13 Effects of Transcranial Direct Current Stimulation (tDCS)

Offline effects of transcranial direct current stimulation on reaction times of lower extremity movements in people after stroke: a pilot cross-over study

13 Effects of Transcranial Direct Current Stimulation (tDCS)

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Unexpected Benefits of tDCS in Depressed Patients

13 Effects of Transcranial Direct Current Stimulation (tDCS)

The application of novel brain stimulation techniques to treat depression, and possibly other neuropsychiatric disorders, is a new and rapidly growing field.

Among these techniques, transcranial direct current stimulation (tDCS) is emerging as one of the most promising approaches because of its relative ease of use, safety and neurobiological effects. tDCS involves the use of weak electric currents (1–2 mA), passed through brain tissue via electrodes placed on the scalp.

The stimulation is too weak to directly cause neuronal firing, but is thought to interact with the neuronal membrane and background neural activity, resulting in modification of synaptic strength.

[1] When given tonically for a few minutes, it can induce lasting changes in neuronal excitability, as evidenced in physiological studies.[2] This is presumably the mechanism by which repeated stimulation sessions can lead to meaningful therapeutic effects, as seen in clinical trials.[3]

One of the most promising therapeutic applications of tDCS has been in the treatment of depression. A recent meta-analysis suggested that tDCS may have robust and clinically meaningful effects in treating depression.

[4] Our group recently published the largest and most definitive sham-controlled trial of tDCS in depression.

[5] Active stimulation was more effective than sham stimulation, and 48% of subjects who received 30 treatments of tDCS (given every weekday over a period of 6 weeks) responded to treatment.

In the course of conducting this trial, it has been observed that tDCS may induce additional benefits that appeared to be independent of mood improvement.

Several subjects spontaneously reported improved attention and concentration during the weeks when they were receiving active stimulation (given under double-blind conditions).

One subject found that tDCS relieved her from neuropathic pain to the same extent as spinal block anesthesia,[6] and another subject reported improvement in a long-standing problem with visual tracking during reading.

One subject additionally showed rapid relief from psychogenic stuttering with commencement of active tDCS treatment. Furthermore, tests administered to all subjects immediately before and after a single session of active or sham tDCS for the purpose of assessing safety revealed that active tDCS significantly improved psychomotor speed.[5]

These observations are consistent with reports in the literature of cognitive enhancement and pain relief with tDCS.

[3] Anodal stimulation of the left dorsolateral prefrontal cortex (the same region stimulated for the treatment of depression) has been shown to enhance task performance across a number of 'executive' cognitive tasks, tapping higher-level cognitive functions, such as working memory,[7] verbal fluency[8] and planning.[9] Other studies have shown specific improvement in language and reading after tDCS.[10,11] Apart from these studies involving a single session of tDCS, several studies suggest that repeated stimulation sessions may usefully enhance motor learning[12] and cognition,[13] although despite subjective reports, no improvement in neuropsychological function was demonstrated after 15 sessions (3 weeks) of active tDCS in our recent depression trial.[5]

The use of tDCS to treat pain syndromes is another area of research that has attracted much interest,[3] with a recent Cochrane systematic review finding promising outcomes in the small evidence base available to date.[14] Therapeutic effects in pain syndromes have been shown with stimulation of motor and frontal areas.

From an understanding of the physics of tDCS, it is conceivable that stimulation administered primarily to frontal brain areas to treat depression may also have other clinical effects, as the stimulation is relatively diffuse.

In recent depression trials conducted since 2000, tDCS was administered between widely spaced electrodes as this approach increases the amount of current entering the cranium (as opposed to being shunted over the scalp).

[15] This wide spacing of electrodes also results in substantial current levels in large areas of the brain, as shown in sophisticated computer models MRI brain scans.[16] Thus, un transcranial magnetic stimulation, tDCS is not particularly focal.

In fact, experimental work has suggested that electrical stimulation preferentially activates white matter tracts.[17] Nevertheless, electrode montage selection is important for optimizing therapeutic effects as currents are maximal under the electrodes and the directionality of the stimulating current is important.

The relatively widespread brain stimulation that occurs with tDCS may actually be an advantage, both in terms of more robust therapeutic effects in disorders in which pathophysiology may primarily occur at the network level, for example, depression,[18] and, as described earlier, in producing beneficial effects other than the primary effect intended. This also means, however, that unexpected adverse effects may also occur and researchers should remain vigilant for these as the applications and limits of stimulation are explored. For example, we recently found that a montage that increased the diffuseness of stimulation may have been more ly to induce mania.[19,20]

tDCS is a rediscovery of an old technology, and many studies are now exploring its therapeutic potential in a range of disorders. The therapeutic effects of a treatment are often weighed against side effects in a cost–benefit analysis.

A treatment that has beneficial 'side effects' would be welcome indeed.

It may even be possible that future stimulation paradigms are designed to utilize the diffuse nature of the stimulation to treat more than one set of symptoms at a time, for example, improving cognition while lifting mood in depression.

Expert Rev Neurother. 2012;12(7):751-753. © 2012  Expert Reviews Ltd.

Source: https://www.medscape.com/viewarticle/769494

Examining Transcranial Direct-Current Stimulation (tDCS) as a Treatment for Hallucinations in Schizophrenia

13 Effects of Transcranial Direct Current Stimulation (tDCS)

Some 50%–70% of individuals with schizophrenia report auditory verbal hallucinations, even during treatment with antipsychotic medication.

For 25%–30% of schizophrenia patients, such hallucinations are refractory to drug treatment, resulting in persistent distress, functional disability, and frequent loss of behavioral control.

System models suggest that abnormal levels of regional cerebral excitation and inhibition may occur, but this has been difficult to study.

Evidence suggests that repetitive transcranial magnetic stimulation (rTMS), a noninvasive neurostimulation technique, could modulate cortical excitability to improve refractory auditory verbal hallucinations in schizophrenia.

Neuroimaging studies have implicated left temporo-parietal hyperactivity during auditory hallucinations (1), and related therapeutic studies have shown reduced severity of hallucinations with low-frequency rTMS (putatively reducing cortical excitability) with the stimulation coil applied midway between T3 and P3 (using the 10-20 EEG international system).

Meta-analyses have supported this approach, reporting a substantial effect size (d values, 0.515–0.88) of low-frequency rTMS on hallucinations (2–5). However, results have been inconsistent, with two recent studies reporting no effect (6, 7).

While the systems involved in speech generation and perception are broad and involve frontal as well as temporo-parietal areas (8), only a few studies have examined low-frequency rTMS targeting these broader brain regions.

While hyperactivity has been reported in Broca's area (9), its right homologue (10), Heschl's gyrus (11, 12), and the middle and superior temporal gyri (8, 13, 14), stimulation of these areas with rTMS was not found to be more effective than sham stimulation (15–19).

It remains unclear whether the left temporo-parietal junction at T3–P3 is the optimal rTMS focus, since recent functional MRI (fMRI) studies cast doubt on the prominence of the temporal-parietal junction in treating these hallucinations and show great interindividual variability (6, 12, 13, 16, 19). Taken together, these results suggest some promise in the development of new neurostimulation approaches that will have a more effective impact on brain systems implicated in auditory verbal hallucinations.

In addition to temporal hyperactivity, hypoactivity in the prefrontal cortex, particularly in the dorsolateral and anterior cingulate regions, has been commonly described in schizophrenia (20, 21). Here, high-frequency rTMS stimulation (putatively increasing neuronal excitability) over the prefrontal cortex has shown some promise in improving negative symptoms (3, 22).

Transcranial direct-current stimulation (tDCS) is a new noninvasive neurostimulation treatment (23) that is being used increasingly for the treatment of neurologic and psychiatric symptoms (24, 25).

With tDCS, the cortical neuronal excitability is increased in the vicinity of the anode (analogous to high-frequency rTMS) and is reduced near the cathode (analogous to low-frequency rTMS) (26).

The first studies investigating the effects of tDCS in humans focused on the motor cortex, where changes in cortical excitability can easily be monitored.

The effects of tDCS on cortical excitability can be explained by neuronal membrane polarization shifts (subthreshold depolarization or hyperpolarization of resting membrane potential) and modifications of NMDA receptor efficacy (26), which result in prolonged synaptic efficacy changes (27).

Electrophysiological studies show increased neuronal activity near anodal tDCS using somatosensory evoked potentials (28) and anodal (stimulation) and cathodal (inhibition) tDCS on visual cortex stimulation (27). Keeser et al. (29) reported that prefrontal anodal tDCS modulates resting-state functional connectivity in predicted functional networks located close to the primary stimulation site and in connected brain regions.

Thus, tDCS could be focused on two nodes of a cortical system, increasing tissue activity in one area and decreasing it in another. It could generate a more potent therapeutic action given these two local effects compared with other neurostimulation approaches, such as rTMS.

Our aim in this study was to confirm our promising observations from two open cases (30) by assessing the efficacy of tDCS in refractory auditory verbal hallucinations. We also assessed the maintenance of the effect of tDCS on these hallucinations across a 3-month follow-up period.

We hypothesized that a tDCS treatment with the cathode on the left temporo-parietal junction and the anode on the left dorsolateral prefrontal cortex can reduce the severity of auditory verbal hallucinations in schizophrenia patients.

We also investigated the impact of tDCS on other schizophrenia symptoms in secondary exploratory outcome analyses.

Thirty patients who met DSM-IV-TR criteria for schizophrenia were included in the study. All of them displayed refractory auditory verbal hallucinations, defined as the persistence of daily hallucinations without remission despite antipsychotic medication at an adequate dosage for at least 3 months. All patients were maintained on their treatment throughout the study period.

The study was approved by the Comité de Protection des Personnes of Sud-Est VI (Lyon, France), and all patients provided written informed consent. A randomized double-blind parallel-arm (raters, experimenters, and patients were blind to randomized treatment assignment) tDCS protocol was used in the study.

Stimulation was done using an Eldith DC stimulator (www.neuroconn.de/dc-stimulator_plus_en/) with two 7×5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl). Electrodes were placed on the basis of the international 10-20 electrode placement system.

The anode was placed with the middle of the electrode over a point midway between F3 and FP1 (left prefrontal cortex: dorsolateral prefrontal cortex, assumed to correspond to a region including Brodmann's areas [BA] 8, 9, 10, and 46, depending on the patient) and the cathode located over a point midway between T3 and P3 (left temporo-parietal junction, assumed to correspond to a region including BA 22, 39, 40, 41, and 42, depending on the patient).

In accordance with recent studies of tDCS in other psychiatric or neurological illnesses (24, 25, 30), the stimulation level was set at 2 mA for 20 minutes.

In line with our previous study using 1-Hz rTMS for auditory verbal hallucinations (31, 32), stimulation sessions were conducted twice a day on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours.

In sham stimulation, the chosen stimulation parameters were displayed, but in fact after 40 seconds of real stimulation (2 mA), only a small current pulse occurred every 550 msec (110 mA over 15 msec) through the remainder of the 20-minute period.

The primary outcome measure was the change over time in the severity of auditory verbal hallucinations, as assessed by an investigator blind to group assignment using the Auditory Hallucination Rating Scale (AHRS). Assessments were conducted at baseline (before the first tDCS session), after the 5 days of tDCS (acute effect), and 1 and 3 months after tDCS (maintenance effect).

An exploratory outcome measure was the severity of other schizophrenia symptoms as quantified by the Positive and Negative Syndrome Scale (PANSS).

The effect of tDCS on overall schizophrenia symptoms was assessed using the total PANSS score and using a dimensional approach of PANSS (33) to distinguish five main dimensions of symptoms: positive, negative, depression, disorganization, and grandiosity/excitement.

The demographic and clinical characteristics of the two groups were compared at baseline using Student's t tests, except for gender, which was assessed by the chi-square test.

To compare the overall effect of treatment on auditory verbal hallucinations over time in the two groups, data from the full intent-to-treat sample were analyzed using a repeated-measures analysis of variance (ANOVA) with treatment as the intergroup factor and time as the intrasubject factor.

Post hoc analyses were performed using Student's t tests for intergroup comparisons. The significance threshold was set at 0.05.

For the exploratory secondary outcome, intergroup comparisons were assessed using Cohen's d (effect size) followed by two-tailed Student's t tests immediately after the tDCS sessions. Analyses compared the percentage of variation in the scores between, before, and after treatment between the groups.

The effect size estimate is slightly biased and is therefore corrected using a factor provided by Hedges and Olkin (34). An effect size is exactly equivalent to a z-score of a standard normal distribution. As suggested by Cohen (35), an effect size of 0.2 could be considered small, 0.5 medium, and 0.8 large.

Thirty patients, all right-handed, were included in the study. Fifteen patients were randomly assigned to the active treatment group and 15 to the sham treatment group (Table 1; see also the CONSORT flow chart in the data supplement that accompanies the online edition of this article).

At baseline, there was no statistically significant difference between groups on any variable (age, gender, education, medication, AHRS score, or PANSS scores). Treatment was well tolerated by all patients.

All patients reported that they could not tell which group they had been allocated to, and all of them described a transient mild tingling or a slight itching sensation associated with the onset of stimulation.

TABLE 1. Baseline Demographic and Clinical Characteristics of 30 Patients With Schizophrenia and Refractory Auditory Verbal Hallucinations Randomly Assigned to Receive Transcranial Direct-Current Stimulation (tDCS) or Sham Stimulationa

Active tDCS (N=15)Sham tDCS (N=15)CharacteristicMeanSDMeanSD
Age (years)40.49.935.17.0
Education (years)10.82.910.62.8
Antipsychotic dosage (mg/day, chlorpromazine equivalents)9947141,209998
Auditory Hallucination Rating Scale score28.33.527.16.9
Positive and Negative Syndrome Scale
  Total score76.916.482.815.4
  Negative score16.25.020.56.5
  Positive score21.26.920.03.5
  Grandiosity/excitement score11.54.410.83.5
  Disorganization score15.13.915.74.8
  Depression score10.83.511.13.5

TABLE 1. Baseline Demographic and Clinical Characteristics of 30 Patients With Schizophrenia and Refractory Auditory Verbal Hallucinations Randomly Assigned to Receive Transcranial Direct-Current Stimulation (tDCS) or Sham Stimulationa

Enlarge table

Compared with the sham condition, a large effect of tDCS on auditory verbal hallucinations was seen in the active group after 5 days of tDCS (d=1.58, p

Source: https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2012.11071091

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