Effects of transcranial direct current stimulation and transcranial random noise stimulation on working memory and task-related EEG in major depressive disorder.

OBJECTIVE: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD). METHODS: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance. RESULTS: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation. CONCLUSIONS: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD. SIGNIFICANCE: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals.

Transcranial random noise stimulation is more effective than transcranial direct current stimulation for enhancing working memory in healthy individuals: Behavioural and electrophysiological evidence.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been shown to improve working memory (WM) performance in healthy individuals, however effects tend to be modest and variable. Transcranial random noise stimulation (tRNS) can be delivered with a direct-current offset (DC-offset) to induce equal or even greater effects on cortical excitability than tDCS. To-date, no research has directly compared the effects of these techniques on WM performance or underlying neurophysiological activity. OBJECTIVE: To compare the effects of anodal tDCS, tRNS + DC-offset, or sham stimulation over the left dorsolateral prefrontal cortex (DLPFC) on WM performance and task-related EEG oscillatory activity in healthy adults. METHODS: Using a between-subjects design, 49 participants were allocated to receive either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left DLPFC. Changes in WM performance were assessed using the Sternberg WM task completed before and 5- and 25-min post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) of oscillatory activity was analysed from EEG recorded during WM encoding and maintenance. RESULTS: tRNS induced more pronounced and consistent enhancements in WM accuracy when compared to both tDCS and sham stimulation. Improvements in WM performance following tRNS were accompanied by increased theta ERS and diminished gamma ERD during WM encoding, which were significantly greater than those observed following anodal tDCS or sham stimulation. CONCLUSIONS: These findings demonstrate the potential of tRNS + DC-offset to modulate cognitive and electrophysiological measures of WM and raise the possibility that tRNS + DC-offset may be more effective and reliable than tDCS for enhancing WM performance in healthy individuals.

Individuals with depression display abnormal modulation of neural oscillatory activity during working memory encoding and maintenance.

PURPOSE: To investigate neural oscillatory activity supporting working memory (WM) processing in depressed individuals and healthy controls. METHODS: Forty-six participants with Major Depressive Disorder (MDD) and 41 healthy controls balanced on age, gender, and WM ability completed a Sternberg verbal WM task with concurrent electroencephalography recording. Oscillatory activity was calculated for upper alpha, theta, and gamma frequency bands during WM encoding and maintenance. RESULTS: WM performance did not differ between groups. When compared to healthy controls, depressed individuals displayed reduced frontal-midline theta power and increased occipital upper alpha power during WM encoding, and reductions in frontal-midline theta power and occipital gamma and upper alpha power during WM maintenance. Higher depression severity was associated with greater reductions upper alpha and gamma power during WM maintenance. CONCLUSIONS: Depressed individuals displayed prominent alterations in oscillatory activity during WM encoding and maintenance, indicating that the neural processes which support WM processing are altered in MDD even when no cognitive impairments are observed.

Neurobiological effects of transcranial direct current stimulation in younger adults, older adults and mild cognitive impairment.

Transcranial direct current stimulation (tDCS) has been investigated as a way to improve motor and cognitive functioning, with largely variable results. Currently, relatively little is known about the neurobiological effects, and possible drivers of variability, in either healthy or clinical populations. Therefore, this study aimed to characterise the neurobiological effects to tDCS in younger adults, older adults and adults with mild cognitive impairment (MCI), and their relationship to cognitive performance. 20 healthy younger adults, 20 healthy older adults and 9 individuals with MCI participated in the study. All completed neuropsychological tasks and TMS-EEG, prior to and following delivery of 20 min of anodal tDCS to the left dorsolateral prefrontal cortex (DLPFC). EEG was also recorded during the 2-Back working memory task. Following tDCS, younger adults demonstrated alterations in early TMS-Evoked Potentials (TEPs), namely P30 and P60. Both younger and older adults exhibited a larger task-related N250 amplitude after stimulation, with contrasting relationships to cognitive performance. The MCI group showed no change in TEPs or ERPs over time. Comparisons between the groups revealed differences in the change in amplitude of early TEP (P60) and ERP (N100) peaks between younger and older adults. Our findings indicate that tDCS was able to modulate cortical activity in younger and older healthy adults, but in varying ways. These findings suggest that varied response to tDCS may be related to factors such as age and the presence/absence of cognitive impairment, and these factors should be considered when assessing the effectiveness of tDCS in healthy and pathological aging.

Differentiating responders and non-responders to rTMS treatment for depression after one week using resting EEG connectivity measures.

BACKGROUND: Non-response to repetitive transcranial magnetic stimulation (rTMS) treatment for depression is costly for both patients and clinics. Simple and cheap methods to predict response would reduce this burden. Resting EEG measures differentiate responders from non-responders, so may have utility for response prediction. METHODS: Fifty patients with treatment resistant depression and 21 controls had resting electroencephalography (EEG) recorded at baseline (BL). Patients underwent 5-8 weeks of rTMS treatment, with EEG recordings repeated at week 1 (W1). Forty-two participants had valid BL and W1 EEG data, and 12 were responders. Responders and non-responders were compared at BL and W1 in measures of theta (4-8 Hz) and alpha (8-13 Hz) power and connectivity, frontal theta cordance and alpha peak frequency. Control group comparisons were made for measures that differed between responders and non-responders. A machine learning algorithm assessed the potential to differentiate responders from non-responders using EEG measures in combination with change in depression scores from BL to W1. RESULTS: Responders showed elevated theta connectivity across BL and W1. No other EEG measures differed between groups. Responders could be distinguished from non-responders with a mean sensitivity of 0.84 (p = 0.001) and specificity of 0.89 (p = 0.002) using cross-validated machine learning classification on the combination of all EEG and mood measures. LIMITATIONS: The low response rate limited our sample size to only 12 responders. CONCLUSION: Resting theta connectivity at BL and W1 differ between responders and non-responders, and show potential for predicting response to rTMS treatment for depression.

Evidence for the improvement of fatigue in fibromyalgia: A 4-week left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation randomized-controlled trial.

BACKGROUND: Fibromyalgia is a complex chronic disorder with few effective treatments currently available. One promising treatment option is repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique that has shown promise in disorders effecting the central nervous system. METHODS: We assessed the efficacy of a course of high-frequency (10 Hz) left-hemisphere dorsolateral prefrontal cortex (DLPFC) rTMS in 26 patients (14 active; 12 sham) with a diagnosis of fibromyalgia. Participants underwent a double-blind stimulation protocol of daily (Monday-Friday) rTMS sessions over four consecutive weeks (total of 20 sessions; 75 × 4-s 10 Hz trains at 120% resting motor threshold). Assessments were conducted at baseline, 4 weeks and at 1-month follow-up. RESULTS: Using mixed-model analysis we did not identify a group difference for our primary outcome measures. However, we found that patients in the active group compared to sham treatment group had significantly greater improvement in the Physical Fatigue (p = 0.045) and General Fatigue (p = 0.023) scales of the Multidimensional Fatigue Inventory-20 at the 1 month follow-up. In a responder analysis, we also found the active group was significantly more likely (2.84 times) to achieve a minimum 30% improvement in pain intensity ratings. (p = 0.024). CONCLUSIONS: High-frequency rTMS applied daily for 4 weeks to the left DLPFC induces significant relief from fatigue and a greater chance of clinically meaningful improvement in pain intensity in patients with fibromyalgia. These results suggest DLPFC rTMS may be a relevant therapy for fibromyalgia. SIGNIFICANCE: This study provides evidence that 4-weeks of daily rTMS to the left DLPFC is able to improve fatigue in fibromyalgia. This novel finding provides impetus for the further investigation of the utility of TMS approaches for the relief of fatigue, an otherwise difficult-to-treat symptom, in fibromyalgia and related disorders.

Responders to rTMS for depression show increased fronto-midline theta and theta connectivity compared to non-responders.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, but only some individuals respond. Predicting response could reduce patient and clinical burden. Neural activity related to working memory (WM) has been related to mood improvements, so may represent a biomarker for response prediction. PRIMARY HYPOTHESES: We expected higher theta and alpha activity in responders compared to non-responders to rTMS. METHODS: Fifty patients with treatment resistant depression and twenty controls performed a WM task while electroencephalography (EEG) was recorded. Patients underwent 5-8 weeks of rTMS treatment, repeating the EEG at week 1 (W1). Of the 39 participants with valid WM-related EEG data from baseline and W1, 10 were responders. Comparisons between responders and non-responders were made at baseline and W1 for measures of theta (4-8 Hz), upper alpha (10-12.5 Hz), and gamma (30-45 Hz) power, connectivity, and theta-gamma coupling. The control group's measures were compared to the depression group's baseline measures separately. RESULTS: Responders showed higher levels of WM-related fronto-midline theta power and theta connectivity compared to non-responders at baseline and W1. Responder's fronto-midline theta power and connectivity was similar to controls. Responders also showed an increase in gamma connectivity from baseline to W1, with a concurrent improvement in mood and WM reaction times. An unbiased combination of all measures provided mean sensitivity of 0.90 at predicting responders and specificity of 0.92 in a predictive machine learning algorithm. CONCLUSION: Baseline and W1 fronto-midline theta power and theta connectivity show good potential for predicting response to rTMS treatment for depression.

Neural evidence that conscious awareness of errors is reduced in depression following a traumatic brain injury.

Impaired error awareness is related to poorer outcome following traumatic brain injury (TBI). Error awareness deficits are also found in major depressive disorder (MDD), but have not been examined in the MDD that follows a TBI (TBI-MDD). This study assessed neural activity related to error awareness in TBI-MDD. Four groups completed a response inhibition task while EEG was recorded- healthy controls (N = 15), MDD-only (N = 15), TBI-only (N = 16), and TBI-MDD (N = 12). Error related EEG activity was compared using powerful randomisation statistics that included all electrodes and time points. Participants with TBI-MDD displayed less frontally distributed neural activity, suggesting reduced contribution from frontal generating sources. Neural activity during this time window is thought to reflect conscious awareness of errors. The TBI-only and MDD-only groups did not differ from controls, and early error processing was unaffected, suggesting early error detection is intact.

Motor overflow in Huntington's disease.

We investigated both motor overflow and ability to control voluntary movement in patients with Huntington's disease (HD). We hypothesised that, compared with controls, overflow would be significantly greater in HD participants and that they would exhibit poorer control of voluntary movement. In a finger flexion task, participants had to maintain target forces representing 25, 50, or 75% of the maximum strength capacity for whichever finger was performing the task; overflow was measured in the corresponding finger of the non-responding hand. HD participants exhibited significantly greater motor overflow than controls, and more difficulty controlling the target force with the active hand. In addition, the degree of overflow in HD participants positively correlated with overall UHDRS motor symptom severity. The presence of exacerbated motor overflow in HD, and its correlation with symptom severity, is an important finding worthy of further investigation.