Self-administered transcranial direct current stimulation for pain in older adults with knee osteoarthritis: A randomized controlled study

BackgroundKnee osteoarthritis (OA) is a leading cause of pain in older adults. Previous studies indicated clinic-based transcranial direct current stimulation (tDCS) was effective to reduce pain in various populations, but no published studies have reported the efficacy of home-based self-administered tDCS in older adults with knee OA using a randomized clinical study.ObjectiveThe purpose of this study was to evaluate the efficacy and feasibility of tDCS on clinical pain intensity in adults with knee OA pain.MethodsOne hundred twenty participants aged 50–85 years with knee OA pain were randomly assigned to receive fifteen daily sessions of 2 mA tDCS for 20 min (n = 60) or sham tDCS (n = 60) over 3 weeks with remote supervision via telehealth. Clinical pain intensity was measured by the Numeric Rating Scale and Western Ontario and McMaster Universities Osteoarthritis Index. Also, we collected data on the tDCS experience via a questionnaire.ResultsParticipants (68% female) had a mean age of 66 years. Active tDCS significantly reduced pain intensity compared to sham tDCS after completion of the fifteen daily sessions (Cohen's d = 1.20; p-value < 0.0001). Participants showed high levels of satisfaction with their tDCS experience, and there have been no adverse events.ConclusionWe demonstrated that home-based self-administered tDCS was feasible and reduced clinical pain intensity in older adults with knee OA, which can increase its accessibility. Future studies with multi-site randomized controlled trials are needed to validate our findings.Trial registrationClinicalTrials.gov Identifier NCT04016272.     

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial

ObjectivesLittle evidence is available on the role of transcranial direct current stimulation (tDCS) in patients affected by chronic migraine (CM) and medication overuse headache (MOH). We aim to investigate the effects of tDCS in patients with CM and MOH as well as its role on brain activity.MethodsTwenty patients with CM and MOH were hospitalized for a 7-day detoxification treatment. Upon admission, patients were randomly assigned to anodal tDCS or sham stimulation delivered over the primary motor cortex contralateral to the prevalent migraine pain side every day for 5 days. Clinical data were recorded at baseline (T0), after 1 month (T2) and 6 months (T3). EEG recording was performed at T0, at the end of the tDCS/Sham treatment, and at T2.ResultsAt T2 and T3, we found a significant reduction in monthly migraine days (p = 0.001), which were more pronounced in the tDCS group when compared to the sham group (p = 0.016).At T2, we found a significant increase of alpha rhythm in occipital leads, which was significantly higher in tDCS group when compared to sham group.ConclusionstDCS showed adjuvant effects to detoxification in the management of patients with CM and MOH. The EEG recording showed a significant potentiation of alpha rhythm, which may represent a correlate of the underlying changes in cortico-thalamic connections.SignificanceThis study suggests a possible role for tDCS in the treatment of CM and MOH. The observed clinical improvement is coupled with a potentiation of EEG alpha rhythm.     

Long-term prophylactic efficacy of transcranial direct current stimulation in chronic migraine. A randomised,patient-assessor blinded,sham-controlled trial

ObjectiveTo assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance.MethodsIn a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups.ResultsThe monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (?21% ± 22 vs. ?2% ±25, p = 0.019) to the end of follow-up (3-month post-treatment) (?32% ± 33 vs. ?6% ±39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks ≥30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043).ConclusionOur results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM.     

Repeated stimulation of the dorsolateral-prefrontal cortex improves executive dysfunctions and craving in drug addiction: A randomized,double-blind,parallel-group study

BackgroundAccording to the neurocognitive model of addiction, the development and maintenance of drug addiction is associated with cognitive control deficits, as well as decreased activity of prefrontal regions, especially the dorsolateral prefrontal cortex (DLPFC). This study investigated how improving executive functions (EFs) impacts methamphetamine-use disorder, which has been less explored compared to craving, but might be a central aspect for the therapeutic efficacy of DLPFC stimulation in drug addiction.MethodsWe assessed the efficacy of 10 repeated sessions of transcranial direct current stimulation (tDCS) over the DLPFC on executive dysfunctions in methamphetamine-use disorder, and its association with craving alterations. 39 of 50 initially recruited individuals with methamphetamine-use disorder who were in the abstinent-course treatment were randomly assigned to “active” and “sham” stimulation groups in a randomized, double-blind parallel-group study. They received active (2 mA, 20 min) or sham tDCS for 10 sessions over 5 weeks. Performance on major EF tasks (e.g., working memory, inhibitory control, cognitive flexibility, and risk-taking behaviour) and craving were measured before, immediately after, and 1 month following the intervention. Participants reported abstinence from drug consumption throughout the experiment, verified by regular urine tests during the course of the study up to the follow-up measurement.ResultsThe group which received active DLPFC tDCS showed significantly improved task performance across all EFs immediately after and 1 month following the intervention, when compared to both pre-stimulation baseline and individuals who received sham tDCS. Similarly, a significant reduction in craving was observed immediately after and 1 month following the intervention in the active, but not sham stimulation group. A significant correlation between cognitive control improvement and craving reduction was found as well.ConclusionsImprovement of cognitive control functions is closely associated with reduced craving. Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction. However, the observed findings require further confirmation by studies that measure relapse/consumption of the respective substances over longer follow-up measurements.     

Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial

BackgroundTranscranial direct current stimulation (tDCS) is a promising intervention for major depression. However, its clinical effects are heterogeneous. We investigated, in a subsample of the randomized, clinical trial Escitalopram versus Electrical Direct Current Therapy for Depression Study (ELECT-TDCS), whether the volumes of left and right prefrontal cortex (PFC) and anterior cingulate cortex (ACC) were associated with prefrontal tDCS response.MethodsBaseline structural T1 weighted MRI data were analyzed from 52 patients (15 males). Patients were randomized to the following conditions: escitalopram 20 mg/day, bifrontal tDCS (2 mA, 30min, 22 sessions), or placebo. Antidepressant outcomes were assessed over a treatment period of 10 weeks. Voxel-based gray matter volumes of PFC and ACC were determined using state-of-the-art parcellation approaches.ResultsAccording to our a priori hypothesis, in the left dorsal PFC, larger gray matter volumes were associated with depression improvement in the tDCS group (n = 15) compared to sham (n = 21) (Cohen's d = 0.3, 95% confidence interval [0.01; 0.6], p = 0.04). Neither right PFC nor ACC volumes were associated with depression improvement. Exploratory analyses of distinct PFC subregions were performed, but no area was associated with tDCS response after correction for multiple comparisons.ConclusionLeft PFC baseline gray matter volume was associated with tDCS antidepressant effects. This brain region and its subdivisions should be investigated further as a potential neurobiological predictor for prefrontal tDCS treatment in depression and might be correlated with tDCS antidepressant mechanisms of action.     

Transcranial direct current stimulation of the right anterior temporal lobe changes interpersonal neural synchronization and shared mental processes

BackgroundPrevious studies have shown that interpersonal neural synchronization (INS) is a ubiquitous phenomenon between individuals, and recent studies have further demonstrated close associations between INS and shared external sensorimotor input and/or internal mental processes within a dyad. However, most previous studies have employed an observational approach to describe the behavior-INS correlation, leading to difficulties in causally disentangling the relationship among INS, external sensorimotor input and the internal mental process.Objective/hypothesisThe present study aimed to directly change the level of INS through anodal transcranial direct current stimulation (tDCS) to test whether the change in INS would directly impact the internal mental process (Hypothesis 1) or indirectly through external sensorimotor input; the interaction behaviors were also changed (Hypothesis 2) or not (Hypothesis 3).MethodsThirty pairs of romantically involved heterosexual couples were recruited for a within-subjects design. Three conditions were assessed: a true stimulation condition with 20-min anodal high-definition tDCS to the right anterior temporal lobe (rATL) of women before they communicated with their partners, a sham stimulation condition and a control brain region stimulation condition. The comparison between the true and sham or control brain region conditions allows us to detect the true effect of brain stimulation on INS. Functional near-infrared spectroscopy (fNIRS) hyperscanning was used to simultaneously collect dyadic participants' hemodynamic signals during communication. INS, empathy, and interaction behaviors were examined and compared among different stimulation conditions.ResultsTrue brain stimulation significantly decreased INS between the rATL of the women and sensorimotor cortex (SMC) of the men compared to the sham stimulation condition (t(27.8) = ?2.821, P = 0.009, d = 0.714) and control brain region stimulation condition (t(27.2) = ?2.606, P = 0.015, d = 0.664) during communication. It also significantly decreased the level of emotional empathy (F(2,145) = 6.893, P = 0.001) but did not change sensorimotor processes, such as verbal or nonverbal interaction behaviors. However, nonverbal behaviors mediated the relationship between the changes in INS and emotional empathy (lower limit confidence interval = 0.01, upper limit confidence interval = 2.66).Conclusion(s)These findings support the third hypothesis, suggesting that INS is associated with the shared internal mental process indirectly via the sensorimotor process, but the sensorimotor process itself does not covary with the INS and the associated internal mental process. These results provide new insight into the hierarchical architecture of dual-brain function from a bottom-up perspective.     

Differential effects of anodal and dual tDCS on sensorimotor functions in chronic hemiparetic stroke patients

Background and purposePrevious tDCS studies in chronic stroke patients reported highly inconsistent effects on sensorimotor functions. Underlying reasons could be the selection of different kinematic parameters across studies and for different tDCS setups. We reasoned that tDCS may not simply induce global changes in a beneficial-adverse dichotomy, but rather that different sensorimotor kinematics are differentially affected. Furthermore, the often-postulated higher efficacy of bilateral-dual (bi-tDCS) over unilateral-anodal (ua-tDCS) could not yet be demonstrated consistently either. We investigated the effects of both setups on a wider range of kinematic parameters from standardized robotic tasks in patients with chronic stroke.MethodsTwenty-four patients with arm hemiparesis received tDCS (20min, 1 mA) concurrent to kinematic assessments in a sham-controlled, cross-over and double-blind clinical trial. Performance was measured on four sensorimotor tasks (reaching, proprioception, cooperative and independent bimanual coordination) from which 30 parameters were extracted. On the group-level, the patterns of changes relative to sham were assessed using paired-samples t-tests and classified as (1) performance increases, (2) decreases and (3) non-significant differences. Correlations between parametric change scores were calculated for each task to assess effects on the individual-level.ResultsBoth setups induced complex effect patterns with varying proportions of performance increases and decreases. On the group-level, more increases were induced in the reaching and coordination tasks while proprioception and bimanual cooperation were overall negatively affected. Bi-tDCS induced more performance increases and less decreases compared to ua-tDCS. Changes across parameters occurred more homogeneously under bi-tDCS than ua-tDCS, which induced a larger proportion of performance trade-offs.ConclusionsOur data demonstrate profound tDCS effects on sensorimotor functions post-stroke, lending support for more pronounced and favorable effects of bi-tDCS compared to ua-tDCS. However, no uniformly beneficial pattern was identified. Instead, the modulations varied depending on the task and electrode setup, with increases in certain parameters occurring at the expense of decreases in others.     

Weak DCS causes a relatively strong cumulative boost of synaptic plasticity with spaced learning

BackgroundElectric fields generated during direct current stimulation (DCS) are known to modulate activity-dependent synaptic plasticity in-vitro. This provides a mechanistic explanation for the lasting behavioral effects observed with transcranial direct current stimulation (tDCS) in human learning experiments. However, previous in-vitro synaptic plasticity experiments show relatively small effects despite using strong fields compared to what is expected with conventional tDCS in humans (20 V/m vs. 1 V/m). There is therefore a need to improve the effectiveness of tDCS at realistic field intensities. Here we leverage the observation that effects of learning are known to accumulate over multiple bouts of learning, known as spaced learning.HypothesisWe propose that effects of DCS on synaptic long-term potentiation (LTP) accumulate over time in a spaced learning paradigm, thus revealing effects at more realistic field intensities.MethodsWe leverage a standard model for spaced learning by inducing LTP with repeated bouts of theta burst stimulation (TBS) in hippocampal slice preparations. We studied the cumulative effects of DCS paired with TBS at various intensities applied during the induction of LTP in the CA1 region of rat hippocampal slices.ResultsAs predicted, DCS applied during repeated bouts of theta burst stimulation (TBS) resulted in an increase of LTP. This spaced learning effect is saturated quickly with strong TBS protocols and stronger fields. In contrast, weaker TBS and the weakest electric fields of 2.5 V/m resulted in the strongest relative efficacies (12% boost in LTP per 1 V/m applied).ConclusionsWeak DCS causes a relatively strong cumulative effect of spaced learning on synaptic plasticity. Staturarion may have masked stronger effects sizes in previous in-vitro studies. Relative effect sizes of DCS are now closer in line with human tDCS experiments.     

Early transcranial direct current stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in hospitalized patients with stroke: A randomized,multicentre, double-blind,clinical trial

BackgroundConstraint-induced movement therapy (CIMT) and transcranial direct current stimulation (tDCS) are used to reduce interhemispheric imbalance after stroke, which is why the combination of these therapies has been used for neurological recovery, but not in the acute phase.ObjectivesTo evaluate the effectiveness of combining active or sham bihemispheric tDCS with modified CIMT (mCIMT) for the recovery of the Upper Limb (UL) in hospitalized patients with acute and subacute stroke.MethodsThis randomized controlled, double-blind, placebo-controlled, parallel group clinical trial was executed between September 2018 to March 2021 recruited 70 patients. The patients were randomized to one of two groups to receive treatment for 7 consecutive days, which included 20 min of active or sham bihemispheric tDCS daily (anodal ipsilesional and cathodal contralesional), with an mCIMT protocol. The primary outcome was the difference in the evolution of motor and functional upper limb recovery with assessment on days 0, 5, 7, 10 and 90. The secondary outcomes were independence in activities of daily living (ADL) and quality of life.ResultsThe active group presented a statistically significant gap compared to the simulated group throughout the trend in the scores of the FMA (motor function and joint pain) and WMFT (functional ability and weight to box) (p < 0.05) and showed a minimal clinically important difference (FMA: difference between groups of 4.9 points [CI: 0.007- 9.799]; WMFT: difference between groups of 6.54 points [CI: 1.10-14.15]). In the secondary outcomes, there was a significant difference between the groups in ADL independence (Functional Independence Measure: difference of 8.63 [CI: 1.37-18.64]) and perceived recovery of quality of life evaluated at 90 days (p = 0.0176).ConclusionsCombining mCIMT with bihemispheric tDCS in patients hospitalized with acute-subacute stroke allows us to maximize the motor and functional recovery of the paretic upper limb in the early stages and independence in ADL, maintaining the effects over time.     

Corticospinal excitability enhancement with simultaneous transcranial near-infrared stimulation and anodal direct current stimulation of motor cortex

ObjectivesNon-invasive brain stimulation (NIBS) is beneficial to many neurological and psychiatric disorders by modulating neuroplasticity and cortical excitability. However, recent studies evidence that single type of NIBS such as transcranial direct current stimulation (tDCS) does not have meaningful clinical therapeutic responses due to their small effect size. Transcranial near-infrared stimulation (tNIRS) is a novel form of NIBS. Both tNIRS and tDCS implement its therapeutic effects by modulating cortical excitability but with different mechanisms. We hypothesized that simultaneous tNIRS and tDCS is superior to single stimulation, leading to a greater cortical excitability.MethodsSixteen healthy subjects participated in a double-blind, sham-controlled, cross-over designed study. Motor evoked potentials (MEPs) were used to measure motor cortex excitability. The changes of MEP were calculated and compared in the sham condition, tDCS stimulation condition, tNIRS condition and the simultaneous tNIRS and anodal tDCS condition.ResultstDCS alone and tNIRS alone both elicited higher MEP after stimulation, while the MEP amplitude in the simultaneous tNIRS and tDCS condition was significantly higher than either tNIRS alone or tDCS alone. The enhancement lasted up to at least 30 minutes after stimulation, indicating simultaneous 820 nm tNIRS with 2 mA anodal tDCS have a synergistic effect on cortical plasticity.ConclusionsSimultaneous application of tNIRS with tDCS produces a stronger cortical excitability effect.SignificanceThe simultaneous tNIRS and tDCS is a promising technology with exciting potential as a means of treatment, neuro-enhancement, or neuro-protection.     

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies.MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS.ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events.ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction.SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.     

Intensified electrical stimulation targeting lateral and medial prefrontal cortices for the treatment of social anxiety disorder: A randomized,double-blind,parallel-group,dose-comparison study

BackgroundSocial Anxiety Disorder (SAD) is the most common anxiety disorder while remains largely untreated. Disturbed amygdala-frontal network functions are central to the pathophysiology of SAD, marked by hypoactivity of the lateral prefrontal cortex (PFC), and hypersensitivity of the medial PFC and the amygdala. The objective of this study was to determine whether modulation of the dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli.MethodsIn this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three tDCS arms (1-mA, 2-mA, sham). SAD symptoms, treatment-related variables (worries, depressive state, emotion regulation, quality of life), and attention bias to threatening stimuli (dot-probe paradigm) were assessed before and right after the intervention. SAD symptoms were also assessed at 2-month follow-up.ResultsBoth 1-mA and 2-mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Improving effect of the 2-mA protocol on avoidance symptoms, worries and depressive state was significantly larger than the 1-mA group. Only the 2-mA protocol reduced attention bias to threat-related stimuli, the avoidance symptom at follow-up, and depressive states, as compared to the sham group.ConclusionsModulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and might thereby result in therapeutic effects. These effects can be larger with 2-mA vs 1-mA intensities, though a linear relationship between intensity and efficacy should not be concluded. Our results need replication in larger trials.     

Parsing the antidepressant effects of non-invasive brain stimulation and pharmacotherapy: A symptom clustering approach on ELECT-TDCS

BackgroundTranscranial direct current stimulation (tDCS) presents small antidepressant efficacy at group level and considerable inter-individual variability of response. Its heterogeneous effects bring the need to investigate whether specific groups of patients submitted to tDCS could present comparable or larger improvement compared to pharmacotherapy. Aggregate measurements might be insufficient to address its effects.Objective/Hypothesis: To determine the efficacy of tDCS, compared to pharmacotherapy and placebo, in depressive symptom clusters.MethodsData from ELECT-TDCS (Escitalopram versus Electrical Direct-Current Therapy for Treating Depression Clinical Study, ClinicalTrials.gov, NCT01894815), in which antidepressant-free, depressed patients were randomized to receive 22 bifrontal tDCS (2 mA, 30 min) sessions (n = 94), escitalopram 20 mg/day (n = 91), or placebo (n = 60) over 10 weeks. Agglomerative hierarchical clustering identified “sleep/insomnia”, “core depressive”, “guilt/anxiety”, and “atypical” clusters that were the dependent measure. Trajectories were estimated using linear mixed regression models. Effect sizes are expressed in raw HAM-D units. P-values were adjusted for multiple comparisons.ResultsFor core depressive symptoms, escitalopram was superior to tDCS (ES = −0.56; CI_95% = -0.94 to −0.17, p = .009), which was superior to placebo (ES = 0.49; CI_95% = 0.06 to 0.92, p = .042). TDCS but not escitalopram was superior to placebo in sleep/insomnia symptoms (ES = 0.87; CI_95% = 0.22 to 1.52, p = .015). Escitalopram but not tDCS was superior to placebo in guilt/anxiety symptoms (ES = 1.66; CI_95% = 0.58 to 2.75, p = .006). No active intervention was superior to placebo for atypical symptoms.ConclusionsPharmacotherapy and non-invasive brain stimulation produce distinct effects in depressive symptoms. TDCS or escitalopram could be chosen according to specific clusters of symptoms for a bigger response.Trial registrationClinicalTrials.gov, NCT01894815     

Comparison between conventional and HD-tDCS of the right inferior frontal gyrus in children and adolescents with ADHD

ObjectiveTo investigate whether the effects of HD-tDCS and conventional tDCS of the right IFG are superior to the effects of sham stimulation for the improvement of working memory performance in ADHD.Methods15 ADHD patients between 10 and 16 years underwent three tDCS sessions in which conventional, HD and sham tDCS of the right IFG were applied. In all sessions a 2-back working memory task was solved and EEG was recorded. Baseline data were assessed from 15 age matched healthy controls.ResultsIn ADHD patients, increased positive values of P300 and N200 mean amplitudes were found after conventional and HD-tDCS. Thus, both components were more in resemblance to ERPs in healthy controls. Behavioral performance was not generally influenced by tDCS but effects of HD-tDCS depended on individual hyperactive/impulsive symptom load. The rate of responders for HD-tDCS was equivalent to the responder rate for conventional tDCS.ConclusionsERP data indicate that HD-tDCS is equally suitable as conventional tDCS for the recruitment of the right IFG in the context of working memory processing.SignificanceHD-tDCS of the right IFG is a promising approach for neuromodulation in ADHD but further research is necessary to develop adaptations that produce reliable behavioral benefits.     

A Single Immediate Use of the Cathodal Transcranial Direct Current Stimulation Induces Neuroprotection of Hippocampal Region Against Global Cerebral Ischemia

ObjectivesGlobal cerebral ischemia (CI) causes severe neuronal injury, mainly in the hippocampal CA1 region. This study aimed to investigate an immediate using transcranial direct current stimulation (tDCS) in reducing neuronal injury induced by CI.Materials and methodsThe 32 Wistar male rats were randomly divided into four groups (n=8 per group). In the ischemia group (I), CI was induced via the 4-vessel occlusion model. In the sham group (Sh), rats did not receive any intervention. In the ischemia+cathodal group (I+c/tDCS), the cathodal current was applied during CI. In the ischemia+anodal group (I+a/tDCS), the anodal current was applied. The current intensity of 400 μA was applied for 15-min during the ischemia. Hippocampal tissue was used to assess levels of NMDAR, IL-1β, TNF-α, MDA, SOD, NOS, and apoptosis markers. Histological assessment and TUNEL staining were performed in CA1 hippocampal region.ResultsThe c/tDCS significantly decreased the levels of IL-1β and TNF-α than the I and a/tDCS groups. The c/tDCS significantly reduced MDA and NOS levels, while increasing the level of SOD than the I and a/tDCS. The c/tDCS caused a significant decrease in NMDAR level than the a/tDCS. Using c/tDCS significantly reduced the Bax and Caspase-3 expressions, while increasing the Bcl-2 expression than the I group. In the c/tDCS group, DNA fragmentation and neuronal death were significantly lower than the I and a/tDCS groups.ConclusionUsing cathodal a direct current could attenuate primary pathophysiological pathways induced by CI, and it eventually reduced neurons death and apoptosis in the CA1 hippocampal region.     

Exploring and optimizing the neuroplastic effects of anodal transcranial direct current stimulation over the primary motor cortex of older humans

BackgroundtDCS modulates cortical plasticity and has shown potential to improve cognitive/motor functions in healthy young humans. However, age-related alterations of brain structure and functions might require an adaptation of tDCS-parameters to achieve a targeted plasticity effect in older humans and conclusions obtained from young adults might not be directly transferable to older adults. Thus, our study aimed to systematically explore the association between tDCS-parameters and induced aftereffects on motor cortical excitability to determine optimal stimulation protocols for older individuals, as well as to investigate age-related differences of motor cortex plasticity in two different age groups of older adults.Methods32 healthy, volunteers from two different age groups of Young-Old (50–65 years, n = 16) and Old-Old (66–80 years, n = 16) participated in this study. Anodal tDCS was applied over the primary motor cortex, with respective combinations of three intensities (1, 2, and 3 mA) and durations (15, 20, and 30 min), in a sham-controlled cross-over design. Cortical excitability alterations were monitored by single-pulse TMS-induced MEPs until the next day morning after stimulation.ResultsAll active stimulation conditions resulted in a significant enhancement of motor cortical excitability in both age groups. The facilitatory aftereffects of anodal tDCS did not significantly differ between age groups. We observed prolonged plasticity in the late-phase range for two protocols with the highest stimulation intensity (i.e., 3 mA-20 min, 3 mA-30 min).ConclusionsOur study highlights the role of stimulation dosage in tDCS-induced neuroplastic aftereffects in the motor cortex of healthy older adults and delivers crucial information about optimized tDCS protocols in the domain of the primary motor cortex. Our findings might set the grounds for the development of optimal stimulation protocols to reinstate neuroplasticity in different cortical areas and induce long-lasting, functionally relevant plasticity in normal aging and in pathological conditions, which would require however systematic tDCS titration studies over respective target areas.     

Transcutaneous cervical vagus nerve stimulation reduces behavioral and physiological manifestations of withdrawal in patients with opioid use disorder: A double-blind,randomized, sham-controlled pilot study

BackgroundOpioid Use Disorder (OUD) is a serious public health problem, and the behavioral and physiological effects of opioid withdrawal can be a major impediment to recovery. Medication for OUD is currently the mainstay of treatment; however, it has limitations and alternative approaches are needed.ObjectiveThe purpose of this study was to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS) on behavioral and physiological manifestations of acute opioid withdrawal.MethodsPatients with OUD undergoing acute opioid withdrawal were randomly assigned to receive double blind active tcVNS (N = 10) or sham stimulation (N = 11) while watching neutral and opioid cue videos. Subjective opioid withdrawal, opioid craving, and anxiety were measured using a Visual Analogue Scale (VAS). Distress was measured using the Subjective Units of Distress Scale (SUDS), and pain was measured using the Numerical Rating Scale (NRS) for pain. Electrocardiogram signals were measured to compute heart rate. The primary outcomes of this initial phase of the clinical trial (ClinicalTrials.gov NCT04556552) were heart rate and craving.ResultstcVNS compared to sham resulted in statistically significant reductions in subjective opioid withdrawal (p = .047), pain (p = .045), and distress (p = .004). In addition, tcVNS was associated with lower heart rate compared to sham (p = .026). Craving did not significantly differ between groups (p = .11).ConclusionstcVNS reduces behavioral and physiological manifestations of opioid withdrawal, and should be evaluated in future studies as a possible non-pharmacologic, easily implemented approach for adjunctive OUD treatment.     

Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison

ObjectiveHigh-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent “theta-burst” stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain.MethodsForty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks.ResultsPain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095–3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques.ConclusionsHigh-frequency rTMS appeared superior to iTBS for neuropathic pain relief.SignificanceAdequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.     

Female and male sleep duration in association with the probability of conception in two representative populations of reproductive age in US and China

ObjectiveSleep duration has been found to affect some reproductive phenotypes but fecundability has been rarely researched. We aim to evaluate the association between female/male sleep duration and the probability of conception in two representative populations.MethodsThe present study uses two datasets, namely, a cross-sectional dataset of 9137 reproductive-age females in the US (National Health Interview Survey, NHIS) and a longitudinal dataset of 2687 reproductive-age females and their male mates in China (China Health and Nutrition Survey, CHNS). Logistic regression or mixed model was used to analyze the association between sleep duration and the probability of conception in the females of both populations and in CHNS males with adjustments for demographic, socioeconomic, behavioral, sleep health and reproductive factors.ResultsAn inverse association was observed between male sleep duration (≥8 h/day) and their mates' conception probability in the CHNS population (P = 0.012). Sleep of 9 h/day and ≥10 h/day in men was associated with 0.65 (0.41–1.02) fold and 0.53 (0.31–0.90) fold of conception probability when compared to 8 h/day sleep. On the other hand, a U-shaped association between female sleep duration and conception probability was observed in both populations. Each hour/day departure (longer or shorter) from 7 h/day sleep was associated with 1.26 (1.12–1.42, P < 0.001) and 1.21 (1.03–1.41, P = 0.019) fold conception probability in the NHIS and CHNS populations, respectively. An adjustment for potential confounders, including spouse characteristics did not substantially attenuate these associations.ConclusionsFemale and male sleep duration may be independent predictors of conception, suggesting there is an intervention target for reproductive health.     

Effect of partial and total sleep deprivation on serum testosterone in healthy males: a systematic review and meta-analysis

BackgroundCurrently, there is no consensus on the effect of sleep deprivation on male serum testosterone. This systematic review and meta-analysis aimed to determine the association between partial/total sleep deprivation and male serum testosterone level.MethodsThe literature related to sleep deprivation and male serum testosterone in the PubMed, Embase, and Cochrane Library databases were searched from their inception to July 15, 2021. Data were pooled using the Stata 15 software. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs).ResultsEighteen studies involving 252 men were included in the systematic review and meta-analysis. The findings revealed that short-term partial sleep deprivation had no significant effect on male serum testosterone (SMD = −0.22; 95% CI: −0.5, 0.06; P = 0.13), while total sleep deprivation reduced the male testosterone levels (SMD = −0.64; 95% CI: −0.87, −0.42; P < 0.001). According to the intervention duration of total sleep deprivation, subgroup analysis was conducted by a fixed-effects model. The results revealed that the serum testosterone was significantly decreased after 24 h total sleep deprivation (SMD = − 0.67; 95% CI = − 0.93, −0.42, P < 0.001), as well as 40–48 h total sleep deprivation (SMD = − 0.74; 95% CI = − 1.22, −0.26, P = 0.002).ConclusionsThis meta-analysis revealed that total sleep deprivation (more than or equal to 24 h) reduces the male testosterone levels, while short-term partial sleep deprivation has no significant effect on male serum testosterone. Sleep duration plays a pivotal role in maintaining male serum testosterone levels.