Response to experimental cold-induced pain discloses a resistant category among endurance athletes, with a distinct profile of pain-related behavior and GABAergic EEG markers: a case-control preliminary study.

Pain is a major public health problem worldwide, with a high rate of treatment failure. Among promising non-pharmacological therapies, physical exercise is an attractive, cheap, accessible and innocuous method; beyond other health benefits. However, its highly variable therapeutic effect and incompletely understood underlying mechanisms (plausibly involving the GABAergic neurotransmission) require further research. This case-control study aimed to investigate the impact of long-lasting intensive endurance sport practice (≥7 h/week for the last 6 months at the time of the experiment) on the response to experimental cold-induced pain (as a suitable chronic pain model), assuming that highly trained individual would better resist to pain, develop advantageous pain-copying strategies and enhance their GABAergic signaling. For this purpose, clinical pain-related data, response to a cold-pressor test and high-density EEG high (Hß) and low beta (Lß) oscillations were documented. Among 27 athletes and 27 age-adjusted non-trained controls (right-handed males), a category of highly pain-resistant participants (mostly athletes, 48.1%) was identified, displaying lower fear of pain, compared to non-resistant non-athletes. Furthermore, they tolerated longer cold-water immersion and perceived lower maximal sensory pain. However, while having similar Hß and Lß powers at baseline, they exhibited a reduction between cold and pain perceptions and between pain threshold and tolerance (respectively -60% and - 6.6%; -179.5% and - 5.9%; normalized differences), in contrast to the increase noticed in non-resistant non-athletes (+21% and + 14%; +23.3% and + 13.6% respectively). Our results suggest a beneficial effect of long-lasting physical exercise on resistance to pain and pain-related behaviors, and a modification in brain GABAergic signaling. In light of the current knowledge, we propose that the GABAergic neurotransmission could display multifaceted changes to be differently interpreted, depending on the training profile and on the homeostatic setting (e.g., in pain-free versus chronic pain conditions). Despite limitations related to the sample size and to absence of direct observations under acute physical exercise, this precursory study brings into light the unique profile of resistant individuals (probably favored by training) allowing highly informative observation on physical exercise-induced analgesia and paving the way for future clinical translation. Further characterizing pain-resistant individuals would open avenues for a targeted and physiologically informed pain management.

Neural correlates of expectations-induced effects of caffeine intake on executive functions.

Placebo effects are defined as the beneficial subjective or behavioral outcomes of an intervention that are not attributable to its inherent properties; Placebo effects thus follow from individuals' expectations about the effects of the intervention. The present study aimed at examining how expectations influence neurocognitive processes. We addressed this question by contrasting three double-blinded within-subjects experimental conditions in which participants were given decaffeinated coffee, while being told they had received caffeinated (condition i) or decaffeinated coffee (ii), and given caffeinated coffee while being told they had received decaffeinated coffee (iii). After each of these three interventions, performance and electroencephalogram was recorded at rest as well as during sustained attention Rapid Visual Information Processing task (RVIP) and a Go/NoGo motor inhibitory control task. We first aimed to confirm previous findings for caffeine-induced enhancement on these executive components and on their associated electrophysiological indexes (The Attention-P3 component, response conflict NoGo-N2 and inhibition NoGo-P3 components (ii vs iii contrast); and then to test the hypotheses that expectations also induce these effects (i vs ii), although with a weaker amplitude (i vs iii). We did not confirm any of our hypotheses for caffeine-induced behavioral improvements and thus did not test the effect of caffeine-related expectations. At the electrophysiological level, however, we confirmed that caffeine increased the Attention-P3 and NoGo-P3 components amplitude but did not confirm an effect on the response-conflict N2 component. We did not confirm that expectations influence any of the investigated electrophysiological indices, but we confirmed that the Attention-P3 Global Field Power values were larger for the caffeine compared to the expectations conditions. We conclude that previously identified behavioral effect size of caffeine and of the related expectations for sustained attention and inhibitory control may have been overestimated, and that caffeine primarily influences the cognitive processes and brain areas supporting attention allocation. Finally, we confirm that caffeine-related expectations induce smaller effects than the substance itself.

Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study.

In predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson's disease. They completed a cued go/no-go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non-operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto-basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.

Prediction of long-term quality of life after severe traumatic brain injury based on variables at hospital admission.

Objectives: Variables collected early after severe traumatic brain injury (sTBI) could predict health-related quality of life (HRQoL). Our aim was to determine the prevalence of patients with a low HRQoL 4 years after sTBI and to develop a prediction model including early variables.Methods: Adult patients with both sTBI [abbreviated injury score of the head region (HAIS) >3] and disease-specific HRQoL assessments using the 'Quality of Life after Brain Injury' (QOLIBRI) were included. The outcome was the total score (TS) of QOLIBRI; cutoff for low HRQoL: <60 points. A multivariate logistic regression model and prediction model were performed.Results: One hundred-sixteen patients [median age 50.8 years (IQR 25.9-62.8; 21.6% >65 years)] were included; 68 (58.6%) with HAIS = 4, 48 (41.4%) with HAIS = 5. Median Glasgow Coma Scale (GCS) was 13 (IQR 3-15). Median TS was 77 (IQR 60-88). Low HRQoL was observed in 28 patients (24.1%). Two variables were associated with low HRQoL: GCS <13, working situation other than employed or retired. The prediction model had an AUROC of 0.765; calibration was moderate (Hosmer Lemeshow Chi2 6.82, p = .556).Conclusion: One in four patients had a low HRQoL after 4 years. A lower GCS and working situations were associated with low HRQoL.

Stimulus Reward Value Interacts with Training-induced Plasticity in Inhibitory Control.

Training inhibitory control, the ability to suppress motor or cognitive processes, not only enhances inhibition processes, but also reduces the perceived value and behaviors toward the stimuli associated with the inhibition goals during the practice. While these findings suggest that inhibitory control training interacts with the aversive and reward systems, the underlying spatio-temporal brain mechanisms remain unclear. We used electrical neuroimaging analyses of event-related potentials to examine the plastic brain modulations induced by training healthy participants to inhibit their responses to rewarding (pleasant chocolate) versus aversive food pictures (unpleasant vegetables) with Go/NoGo tasks. Behaviorally, the training resulted in a larger improvement in the aversive than in the rewarding NoGo stimuli condition, suggesting that reward responses impede inhibitory control learning. The electrophysiological results also revealed an interaction between reward responses and inhibitory control plasticity: we observed different effects of practice on the rewarding vs. aversive NoGo stimuli at 200 ms post-stimulus onset, when the conflicts between automatic response tendency and task demands for response inhibition are processed. Electrical source analyses revealed that this effect was driven by an increase in right orbito-cingulate and a decrease in temporo-parietal activity to the rewarding NoGo stimuli and the reverse pattern to the aversive stimuli. Our collective results provide direct neurophysiological evidence for interactions between stimulus reward value and executive control training, and suggest that changes in the assessment of stimuli with repeated motoric inhibition likely follow from associative learning and behavior-stimulus conflicts reduction mechanisms.

Steady-state evoked potentials distinguish brain mechanisms of self-paced versus synchronization finger tapping.

Sensorimotor synchronization (SMS) requires aligning motor actions to external events and represents a core part of both musical and dance performances. In the current study, to isolate the brain mechanisms involved in synchronizing finger tapping with a musical beat, we compared SMS to pure self-paced finger tapping and listen-only conditions at different tempi. We analyzed EEG data using frequency domain steady-state evoked potentials (SSEPs) to identify sustained electrophysiological brain activity during repetitive tasks. Behavioral results revealed different timing modes between SMS and self-paced finger tapping, associated with distinct scalp topographies, thus suggesting different underlying brain sources. After subtraction of the listen-only brain activity, SMS was compared to self-paced finger tapping. Resulting source estimations showed stronger activation of the left inferior frontal gyrus during SMS, and stronger activation of the bilateral inferior parietal lobule during self-paced finger tapping. These results point to the left inferior frontal gyrus as a pivot for perception-action coupling. We discuss our findings in the context of the ongoing debate about SSEPs interpretation given the variety of brain events contributing to SSEPs and similar EEG frequency responses.

Modulation of inhibitory control by prefrontal anodal tDCS: A crossover double-blind sham-controlled fMRI study.

Prefrontal anodal transcranial direct current stimulation (tDCS) has been proposed as a potential approach to improve inhibitory control performance. The functional consequences of tDCS during inhibition tasks remain, however, largely unresolved. We addressed this question by analyzing functional magnetic resonance imaging (fMRI) recorded while participants completed a Go/NoGo task after right-lateralized prefrontal anodal tDCS with a crossover, sham-controlled, double-blind experimental design. We replicated previous evidence for an absence of offline effect of anodal stimulation on Go/NoGo performance. The fMRI results revealed a larger increase in right ventrolateral prefrontal activity for Go than NoGo trials in the anodal than sham condition. This pattern suggests that tDCS-induced increases in cortical excitability have larger effects on fMRI activity in regions with a lower task-related engagement. This was the case for the right prefrontal cortex in the Go condition in our task because while reactive inhibition was not engaged during execution trials, the unpredictability of the demand for inhibitory control still incited an engagement of proactive inhibition. Exploratory analyses further revealed that right prefrontal stimulation interacted with task-related functional demands in the supplementary motor area and the thalamus. Our collective results emphasize the dependency of offline tDCS functional effects on the task-related engagement of the stimulated areas and suggest that this factor might partly account for the discrepancies in the functional effects of tDCS observed in previous studies.

Electrical Neuroimaging of Music Processing Reveals Mid-Latency Changes with Level of Musical Expertise.

This original research focused on the effect of musical training intensity on cerebral and behavioral processing of complex music using high-density event-related potential (ERP) approaches. Recently we have been able to show progressive changes with training in gray and white matter, and higher order brain functioning using (f)MRI [(functional) Magnetic Resonance Imaging], as well as changes in musical and general cognitive functioning. The current study investigated the same population of non-musicians, amateur pianists and expert pianists using spatio-temporal ERP analysis, by means of microstate analysis, and ERP source imaging. The stimuli consisted of complex musical compositions containing three levels of transgression of musical syntax at closure that participants appraised. ERP waveforms, microstates and underlying brain sources revealed gradual differences according to musical expertise in a 300-500 ms window after the onset of the terminal chords of the pieces. Within this time-window, processing seemed to concern context-based memory updating, indicated by a P3b-like component or microstate for which underlying sources were localized in the right middle temporal gyrus, anterior cingulate and right parahippocampal areas. Given that the 3 expertise groups were carefully matched for demographic factors, these results provide evidence of the progressive impact of training on brain and behavior.

Spatiotemporal brain dynamics supporting the immediate automatization of inhibitory control by implementation intentions.

While cognitive interventions aiming at reinforcing intentional executive control of unwanted response showed only modest effects on impulse control disorders, the establishment of fast automatic, stimulus-driven inhibition of responses to specific events with implementation intention self-regulation strategies has proven to be an effective remediation approach. However, the neurocognitive mechanisms underlying implementation intentions remain largely unresolved. We addressed this question by comparing electrical neuroimaging analyses of event-related potentials recorded during a Go/NoGo task between groups of healthy participants receiving either standard or implementation intentions instructions on the inhibition stimuli. Inhibition performance improvements with implementation intentions were associated with a Group by Stimulus interaction 200-250 ms post-stimulus onset driven by a selective decrease in response to the inhibition stimuli within the left superior temporal gyrus, the right precuneus and the right temporo-parietal junction. We further observed that the implementation intentions group showed already at the beginning of the task the pattern of task-related functional activity reached after practice in the group having received standard instructions. We interpret our results in terms of an immediate establishment of an automatic, bottom-up form of inhibitory control by implementation intentions, supported by stimulus-driven retrieval of verbally encoded stimulus-response mapping rules, which in turn triggered inhibitory processes.

Trajectory of disability and quality-of-life in non-geriatric and geriatric survivors after severe traumatic brain injury.

OBJECTIVE: The objective was to investigate disability and health-related quality-of-life (HRQoL) 3, 6 and 12 months after traumatic brain injury (TBI) in non-geriatric (≤ 65 years) and geriatric patients (> 65 years). METHODS: Patients ≥ 16 years who sustained a severe TBI (Abbreviated Injury Scale of the head region > 3) were included in this prospective, multi-centre study. Outcome measures were Glasgow Outcome Scale Extended (GOSE; disability), SF-12 (HRQoL). Mixed linear model analyses were performed. RESULTS: Three hundred and fifty-one patients (median age = 50 years; interquartile range (IQR) = 27-67) were included; 73.2% were male and 27.6% were geriatric patients. Median GOSE at 3, 6 and 12 months was 5 (IQR = 3-7), 6 (IQR = 4-8) and 7 (IQR = 5-8); this increase (slopetime = 0.22, p < 0.0001) was age dependent (slopeage*time = -0.06, p = 0.003). Median SF-12 physical component scale score at 3, 6 and 12 months was 42.1 (IQR = 33.6-50.7), 46.6 (IQR = 37.4-53.9) and 50.4 (IQR = 39.2-55.1); this increase (slopetime = 1.52, p < 0.0001) was not age dependent (slopeage*time = -0.30, p = 0.083). SF-12 mental component scale scores were unchanged. CONCLUSIONS: Disability decreased and HRQoL improved after TBI between 3-12 months. In geriatric patients this improvement was relevant for HRQoL only.

State dependency of inhibitory control performance: an electrical neuroimaging study.

Behavioral and brain responses to stimuli not only depend on their physical features but also on the individuals' neurocognitive states before stimuli onsets. While the influence of pre-stimulus fluctuations in brain activity on low-level perceptive processes is well established, the state dependency of high-order executive processes remains unclear. Using a classical inhibitory control Go/NoGo task, we examined whether and how fluctuations in the brain activity during the period preceding the stimuli triggering inhibition influenced inhibitory control performance. Seventeen participants completed the Go/NoGo task while 64-channel electroencephalogram was recorded. We compared the event-related potentials preceding the onset of the NoGo stimuli associated with inhibition failures false alarms (FA) vs. successful inhibition correct rejections (CR) with data-driven statistical analyses of global measures of the topography and strength of the scalp electric field. Distributed electrical source estimations were used to localize the origin of the event-related potentials modulations. We observed differences in the global field power of the event-related potentials (FA > CR) without concomitant topographic modulations over the 40 ms period immediately preceding NoGo stimuli. This result indicates that the same brain networks were engaged in the two conditions, but more strongly before FA than CR. Source estimations revealed that this effect followed from a higher activity before FA than CR within bilateral inferior frontal gyri and the right inferior parietal lobule. These findings suggest that uncontrolled quantitative variations in pre-stimulus activity within attentional and control brain networks influence inhibition performance. The present data thereby demonstrate the state dependency of cognitive processes of up to high-order executive levels.

Time course of brain activity during change blindness and change awareness: performance is predicted by neural events before change onset.

People often remain "blind" to visual changes occurring during a brief interruption of the display. The processing stages responsible for such failure remain unresolved. We used event-related potentials to determine the time course of brain activity during conscious change detection versus change blindness. Participants saw two successive visual displays, each with two faces, and reported whether one of the faces changed between the first and second displays. Relative to blindness, change detection was associated with a distinct pattern of neural activity at several successive processing stages, including an enhanced occipital P1 response and a sustained frontal activity (CNV-like potential) after the first display, before the change itself. The amplitude of the N170 and P3 responses after the second visual display were also modulated by awareness of the face change. Furthermore, a unique topography of event-related potential activity was observed during correct change and correct no-change reports, but not during blindness, with a recurrent time course in the stimulus sequence and simultaneous sources in the parietal and temporo-occipital cortex. These results indicate that awareness of visual changes may depend on the attentional state subserved by coordinated neural activity in a distributed network, before the onset of the change itself.