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This study uses EEG in humans to isolate and track an evolving, domain-general decision signal, which varies with accumulated evidence, but is independent of overt actions. In theoretical accounts of perceptual decision-making, a decision variable integrates noisy sensory evidence and determines action through a boundary-crossing criterion. Signals bearing these very properties have been characterized in single neurons in monkeys, but have yet to be directly identified in humans. Using a gradual target detection task, we isolated a freely evolving decision variable signal in human subjects that exhibited every aspect of the dynamics observed in its single-neuron counterparts. This signal could be continuously tracked in parallel with fully dissociable sensory encoding and motor preparation signals, and could be systematically perturbed mid-flight during decision formation. Furthermore, we found that the signal was completely domain general: it exhibited the same decision-predictive dynamics regardless of sensory modality and stimulus features and tracked cumulative evidence even in the absence of overt action. These findings provide a uniquely clear view on the neural determinants of simple perceptual decisions in humans.

The stabilizing influence of a light touch (LT) on a postural sway has been consistently shown in the literature, however there is still no consensus in what way attentional resources are used when adopting LT during standing. To better elucidate the underlying mechanisms we introduced additional feedback (LT), which seems to distracts from postural control, and verified it by center of pressure (COP) regularity level and simple reaction time task. 25 healthy students randomly performed eight postural tasks, four without (NoRT)/ four with simple reaction task (RT). COP displacements were measured on a force plate in two visual conditions: eyes open/closed and two sensory conditions: without (NoLT)/with light touch (LT). Participants were asked to consider the postural task as the primary task. Although simple reaction time did not differ between postural conditions ( p  > 0.05), LT decreased postural sway velocity in anteroposterior direction ( p  < 0.001, η2 = 0.86) and decreased standard deviation ( p  < 0.001, η2 = 0.91) in both, reaction and visual conditions. Interestingly, RT task modified subjects behavior in NoLT conditions and caused slower COP velocity ( p  < 0.001, η2 = 0.53) without changes in signal regularity. Results also showed a significant increase in irregularity during standing with LT ( p  < 0.001, η2 = 0.86) in both vision and reaction conditions, suggesting that the signal was more random. Current results suggests that providing LT enhance postural steadiness and also seem to redirect attention externally, as shown by increased signal irregularity. Hence, LT possibly reduce the attention invested in the postural task itself. A RT task can be not sensitive enough to detect such subtle changes.

Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT2A receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease.ObjectiveThis study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response.MethodsThis was a phase 1 double-blind, placebo-controlled, randomized study. Volunteers were randomly assigned to 1 of 4 dose groups (5 μg, 10 μg, 20 μg LSD, and placebo), and received their assigned dose on six occasions (i.e., every 4 days).ResultsForty-eight older healthy volunteers (mean age = 62.9 years) received placebo (n = 12), 5 μg (n = 12), 10 μg (n = 12), or 20 μg (n = 12) LSD. LSD plasma levels were undetectable for the 5 μg group and peak blood plasma levels for the 10 μg and 20 μg groups occurred at 30 min. LSD was well tolerated, and the frequency of adverse events was no higher than for placebo. Assessments of cognition, balance, and proprioception revealed no impairment.ConclusionsOur results suggest safety and tolerability of orally administered 5 μg, 10 μg, and 20 μg LSD every fourth day over a 21-day period and support further clinical development of LSD for the treatment and prevention of Alzheimer’s disease (AD).

Polanía et al. show that, similarly to sensory signals, subjective preferences guiding choice are represented by the brain in a manner that accounts for regularities of the environment, thereby optimizing use of limited neural processing resources.

The ability of cortical networks to integrate information from different sources is essential for cognitive processes. On one hand, sensory areas exhibit fast dynamics often phase-locked to stimulation; on the other hand, frontal lobe areas with slow response latencies to stimuli must integrate and maintain information for longer periods. Thus, cortical areas may require different timescales depending on their functional role. Studying the cortical somatosensory network while monkeys discriminated between two vibrotactile stimulus patterns, we found that a hierarchical order could be established across cortical areas based on their intrinsic timescales. Further, even though subareas (areas 3b, 1, and 2) of the primary somatosensory (S1) cortex exhibit analogous firing rate responses, a clear differentiation was observed in their timescales. Importantly, we observed that this inherent timescale hierarchy was invariant between task contexts (demanding vs. nondemanding). Even if task context severely affected neural coding in cortical areas downstream to S1, their timescales remained unaffected. Moreover, we found that these time constants were invariant across neurons with different latencies or coding. Although neurons had completely different dynamics, they all exhibited comparable timescales within each cortical area. Our results suggest that this measure is demonstrative of an inherent characteristic of each cortical area, is not a dynamical feature of individual neurons, and does not depend on task demands.

Subjects routinely control the vigor with which they emit motoric responses. However, the bulk of formal treatments of decision-making ignores this dimension of choice. A recent theoretical study suggested that action vigor should be influenced by experienced average reward rate and that this rate is encoded by tonic dopamine in the brain. We previously examined how average reward rate modulates vigor as exemplified by response times and found a measure of agreement with the first suggestion. In the current study, we examined the second suggestion, namely the potential influence of dopamine signaling on vigor. Ninety healthy subjects participated in a double-blind experiment in which they received one of the following: placebo, L-DOPA (which increases dopamine levels in the brain), or citalopram (which has a selective, if complex, effect on serotonin levels). Subjects performed multiple trials of a rewarded odd-ball discrimination task in which we varied the potential reward over time in order to exercise the putative link between vigor and average reward rate. Replicating our previous findings, we found that a significant fraction of the variance in subjects' responses could be explained by our experimentally manipulated changes in average reward rate. Crucially, this relationship was significantly stronger under L-Dopa than under Placebo, suggesting that the impact of average reward levels on action vigor is indeed subject to a dopaminergic influence.

PurposeBoth cognitive motor dual-tasks (CMDT) protocols and hypoxic environments have been associated with significant impairments in cognitive and physical performance. We aimed to determine the effects of hypoxia on cognitive performance and neuromuscular fatigue during a highly physically demanding CMDT.MethodsFifteen young adults completed a first session involving a cognitive task (CTLCOG) followed by cycling exercise (CTLEX) in normoxia. After that, they randomly participated in CMDT sessions in normoxia (DTNOR) and hypoxia (DTHYP). The physical exercise consisted of 20 min cycling at a “hard” perceived effort, and the cognitive task consisted of 15 min sustained attention to response time task (SART). Concurrent psycho-physiological measurements included: quadriceps neuromuscular fatigue (peripheral/central components from femoral nerve electrostimulation), prefrontal cortex (PFC) oxygenation by near-infrared spectroscopy, and perception of effort.ResultsSART performance significantly decreased in DTNOR (-15.7 ± 15.6%, P < 0.01) and DTHYP (-26.2 ± 16.0%, P < 0.01) compared to CTLCOG (-1.0 ± 17.7%, P = 0.61). Peripheral fatigue similarly increased across conditions, whereas the ability of the central nervous system to activate the working muscles was impaired similarly in DTNOR (-6.1 ± 5.9%, P < 0.001) and DTHYP (-5.4 ± 7.3%, P < 0.001) compared to CTLEX (-1.1 ± 0.2%, P = 0.52). Exercise-induced perception of effort was higher in DTHYP vs. DTNOR and in DTNOR vs. CTLEX. This was correlated with cognitive impairments in both normoxia and hypoxia. PFC deoxygenation was more pronounced in DTHYP compared to DTNOR and CTLEX.ConclusionIn conclusion, performing a sustained attention task together with physically challenging cycling exercise promotes central neuromuscular fatigue and impairs cognitive accuracy; the latter is particularly noticeable when the CMDT is performed in hypoxia.

Sustained attention, often referred to as vigilance in humans, is the ability to maintain goal-directed behavior for extended periods of time and respond to intermittent targets in the environment. With greater time-on-task the ability to detect targets decreases and reaction time increases—a phenomenon termed the vigilance decrement. The purpose of this study was to examine the role of dorsolateral prefrontal cortex in the vigilance decrement. Subjects (n=19) received prefrontal transcranial direct current stimulation (tDCS) at one of two different time points during a vigilance task (early or late). The impact of tDCS was examined using measures of behavior, hemispheric blood flow velocity, and regional blood oxygenation relative to sham stimulation. In the sham condition greater time-on-task was accompanied by fewer target detections and slower reaction times, indicating a vigilance decrement, and decreased blood flow velocity. tDCS significantly altered baseline task-induced physiologic and behavioral changes, dependent on the time of stimulation administration and electrode configuration (determining polarity of stimulation). Compared to the sham condition, with more time-on-task blood flow velocity decreased less and cerebral oxygenation increased more in the tDCS condition. Behavioral measures showed a significant improvement in target detection performance with tDCS compared to the sham stimulation. Signal detection analysis revealed a significant change in operator discriminability and response bias with increased time-on-task, as well as interactions between time of stimulation administration and electrode configuration. Current density modeling of tDCS showed high densities in the medial prefrontal cortex and anterior cingulate cortex. These findings confirm that cerebral hemodynamic measures provide an index of resource utilization and point to the central role of the frontal cortex in vigilance. Further, they suggest that modulation of the frontal cortices—and connected structures—influences the availability of vigilance resources. These findings indicate that tDCS may be well-suited to mitigate performance degradation in work settings requiring sustained attention or as a possible treatment for neurological or psychiatric disorders involving sustained attention. ► We characterize effects of a vigil in brain oxygenation and blood flow velocity. ► We apply transcranial direct current stimulation during vigil. ► Stimulation improved target detection compared to sham. ► Blood flow velocity decreased less in response to active stimulation. ► Cerebral oxygenation increased in response to active stimulation.

Technological approaches that promote cognitive-motor abilities through visual information have recently become increasingly prevalent. This study aims to verify the effects of balance-based visual reaction time exercises on physical and cognitive performance in older adults. In this randomized controlled trial, 31 participants (aged 71.70 ± 5.67 years) were randomly allocated into two groups. The intervention group ( n  = 16) was enrolled in a balanced-based visual reaction exercise program, and the control group ( n  = 15) in a functional balance exercise program. The participants were assessed both prior to and following the intervention. Primary outcomes included global cognitive function, assessed using the Montreal Cognitive Assessment (MoCA); executive function, measured through the Stroop Test; and reaction time, evaluated using the BlazePod system and the New Test. Secondary outcomes focused on physical performance and included the Five Times Sit-to-Stand Test (FTSS), Timed Up and Go Test (TUG), Four Square Step Test (FSST), Short Physical Performance Battery (SPPB), and the Falls Efficacy Scale (FES) to assess fear of falling. At reassessment, the intervention group exhibited a significantly faster reaction time and made fewer mistakes on the Stroop test compared to the control group ( p  < 0.05). The intervention group also exhibited better physical performance and less fear of falling ( p  < 0.05). However, no significant improvements were observed in global cognitive function, as measured by the Montreal Cognitive Assessment (MoCA), or in Stroop Interference scores (p 0.05). Two-model multiple linear regression analysis revealed that the changes in BlazePod reaction affected the improvement in TUG (β = 0.006, adjusted R 2  = 0.24) and FES (β = 0.013, adjusted R 2  = 0.15). In addition, the enhancement in FSST was influenced by changes in the BlazePod stroke (β=-0.585, Delta R 2  = 0.22). This study demonstrated that balance-based visual reaction time exercises significantly improved reaction time and physical performance in older adults, while no significant changes were observed in executive function measures. These findings highlight the potential of visually guided dual-task training as a feasible strategy to enhance functional outcomes in this population.

BackgroundProgression of Parkinson's disease (PD) is characterised by motor deficits which eventually respond less to dopaminergic therapy and thus pose a therapeutic challenge. Deep brain stimulation has proven efficacy but carries risks and is not possible in all patients. Non-invasive brain stimulation has shown promising results and may provide a therapeutic alternative.ObjectiveTo investigate the efficacy of transcranial direct current stimulation (tDCS) in the treatment of PD.DesignRandomised, double blind, sham controlled study.SettingResearch institution.MethodsThe efficacy of anodal tDCS applied to the motor and prefrontal cortices was investigated in eight sessions over 2.5 weeks. Assessment over a 3 month period included timed tests of gait (primary outcome measure) and bradykinesia in the upper extremities, Unified Parkinson's Disease Rating Scale (UPDRS), Serial Reaction Time Task, Beck Depression Inventory, Health Survey and self-assessment of mobility.ResultsTwenty-five PD patients were investigated, 13 receiving tDCS and 12 sham stimulation. tDCS improved gait by some measures for a short time and improved bradykinesia in both the on and off states for longer than 3 months. Changes in UPDRS, reaction time, physical and mental well being, and self-assessed mobility did not differ between the tDCS and sham interventions.ConclusiontDCS of the motor and prefrontal cortices may have therapeutic potential in PD but better stimulation parameters need to be established to make the technique clinically viable.This study was publicly registered(clinicaltrials.org: NCT00082342).