its relation to other chronic dysimmune neuropathies; the degree of CB necessary for the diagnosis of MMN; the existence of an axonal form of MMN; the pathophysiological basis of CB; the pathogenetic role of antiganglioside antibodies; the mechanism of action of IVIg treatments in MMN and the most effective regimen; and the treatment to be used in unresponsive patients. These issues are addressed in this review of the main clinical, electrophysiological, immunological, and therapeutic features of this neuropathy. Muscle Nerve, 2005

Prolonged visual memory enhancement after direct current stimulation in Alzheimer's disease

BACKGROUND Immediately after patients with Alzheimers disease (AD) receive a single anodal transcranial direct current stimulation (tDCS) session their memory performance improves. Whether multiple tDCS sessions improve memory performance in the longer term remains unclear. OBJECTIVE In this study we aimed to assess memory changes after five consecutive sessions of anodal tDCS applied over the temporal cortex in patients with AD. METHODS A total of 15 patients were enrolled in two centers. Cognitive functions were evaluated before and after therapeutic tDCS. tDCS was delivered bilaterally through two scalp anodal electrodes placed over the temporal regions and a reference electrode over the right deltoid muscle. The stimulating current was set at 2 mA intensity and was delivered for 30 minutes per day for 5 consecutive days. RESULTS After patients received tDCS, their performance in a visual recognition memory test significantly improved. We found a main effect of tDCS on memory performance, i.e., anodal stimulation improved it by 8.99% from baseline, whereas sham stimulation decreased it by 2.62%. tDCS failed to influence differentially general cognitive performance measures or a visual attention measure. CONCLUSIONS Our findings show that after patients with AD receive anodal tDCS over the temporal cerebral cortex in five consecutive daily sessions their visual recognition memory improves and the improvement persists for at least 4 weeks after therapy. These encouraging results provide additional support for continuing to investigate anodal tDCS as an adjuvant treatment for patients with AD.

Transcranial direct current stimulation (tDCS) and language

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.

The effects of levodopa and ongoing deep brain stimulation on subthalamic beta oscillations in Parkinson's disease

Local field potentials (LFPs) recorded through electrodes implanted in the subthalamic nucleus (STN) for deep brain stimulation (DBS) in patients with Parkinsons disease (PD) show that oscillations in the beta frequency range (8-20 Hz) decrease after levodopa intake. Whether and how DBS influences the beta oscillations and whether levodopa- and DBS-induced changes interact remains unclear. We examined the combined effect of levodopa and DBS on subthalamic beta LFP oscillations, recorded in nine patients with PD under four experimental conditions: without levodopa with DBS turned off; without levodopa with DBS turned on; with levodopa with DBS turned on; and with levodopa with DBS turned off. The analysis of STN-LFP oscillations showed that whereas levodopa abolished beta STN oscillations in all the patients (p=0.026), DBS significantly decreased the beta oscillation only in five of the nine patients studied (p=0.043). Another difference was that whereas levodopa completely suppressed beta oscillations, DBS merely decreased them. When we combined levodopa and DBS, the levodopa-induced beta disruption prevailed and combining levodopa and DBS induced no significant additive effect (p=0.500). Our observations suggest that levodopa and DBS both modulate LFP beta oscillations.