Angelo Alonzo

Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial {

BACKGROUND Preliminary evidence suggests transcranial direct current stimulation (tDCS) has antidepressant efficacy. AIMS To further investigate the efficacy of tDCS in a double-blind, sham-controlled trial (registered at www.clinicaltrials.gov: NCT00763230). METHOD Sixty-four participants with current depression received active or sham anodal tDCS to the left prefrontal cortex (2 mA, 15 sessions over 3 weeks), followed by a 3-week open-label active treatment phase. Mood and neuropsychological effects were assessed. RESULTS There was significantly greater improvement in mood after active than after sham treatment (P<0.05), although no difference in responder rates (13% in both groups). Attention and working memory improved after a single session of active but not sham tDCS (P<0.05). There was no decline in neuropsychological functioning after 3-6 weeks of active stimulation. One participant with bipolar disorder became hypomanic after active tDCS. CONCLUSIONS Findings confirm earlier reports of the antidepressant efficacy and safety of tDCS. Vigilance for mood switching is advised when administering tDCS to individuals with bipolar disorder.

A double-blind, sham-controlled trial of transcranial direct current stimulation for the treatment of depression

Two recent sham-controlled studies found that transcranial direct current stimulation (tDCS) was an effective treatment for depression. As tDCS is painless, relatively safe and inexpensive, its efficacy in treating depression warrants further investigation. This double-blind, randomized study tested tDCS at the same stimulation parameters as a previous positive study (1 mA current strength, five treatment sessions, active or sham, given on alternate days) in 40 depressed participants. Anodal stimulation was centred over the left dorsolateral prefrontal cortex, with the cathode placed on the lateral aspect of the contralateral orbit. tDCS was continued up to a total of ten active sessions per participant. Mood outcomes were measured by psychiatrist raters blind to treatment condition using the Montgomery-Asberg and other depression rating scales. Psychomotor speed was assessed immediately before and after a single tDCS session and attention, frontal executive function, working memory and verbal learning were assessed after each group of five sessions. Overall depression scores improved significantly over ten tDCS treatments, but there was no between-group difference in the five-session, sham-controlled phase. tDCS was found to be safe, with no adverse effects on neuropsychological function, and only minor side-effects. It is recommended that the efficacy of tDCS in depression be further evaluated over a longer treatment period, using enhanced stimulation parameters.

Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation

BACKGROUND Evidence from recent clinical trials suggests that transcranial direct current stimulation (tDCS) may have potential in treating neuropsychiatric disorders. However, the optimal frequency at which tDCS sessions should be administered is unknown. OBJECTIVE/HYPOTHESIS This study investigated the effects of daily or second daily tDCS sessions on motor cortical excitability, over a 5-day period. METHODS Twelve healthy volunteers received daily or second daily sessions of tDCS to the left primary motor cortex over the study period, in a randomized, intraindividual crossover design. Motor cortical excitability was assessed before and after tDCS at each session through responses to transcranial magnetic stimulation. RESULTS Over a fixed 5-day period, tDCS induced greater increases in MEP amplitude when given daily rather than second daily. Analyses showed that this difference reflected greater cumulative effects between sessions rather than a greater response to each individual tDCS session. CONCLUSIONS These results demonstrate that in the motor cortex of healthy volunteers, tDCS alters cortical excitability more effectively when given daily rather than second daily over a 5-day period.

Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: An open-label pilot study

BACKGROUND Several recent trials have reported transcranial direct current stimulation (tDCS) to be effective in treating depression, though the relative benefits of different electrode montages remain unexplored. Whereas all recent studies have used a bifrontal (BF) electrode montage, studies published in the 1960s and 1970s placed one electrode in an extracephalic position, with some positive reports of efficacy. This study investigated the efficacy and safety of tDCS given with a fronto-extracephalic (F-EX) montage. METHODS 2 mA tDCS was administered for 20 min every weekday over four weeks in 11 participants with a Major Depressive Episode who had previously shown inadequate response to, or relapsed following, a course of BF tDCS. For F-EX tDCS the anode was placed on the left dorsolateral prefrontal cortex and the cathode on the right upper arm. Depression severity and neuropsychological function were assessed before and after the treatment course. Antidepressant response was compared across an equivalent treatment period for both montages. RESULTS F-EX tDCS was shown to be safe and well tolerated. Depression ratings improved after acute treatment on the Montgomery Åsberg Depression Rating Scale (p < 0.001). Participants showed greater initial treatment response with F-EX tDCS than with BF tDCS (p < 0.001). LIMITATIONS This was an open label pilot study. The two comparison treatments were applied consecutively. CONCLUSION F-EX tDCS appears to be safe and to have antidepressant effects, and may lead to more rapid improvement than tDCS given with a BF montage.

Neuroplasticity in Depressed Individuals Compared with Healthy Controls

Several lines of evidence suggest that neuroplasticity is impaired in depression. This study aimed to compare neuroplasticity in 23 subjects with DSM-IV major depressive episode and 23 age- and gender-matched healthy controls, using an objective test that is independent of subject effort and motivation. Neuroplasticity was assessed in the motor cortex using a brain stimulation paradigm known as paired associative stimulation (PAS), which induces transient changes in motor cortical function. Motor cortical excitability was assessed before and after PAS using single-pulse transcranial magnetic stimulation (TMS) to induce motor evoked potentials (MEPs) in a hand muscle. After PAS, MEP amplitudes significantly increased in healthy controls compared with depressed subjects (P=0.002). The functional significance of motor cortical changes was assessed using a motor learning task—a computerized version of the rotor pursuit task. Healthy controls also performed better on motor learning (P=0.02). BDNF blood levels and genotype were assayed to determine any relationship with motor cortical plasticity. However, PAS results did not correlate with motor learning, nor appear to be related to BDNF measures. The significance of these findings is that it provides one of the first direct demonstrations of reduced neuroplasticity in depressed subjects, using an objective test.

Hypomania induction in a patient with bipolar II disorder by transcranial direct current stimulation (tDCS).

Objectives: To report a case of hypomania induced by transcranial direct current stimulation (tDCS) given with an extracephalic reference electrode. Transcranial direct current stimulation is a noninvasive brain stimulation technique in which a weak current is applied through the scalp to produce changes in neuronal excitability in the underlying cerebral tissue. Recent clinical trials have shown promising results with left anodal prefrontal tDCS in treating depression. When the reference cathodal electrode in tDCS is moved from the cranium to an extracephalic position, larger areas of both cerebral hemispheres are stimulated, with potential implications for both efficacy and safety. Methods: We report the case of a 33-year-old female with bipolar II disorder, on mood stabilizer medication, who had previously participated in a clinical trial of tDCS given with a bifrontal electrode montage for the treatment of major depression without incident, but became hypomanic when she received a later course of tDCS given with a frontoextracephalic configuration. Factors contributing to the development of hypomania in the second course of tDCS are examined. Results: No substantial differences were found in the patients clinical presentation between the 2 tDCS courses to explain the emergence of hypomania only after the second course. The different montage used in the second course appeared to be the main contributory factor in the induction of hypomania. Conclusions: The reported case suggests that frontoextracephalic tDCS has antidepressant properties and the potential to induce hypomanic symptoms. In particular, it raises the question of whether frontoextracephalic tDCS requires additional precautions when administered to bipolar patients compared to bifrontal tDCS.

Avoiding skin burns with transcranial direct current stimulation: preliminary considerations

Interest is rapidly developing in transcranial direct current stimulation (tDCS) as an emerging tool in neurology and psychiatry. tDCS involves the application of weak, unidirectional currents through scalp electrodes to alter neuronal excitability, that may outlast the period of stimulation (Arul-Anandam & Loo, 2009). In addition to being a tool for neurophysiological investigations, tDCS has been examined as a treatment for many neuropsychiatric disorders (Nitsche et al. 2008), in particular depression (Boggio et al. 2008; Fregni et al. 2006; Loo et al. 2010). Clinical application of tDCS in neuropsychiatric disorders often involves repeated stimulation sessions, typically on consecutive days, in an attempt to create robust and lasting changes in neuronal functioning. Stimulation parameters (current intensity, stimulation duration, etc.) have been gradually adjusted to optimize therapeutic effects (Arul-Anandam & Loo, 2009). Skin burns have recently been reported in treatment trials of tDCS in depression involving multiple stimulation sessions given at the upper range of stimulation parameters, and when applied repeatedly to the same scalp sites (Frank et al. 2010; Palm et al. 2008). Other researchers have provided guidance on safety issues in tDCS technique (Nitsche et …

Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user’s capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population’s level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Increase in PAS-induced neuroplasticity after a treatment courseof transcranial direct current stimulation for depression

BACKGROUND Several lines of evidence suggest that neuroplasticity is impaired in depression and improves with effective treatment. However until now, this evidence has largely involved measures such as learning and memory which can be influenced by subject effort and motivation. This pilot study aimed to objectively measure neuroplasticity in the motor cortex using paired associative stimulation (PAS), which induces short term neuroplastic changes. It is hypothesized that neuroplasticity would improve after effective treatment for depression. METHODS Neuroplasticity was measured in 18 depressed subjects before and after a course of anodal transcranial direct current stimulation (tDCS), given as treatment for depression. The relationships between PAS results, mood state and brain-derived neurotrophic factor (BDNF) serum levels were examined. RESULTS Neuroplasticity (PAS-induced change) was increased after a course of tDCS (t(17)=-2.651, p=0.017). Treatment with tDCS also led to significant mood improvement, but this did not correlate with improved neuroplasticity. Serum BDNF levels did not change after tDCS, or correlate with change in neuroplasticity after tDCS treatment. LIMITATIONS While this study showed evidence of improved neuroplasticity in the motor cortex after effective treatment, we are unable to present evidence that this change is generalized in the depressed brain. Also, the presence of antidepressant medications and the small sample of patients (n=18) meant the study could not definitively resolve the relationship between neuroplasticity, mood and BDNF. CONCLUSION This novel preliminary study provides evidence that a treatment course of tDCS can improve neuroplasticity in depressed patients.

A pilot study of alternative transcranial direct current stimulation electrode montages for the treatment of major depression

BACKGROUND Typically, transcranial direct current stimulation (tDCS) treatments for depression have used bifrontal montages with anodal (excitatory) stimulation targeting the left dorsolateral prefrontal cortex (DLPFC). There is limited research examining the effects of alternative electrode montages. OBJECTIVE/HYPOTHESIS This pilot study aimed to examine the feasibility, tolerability and safety of two alternative electrode montages and provide preliminary data on efficacy. The montages, Fronto-Occipital (F-O) and Fronto-Cerebellar (F-C), were designed respectively to target midline brain structures and the cerebellum. METHODS The anode was placed over the left supraorbital region and the cathode over the occipital and cerebellar region for the F-O and F-C montages respectively. Computational modelling was used to determine the electric fields produced in the brain regions of interest compared to a standard bifrontal montage. The two montages were evaluated in an open label study of depressed participants (N=14). Mood and neuropsychological functioning were assessed at baseline and after four weeks of tDCS. RESULTS Computational modelling revealed that the novel montages resulted in greater activation in the anterior cingulate cortices and cerebellum than the bifrontal montage, while activation of the DLPFCs was higher for the bifrontal montage. After four weeks of tDCS, overall mood improvement rates of 43.8% and 15.9% were observed under the F-O and F-C conditions, respectively. No significant neuropsychological changes were found. LIMITATIONS The clinical pilot was open-label, without a control condition and computational modelling was based on one healthy participant. CONCLUSIONS Results found both montages safe and feasible. The F-O montage showed promising antidepressant potential.