Although contemporary models of obsessive-compulsive disorder (OCD) have primarily emphasized fear, recent accounts suggest that abnormal disgust learning may also contribute to OCD pathology, particularly in contamination-related OCD (C-OCD). The present study examined the neural correlates of disgust learning in individuals with elevated contamination-related obsessive-compulsive symptoms. Event-related potentials (ERPs) were recorded while 28 participants high in contamination-related obsessive-compulsive symptoms (HC) and 30 participants low in such symptoms (LC) completed disgust acquisition and extinction tasks. Behavioral measures included unconditioned stimulus (US) expectancy and conditioned stimulus (CS) disgust ratings, alongside electrophysiological indices of conditioned disgust. During acquisition, the HC group showed higher US expectancy for the CS+ than the LC group. At the neural level, both groups showed larger P3 amplitudes to the CS+ than to the CS-, indicating enhanced attentional significance. However, the HC group exhibited smaller overall P3 amplitudes than the LC group, which may reflect greater avoidance during disgust learning. During extinction, US expectancy differences between the CS+ and CS- remained evident in both groups, whereas P3 differences were no longer observed, suggesting a dissociation between self-reported and neural responses. Overall, these findings indicate that individuals with elevated contamination fear show enhanced disgust acquisition and altered neural processing during disgust learning, which may help clarify how maladaptive disgust responses are formed and maintained in contamination-related OCD.

BACKGROUND:Physiological mechanisms explaining why cardiorespiratory fitness (CRF) predicts cardiovascular morbidity and mortality are incompletely understood. We examined if CRF modifies vagally mediated heart rate variability (HRV) during acute physical or psychosocial stress or night-time sleep in adults with cardiovascular risk factors. METHODS:Seventy-eight adults (age 56 years [IQR 50-60], 74% female, body mass index 28 kg/m2 [IQR 25-31]) with frequent cardiovascular risk factors participated in this cross-sectional study. They went through physical (treadmill cardiopulmonary exercise test [CPET]) and psychosocial (Trier Social Stress Test for Groups [TSST-G]) stress tests and night-time sleep monitoring (polysomnography). Heart rate (HR) and vagally mediated HRV (root mean square of successive differences between normal R-R intervals [RMSSD]) were recorded during the experiments and analyzed by taking account of potential confounders. RESULTS:CRF (peak O2 uptake) averaged 99% (range 78-126) in relation to reference data. From pre-rest to moderate intensities during CPET and throughout TSST-G, HR did not differ between participants with CRF below median (CRFlower) and CRF equal to or above median (CRFhigher), whereas CRFhigher had higher HRV than CRFlower, and CRF correlated positively with HRV in all participants. Meanwhile, CRF had no independent associations with HR or HRV levels during slow-wave sleep, the presence of metabolic syndrome was not associated with recorded HR or HRV levels, and single factors predicted HRV responsiveness independently only to limited extents. CONCLUSIONS:CRF is positively associated with prevailing vagally mediated HRV at everyday levels of physical and psychosocial stress in adults with cardiovascular risk factors.

Disgust imagery represents a potential pathological mechanism for disgust-related disorders. However, it remains controversial as to whether disgust can be conditioned with disgust-evoking mental imagery serving as the unconditioned stimulus (US). Therefore, we examined this using a conditioned learning paradigm in combination with event-related potential (ERP) analysis in 35 healthy college students. The results indicated that the initial neutral face (conditioned stimulus, CS+) became more disgust-evoking, unpleasant, and arousing after pairing with disgust-evoking imagery (disgust CS+), compared to pairing with neutral (neutral CS+) and no (CS-) imagery. Moreover, we observed that mental imagery-based disgust conditioning was resistant to extinction. While the disgust CS + evoked larger P3 and late positive potential amplitudes than CS- during acquisition, no significant differences were found between disgust CS+ and neutral CS+, indicating a dissociation between selfreported and neurophysiological responses. Future studies may additionally acquire facial EMG as an implicit index of conditioned disgust. This study provides the first neurobiological evidence that associative disgust learning can occur without aversive physical stimuli, with implications for understanding how disgust-related disorders may manifest or deteriorate without external perceptual aversive experiences, such as in obsessivecompulsive disorder (OCD).

Behavior is guided by the compatibility of expectations based on past experience and the outcome. In a recent study, Fouragnan and colleagues report that absolute prediction error (PE)-related heart-evoked potentials (HEPs) differ according to the cardiac cycle phase at outcome, and that the magnitude of this effect positively correlates with reward learning in healthy adults.

We trained healthy elderly individuals in trace eyeblink conditioning, either at inspiration-systole or at expiration-diastole. Those who learned exhibited more conditioned responses when trained at expiration-diastole rather than inspiration-systole. However, there was no difference between the experimental groups in the proportion of individuals who learned or did not learn.

Pavlovian fear conditioning and extinction represent learning mechanisms underlying exposure-based interventions. While increasing evidence indicates a pivotal role of disgust in the development of contamination-based obsessive-compulsive disorder (C-OCD), dysregulations in conditioned disgust acquisition and maintenance, in particular driven by higher-order conceptual processes, have not been examined. Here, we address this gap by exposing individuals with high (HCC, n = 41) or low (LCC, n = 41) contamination concern to a conceptual-level disgust conditioning and extinction paradigm. Conditioned stimuli (CS+) were images from one conceptual category partially reinforced by unconditioned disgust-eliciting stimuli (US), while images from another category served as non-reinforced conditioned stimuli (CS-). Skin conductance responses (SCRs), US expectancy and CS valence ratings served as primary outcomes to quantify conditioned disgust responses. Relative to LCC, HCC individuals exhibited increased US expectancy and CS+ disgust experience, but comparable SCR levels following disgust acquisition. Despite a decrease in conditioned responses from the acquisition phase to the extinction phase, both groups did not fully extinguish the learned disgust. Importantly, the extinction resilience of acquired disgust was more pronounced in HCC individuals. Together, our findings suggest that individuals with high self-reported contamination concern exhibit increased disgust acquisition and resistance to extinction. The findings provide preliminary evidence on how dysregulated disgust learning mechanism across semantically related concepts may contribute to C-OCD.

Good aerobic and metabolic fitness associates with better cognitive performance and brain health. Conversely, poor metabolic health predisposes to neurodegenerative diseases. Our previous findings indicate that rats selectively bred for Low Capacity for Running (LCR) show less synaptic plasticity and more inflammation in the hippocampus and perform worse in tasks requiring flexible cognition than rats bred for High Capacity for Running (HCR). Here we aimed to determine whether hippocampal electrophysiological activity related to learning and memory would be impaired in LCR compared to HCR rats. We also studied whether an exercise intervention could even out the possible differences. We conducted in vivo recordings from the dorsal hippocampus under terminal urethane anesthesia in middle-aged sedentary males and female rats, and in females allowed to access running wheels for 6 weeks. Our results indicate stronger long-term potentiation (LTP) in the CA3-CA1 synapse in HCR than LCR rats, and in female than male rats. Compared to LCR rats, HCR rats had more dentate spikes and more gamma epochs, the occurrence of which also correlated positively with the magnitude of LTP. Voluntary running reduced the differences between female LCR and HCR rats. In conclusion, low innate fitness links to reduced hippocampal function and plasticity which can seems to improve with voluntary aerobic exercise even in middle age.

BACKGROUND: Pragmatic skills' impairment and communication difficulties are common in Autism Spectrum Disorder (ASD), regardless of symptoms severity [1].The social-reciprocity deficit was considered an important risk factor for social isolation [2].Recently, it has been assumed that the hypoactivation of Broca's area has a pivotal role in atypical communication [3].In this context, non-invasive brain stimulation methods, including transcranial direct current stimulation (tDCS), have been examined as promising therapeutic options to modify aberrant neuroplasticity involved in neuropsychiatric disorders, including ASD [4].OBJECTIVES: The aim of the study is to assess the effect of anodal tDCS application combined with a cognitive-behavioral therapy (CBT) for the improvement of pragmatic skills, the increase of spontaneous speech and the enhancement of social interaction quality within a group of individuals with ASD.METHODS: 8 young males diagnosed with ASD were enrolled (age range 18-22 years) so far.At the baseline (T0) each patient performed a neuropsychiatric assessment of: cognitive abilities (Wechsler Adult Intelligence Scale -Revised), adaptive skills (Adaptive Behavior Assessment System-Second Edition), autistic symptoms (Autism Diagnostic Observation Schedule-Second Edition) and communication abilities (Assessment Battery for Communication-ABaCo).The evaluation of communication abilities was repeated at the end of each conditions (T1,T2).After the baseline, each patient underwent a treatment with both anodal real tDCS (20 minutes, 1mA) and sham tDCS (30 seconds, 1 mA) on the left Broca's area (F5).Each condition was delivered for 5 consecutive days, for a total of 10 sessions, interspersed with a 14-day break.The order of the conditions was blindly randomized.In each conditions the cathod was located on the contralateral orbitofrontal cortex and the CBT was delivered simultaneously with tDCS.RESULTS: Preliminary results on 5 males (age MAEDS 20.4AE2.1) reported no significant differences in clinical profiles at the baseline in terms of cognitive (MAEDS 87.7AE17.4),adaptive skills (MAEDS 82AE9.5),autistic symptoms (MAEDS 6.75AE1.2) and communication abilities (MAEDS 63.2AE10.5).Paired t test analyses revealed statistically significant improvement of global communication abilities measured through the Global Index of ABaCo battery after 5 consecutive sessions of anodal real tDCS associated with CBT (t (4) ¼ 3.01 ; p ¼ 0.03), in comparison to sham condition associated with CBT (t (4) ¼ 0.04; p ¼ 0.70).Interestingly, the comparison between real tDCS and sham condition revealed an increasing also in paralinguistic comprehension after real tDCS sessions (t (4) ¼ 2.75; p ¼ 0.05).Even if not significant, (t (4) ¼ 0.47; p ¼ 0.07) we found an enhancement of the communication behaviours' appropriateness after real tDCS condition (MAEDS100AE0), in comparison to sham (MAEDS 70AE27).CONCLUSIONS: Preliminary results show that the application of anodal tDCS stimulation of left Broca's area (F5) associated with CBT focused on communication and pragmatic skills, significantly improved global conversational abilities in young adults with ASD.Surprisingly, the improvement of paralinguistic comprehension abilities suggests the involvement of Broca's area not only in verbal and non-verbal production, but also in comprehension.Aware that CBT is the first line intervention for ASD, its association with tDCS may represent a promising approach to improve rehabilitation's outcomes.References

Introduction:While gas narcosis is familiar to most divers conducting deep (> 30 metres) dives, its effects are often considered minuscule or subtle at 30 metres. However, previous studies have shown that narcosis may affect divers at depths usually considered safe from its influence, but little knowledge exists on the effects of gas narcosis on higher cognitive functions such as decision-making in relatively shallow water at 30 metres. Impaired decision-making could be a significant safety issue for a multitasking diver. Methods:We conducted a study exploring the effects of gas narcosis on decision-making in divers breathing compressed air underwater. The divers (n = 22) were evenly divided into 5-metre and 30-metre groups. In the water, we used underwater tablets equipped with the Iowa Gambling Task (IGT), a well-known psychological task used to evaluate impairment in decision-making. Results:The divers at 30 metres achieved a lower score (mean 1,584.5, standard deviation 436.7) in the IGT than the divers at 5 metres (mean 2,062.5, standard deviation 584.1). Age, body mass index, gender, or the number of previous dives did not affect performance in the IGT. Conclusions:Our results suggest that gas narcosis may affect decision-making in scuba divers at 30 metres depth. This supports previous studies showing that gas narcosis is present at relatively shallow depths and shows that it may affect higher cognitive functions.

Good aerobic fitness associates positively with cognitive performance and brain health and conversely, low aerobic fitness predisposes to neurodegenerative diseases. To study how genotype together with exercise, started at older age, affects brain and behavior, we utilized rats that differ in inherited aerobic fitness. Rats bred for Low Capacity for Running (LCR) are shown to display less synaptic plasticity and more inflammation in the hippocampus and perform worse than rats bred for a High Capacity for Running (HCR) in tasks requiring flexible cognition. Here we used middle-aged (∼ 16 months) HCR and LCR rats to study how genotype and sex associate with anxiety and neural information filtering, termed sensory gating. Further, we assessed how inherited aerobic capacity associates with hippocampus-dependent learning, measured with contextual fear conditioning task. In females, we also investigated the effects of voluntary wheel running (5 weeks) on these characteristics. Our results indicate that independent of sex or voluntary running, HCR rats were more anxious in open-field tasks, exhibited lower sensory gating and learned more efficiently in contextual fear conditioning task than LCR rats. Voluntary running did not markedly affect innate behavior but slightly decreased the differences between female LCR and HCR rats in fear learning. In conclusion, inherited fitness seems to determine cognitive and behavioral traits independent of sex. Although the traits proved to be rather resistant to change at adult age, learning was slightly improved following exercise in LCR females, prone to obesity and poor fitness.

A recent meta-analysis by Schroeder et al. (2020) [[1]Schroeder P.A. Schwippel T. Wolz I. Svaldi J. Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control.Brain Stimul. 2020; 13: 1159-1167https://doi.org/10.1016/j.brs.2020.05.006Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar] thoroughly summarised the accumulated knowledge on the potential of transcranial direct current stimulation (tDCS) in modulating inhibitory control. They concluded that the overall effect of tDCS appears to be small but significant and that targeting the right inferior frontal gyrus (rIFG) over the dorsolateral prefrontal cortex (DLPFC) might be more effective. Additionally, the stop-signal task (SST) as an outcome measure appeared to best capture the impact of tDCS on inhibitory control. Similarly, another recent meta-analysis by de Boer et al. (2021) [[2]de Boer N.S. Schluter R.S. Daams J.G. van der Werf Y.D. Goudriaan A.E. van Holst R.J. The effect of non-invasive brain stimulation on executive functioning in healthy controls: a systematic review and meta-analysis.Neurosci Biobehav Rev. 2021; 125: 122-147https://doi.org/10.1016/j.neubiorev.2021.01.013Crossref PubMed Scopus (9) Google Scholar] supported tDCS as a potential means to improve inhibitory performance, as measured by the go/no-go (GNG) task and SST.Despite the above interesting findings, there is a scarcity of data on other transcranial electric stimulation (tES) methods in terms of their usability in modulating inhibitory control. Therefore, we describe here our experiment conducted to investigate the impact of transcranial random noise stimulation (tRNS), targeting the dorsolateral prefrontal cortex (DLPFC), on the modulation of inhibitory control. We recruited a mixed-gender sample of 60 healthy, right-handed volunteers aged 20–45 years (mean age 26.7 years). The study protocol was approved by the Ethics Committee of the North Savo Hospital District, Finland. Written informed consent was obtained from all the participants.All the participants received one tRNS session and one sham stimulation session in a randomised, double-blinded, cross-over setting. TRNS was applied over the F3 and the F4 (corresponding to the left and right DLPFC), according to the international 10–20 system. Conductive rubber electrodes (5 × 5 cm), placed in two rectangle-shaped saline-soaked sponges, were used. The duration of the 2-mA high-frequency stimulation was 20 minutes, with a ramp-up period at the beginning and a ramp-down period at the end. Sham stimulation consisted of the ramping period only. Stimulation was performed with the DC-STIMULATOR PLUS (NeuroConn GmbH, Ilmenau, Germany). During the stimulation, participants sat calmly in a chair and followed a video with a windscreen view of a train journey. A cued GNG task [[3]Fillmore M.T. Drug abuse as a problem of impaired control: current approaches and findings.Behav Cognit Neurosci Rev. 2003; 2: 179-197https://doi.org/10.1177/1534582303257007Crossref PubMed Scopus (217) Google Scholar] and SST [[4]Verbruggen F. Logan G.D. Stevens M.A. STOP-IT: Windows executable software for the stop-signal paradigm.Behav Res Methods. 2008; 40: 479-483https://doi.org/10.3758/BRM.40.2.479Crossref PubMed Scopus (309) Google Scholar] were used to measure selective attention and response inhibition before and after the tRNS/sham in both sessions.Data were analysed with SPSS 27 statistical software (IBM SPSS Statistics for Windows, version 27.0. Armonk, NY: IBM Corp) and R version 4.1.1 (R Core Team (2021); R: A language and environment for statistical computing; R Foundation for Statistical Computing; Vienna, Austria). A mixed between–within subjects analysis of variance (ANOVA) was conducted to assess the impact of tRNS on the inhibitory failure rate in the GNG task and the stop-signal reaction time (SSRT) in the SST. Subjects who had significantly inhibited more or less than 50% of the time were excluded prior to the analysis, as the subtraction method was used to calculate SSRTs [[4]Verbruggen F. Logan G.D. Stevens M.A. STOP-IT: Windows executable software for the stop-signal paradigm.Behav Res Methods. 2008; 40: 479-483https://doi.org/10.3758/BRM.40.2.479Crossref PubMed Scopus (309) Google Scholar]. Power calculations were performed to compute the numbers of individuals required to detect the effect of tRNS on performance in either the GNG task or SSRT as significant. We used a simulation-based method with the “simr” R package, in which the number of participants was artificially extended to a large enough number to give an adequate degree of power for a linear mixed model analysis corresponding to the utilized ANOVA.No main effect of stimulation was observed on inhibitory failure rates in the GNG task (Wilks' Lambda = 1.0, F(1, 58) = 0.015, p = .904, ηp2 = 0.000), and the interaction of stimulation x time was non-significant (Wilks' Lambda = 0.967, F(1, 58) = 1.992, p = .163, ηp2 = 0.033). There was, however, a significant effect for time before vs. after the intervention (Wilks' Lambda = 0.894, F(1, 58) = 6.908, p = .011, ηp2 = 0.106). Similarly, SSRTs showed neither a significant main effect for stimulation (Wilks' Lambda = 0.977, F(1, 42) = 0.969, p = .331, ηp2 = 0.023) nor a significant interaction of stimulation x time (Wilks' Lambda = 0.999, F(1, 42) = 0.046, p = .831, ηp2 = 0.001). A significant main effect was again observed for time before vs. after the intervention (Wilks’ Lambda = 0.797, F(1, 42) = 10.710, p = .002, ηp2 = 0.203). The SSRT achieved a projected power of 80% at approximately 10,000 participants, whereas the GNG task achieved a power of 80% at approximately 150 participants. (see Fig. 1)We observed no effect of tRNS on SSRT or inhibitory failure rates in the GNG task. Nevertheless, time predicted an improvement in performance in both tasks, suggesting a learning effect. In their meta-analysis, Schroeder et al. (2020) suggested that the overall effect of tDCS was small but significant. Targeting the right inferior frontal gyrus (rIFG) appeared to surpass the DLPFC in effect, which may partially explain our findings. Nevertheless, Schroeder et al. (2020) observed that the stimulation effect diminished significantly after trim-and-fill analysis of bias and was not statistically significant after PET–PEESE analysis. Furthermore, to the best of our knowledge, the impact of tRNS on inhibitory control has only been investigated in three previous studies [5Brauer H. Kadish N.E. Pedersen A. Siniatchkin M. Moliadze V. No modulatory effects when stimulating the right inferior frontal gyrus with continuous 6 Hz TACs and TRNs on response inhibition: a behavioral study.Neural Plast. 2018; 2018https://doi.org/10.1155/2018/3156796Crossref PubMed Scopus (8) Google Scholar, 6Brevet-Aeby C. Mondino M. Poulet E. Brunelin J. Three repeated sessions of transcranial random noise stimulation (tRNS) leads to long-term effects on reaction time in the Go/No Go task.Neurophysiol Clin. 2019; 49: 27-32https://doi.org/10.1016/j.neucli.2018.10.066Crossref PubMed Scopus (17) Google Scholar, 7Jooss A. Haberbosch L. Köhn A. Rönnefarth M. Bathe-Peters R. Kozarzewski L. et al.Motor task-dependent dissociated effects of transcranial random noise stimulation in a finger-tapping task versus a go/No-go task on corticospinal excitability and task performance.Front Neurosci. 2019; 13https://doi.org/10.3389/fnins.2019.00161Crossref Scopus (10) Google Scholar]. In line with our findings, no effect was observed for online or offline tRNS in a GNG task when stimulating rIFG [[5]Brauer H. Kadish N.E. Pedersen A. Siniatchkin M. Moliadze V. No modulatory effects when stimulating the right inferior frontal gyrus with continuous 6 Hz TACs and TRNs on response inhibition: a behavioral study.Neural Plast. 2018; 2018https://doi.org/10.1155/2018/3156796Crossref PubMed Scopus (8) Google Scholar]. However, another study found a decrease in go-trial reaction times after repeated sessions of tRNS on the DLPFC [[6]Brevet-Aeby C. Mondino M. Poulet E. Brunelin J. Three repeated sessions of transcranial random noise stimulation (tRNS) leads to long-term effects on reaction time in the Go/No Go task.Neurophysiol Clin. 2019; 49: 27-32https://doi.org/10.1016/j.neucli.2018.10.066Crossref PubMed Scopus (17) Google Scholar]. Furthermore, 10 minutes of tRNS over the dominant primary motor cortex led to slowed reaction times and enhanced task accuracy in the GNG task during and after stimulation [[7]Jooss A. Haberbosch L. Köhn A. Rönnefarth M. Bathe-Peters R. Kozarzewski L. et al.Motor task-dependent dissociated effects of transcranial random noise stimulation in a finger-tapping task versus a go/No-go task on corticospinal excitability and task performance.Front Neurosci. 2019; 13https://doi.org/10.3389/fnins.2019.00161Crossref Scopus (10) Google Scholar].A large degree of heterogeneity is characteristic of tES studies. The current types, stimulation times and electrode placements vary, and tES has been applied both online and offline, and in single and multiple session settings. Therefore, direct comparisons of the conducted studies are very challenging [[8]Mayer J.T. Chopard G. Nicolier M. Gabriel D. Masse C. Giustiniani J. et al.Can transcranial direct current stimulation (tDCS) improve impulsivity in healthy and psychiatric adult populations? A systematic review.Prog Neuro Psychopharmacol Biol Psychiatr. 2020; 98: 109814https://doi.org/10.1016/j.pnpbp.2019.109814Crossref PubMed Scopus (13) Google Scholar], and it remains unclear which factors contribute most when investigating the potential effects of tES on inhibitory control. These issues remain topics for future study. Furthermore, our power calculations indicate that a future experiment to detect an observable effect of tRNS could be credibly achieved for the GNG task, but not for the SST. In the light of our power calculations, many of the previously conducted studies appear modest in size. To improve the quality of future studies, we would recommend a standard practice of publishing sample size calculations based on each new study to provide more specific guidance for future research. A recent meta-analysis by Schroeder et al. (2020) [[1]Schroeder P.A. Schwippel T. Wolz I. Svaldi J. Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control.Brain Stimul. 2020; 13: 1159-1167https://doi.org/10.1016/j.brs.2020.05.006Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar] thoroughly summarised the accumulated knowledge on the potential of transcranial direct current stimulation (tDCS) in modulating inhibitory control. They concluded that the overall effect of tDCS appears to be small but significant and that targeting the right inferior frontal gyrus (rIFG) over the dorsolateral prefrontal cortex (DLPFC) might be more effective. Additionally, the stop-signal task (SST) as an outcome measure appeared to best capture the impact of tDCS on inhibitory control. Similarly, another recent meta-analysis by de Boer et al. (2021) [[2]de Boer N.S. Schluter R.S. Daams J.G. van der Werf Y.D. Goudriaan A.E. van Holst R.J. The effect of non-invasive brain stimulation on executive functioning in healthy controls: a systematic review and meta-analysis.Neurosci Biobehav Rev. 2021; 125: 122-147https://doi.org/10.1016/j.neubiorev.2021.01.013Crossref PubMed Scopus (9) Google Scholar] supported tDCS as a potential means to improve inhibitory performance, as measured by the go/no-go (GNG) task and SST. Despite the above interesting findings, there is a scarcity of data on other transcranial electric stimulation (tES) methods in terms of their usability in modulating inhibitory control. Therefore, we describe here our experiment conducted to investigate the impact of transcranial random noise stimulation (tRNS), targeting the dorsolateral prefrontal cortex (DLPFC), on the modulation of inhibitory control. We recruited a mixed-gender sample of 60 healthy, right-handed volunteers aged 20–45 years (mean age 26.7 years). The study protocol was approved by the Ethics Committee of the North Savo Hospital District, Finland. Written informed consent was obtained from all the participants. All the participants received one tRNS session and one sham stimulation session in a randomised, double-blinded, cross-over setting. TRNS was applied over the F3 and the F4 (corresponding to the left and right DLPFC), according to the international 10–20 system. Conductive rubber electrodes (5 × 5 cm), placed in two rectangle-shaped saline-soaked sponges, were used. The duration of the 2-mA high-frequency stimulation was 20 minutes, with a ramp-up period at the beginning and a ramp-down period at the end. Sham stimulation consisted of the ramping period only. Stimulation was performed with the DC-STIMULATOR PLUS (NeuroConn GmbH, Ilmenau, Germany). During the stimulation, participants sat calmly in a chair and followed a video with a windscreen view of a train journey. A cued GNG task [[3]Fillmore M.T. Drug abuse as a problem of impaired control: current approaches and findings.Behav Cognit Neurosci Rev. 2003; 2: 179-197https://doi.org/10.1177/1534582303257007Crossref PubMed Scopus (217) Google Scholar] and SST [[4]Verbruggen F. Logan G.D. Stevens M.A. STOP-IT: Windows executable software for the stop-signal paradigm.Behav Res Methods. 2008; 40: 479-483https://doi.org/10.3758/BRM.40.2.479Crossref PubMed Scopus (309) Google Scholar] were used to measure selective attention and response inhibition before and after the tRNS/sham in both sessions. Data were analysed with SPSS 27 statistical software (IBM SPSS Statistics for Windows, version 27.0. Armonk, NY: IBM Corp) and R version 4.1.1 (R Core Team (2021); R: A language and environment for statistical computing; R Foundation for Statistical Computing; Vienna, Austria). A mixed between–within subjects analysis of variance (ANOVA) was conducted to assess the impact of tRNS on the inhibitory failure rate in the GNG task and the stop-signal reaction time (SSRT) in the SST. Subjects who had significantly inhibited more or less than 50% of the time were excluded prior to the analysis, as the subtraction method was used to calculate SSRTs [[4]Verbruggen F. Logan G.D. Stevens M.A. STOP-IT: Windows executable software for the stop-signal paradigm.Behav Res Methods. 2008; 40: 479-483https://doi.org/10.3758/BRM.40.2.479Crossref PubMed Scopus (309) Google Scholar]. Power calculations were performed to compute the numbers of individuals required to detect the effect of tRNS on performance in either the GNG task or SSRT as significant. We used a simulation-based method with the “simr” R package, in which the number of participants was artificially extended to a large enough number to give an adequate degree of power for a linear mixed model analysis corresponding to the utilized ANOVA. No main effect of stimulation was observed on inhibitory failure rates in the GNG task (Wilks' Lambda = 1.0, F(1, 58) = 0.015, p = .904, ηp2 = 0.000), and the interaction of stimulation x time was non-significant (Wilks' Lambda = 0.967, F(1, 58) = 1.992, p = .163, ηp2 = 0.033). There was, however, a significant effect for time before vs. after the intervention (Wilks' Lambda = 0.894, F(1, 58) = 6.908, p = .011, ηp2 = 0.106). Similarly, SSRTs showed neither a significant main effect for stimulation (Wilks' Lambda = 0.977, F(1, 42) = 0.969, p = .331, ηp2 = 0.023) nor a significant interaction of stimulation x time (Wilks' Lambda = 0.999, F(1, 42) = 0.046, p = .831, ηp2 = 0.001). A significant main effect was again observed for time before vs. after the intervention (Wilks’ Lambda = 0.797, F(1, 42) = 10.710, p = .002, ηp2 = 0.203). The SSRT achieved a projected power of 80% at approximately 10,000 participants, whereas the GNG task achieved a power of 80% at approximately 150 participants. (see Fig. 1) We observed no effect of tRNS on SSRT or inhibitory failure rates in the GNG task. Nevertheless, time predicted an improvement in performance in both tasks, suggesting a learning effect. In their meta-analysis, Schroeder et al. (2020) suggested that the overall effect of tDCS was small but significant. Targeting the right inferior frontal gyrus (rIFG) appeared to surpass the DLPFC in effect, which may partially explain our findings. Nevertheless, Schroeder et al. (2020) observed that the stimulation effect diminished significantly after trim-and-fill analysis of bias and was not statistically significant after PET–PEESE analysis. Furthermore, to the best of our knowledge, the impact of tRNS on inhibitory control has only been investigated in three previous studies [5Brauer H. Kadish N.E. Pedersen A. Siniatchkin M. Moliadze V. No modulatory effects when stimulating the right inferior frontal gyrus with continuous 6 Hz TACs and TRNs on response inhibition: a behavioral study.Neural Plast. 2018; 2018https://doi.org/10.1155/2018/3156796Crossref PubMed Scopus (8) Google Scholar, 6Brevet-Aeby C. Mondino M. Poulet E. Brunelin J. Three repeated sessions of transcranial random noise stimulation (tRNS) leads to long-term effects on reaction time in the Go/No Go task.Neurophysiol Clin. 2019; 49: 27-32https://doi.org/10.1016/j.neucli.2018.10.066Crossref PubMed Scopus (17) Google Scholar, 7Jooss A. Haberbosch L. Köhn A. Rönnefarth M. Bathe-Peters R. Kozarzewski L. et al.Motor task-dependent dissociated effects of transcranial random noise stimulation in a finger-tapping task versus a go/No-go task on corticospinal excitability and task performance.Front Neurosci. 2019; 13https://doi.org/10.3389/fnins.2019.00161Crossref Scopus (10) Google Scholar]. In line with our findings, no effect was observed for online or offline tRNS in a GNG task when stimulating rIFG [[5]Brauer H. Kadish N.E. Pedersen A. Siniatchkin M. Moliadze V. No modulatory effects when stimulating the right inferior frontal gyrus with continuous 6 Hz TACs and TRNs on response inhibition: a behavioral study.Neural Plast. 2018; 2018https://doi.org/10.1155/2018/3156796Crossref PubMed Scopus (8) Google Scholar]. However, another study found a decrease in go-trial reaction times after repeated sessions of tRNS on the DLPFC [[6]Brevet-Aeby C. Mondino M. Poulet E. Brunelin J. Three repeated sessions of transcranial random noise stimulation (tRNS) leads to long-term effects on reaction time in the Go/No Go task.Neurophysiol Clin. 2019; 49: 27-32https://doi.org/10.1016/j.neucli.2018.10.066Crossref PubMed Scopus (17) Google Scholar]. Furthermore, 10 minutes of tRNS over the dominant primary motor cortex led to slowed reaction times and enhanced task accuracy in the GNG task during and after stimulation [[7]Jooss A. Haberbosch L. Köhn A. Rönnefarth M. Bathe-Peters R. Kozarzewski L. et al.Motor task-dependent dissociated effects of transcranial random noise stimulation in a finger-tapping task versus a go/No-go task on corticospinal excitability and task performance.Front Neurosci. 2019; 13https://doi.org/10.3389/fnins.2019.00161Crossref Scopus (10) Google Scholar]. A large degree of heterogeneity is characteristic of tES studies. The current types, stimulation times and electrode placements vary, and tES has been applied both online and offline, and in single and multiple session settings. Therefore, direct comparisons of the conducted studies are very challenging [[8]Mayer J.T. Chopard G. Nicolier M. Gabriel D. Masse C. Giustiniani J. et al.Can transcranial direct current stimulation (tDCS) improve impulsivity in healthy and psychiatric adult populations? A systematic review.Prog Neuro Psychopharmacol Biol Psychiatr. 2020; 98: 109814https://doi.org/10.1016/j.pnpbp.2019.109814Crossref PubMed Scopus (13) Google Scholar], and it remains unclear which factors contribute most when investigating the potential effects of tES on inhibitory control. These issues remain topics for future study. Furthermore, our power calculations indicate that a future experiment to detect an observable effect of tRNS could be credibly achieved for the GNG task, but not for the SST. In the light of our power calculations, many of the previously conducted studies appear modest in size. To improve the quality of future studies, we would recommend a standard practice of publishing sample size calculations based on each new study to provide more specific guidance for future research. None. MV has received a grant from the Finnish Medical Foundation . Appendix A. Supplementary dataThe following is the Supplementary data to this article: Download .docx (.02 MB) Help with docx files Multimedia component 1 The following is the Supplementary data to this article: Download .docx (.02 MB) Help with docx files Multimedia component 1

Background Cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. Adding CRF to conventional risk factors (eg, smoking, hypertension, impaired glucose metabolism, and dyslipidemia) improves the prediction of an individual’s risk for adverse health outcomes such as those related to cardiovascular disease. Consequently, it is recommended to determine CRF as part of individualized risk prediction. However, CRF is not determined routinely in everyday clinical practice. Wearable technologies provide a potential strategy to estimate CRF on a daily basis, and such technologies, which provide CRF estimates based on heart rate and body acceleration, have been developed. However, the validity of such technologies in estimating individual CRF in clinically relevant populations is poorly known. Objective The objective of this study is to evaluate the validity of a wearable technology, which provides estimated CRF based on heart rate and body acceleration, in working-aged adults with cardiovascular risk factors. Methods In total, 74 adults (age range 35-64 years; n=56, 76% were women; mean BMI 28.7, SD 4.6 kg/m2) with frequent cardiovascular risk factors (eg, n=64, 86% hypertension; n=18, 24% prediabetes; n=14, 19% type 2 diabetes; and n=51, 69% metabolic syndrome) performed a 30-minute self-paced walk on an indoor track and a cardiopulmonary exercise test on a treadmill. CRF, quantified as peak O2 uptake, was both estimated (self-paced walk: a wearable single-lead electrocardiogram device worn to record continuous beat-to-beat R-R intervals and triaxial body acceleration) and measured (cardiopulmonary exercise test: ventilatory gas analysis). The accuracy of the estimated CRF was evaluated against that of the measured CRF. Results Measured CRF averaged 30.6 (SD 6.3; range 20.1-49.6) mL/kg/min. In all participants (74/74, 100%), mean difference between estimated and measured CRF was −0.1 mL/kg/min (P=.90), mean absolute error was 3.1 mL/kg/min (95% CI 2.6-3.7), mean absolute percentage error was 10.4% (95% CI 8.5-12.5), and intraclass correlation coefficient was 0.88 (95% CI 0.80-0.92). Similar accuracy was observed in various subgroups (sexes, age, BMI categories, hypertension, prediabetes, and metabolic syndrome). However, mean absolute error was 4.2 mL/kg/min (95% CI 2.6-6.1) and mean absolute percentage error was 16.5% (95% CI 8.6-24.4) in the subgroup of patients with type 2 diabetes (14/74, 19%). Conclusions The error of the CRF estimate, provided by the wearable technology, was likely below or at least very close to the clinically significant level of 3.5 mL/kg/min in working-aged adults with cardiovascular risk factors, but not in the relatively small subgroup of patients with type 2 diabetes. From a large-scale clinical perspective, the findings suggest that wearable technologies have the potential to estimate individual CRF with acceptable accuracy in clinically relevant populations.

Objective. Autonomic nervous system function and thereby bodily stress and recovery reactions may be assessed by wearable devices measuring heart rate (HR) and its variability (HRV). So far, the validity of HRV-based stress assessments has been mainly studied in healthy populations. In this study, we determined how psychosocial stress affects physiological and psychological stress responses in both young (18–30 years) and middle-aged (45–64 years) healthy individuals as well as in patients with arterial hypertension and/or either prior evidence of prediabetes or type 2 diabetes. We also studied how an HRV-based stress index (Relax-Stress Intensity, RSI) relates to perceived stress (PS) and cortisol (CRT) responses during psychosocial stress. Approach. A total of 197 participants were divided into three groups: (1) healthy young (HY, N = 63), (2) healthy middle-aged (HM, N = 61) and (3) patients with cardiometabolic risk factors (Pts, N = 73, 32–65 years). The participants underwent a group version of Trier Social Stress Test (TSST-G). HR, HRV (quantified as root mean square of successive differences of R–R intervals, RMSSD), RSI, PS, and salivary CRT were measured regularly during TSST-G and a subsequent recovery period. Main results. All groups showed significant stress reactions during TSST-G as indicated by significant responses of HR, RMSSD, RSI, PS, and salivary CRT. Between-group differences were also observed in all measures. Correlation and regression analyses implied RSI being the strongest predictor of CRT response, while HR was more closely associated with PS. Significance. The HRV-based stress index mirrors responses of CRT, which is an independent marker for physiological stress, around TSST-G. Thus, the HRV-based stress index may be used to quantify physiological responses to psychosocial stress across various health and age groups.

Metabolic syndrome (MetS) is a known risk factor for cognitive decline. Using polygenic rat models selectively bred for high and low intrinsic exercise capacity and simultaneously modelling as low and high innate risk factor for MetS respectively, we have previously shown that adult animals with lower exercise capacity/higher MetS risk perform poorly in tasks requiring flexible cognition. However, it is not known whether these deficits in cognition are present already at young age. Also, it is unclear whether the high risk genome is related also to lower-level cognition, such as sensory gating measured as prepulse inhibition. In this study, young and adult (5-8 weeks and ~9 months) rats selectively bred for 36 generations as High-Capacity Runners (HCR) or Low-Capacity Runners (LCR) were tested for behavior in an open field task, modulation of startle reflex, and spatial learning in a T-maze. HCR rats were more active in the open field than LCR rats independent of age. Responses to the startle stimulus habituated to the same extent in LCR compared to HCR rats when young, but as adults, stronger habituation was seen in the HCR animals. The prepulse inhibition of startle response was equally strong in young HCR and LCR animals but the effect was shorter lasting in HCR animals. In T-maze, adult HCR animals unexpectedly showed attenuated learning, but we interpret this finding to stem from differences in motivation rather than learning ability. Overall, in the LCR rats with the risk genome for poor aerobic fitness and MetS, indications of compromised cognitive function are present already at a young age.

Background: Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats. Methods: We examined markers for inflammation and brain plasticity in the hippocampi of LCR rats and compared them to HCR rats. The effect of age was determined by studying the rats at a young age (8 weeks) and later in life (40 weeks). We used western blots and immunohistochemistry to quantify the expression of target proteins. Results: Our study showed that the number of adult-born new neurons in the hippocampus was significantly lower in LCR rats than it was in HCR rats already at a young age and that the difference became more pronounced with age. The expression of synaptic proteins was higher in young animals relative to older ones. Brain inflammation tended to be higher in LCR rats than it was in the HCR rats, and more prominent in older rats than in young ones. Conclusion: Our study is the first to demonstrate that low intrinsic aerobic fitness that is associated with obesity and poor metabolic health is also linked with reduced hippocampal structural plasticity at a young age. Our results also suggest that inflammation of the brain could be one factor mediating the link between obesity and poor cognitive performance.

Transcranial electrical stimulation (tES) has shown promise in the treatment of conditions such as depression and chronic pain with mild-to-moderate adverse effects (AEs). Few previous studies have attempted to identify factors predicting tES-induced AEs. In particular, AEs resulting from repeated sessions of tES remain understudied. We conducted an exploratory retrospective analysis of two independent randomized controlled studies to investigate whether lifestyle factors (i.e. chronic alcohol use, smoking, exercise, and quality and length of sleep) modify the severity and frequency of tES-induced AEs, and evaluated the progression of AEs over repeated sessions. We utilized two double-blinded samples: 1) a male sample (n=82) randomized to receive transcranial direct current stimulation (tDCS) or sham for 5 days, and 2) a mixed-sex sample (n=60) who received both transcranial random noise stimulation (tRNS) and sham in a crossover setting. The severity of AEs was recorded on a scale of 0-100. The data was analysed using negative binomial models. In addition, we performed power calculations and, to guide future research, evaluated the numbers of individuals needed to detect non-significant observations as significant. By day 5, the tDCS group experienced more sensations under the electrodes than the sham group. Alcohol use, smoking, exercise, or quality or duration of sleep did not appear to be associated with the intensity of the AEs. The subsequent power analyses indicated that substantially larger samples would be needed to detect the observed associations as significant. Repetitive sessions do not appear to introduce additional AE burden to individuals receiving either tDCS or tRNS, at least with protocols lasting up to 5 days. Alcohol use, smoking, exercise, or quality or duration of sleep appear to only have an effect of negligible size, if any, on AEs induced by tDCS or tRNS, and studies with sample sizes ranging from roughly 100 individuals to hundreds of thousands of individuals would be required to detect such effects as significant.

Two themes have puzzled the research on developmental and learning disorders for decades. First, some of the risk and protective factors behind developmental challenges are suggested to be shared and some are suggested to be specific for a given condition. Second, language-based learning difficulties like dyslexia are suggested to result from or correlate with non-linguistic aspects of information processing as well. In the current study, we investigated how adults with developmental dyslexia or ADHD as well as healthy controls cluster across various dimensions designed to tap the prominent non-linguistic theories of dyslexia. Participants were 18–55-year-old adults with dyslexia (n = 36), ADHD (n = 22), and controls (n = 35). Non-linguistic theories investigated with experimental designs included temporal processing impairment, abnormal cerebellar functioning, procedural learning difficulties, as well as visual processing and attention deficits. Latent profile analysis (LPA) was used to investigate the emerging groups and patterns of results across these experimental designs. LPA suggested three groups: (1) a large group with average performance in the experimental designs, (2) participants predominantly from the clinical groups but with enhanced conditioning learning, and (3) participants predominantly from the dyslexia group with temporal processing as well as visual processing and attention deficits. Despite the presence of these distinct patterns, participants did not cluster very well based on their original status, nor did the LPA groups differ in their dyslexia or ADHD-related neuropsychological profiles. Remarkably, the LPA groups did differ in their intelligence. These results highlight the continuous and overlapping nature of the observed difficulties and support the multiple deficit model of developmental disorders, which suggests shared risk factors for developmental challenges. It also appears that some of the risk factors suggested by the prominent non-linguistic theories of dyslexia relate to the general level of functioning in tests of intelligence.

Transcranial electrical stimulation (tES) has shown promise in the treatment of conditions such as depression and chronic pain with mild-to-moderate adverse effects (AEs). Few previous studies have attempted to identify factors predicting tES-induced AEs. In particular, AEs resulting from repeated sessions of tES remain understudied. We conducted an exploratory retrospective analysis of two independent randomized controlled studies to investigate whether lifestyle factors (i.e. chronic alcohol use, smoking, exercise, and quality and length of sleep) modify the severity and frequency of tES-induced AEs, and evaluated the progression of AEs over repeated sessions. We utilized two double-blinded samples: 1) a male sample (n=82) randomized to receive transcranial direct current stimulation (tDCS) or sham for 5 days, and 2) a mixed-sex sample (n=60) who received both transcranial random noise stimulation (tRNS) and sham in a crossover setting. The severity of AEs was recorded on a scale of 0-100. The data was analysed using negative binomial models. In addition, we performed power calculations and, to guide future research, evaluated the numbers of individuals needed to detect non-significant observations as significant. By day 5, the tDCS group experienced more sensations under the electrodes than the sham group. Alcohol use, smoking, exercise, or quality or duration of sleep did not appear to be associated with the intensity of the AEs. The subsequent power analyses indicated that substantially larger samples would be needed to detect the observed associations as significant. Repetitive sessions do not appear to introduce additional AE burden to individuals receiving either tDCS or tRNS, at least with protocols lasting up to 5 days. Alcohol use, smoking, exercise, or quality or duration of sleep appear to only have an effect of negligible size, if any, on AEs induced by tDCS or tRNS, and studies with sample sizes ranging from roughly 100 individuals to hundreds of thousands of individuals would be required to detect such effects as significant. THE IMPACT OF LIFESTYLE FACTORS ON THE INTENSITY OF ADVERSE EFFECTS IN SINGLE AND REPEATED SESSION PROTOCOLS OF TRANSCRANIAL ELECTRICAL STIMULATION: AN EXPLORATORY PILOT STUDY AARON KORTTEENNIEMI, ALFREDO ORTEGA-ALONSO, AMIR-HOMAYOUN JAVADI, OWEN THOMAS, TOMMI TOLMUNEN, TUUKKA KOTILAINEN, JAN WIKGREN , SOILI M. LEHTO