Sham Session Research Articles

0267 Development and validation of low-level Transcranial Electrical Stimulation to enhance slow oscillations during human NREM sleep

Abstract Introduction Sleep disruption, and in particular decreased NREM stage N3 sleep, has been implicated in cognition and pathogenesis of Alzheimer's Disease (AD). Several recent findings suggest that enhancing N3 sleep may mitigate impairments due to chronic sleep disruption. However, approaches such as transcranial electrical stimulation (TES) have been limited by discomfort, awakenings, and lack of blinding. In response to the need to develop low-level TES, our team first identified the source of slow oscillations (SOs) of N3 sleep using high-density EEG array modeling (Sourcerer®), which localized within anterior limbic brain structures. Next, we showed that low-level TES targeted to this region induced and enhanced SOs during N3 sleep in the laboratory. More recently, we developed a portable TES device with the minimum deployable set of stimulation electrodes targeting the anterior limbic SO-generating regions: Wireless Interface Sensor Pod (WISP). Methods Thirteen healthy adults (m = 42 years) participated in three all-night sleep EEG recordings where they received low level (0.5 mA) TES designed to target anterior limbic SO-generating regions and a sham stimulation (placebo). TES was initiated after 4 minutes of naturally occurring NREM N2 sleep and included five TES blocks of five minutes each separated by one minute rest periods. Subjects were blinded to stimulation and sham conditions, and outcomes included feasibility, acceptability, and total time in each sleep stage. A convolutional neural network (CNN) was developed, trained, and tested on manually scored EEG sleep staging for automated sleep scoring. Results Subjects rated that the WISP device was highly feasible and acceptable. Subjects were adequately blinded to sham versus stimulation. When compared to the sham session, limbic-targeted TES significantly increased the duration of N3 sleep and spectral power in the 0.5-1 Hz frequency band. Finally, our CNN was able to detect sleep stages with good accuracy (84%, kappa 0.77). Conclusion These results suggest that low-level portable TES using a minimum deployable set of electrodes, when specifically targeting anterior limbic sites, is feasible, acceptable, maintains blinding, and increases deep (N3) sleep. The WISP device is a promising method to both assess and manipulate sleep in the home setting. Support (if any) DoD MOMRP MTEC-21-06-MPAI-129

Does selective inhibition training reduce relapse rates when added to standard treatment of alcohol use disorder? A randomized controlled trial.

Alcohol-dependent individuals tend to selectively approach alcohol cues in the environment, demonstrating an alcohol approach bias. Because approach bias modification (ApBM) training can reduce the approach bias and decrease relapse rates in alcohol-dependent patients when added to abstinence-focused treatment, it has become a part of regular treatment. Moreover, in selective inhibition (SI) training, responses to one category of stimuli (i.e., alcohol stimuli) are selectively inhibited in an adapted Go/No-Go task. SI-Training has been found to effectively devalue the inhibited category and to reduce consumption of alcohol among social drinkers. This study investigated whether SI-Training can further improve the effects of treatment as usual that includes ApBM, and if so, whether the effect is mediated by a devaluation of the inhibited alcohol stimuli. Abstinent alcohol-dependent inpatients (N=434) were randomly assigned to receive 6 sessions of either active (n=214, 32% female) or sham (n=220, 38% female) SI-Training, in addition to standard treatment that includes active ApBM. Ratings were used to assess changes in the evaluation of alcohol stimuli after the training. Relapse rates were assessed 3 and 12 months after treatment discharge. Alcohol stimuli were rated negatively before and after the training, and the training did not influence these ratings. Evaluation of nonalcoholic drinks became more positive after active SI-Training. Both ApBM and SI-Training showed the expected training effects on reaction times. Contrary to expectations, SI-Training conditions did not yield different abstinence rates 3 or 12 months after treatment. We found no evidence supporting the hypothesis that SI-Training amplifies the relapse-preventing effect of ApBM. Moreover, alcohol stimuli were rated negatively before and after treatment and were not influenced by SI-Training.

A dual-mode neurostimulation approach to enhance athletic performance outcome in experienced taekwondo practitioners

Transcranial Direct Current Stimulation (tDCS) is a growing empirical approach to improve athletic performance. Some recent studies have investigated the effects of transcutaneous spinal direct current stimulation (tsDCS) on the motor performance such as reaction time. TDCS and tsDCS can lead to alteration of the spontaneous neural activity, and the membrane potentials of motor neurons in cerebral cortex and spinal interneurons, respectively. Given the paucity of experimental studies on the non-invasive brain stimulation in the field of sports neuroscience, especially martial sports, the present study aimed at investigating the effects of neurostimulation in potentiating the motor and cognitive functions in experienced taekwondo practitioners. The study sample included 15 experienced male taekwondo players who received real or sham direct current stimulation on the primary motor cortex (M1) and the lumbar spinal segment (T12-L2) over two sessions, 72 h apart. Next, the performance of the participants was evaluated through a simulation of taekwondo exercise directly after the sham and real sessions. Moreover, a cognitive platform (CBS: Cambridge Brain Science) was used to investigate the participants’ cognitive profile in each instance. Unlike sham stimulation, real tDCS was associated with improved selective attention and reaction time in both in the simulated task performance and cognitive examination. The concurrent cortical and trans-spinal tDCS was found to improve selective attention (31% performance improvement) (P < 0.0001) [EFFECT SIZE; 1.84]. and reduce reaction time (4.7% performance improvement) (P < 0.0001) [EFFECT SIZE; 0.02]. Meanwhile, the intervention failed to leave a significant change in cognitive functions evaluated through CBS (P > 0.05). As informed by our results, the present dual-mode neurostimulation could improve motor functions potentially through the effect of tsDCS over the spinal interneurons and tDCS over the primary motor cortex. Likewise, our findings suggested an improved performance in simulated taekwondo task after real- but not sham-stimulation. This study paves the way for designing neurostimulation protocols to improve the performance of professional athletes, namely martial art practitioners, including their accuracy and velocity of reactions. Such positive effects of neuostimulation in athletic performance as demonstrated in this research and similar reports are expected to enhance the athletes’ success in professional competitions.

Excitability Changes in Occipital Cortex After Continuous Theta-Burst Stimulation.

Modulation of visual cortical structures by repetitive transcranial magnetic stimulation is rarely observed in literature. In this study; the researchers aimed to investigate the neurophysiological alterations by using continuous theta burst stimulation (cTBS) protocol over the occipital cortex in healthy subjects. Twenty-five (15 female, 10 male) (mean age 29.84±4.7 years) healthy individuals were included in sham and real cTBS occipital stimulation sessions. Before and after each session, neurophysiological studies including phosphene threshold and visual evoked potential (VEP) responses were recorded. The P100 latency values and maximum amplitude values between N75-P100 peaks of 100 responses of 1000 uninterrupted continuous visual stimuli were measured. The VEP habituation and phosphene thresholds were compared in sham and real cTBS sessions. The phosphene threshold values increased to statistically significant levels after the real cTBS session. Visual evoked potential habituation was observed in both sham and real cTBS sessions in individuals without significant differences. Also, no difference between the P100 latencies and N75-P100 amplitude values in the sham and real cTBS sessions was observed. Phosphene threshold measurements demonstrated the modulation of the occipital cortex excitability via cTBS in healthy subjects.

Respostas hemodinâmicas durante exercício muscular inspiratório em jovens saudáveis

ABSTRACT The literature on hemodynamic responses during inspiratory muscle exercise (IME) lacks a consensus. To evaluate and compare hemodynamic responses during an IME session with and without resistive load, 15 sedentary men were subjected to two randomized IME sessions: one with 40% of maximal inspiratory pressure (IME 40%) and another without a resistive load (Sham), both of which were performed for two minutes over eight sessions with one-minute intervals. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), total peripheral resistance (TPR), stroke volume (SV), cardiac output (CO), and heart rate (HR) were measured by infrared digital photoplethysmography during five basal minutes and during the IME sessions. One-way analysis of variance and the Student’s t test for paired data were used to analyze hemodynamic response and delta values between sessions. Effect size was evaluated by Cohen’s D. A 5% significance level was adopted. SBP responses (sham: ∆−1±2 vs. 40%: ∆−4±2mmHg, p=0.27), DBP (sham: ∆2±1 vs. 40%: ∆1±2mmHg, p=0.60) and MBP (sham: ∆2±1 vs. 40%: ∆0±2mmHg, p=0.28) were similar between sessions. HR increases were higher in the 40% IME session than in the sham session (sham: ∆9±2 vs. 40%: ∆3±2bpm, p=0.001). SV only decreased during the sham session but responses were similar between sessions (sham: ∆−2±2 vs. IME 40%: ∆−6±2ml, p=0.13). Both sessions did not change SBP, DBP, MBP, CO, and TPR, but we observed a greater increase in HR in the IME 40% session. Only the Sham session decreased SV.

A randomized trial of one versus three hyperbaric oxygen sessions for acute carbon monoxide poisoning

Introduction: Hyperbaric oxygen (HBO2) improves outcome in patients with acute carbon monoxide (CO) poisoning, but optimal dose/timing are unknown. In this double-blind, sham-controlled randomized trial, we compared neuropsychological sequelae at 6 weeks and 6 months in patients receiving 3 HBO2 sessions or 1 HBO2 session and 2 sham chamber sessions after acute CO poisoning. Methods: After completing 1 HBO2 session (3.0 ATA, 60 minutes, 2.0 ATA, 65 minutes), CO-poisoned patients were randomized (1:1): 2 sham chamber sessions (1 ATA air, 120 minutes) or 2 additional HBO2 sessions (2.0 ATA, 90 minutes at pressure, 120 minutes in chamber) completed within 24 hours. Eligible patients were &lt;24 hours from accidental poisoning, English-speaking, and not intubated. We planned 150 participants. Results: The study was stopped early for enrollment futility. From 2006-2016, we screened 395 patients, 136 were deemed eligible to participate, and 75 signed informed consent. Two were later withdrawn for past brain injury/PTSD (1 sham, 1 HBO2), and 1 for performance validity (sham). Of the 72 analyzed, mean age was 42±15 years, 40 (56%) were male, 20 (28%) had loss of consciousness, and mean initial carboxyhemoglobin was 22±9%. The rate of 6-week neuropsychological sequelae was 50% in the 1 HBO2 session group and 55% in the 3 HBO2 sessions group (p=0.80), and at 6 months was 42% vs 46%, respectively (p=0.76). Conclusions: There was no difference in the rate of neuropsychological sequelae in those who received 3 HBO2 sessions and those who received 1 HBO2 sessions and 2 sham sessions. The higher rate of neuropsychological sequelae compared to an earlier study may be due to neuropsychological test-retest effects or previously identified risk factors for cognitive sequelae (age, duration of poisoning, cerebellar dysfunction). This study’s rates of cognitive difficulties, affective complaints, and other symptoms suggest brain injury after CO poisoning is common.

Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop.

In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks. We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation. Patients were assigned to 10 sessions of real or sham 1-Hz stimulation over the right posterior superior temporal gyrus. Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by a speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at Weeks 6 and 10 after the baseline. Altogether, data from 33 patients were analyzed. A linear mixed model revealed significant time-by-group interaction (p= 0.006) for the relative changes of fractional anisotropy of the AAF; the value increases were associated with the temporal evolution of the Phonetics score (R= 0.367, p= 0.028) in the real stimulation group. Real rTMS treatment for HD in PD as compared to sham stimulation led to increases of white matter integrity of the auditory-motor loop during the 2-month follow-up period. The changes were related to motor speech improvements.

Short-term neurochemical effects of transcutaneous trigeminal nerve stimulation using 7T magnetic resonance spectroscopy.

The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh-field magnetic resonance spectroscopy. This double-blinded study tested 32 healthy males (age: 25.4±7.3years) on two separate occasions where participants received either a 20-minute TNS or sham session. Participants were scanned at baseline and twice post-TNS/sham administration. There were no group differences in concentration changes of glutamate, gamma-aminobutyric acid, glutamine, myoinositol (mI), total N-acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post-TNS/sham scan and between the first and second post-TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post-TNS/sham scan, changes in tCr (mean difference=0.280mM [0.075 to 0.485], p=.026) and mI (mean difference=0.662mM [0.203 to 1.122], p=.026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change=-0.201mM [-0.335 to -0.067], p=.003) and no change in mI (mean change=-0.327mM [-0.737 to 0.083], p=.118) in the TNS group; conversely, there was no change in tCr (mean change=-0.100mM [-0.074 to 0.274], p=.259) and an increase in mI (mean change=0.347mM [0.106 to 0.588], p=.005) in the sham group. These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region.

Neurofeedback for Attention Deficit Disorder in preschoolers (NeFAP): A randomized, sham-controlled, efficacy study protocol of a novel non-pharmacological therapy

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is an impairing condition that widely affects a child's life. Current treatment guidelines for preschool-aged children suggest prescribing evidence-based parent or teacher-administered behavior therapy (BT) as the first line of treatment. Psychostimulants can be prescribed for non-respondents and moderate-to-severe cases, but they have side effects. Alternative therapy is neurofeedback, which has already shown effectiveness in the older children population but not in preschoolers. Objective: To evaluate if neurofeedback associated with behavioral therapy is superior in efficacy compared to sham neurofeedback plus behavioral therapy for treating newly diagnosed ADHD in preschoolers.Methods: This will be a multicenter, randomized, single-blinded, parallel-group, superiority phase III study including 274 patients in five sites. Participants are children aged 4 to 6 years old with a confirmed diagnosis of moderate-severe ADHD by a treating physician. Both groups will receive 48 neurofeedback or sham sessions in 24 weeks plus BT, with 6-month follow-up up to 36 months. The primary outcome is the improvement of ADHD symptoms measured by the ADHD Rating Scale-IV (ADHD-RS-IV). After six months, participants will be allowed to use medication if needed. Therefore, one of our secondary endpoints will be time-to-medication. Two hundred seventy-four participants will be enrolled.Discussion: The NeFAP study is an innovative study of NF to treat symptoms of ADHD in preschoolers. If positive results are obtained, it may change the treatment landscape for preschoolers who typically have difficulty adhering to drug-based treatments.

Repetitive bout of controlled soccer heading does not alter heart rate variability metrics: A preliminary investigation.

There is elevated unease regarding how repetitive head impacts, such as those associated with soccer heading, contribute to alterations in brain function. This study examined the extent heart rate variability (HRV) and cardiac baroreceptor sensitivity (BRS) metrics are altered immediately following an acute bout of soccer heading. Seven male elite soccer players (24.1 ± 1.5 years) completed 40 successful soccer headers in 20-min. The headers were performed under controlled circumstances using a soccer ball launcher located 25 meters away and using an initial ball velocity of 77.5 ± 3.7 km/h (heading condition). An accelerometer (xPatch) on the right mastoid process quantified linear/rotational head accelerations. Participants also completed sham (body contact) and control (non-contact) sessions. A three-lead ECG and finger photoplethysmography characterized short-term spontaneous HRV/cardiac BRS, before and after each condition. The SCAT3 indexed symptom scores pre-post exposures to all three conditions. During the heading condition, cumulative linear and rotational accelerations experienced were 1,574 ± 97.9 g and 313,761 ± 23,966 rad/s2, respectively. Heart rate trended toward an increase from pre- to post-heading (p = 0.063), however HRV metrics in the time-domain (ps > 0.260) and frequency-domain (ps > 0.327) as well as cardiac BRS (ps > 0.144) were not significantly changed following all three conditions. Following the heading condition, SCAT3 symptom severity increased (p = 0.030) with a trend for symptom score augmentation (p = 0.078) compared to control and sham. Whereas, symptoms as measured by the SCAT3 were induced following an acute bout of controlled soccer heading, these preliminary findings indicate they were not accompanied by alterations to autonomic function. Ultimately, this demonstrates further research is needed to understand the physiological underpinnings of alterations in brain function occurring immediately after a bout of soccer heading and how these may, over time, contribute to long-term neurological impairments.

Immediate Effects of Dry Needling on Central Pain Processing and Skin Conductance in Patients with Chronic Nonspecific Neck Pain: A Randomized Controlled Trial.

Although current evidence supports the use of dry needling for improving some clinical outcomes in people with neck pain, no previous research explored the effects of dry needling on the central processing of pain and autonomic nervous system in this population. Therefore, this clinical trial aimed to compare the effects of real and sham dry needling on autonomic nervous system function, pain processing as well as clinical and psychological variables in patients with chronic nonspecific neck pain. A double-blinded randomized clinical trial including 60 patients with neck pain was conducted. Patients were randomized to the real needling (n = 30) or sham needling (n = 30) group. Skin conductance (SC), pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM) as well as pain intensity, related-disability, catastrophism, and kinesiophobia levels were assessed by an assessor blinded to the allocation intervention. The results did not find significant group * time interactions for most outcomes, except for the global percentage of change of SC values (mean: F = 35.90, p &lt; 0.001, ηp2 = 0.459; minimum: F = 33.99, p = 0.839, ηp2 = 0.371; maximum: F = 24.71, p &lt; 0.001, ηp2 = 0.037) and PPTs at C5-C6 joint in the same side of needling (F = 9.982; p = 0.003; = 0.147), in favor of the dry needling group. Although the proportion of subjects experiencing moderate to large self-perceived improvement after the intervention was significantly higher (X2 = 8.297; p = 0.004) within the dry needling group (n = 18, 60%) than in the sham needling group (n = 7, 23.3%), both groups experienced similar improvements in clinical and psychological variables. Our results suggested that dry needling applied to patients with chronic nonspecific neck pain produced an immediate decrease in mechanical hyperalgesia at local sites and produced an increase in skin conductance as compared with sham needling. No changes in central pain processing were observed. A single session of sham or real dry needling was similarly effective for decreasing related disability, pain intensity, catastrophism, and kinesiophobia levels. Further studies are needed to better understand the clinical implications of autonomic nervous system activation on central sensitization and pain processing in the long-term after the application of dry needling.

The effects of extracorporeal shock wave therapy on hemineglect following a stroke. A case report study

Extracorporeal shock wave therapy (ESWT) is a non-invasive repetitive peripheral mechanical stimulation and might promote neuroplasticity in hemineglect syndrome. Two out of 15 patients with hemi spatial neglect following chronic stroke were completed the inclusion criterions and underwent one session of sham (placebo) and then one session of real ESWT. Both of the cases responded successfully to the ESWT by diminishing the neglect symptoms in comparison to their baseline evaluation, which maintained during one week of follow up evaluation session, but we did not observe changes in hemineglect syndrome in sham group. Our data showed that ESWT could be considered a promising tool in the treatment of neglect syndrome, however further studies are needed to confirm the effectiveness of ESWT.

Efficacy of twice-daily high-frequency repetitive transcranial magnetic stimulation on associative memory.

ObjectivesSeveral studies have examined the effects of repetitive transcranial magnetic stimulation (rTMS) on associative memory (AM) but findings were inconsistent. Here, we aimed to test whether twice-daily rTMS could significantly improve AM.MethodsIn this single-blind, sham-controlled experiment, 40 participants were randomized to receive twice-daily sham or real rTMS sessions for five consecutive days (a total of 16,000 pulses). The stimulation target in left inferior parietal lobule (IPL) exhibiting peak functional connectivity to the left hippocampus was individually defined for each participant. Participants completed both a picture-cued word association task and Stroop test at baseline and 1 day after the final real or sham rTMS session. Effects of twice-daily rTMS on AM and Stroop test performance were compared using two-way repeated measures analysis of variance with main factors Group (real vs. sham) and Time (baseline vs. post-rTMS).ResultsThere was a significant Group × Time interaction effect. AM score was significantly enhanced in the twice-daily real group after rTMS, but this difference could not survive the post hoc analysis after multiple comparison correction. Further, AM improvement in the twice-daily real group was not superior to a previously reported once-daily rTMS group receiving 8,000 pulses. Then, we combined the twice- and once-daily real groups, and found a significant Group × Time interaction effect. Post hoc analysis indicated that the AM score was significantly enhanced in the real group after multiple comparisons correction.ConclusionOur prospective experiment did not show significant rTMS effect on AM, but this effect may become significant if more participants could be recruited as revealed by our retrospective analysis.

Hyperbaric oxygen therapy in children with post-concussion syndrome improves cognitive and behavioral function: a randomized controlled trial

Persistent post-concussion syndrome (PPCS) is a common and significant morbidity among children following traumatic brain injury (TBI) and the evidence for effective PPCS treatments remains limited. Recent studies have shown the beneficial effects of hyperbaric oxygen therapy (HBOT) in PPCS adult patients. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT) on children (age 8–15) suffering from PPCS from mild-moderate TBI events six months to 10 years prior. Twenty-five children were randomized to receive 60 daily sessions of HBOT (n = 15) or sham (n = 10) treatments. Following HBOT, there was a significant increase in cognitive function including the general cognitive score (d = 0.598, p = 0.01), memory (d = 0.480, p = 0.02), executive function (d = 0.739, p = 0.003), PPCS symptoms including emotional score (p = 0.04, d = – 0.676), behavioral symptoms including hyperactivity (d = 0.244, p = 0.03), global executive composite score (d = 0.528, p = 0.001), planning/organizing score (d = 1.09, p = 0.007). Clinical outcomes correlated with significant improvements in brain MRI microstructural changes in the insula, supramarginal, lingual, inferior frontal and fusiform gyri. The study suggests that HBOT improves both cognitive and behavioral function, PPCS symptoms, and quality of life in pediatric PPCS patients at the chronic stage, even years after injury. Additional data is needed to optimize the protocol and to characterize the children who can benefit the most.

Safety and effects of transcranial direct current stimulation on hand function in preschool children with hemiplegic cerebral palsy: A pilot study.

Transcranial direct current stimulation (tDCS) has shown a promising prospect in improving function and spasticity in school-aged children with cerebral palsy, but little is known in preschool children. The aim of this study was to explore the safety and effects of tDCS on hand function in preschool children (aged 3–6 years) with hemiplegic cerebral palsy (HCP). We designed a crossover, single-blind, sham-controlled study in 30 preschool children with HCP, who were recruited to receive one session of sham and one session of active anodal tDCS (1.5 mA, 20 min) on the primary motor cortex of the affected hemisphere, with a 24-h interval between the two sessions. Questionnaire was completed by each participant and their attendants immediately, 90 min, and 24 h after each session to monitor common adverse events of tDCS, such as skin irritation, skin erythema, burning sensation, headache, dizziness, etc. Box and Block Test, Selective Control of the Upper Extremity Scale, Modified Ashworth Scale, and Melbourne Assessment 2 were conducted at baseline, immediately, and 90 min after each session. No severe adverse event occurred during the study and only a few of them felt transient and slight discomfort. Results also showed that all participants performed better at Box and Block Test of the hemiplegic hand immediately after a single anodal tDCS (P < 0.05) and this improvement lasted at least 90 min and more than 24 h. However, there was no significant improvement in Selective Control of the Upper Extremity Scale of both hands, Box and Block Test of the non-hemiplegic hand, Modified Ashworth Scale, and Melbourne Assessment 2 of the hemiplegic upper limb (P > 0.05). Shortly, this study supported the safety and effects of a single anodal tDCS on improving the manual dexterity of the hemiplegic hand for preschool children with HCP. Further researches with larger samples about the optimal dose and treatment cycle of tDCS for preschool children with HCP are warranted. This study gained the approval of ethics committee of the organization and was registered at chictr.org (ChiCTR2000031141).

Effects of Low-Concentration Carbon Dioxide Exposure at Bedtime on Sleep in Adults With Insomnia Symptoms

Objectives: Carbon dioxide (CO2) accumulation in an enclosed space might cause drowsiness. This study aimed to assess the effect of bedtime exposure to low concentrations of CO2 gas on the sleep quality of adults with insomnia.Methods: In this double-blind, randomized, sham-controlled cross-over study, we consecutively recruited 24 adults (9 men; age, 55.4±6.3 y) complaining of sleep disturbances (Pittsburgh Sleep Quality Index ≥5). The following two interventions were used in the study: exposure to 2% low-concentration edible CO2 gas (experimental intervention) and exposure to room air (sham-controlled intervention). A sleep air device (Gosleep®, NYX), which atomizes CO2 gas, was used in both experimental and sham-controlled interventions. For the sham session, room air was generated for 18 min, and then, gradually reduced by degrees in the next 5 min with the device finally being turned off.Results: The group exposed to CO2 gas had longer time in bed (361.3±55.2 min vs. 347.2±35.7 min, p=0.034) and total sleep time (311.0±74.3 min vs. 287.2±69.4 min, p=0.010) than the group exposed to room air. Meanwhile, the total arousal (19.7±9.5/h vs. 24.0±13.7/h, p=0.011) and non-REM arousal (20.9±11.3/h vs. 25.1±14.9/h, p=0.008) indices were lower in the group exposed to CO2 gas than in the group exposed to room air. However, perceived total sleep time or sleep latency and Karolinska Sleepiness Scale scores were not significantly different between the two groups.Conclusion: Exposure to low concentrations of CO2 improved the total sleep time and arousal index in adults with insomnia. Unexpectedly, CO2 administration was found to be effective for sleep maintenance.

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial

Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1–3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = − 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Detection of Transcranial Alternating Current Stimulation Aftereffects Is Improved by Considering the Individual Electric Field Strength and Self-Rated Sleepiness.

Non-invasive electrical stimulation methods, such as transcranial alternating current stimulation (tACS), are increasingly used in human neuroscience research and offer potential new avenues to treat neurological and psychiatric disorders. However, their often variable effects have also raised concerns in the scientific and clinical communities. This study aims to investigate the influence of subject-specific factors on the alpha tACS-induced aftereffect on the alpha amplitude (measured with electroencephalography, EEG) as well as on the connectivity strength between nodes of the default mode network (DMN) [measured with functional magnetic resonance imaging (fMRI)]. As subject-specific factors we considered the individual electrical field (EFIELD) strength at target regions in the brain, the frequency mismatch between applied stimulation and individual alpha frequency (IAF) and as a covariate, subject’s changes in mental state, i.e., sleepiness. Eighteen subjects participated in a tACS and a sham session conducted on different days. Each session consisted of three runs (pre/stimulation/). tACS was applied during the second run at each subject’s individual alpha frequency (IAF), applying 1 mA peak-to-peak intensity for 7 min, using an occipital bihemispheric montage. In every run, subjects watched a video designed to increase in-scanner compliance. To investigate the aftereffect of tACS on EEG alpha amplitude and on DMN connectivity strength, EEG data were recorded simultaneously with fMRI data. Self-rated sleepiness was documented using a questionnaire. Conventional statistics (ANOVA) did not show a significant aftereffect of tACS on the alpha amplitude compared to sham stimulation. Including individual EFIELD strengths and self-rated sleepiness scores in a multiple linear regression model, significant tACS-induced aftereffects were observed. However, the subject-wise mismatch between tACS frequency and IAF had no contribution to our model. Neither standard nor extended statistical methods confirmed a tACS-induced aftereffect on DMN functional connectivity. Our results show that it is possible and necessary to disentangle alpha amplitude changes due to intrinsic mechanisms and to external manipulation using tACS on the alpha amplitude that might otherwise be overlooked. Our results suggest that EFIELD is really the most significant factor that explains the alpha amplitude modulation during a tACS session. This knowledge helps to understand the variability of the tACS-induced aftereffects.

Cingulate transcranial direct current stimulation in adults with HIV.

BackgroundNeuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)—with its capability to improve neuronal function—may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC).MethodsEleven PWH (47–69 years old, 2 females, 100% African Americans, disease duration 16–36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2–3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1.ResultsCompared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test—Part B (TMT-B) to TMT—Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS.ConclusionsCingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted.

Infra-Low Frequency Neurofeedback in Tension-Type Headache: A Cross-Over Sham-Controlled Study.

Primary headaches are highly prevalent and represent a major cause of disability in young adults. Neurofeedback is increasingly used in the treatment of chronic pain; however, there are few studies investigating its efficacy in patients with headaches. We report the results of a cross-over sham-controlled study on the efficacy of neurofeedback in the prophylactic treatment of tension-type headache (TTH). Participants received ten sessions of infra-low frequency electroencephalographic neurofeedback and ten sessions of sham-neurofeedback, with the order of treatments being randomized. The study also included a basic psychotherapeutic intervention — a psychoeducational session performed before the main study phases and emotional support provided throughout the study period. The headache probability was modeled as a function of the neurofeedback and sham-neurofeedback sessions performed to date. As a result, we revealed a strong beneficial effect of neurofeedback and no influence of the sham sessions. The study supports the prophylactic use of infra-low frequency neurofeedback in patients with TTH. From a methodological point of view, we advocate for the explicit inclusion of psychotherapeutic components in neurofeedback study protocols.