Combining proactive transcranial stimulation and cardiac biofeedback to substantially manage harmful stress effects

BackgroundPrevious studies have identified the dorsolateral prefrontal cortex (dlPFC) as a core region in cognitive emotional regulation. Transcranial direct current stimulations of the dlPFC (tDCS) and heart-rate variability biofeedback (BFB) are known to regulate emotional processes. However, the effect of these interventions applied either alone or concomitantly during an anticipatory stress remains unexplored.ObjectiveThe study investigated the effect of anodal tDCS and BFB, alone or combined, on psychophysiological stress responses and cognitive functioning.MethodsFollowing a stress anticipation induction, 80 participants were randomized into four groups and subjected to a 15-min intervention: neutral video viewing (ctrl), left dlPFC anodal tDCS (tdcs), heart-rate variability biofeedback (bfb), or a combined treatment (bfb + tdcs). Participants were then immediately confronted with the stressor, which was followed by an assessment of executive functions. Psychophysiological stress responses were assessed throughout the experiment (heart rate, heart-rate variability, salivary cortisol).ResultsThe tdcs did not modulate stress responses. Compared with both ctrl and tdcs interventions, bfb reduced physiological stress and improved executive functions after the stressor. The main finding revealed that bfb + tdcs was the most effective intervention, yielding greater reduction in psychological and physiological stress responses than bfb.ConclusionsCombining preventive tDCS with BFB is a relevant interventional approach to reduce psychophysiological stress responses, hence offering a new and non-invasive treatment of stress-related disorders. Biofeedback may be particularly useful for preparing for an important stressful event when performance is decisive.     

The Effects of Acute Transcranial Direct Current Stimulation on Attentional Bias in Pedophilic Disorder: A Preregistered Pilot Study

ObjectivesIndividuals with pedophilic disorder (PD) experience personal and interpersonal difficulties and are at risk of sexually offending against children. As such, innovative and empirically validated treatments are needed. Recent studies have indicated that men who have sexually offended against children (SOC) with PD display an automatic attention bias for child-related stimuli as well as reduced activity in the dorsolateral prefrontal cortex (dlPFC), a brain area involved in cognitive control, including control over sexual arousal. In this preregistered pilot study, we are the first to investigate whether acutely increasing prefrontal activity could reduce the putative pedophilic attention bias.Materials and MethodsWe delivered a single 20-min session of active anodal versus sham transcranial direct current stimulation (tDCS) over the left dlPFC to 16 SOC with PD and 16 matched healthy controls, while they performed a task requiring controlled attention to computer-generated images of clothed and nude children and adults. We collected responses unobtrusively by recording eye movements.ResultsOur results did not support the presence of the expected automatic attention bias across outcome measures. Nonetheless, we found a response facilitation with child targets in patients and, unexpectedly, in controls, likely due to unwanted salience effects. Active versus sham tDCS reduced this bias across groups, as indicated by a significant group*condition interaction (p = 0.04). However, no attentional bias and no tDCS effects on attentional responses to child and adult images emerged following tDCS.ConclusionsThese results suggest enhanced cognitive control in response to salient stimuli during active tDCS. Thus, to assist future studies on neuromodulation in PD, we provide suggestions for design improvement.     

Bad and worse: neural systems underlying reappraisal of high- and low-intensity negative emotions

One of the most effective strategies for regulating emotional responses is cognitive reappraisal. While prior work has made great strides in characterizing reappraisal’s neural mechanisms and behavioral outcomes, the key issue of how regulation varies as a function of emotional intensity remains unaddressed. We compared the behavioral and neural correlates of reappraisal of high- and low-intensity emotional responses using functional magnetic resonance imaging (fMRI). We found that successful reappraisal of both high- and low-intensity emotions depends upon recruitment of dorsomedial (dmPFC) as well as left dorsolateral (dlPFC) and ventrolateral (vlPFC) prefrontal cortex. However, reappraisal of high-intensity emotions more strongly activated left dlPFC, and in addition, activated right lateral and dorsomedial PFC regions not recruited by low-intensity reappraisal. No brain regions were more strongly recruited during reappraisal of low when compared with high-intensity emotions. Taken together, these results suggest that reappraisal of high-intensity emotion requires greater cognitive resources as evidenced by quantitative and qualitative differences in prefrontal recruitment. These data have implications for understanding how and when specific PFC systems are needed to regulate different types of emotional responses.     

Dopamine depletion effects on cognitive flexibility as modulated by tDCS of the dlPFC

BackgroundRecent evidence suggests that transcranial direct current stimulation (tDCS) may interact with the dopaminergic system to affect cognitive flexibility.Objective/hypotheses: We examined whether putative reduction of dopamine levels through the acute phenylalanine/tyrosine depletion (APTD) procedure and excitatory anodal tDCS of the dorsolateral prefrontal cortex (dlPFC) are causally related to cognitive flexibility as measured by task switching and reversal learning.MethodA double-blind, sham-controlled, randomised trial was conducted to test the effects of combining anodal tDCS and depletion of catecholaminergic precursor tyrosine on cognitive flexibility.ResultsAnodal tDCS and tyrosine depletion had a significant effect on task switching, but not reversal learning. Whilst perseverative errors were significantly improved by anodal tDCS, the APTD impaired reaction times. Importantly, the combination of APTD and anodal tDCS resulted in cognitive performance which did not statistically differ to that of the control condition.ConclusionsOur results suggest that the effects of tDCS on cognitive flexibility are modulated by dopaminergic tone.     

Noninvasive brain stimulation in children and adults with attention-deficit/hyperactivity disorder: a systematic review and meta-analysis

BackgroundRepetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) could provide treatment alternatives to stimulant medication for attention-deficit/hyperactivity disorder (ADHD), given some evidence for improvements in cognition and clinical symptoms. However, despite a lack of solid evidence for their use, rTMS and tDCS are already offered clinically and commercially in ADHD. This systematic review and meta-analysis aimed to critically appraise rTMS and tDCS studies in ADHD to inform good research and clinical practice.MethodsA systematic search (up to February 2019) identified 18 studies (rTMS 4, tDCS 14; 311 children and adults with ADHD) stimulating mainly the dorsolateral prefrontal cortex (dlPFC). We included 12 anodal tDCS studies (232 children and adults with ADHD) in 3 random-effects meta-analyses of cognitive measures of attention, inhibition and processing speed.ResultsThe review of rTMS and tDCS showed positive effects in some functions but not others, and little evidence for clinical improvement. The meta-analyses of 1 to 5 sessions of anodal tDCS over mainly the left or bilateral dlPFC showed trend-level improvements in inhibition and processing speed, but not in attention.LimitationsHeterogeneity in stimulation parameters, patient age and outcome measures limited the interpretation of findings.ConclusionThe review and meta-analysis showed limited evidence that 1 to 5 sessions of rTMS and tDCS, mostly of the dlPFC, improved clinical or cognitive measures of ADHD. These findings did not support using rTMS or tDCS of the dlPFC as an alternative neurotherapy for ADHD as yet. Larger, multi-session stimulation studies identifying more optimal sites and stimulation parameters in combination with cognitive training could achieve larger effects.     

Enhancing cognitive control training with transcranial direct current stimulation: a systematic parameter study

BackgroundCognitive control (CC) is an important prerequisite for goal-directed behaviour and efficient information processing. Impaired CC is associated with reduced prefrontal cortex activity and various mental disorders, but may be effectively tackled by transcranial direct current stimulation (tDCS)-enhanced training. However, study data are inconsistent as efficacy depends on stimulation parameters whose implementations vary widely between studies.ObjectiveWe systematically tested various tDCS parameter effects (anodal/cathodal polarity, 1/2 mA stimulation intensity, left/right prefrontal cortex hemisphere) on a six-session CC training combined with tDCS.MethodsNine groups of healthy humans (male/female) received either anodal/cathodal tDCS of 1/2 mA over the left/right PFC or sham stimulation, simultaneously with a CC training (modified adaptive Paced Auditory Serial Addition Task [PASAT]). Subjects trained thrice per week (19 min each) for two weeks. We assessed performance progress in the PASAT before, during, and after training. Using a hierarchical approach, we incrementally narrowed down on optimal stimulation parameters supporting CC. Long-term CC effects as well as transfer effects in a flanker task were assessed after the training period as well as three months later.ResultsCompared to sham stimulation, anodal but not cathodal tDCS improved performance gains. This was only valid for 1 mA stimulation intensity and particularly detected when applied to the left PFC.ConclusionsOur results confirm beneficial, non-linear effects of anodal tDCS on cognitive training in a large sample of healthy subjects. The data consolidate the basis for further development of functionally targeted tDCS, supporting cognitive control training in mental disorders and guiding further development of clinical interventions.     

Neurophysiological and behavioral effects of multisession prefrontal tDCS and concurrent cognitive remediation training in patients with autism spectrum disorder (ASD): A double-blind,randomized controlled fNIRS study

BackgroundThe clinical effects and neurophysiological mechanisms of prefrontal tDCS and concurrent cognitive remediation training in individuals with autism spectrum disorder (ASD) remain unclear.ObjectiveThis two-armed, double-blind, randomized, sham-controlled trial aimed to investigate the beneficial effects of tDCS combined with concurrent cognitive remediation training on adolescents and young adults with ASD.MethodsParticipants were randomly assigned to either active or sham tDCS groups and received 1.5 mA prefrontal tDCS with left dorsolateral prefrontal cortex (dlPFC) cathode placement and right supraorbital region anode placement for 20 minutes over two consecutive weeks. tDCS was delivered concurrently with a computerized cognitive remediation training program. Social functioning and its underlying cognitive processes, as well as prefrontal resting-state functional connectivity (rsFC), were measured.ResultsThe results from 41 participants indicated that multisession prefrontal tDCS, compared to sham tDCS, significantly enhanced the social functioning of ASD individuals [F(1,39) = 4.75, p = .035, η_p² = 0.11]. This improvement was associated with enhanced emotion recognition [F(1,39) = 8.34, p = .006, η_p² = 0.18] and cognitive flexibility [F(1,39) = 4.91, p = .033, η_p² = 0.11]. Specifically, this tDCS protocol optimized information processing efficiency [F(1,39) = 4.43, p = .042, η_p² = 0.10], and the optimization showed a trend to be associated with enhanced rsFC in the right medial prefrontal cortex (ρ = 0.339, pFDR = .083).ConclusionMultisession tDCS with left dlPFC cathode placement and right supraorbital region anode placement paired with concurrent cognitive remediation training promoted social functioning in individuals with ASD. This appeared to be associated with the enhancement of the functional connectivity of the right medial PFC, a major hub for flexible social information processing, allowing these individuals to process information more efficiently in response to different social situations.Trial registrationClinicalTrials.gov (ID: NCT03814083)     

Transcranial direct current stimulation (tDCS) alters the pattern of information processing in children with ADHD: Evidence from drift diffusion modeling

ObjectivePerformance accuracy and reaction time in cognitive tasks are routinely used to evaluate the efficacy of tDCS to affect cognitive task performance. tDCS alters the excitability of targeted brain areas and thereby alters performance of cognitive tasks. The drift diffusion model (DDM) provides some additional measures to explore information processing style, such as (non)decision time, bias for decision, and speed of information processing. DDM parameters are informative for the study of cognitive impairments in children with ADHD. In the present study, we aimed to evaluate the impact of tDCS on cognitive performance via DDM measures.MethodsThis study conducted DDM modeling and reanalysis of two exploratory, single-blinded, within-subject design experiments, which were published earlier. In the first experiment, twenty- four children with ADHD performed a Go/ No- Go task during anodal or sham tDCS over the right dlPFC. In the second experiment, twenty- five children with ADHD performed the 1- back working memory task during anodal or sham tDCS over the left dlPFC. We reanalyzed the data after DDM modeling.ResultsThe conventional performance measures revealed no significant effect of tDCS on No- Go accuracy in the first experiment and 1-back accuracy in the second experiment. The 1-back reaction time and speed-accuracy tradeoff were however improved under the real stimulation condition. The DDM measures identified increased No-Go- bias and decision time with respect to inhibitory control, and an increased threshold and amount of information required for response in the 1- back test.ConclusionIn children with ADHD, anodal tDCS over the right dlPFC induces more conservative and less impulsive decisions. Furthermore, anodal tDCS over the left dlPFC enhanced efficacy of working memory performance with respect to agility and capacity. The experimental results show that drift diffusion modeling is useful for evaluation of the impact of tDCS on the style of information processing.     

Transcranial direct current stimulation facilitates category learning

BackgroundAfter two decades of transcranial direct current stimulation (tDCS) research, it is still unclear which applications benefit most from which tDCS protocols. One prospect is the acceleration of learning, where previous work has demonstrated that anodal tDCS applied to the right ventrolateral prefrontal cortex (rVLPFC) is capable of doubling the rate of learning in a visual camouflaged threat detection and category learning task.GoalsQuestions remain as to the specific cognitive mechanisms underlying this learning enhancement, and whether it generalizes to other tasks. The goal of the current project was to expand previous findings by employing a novel category learning task.MethodsParticipants learned to classify pictures of European streets within a discovery learning paradigm. In a double-blind design, 54 participants were randomly assigned to 30 min of tDCS using either 2.0 mA anodal (n = 18), cathodal (n = 18), or 0.1 mA sham (n = 18) tDCS over the rVLPFC.ResultsA linear mixed-model revealed a significant effect of tDCS condition on classification accuracy across training (p = 0.001). Compared to a 4.2% increase in sham participants, anodal tDCS over F10 increased performance by 20.6% (d = 1.71) and cathodal tDCS by 14.4% (d = 1.16).ConclusionsThese results provide further evidence for the capacity of tDCS applied to rVLPFC to enhance learning, showing a greater than quadrupling of test performance after training (491% of sham) in a difficult category learning task. Combined with our previous studies, these results suggest a generalized performance enhancement. Other tasks requiring sustained attention, insight and/or category learning may also benefit from this protocol.     

Testing a Neurobiological Model of Depersonalization Disorder Using Repetitive Transcranial Magnetic Stimulation

BackgroundDepersonalization disorder (DPD) includes changes in subjective experiencing of self, encompassing emotional numbing. Functional magnetic resonance imaging (fMRI) has pointed to ventrolateral prefrontal cortex (VLPFC) inhibition of insula as a neurocognitive correlate of the disorder.ObjectiveWe hypothesized that inhibition to right VLPFC using repetitive transcranial magnetic stimulation (rTMS) would lead to increased arousal and reduced symptoms.MethodsPatients with medication-resistant DSM-IV DPD (N = 17) and controls (N = 20) were randomized to receive one session of right-sided rTMS to VLPFC or temporo-parietal junction (TPJ). 1Hz rTMS was guided using neuronavigation and delivered for 15 min. Co-primary outcomes were: (a) maximum skin conductance capacity, and (b) reduction in depersonalization symptoms (Cambridge Depersonalisation Scale (CDS) [state version]). Secondary outcomes included spontaneous fluctuations (SFs) and event-related skin conductance responses.ResultsIn patients with DPD, rTMS to VLPFC led to increased electrodermal capacity, namely maximum skin conductance deflections. Patients but not controls also showed increased SFs post rTMS. Patients who had either VLPFC or TPJ rTMS showed a similar significant reduction in symptoms. Event-related electrodermal activity did not change.ConclusionsA single session of right-sided rTMS to VLPFC (but not TPJ) significantly increased physiological arousal capacity supporting our model regarding the relevance of increased VLPFC activity to emotional numbing in DPD. rTMS to both sites led to reduced depersonalization scores but since this was independent of physiological arousal, this may be a non-specific effect. TMS is a potential therapeutic option for DPD; modulation of VLPFC, if replicated, is a plausible mechanism.     

Modulating affective experience and emotional intelligence with loving kindness meditation and transcranial direct current stimulation: A pilot study

Positive emotional perceptions and healthy emotional intelligence (EI) are important for social functioning. In this study, we investigated whether loving kindness meditation (LKM) combined with anodal transcranial direct current stimulation (tDCS) would facilitate improvements in EI and changes in affective experience of visual stimuli. LKM has been shown to increase positive emotional experiences and we hypothesized that tDCS could enhance these effects. Eighty-seven undergraduates were randomly assigned to 30 minutes of LKM or a relaxation control recording with anodal tDCS applied to the left dorsolateral prefrontal cortex (left dlPFC) or right temporoparietal junction (right TPJ) at 0.1 or 2.0 milliamps. The primary outcomes were self-reported affect ratings of images from the International Affective Picture System and EI as measured by the Mayer, Salovey and Caruso Emotional Intelligence Test. Results indicated no effects of training on EI, and no main effects of LKM, electrode placement, or tDCS current strength on affect ratings. There was a significant interaction of electrode placement by meditation condition (p = 0.001), such that those assigned to LKM and right TPJ tDCS, regardless of current strength, rated neutral and positive images more positively after training. Results suggest that LKM may enhance positive affective experience.     

Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial

ObjectivesWe aimed to examine the effects of multisite anodal transcranial direct current stimulation (tDCS) combined with cognitive stimulation (CS) over 2 months on cognitive performance and brain activity, and the relationship between them, in patients with Alzheimer's disease (AD).MethodsPatients with AD were randomly assigned to an active tDCS+CS (n=18) or a sham tDCS+CS (n=18) group. Cognitive performance was assessed using the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain activity using EEG (spectral power and coherence analysis) before and after the intervention. Multisite anodal tDCS (2 mA, 30 min) was applied over six brain regions [left and right dorsolateral prefrontal cortex (F3 and F4), Broca's area (F5), Wernicke's area (CP5), left and right somatosensory association cortex (P3 and P4)] for 24 sessions (three times a week). Both groups performed CS during tDCS.ResultsAnodal tDCS+CS delays cognitive decline (ADAS-cog change) to a greater extent than sham tDCS+CS (-3.4±1.1 vs. -1.7±0.4; p=.03). Bilateral EEG coherence at high and low frequencies was greater for the active tDCS+CS than sham+CS group for most electrode pairs assessed (p < .05). The post-intervention ADAS-cog change score was predictive for EEG coherence at different sites (R²=.59 to .68; p < .05) in the active but not in the sham tDCS+CS group.ConclusionAnodal tDCS+CS improved overall cognitive function and changed EEG brain activity compared to sham tDCS+CS. Changes in cognitive performance were associated with changes in EEG measures of brain activity. Anodal tDCS+CS appears to be a promising therapeutic strategy to modulate cortical activity and improve cognitive function in patients with AD.     

Scaffolding the attention-deficit/hyperactivity disorder brain using transcranial direct current and random noise stimulation: A randomized controlled trial

ObjectiveImproving symptomology and cognitive deficits in neurodevelopmental disorders is a crucial challenge. We examined whether neurostimulation protocols, which have been shown to yield long-term effects when combined with cognitive training, could benefit children with Attention-deficit/hyperactivity-disorder (ADHD), the most common neurodevelopmental disorder in childhood.MethodsWe used a randomized double-blind active-controlled crossover study of 19 unmedicated children with ADHD, who received either anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (dlPFC) or random noise stimulation (tRNS) over the bilateral dlPFC, while completing executive functions training.ResultsFor our primary outcome, tRNS yielded a clinical improvement as indicated by the reduced ADHD rating-scale score from baseline, and in comparison to the changes observed in tDCS. The effect of brain stimulation one week after completion of treatment yielded further improvement, suggesting a neuroplasticity-related effect. Finally, tRNS improved working memory compared to tDCS, and a larger tRNS effect on ADHD rating-scale was predicted for those who showed the greatest improvement in working memory.ConclusionsWe found that our intervention can have a lasting effect, rather than a merely immediate effect as was shown for in previous medical interventions in ADHD.SignificanceOur results provide a promising direction toward a novel intervention in ADHD.     

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

BackgroundTranscranial 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.ObjectiveTo 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.MethodsUsing 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.ResultstRNS 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.ConclusionsThese 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.     

Enhancing decision-making and cognitive impulse control with transcranial direct current stimulation (tDCS) applied over the orbitofrontal cortex (OFC): A randomized and sham-controlled exploratory study

BackgroundDecision-making and impulse control (both cognitive and motor) are complex interrelated processes which rely on a distributed neural network that includes multiple cortical and subcortical regions. Among them, the orbitofrontal cortex (OFC) seems to be particularly relevant as demonstrated by several neuropsychological and neuroimaging investigations.MethodsIn the present study we assessed whether transcranial direct current stimulation (tDCS) applied bilaterally over the OFC is able to modulate decision-making and cognitive impulse control. More specifically, 45 healthy subjects were randomized to receive a single 30-min session of active or sham anodal tDCS (1.5 mA) applied over either the left or the right OFC (coupled with contralateral cathodal tDCS). They were also assessed pre- and post-tDCS with a battery of computerized tasks.ResultsOur results show that participants who received active anodal tDCS (irrespective of laterality), vs. those who received sham tDCS, displayed more advantageous decision-making (i.e., increased Iowa Gambling Task “net scores” [p = 0.04]), as well as improved cognitive impulse control (i.e., decreased “interference” in the Stroop Word-Colour Task [p = 0.007]). However, we did not observe tDCS-related effects on mood (assessed by visual analogue scales), attentional levels (assessed by the Continuous Performance Task) or motor impulse control (assessed by the Stop-Signal Task).ConclusionsOur study potentially serves as a key translational step towards the development of novel non-invasive neuromodulation-based therapeutic interventions directly targeting vulnerability factors for psychiatric conditions such as suicidal behaviour and addiction.     

Acquisition of Conditioned Eyeblink Responses is Modulated by Cerebellar tDCS

BackgroundClassical conditioning of the eyeblink reflex is a simple form of motor learning which depends on the integrity of the cerebellum. Acquisition of conditioned eyeblink responses is markedly reduced in patients with cerebellar disorders. Noninvasive transcranial direct current stimulation (tDCS) has been reported to modify the excitability of the cerebellar cortex.ObjectiveThe aim of the study was to assess whether acquisition of conditioned eyeblink responses (CR) is altered by cerebellar tDCS.MethodsA standard delay conditioning paradigm with a 540 ms tone as conditioned stimulus (CS) coterminating with a 100 ms air puff as unconditioned stimulus (US) was used in a total of 30 healthy subjects (18 female, 12 male, mean age 23.4 ± 1.9 years). One hundred paired CS-US trials and 30 extinction CS alone trials were given. tDCS (2 mA intensity, ramp like onset) was applied over the right cerebellar hemisphere ipsilaterally to the US during the acquisition phase. Subjects were randomly assigned to three groups (n = 10) using anodal, cathodal or sham stimulation. The investigator as well as the participants was blinded to the stimulation modality.ResultsCR acquisition was significantly enhanced by anodal tDCS (mean total CR incidence 73.4 ± 25.2%) and significantly reduced by cathodal stimulation (12.6 ± 17.2%) compared to sham stimulation (43.8 ± 24.1%). During anodal tDCS CR onset occurred significantly earlier, that is mean onset of responses was shifted closer to CS onset.ConclusionAcquisition and timing of conditioned eyeblink responses is modified by cerebellar tDCS in a polarity dependent manner.     

Transcranial Direct Current Stimulation (tDCS) Enhances Reconsolidation of Long-Term Memory

A new and weak memory trace undergoes consolidation to gain resistance against interfering stimuli. When an encoded memory is recalled, it becomes labile and another round of consolidation, or reconsolidation, is required to restore its stability. Transcranial direct current stimulation (tDCS) is a non-invasive method of altering cortical excitability. The aim of this study was to examine the effects of tDCS on the reconsolidation of long-term verbal memory. Participants (n = 15) memorized words in the encoding session, then reactivated the memory of the words 3 h later using an old–new recognition task under anodal, cathodal and sham stimulation to the left dorsolateral prefrontal cortex (DLPFC). Finally, after another 5 h, they performed another round of the old–new recognition task and rated their confidence. Anodal tDCS during the second session resulted in significantly more words recognized in the third session as compared to cathodal and sham stimulation. Cathodal tDCS did not affect the recognition performance compared to sham stimulation. These results cannot be attributed to differences in response times and confidence ratings, as they were comparable in all conditions. In order to study whether the activation of a memory was crucial for the enhancing effects of anodal tDCS, a group of controls (n = 15) did not perform the recognition task in the second session but still underwent stimulation. Contrary to the main group, anodal stimulation did not enhance the memory performance for the control group. This result suggests that anodal tDCS over the left DLPFC can enhance the reconsolidation of long-term memory only when the memory has been reactivated.     

The Adjunct of Electric Neurostimulation to Rehabilitation Approaches in Upper Limb Stroke Rehabilitation: A Systematic Review With Network Meta-Analysis of Randomized Controlled Trials

ObjectiveThis review analyzed the current evidence and the potential for the application of electric neurostimulation such as transcranial direct current stimulation (tDCS) and vagus nerve stimulation (VNS) in upper limb stroke rehabilitation.Materials and MethodsWe performed a systematic review of randomized controlled trials (RCTs) using network meta-analysis (NMA), searching the following data bases: PubMed, Web of Science, Cochrane, and Google Scholar, using specific keywords, from January 2010 to April 2021, and assessing the effects of “tDCS” or “VNS” combined with other therapies on upper limb motor function and activities of daily living (ADL) after stroke.ResultsWe included 38 RCTs with 1261 participants. Pairwise NMA showed transcutaneous VNS (tVNS) and anodal tDCS were effective in improving upper limb motor function (tVNS: mean difference [MD]: 5.50; 95% CI [0.67–11.67]; p < 0.05; anodal tDCS: MD: 5.23; 95% CI [2.45–8.01]; p < 0.05). tVNS and tDCS (anodal and cathodal) were also effective in improving ADL performance after stroke (tVNS: standard MD [SMD]: 0.96; 95% CI [0.15–2.06]; p < 0.05; anodal tDCS: SMD: 3.78; 95% CI [0.0–7.56]; p < 0.05; cathodal tDCS: SMD: 5.38; 95% CI [0.22–10.54]; p < 0.05). Surface under the cumulative ranking curve analysis revealed that tVNS is the best ranked treatment in improving upper limb motor function and performance in ADL after stroke. There was no difference in safety between VNS and its control interventions, measured by reported adverse events (VNS: risk ratio = 1.02 [95% CI = 0.48–2.17; I² = 0; p = 0.96]).ConclusionModerate- to high-quality evidence suggests that tVNS and anodal tDCS were effective in improving upper limb motor function in both acute/subacute and chronic stroke. In addition to tVNS and anodal tDCS, cathodal tDCS is also effective in improving ADL performance after stroke.     

Regulation of emotional responses elicited by threat-related stimuli

The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self-report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat-related pictures and were asked to up- and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial-by-trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left-hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up- and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat-related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state.     

Effects of a Non-focal Plasticity Protocol on Apathy in Moderate Alzheimer's Disease: A Randomized,Double-blind,Sham-controlled Trial

BackgroundApathy is the most common neuropsychiatric symptom in Alzheimer's disease (AD) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions. To date no effective treatment for apathy has been demonstrated.ObjectiveWe aimed to investigate the effects and safety of repetitive transcranial direct current stimulation (tDCS) on apathy in moderate AD patients.MethodsForty patients were randomized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex (DLPFC). Patients received six sessions of intervention during 2 weeks and were evaluated at baseline, at week 1 and 2, and after 1 week without intervention. Clinical raters, patients, and caregivers were blinded. The primary outcome was apathy. Global cognition and neuropsychiatric symptoms were examined as secondary outcomes.ResultsThe mean MMSE score at baseline was 15.2 ± 2.9 and the mean Apathy Scale score was 27.7 ± 6.7. Changes on apathy scores over time were not different between active and sham tDCS (P = 0.552 for repeated measures). Further analyses confirm that changes from baseline did not differ between groups after the sixth session (active tDCS −1.95 (95%CI −3.49, −0.41); sham-tDCS −2.05 (95%CI −3.68, −0.42); P = 0.989]. Similarly, tDCS had no effect on secondary outcomes (P > 0.40). tDCS was well tolerated and not associated with significant adverse effects.ConclusionIn this adequately powered study for minimal clinically significant difference, our findings show that using the parameters we chose for this study, repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD.