Influence of age and cognitive demand on motor decision making under uncertainty: a study on goal directed reaching movements.

In everyday life, we constantly make decisions about actions to be performed subsequently. Research on motor decision making has provided empirical evidence for an influence of decision uncertainty on movement execution in young adults. Further, decision uncertainty was suggested to be increased in older adults due to limited cognitive resources for the integration of information and the prediction of the decision outcomes. However, the influence of cognitive aging on decision uncertainty during motor decision making and movement execution has not been investigated, yet. Thus, in the current study, we presented young and older adults with a motor decision making task, in which participants had to decide on pointing towards one out of five potential targets under varying cognitive demands. Statistical analyses revealed stronger decreases in correctly deciding upon the pointing target, i.e. task performance, from low to higher cognitive demand in older as compared to young adults. Decision confidence also decreased more strongly in older adults with increasing cognitive demand, however, only when collapsing across correct and incorrect decision trials, but not when considering correct decision trials, only. Further, older adults executed reaching movements with longer reaction times and increased path length, though the latter, again, not when considering correct decision trials, only. Last, reaction time and variability in movement execution were both affected by cognitive demand. The outcomes of this study provide a differentiated picture of the distinct and joint effects of aging and cognitive demand during motor decision making.

What mechanisms mediate prior probability effects on rapid-choice decision-making?

Rapid-choice decision-making is biased by prior probability of response alternatives. Conventionally, prior probability effects are assumed to selectively affect, response threshold, which determines the amount of evidence required to trigger a decision. However, there may also be effects on the rate at which evidence is accumulated and the time required for non-decision processes (e.g., response production). Healthy young (n = 21) and older (n = 20) adults completed a choice response-time task requiring left- or right-hand responses to imperative stimuli. Prior probability was manipulated using a warning stimulus that informed participants that a particular response was 70% likely (i.e., the imperative stimulus was either congruent or incongruent with the warning stimulus). In addition, prior probability was either fixed for blocks of trials (block-wise bias) or varied from trial-to-trial (trial-wise bias). Response time and accuracy data were analysed using the racing diffusion evidence-accumulation model to test the selective influence assumption. Response times for correct responses were slower on incongruent than congruent trials, and older adults' responses were slower, but more accurate, than young adults. Evidence-accumulation modelling favoured an effect of prior probability on both response thresholds and nondecision time. Overall, the current results cast doubt on the selective threshold influence assumption in the racing diffusion model.

Investigating the role of contextual cues and interhemispheric inhibitory mechanisms in response-selective stopping: a TMS study.

Response-selective stopping requires cancellation of only one component of a multicomponent action. While research has investigated how delays to the continuing action components ("stopping interference") can be attenuated by way of contextual cues of the specific stopping demands ("foreknowledge"), little is known of the underlying neural mechanisms. Twenty-seven, healthy, young adults undertook a multicomponent stop-signal task. For two thirds of trials, participants responded to an imperative (go) stimulus (IS) with simultaneous button presses using their left and right index fingers. For the remaining one third of trials, the IS was followed by a stop-signal requiring cancellation of only the left, or right, response. To manipulate foreknowledge of stopping demands, a cue preceded the IS that informed participants which hand might be required to stop (proactive) or provided no such information (reactive). Transcranial magnetic stimulation (TMS) assessed corticospinal excitability (CSE) as well as short- and long-interval interhemispheric inhibition (SIHI, LIHI) between the primary motor cortices. Proactive cues reduced, but did not eliminate, stopping interference relative to the reactive condition. Relative to TMS measures at cue onset, decreases in CSE (both hands and both cue conditions) and LIHI (both hands, proactive condition only) were observed during movement preparation. During movement cancellation, LIHI reduction in the continuing hand was greater than that in the stopping hand and greater than LIHI reductions in both hands during execution of multicomponent responses. Our results indicate that foreknowledge attenuates stopping interference and provide evidence for a novel role of LIHI, mediated via prefrontal regions, in facilitating continuing action components.

Influence of tDCS over right inferior frontal gyrus and pre-supplementary motor area on perceptual decision-making and response inhibition: A healthy ageing perspective.

A wide body of literature suggests that transcranial direct current stimulation (tDCS) administered over the prefrontal cortex can improve executive function - including decision-making and inhibitory control - in healthy young adults. However, the effects of tDCS in older adults are largely unknown. Here, using a double-blind, sham-controlled approach, changes in a combined perceptual decision-making and inhibitory control task were assessed before and after the application of tDCS (1 mA, 20 minute) targeting the right inferior frontal gyrus (rIFG) or pre-supplementary motor area (preSMA) in 42 young (18-34 years) and 41 older (60-80 years) healthy adults. Compared to sham stimulation, anodal tDCS over the preSMA improved decision-making speed for both age groups. Furthermore, the inhibitory control performance of older and younger adults was improved by preSMA and rIFG stimulation, respectively. This study provides evidence that tDCS can improve both perceptual decision-making and inhibitory control in healthy older adults, with the causal role of the preSMA and rIFG regions in cognitive control appearing to vary as a function of healthy ageing.

OSARI, an Open-Source Anticipated Response Inhibition Task.

The stop-signal paradigm has become ubiquitous in investigations of inhibitory control. Tasks inspired by the paradigm, referred to as stop-signal tasks, require participants to make responses on go trials and to inhibit those responses when presented with a stop-signal on stop trials. Currently, the most popular version of the stop-signal task is the 'choice-reaction' variant, where participants make choice responses, but must inhibit those responses when presented with a stop-signal. An alternative to the choice-reaction variant of the stop-signal task is the 'anticipated response inhibition' task. In anticipated response inhibition tasks, participants are required to make a planned response that coincides with a predictably timed event (such as lifting a finger from a computer key to stop a filling bar at a predefined target). Anticipated response inhibition tasks have some advantages over the more traditional choice-reaction stop-signal tasks and are becoming increasingly popular. However, currently, there are no openly available versions of the anticipated response inhibition task, limiting potential uptake. Here, we present an open-source, free, and ready-to-use version of the anticipated response inhibition task, which we refer to as the OSARI (the Open-Source Anticipated Response Inhibition) task.

Response bias reveals the role of interhemispheric inhibitory networks in movement preparation and execution.

Human movement is influenced by various cognitive processes, such as bias, that dynamically shape competing movement representations. However, the neurophysiological mechanisms underlying the effects of bias on movement selection across the lifespan remains poorly understood. Healthy young (n = 21) and older (n = 20) adults completed a choice reaction-time task necessitating left- or right-hand responses to imperative stimuli (IS). Response bias was manipulated via a cue that informed participants a particular response was 70% likely (i.e., the IS was either congruent, or incongruent, with the cue); biasing was either fixed for blocks of trials (block-wise bias) or varied from trial-to-trial (trial-wise bias). As well as assessing the behavioural manifestations of bias, we used transcranial magnetic stimulation to determine changes in corticospinal excitability (CSE) and short- and long-interval interhemispheric inhibition (SIHI, LIHI) during movement preparation and execution. Participants responded more quickly, and accurately, in congruent compared to incongruent trials. CSE decreases occurred in both hands following the cue, consistent with the 'inhibition for impulse control' hypothesis of preparatory inhibition. In contrast, IHI modulations occurred in a hand-specific manner. Greater SIHI was observed during movement preparation in the hand biased away from, compared to the hand biased towards, the cue; furthermore, greater SIHI was observed during movement execution in the hand biased towards the cue when it was not required to respond (i.e., incongruent trial) compared to when it was required to respond (congruent trial). Additionally, during the movement preparation period, the LIHI ratio of the hand biased towards, compared to the hand biased away from, the cue was greatest when the cue varied trial-by-trial. Overall, the IHI results provide support for the 'inhibition for competition resolution' hypothesis, with hand specific modulation of inhibition during movement preparation and execution.

Functional Near-infrared Spectroscopy Reveals the Compensatory Potential of Pre-frontal Cortical Activity for Standing Balance in Young and Older Adults.

Recent evidence suggests increased activity of the pre-frontal cortex (PFC) is associated with sensorimotor disturbances of standing balance. Here we manipulate sensorimotor inputs and concurrently load cognitive resources in order to investigate the functional role of PFC activity during standing balance, and how this changes with healthy ageing. Healthy younger (n = 24; mean age = 20.8 years) and older (n = 25; mean age = 70.6 years) adults maintained balance while sensorimotor inputs were manipulated by removing vision, reducing the base of support, and reducing proprioceptive feedback. To load cognitive resources, each balance condition was undertaken alone or simultaneously with a cognitive task (dual-task). Functional near infrared spectroscopy (fNIRS) measured PFC activity and a force-plate measured postural sway. When comparing dual-tasks relative to single balance tasks (dual-task effect), at lower levels of balance task demand, the older adults exhibited increased PFC activity and similar levels of postural sway. However, at higher levels of balance task demand, a limit to PFC activity was observed and postural sway became more unstable in older adults. In contrast, for younger adults at higher levels of balance task demand, the dual-task effect resulted in an increase in PFC activity and postural sway was not unduly affected. These results suggest that PFC activity is compensating for sensorimotor deficits to maintain stability, and that a cognitive resource limit is reached for easier balance tasks in older people compared to younger people. These results suggest that increasing cortical capacity in older people may improve their balance.

Response inhibition in humans: a whistle stop review.

This Neuro Forum presents insights from recent literature on the neurophysiology and pathoneurophysiology of reactive (speed of action stopping) and proactive (slowing of action in anticipation of stopping) response inhibition. We discuss recent studies using novel brain stimulation and spectroscopy techniques that reveal the role of cortico-subcortical networks and the neurotransmitter γ-aminobutyric acid (GABA) and how these mechanisms are influenced by healthy aging. Furthermore, we also briefly discuss computational modeling approaches, which assist in establishing meaningful differences in response inhibition.

Using transcranial magnetic stimulation to investigate the neural mechanisms of inhibitory control.

Many everyday actions require inhibitory control. The success of these actions depends on the availability of prior information regarding stopping demands. Using transcranial magnetic stimulation (TMS), Cirillo and colleagues (Cirillo J, Cowie MJ, MacDonald HJ, Byblow WD. J Neurophysiol 119: 877-886, 2018) provide novel neurophysiological evidence for distinct roles of intracortical inhibitory mechanisms underlying inhibitory control. Other, nonexclusive mechanisms such as disfacilitation of excitatory pathways and interhemispheric inhibition may also contribute to inhibitory control. Accordingly, diverse TMS protocols are a valuable assessment tool to investigate these mechanisms.

Low intensity repetitive transcranial magnetic stimulation modulates skilled motor learning in adult mice.

Repetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical plasticity in clinical and non-clinical populations. Clinically, rTMS is delivered to targeted regions of the cortex at high intensities (>1 T). We have previously shown that even at low intensities, rTMS induces structural and molecular plasticity in the rodent cortex. To determine whether low intensity rTMS (LI-rTMS) alters behavioural performance, daily intermittent theta burst LI-rTMS (120 mT) or sham was delivered as a priming or consolidating stimulus to mice completing 10 consecutive days of skilled reaching training. Relative to sham, priming LI-rTMS (before each training session), increased skill accuracy (~9%) but did not alter the rate of learning over time. In contrast, consolidating LI-rTMS (after each training session), resulted in a small increase in the rate of learning (an additional ~1.6% each day) but did not alter the daily skill accuracy. Changes in behaviour with LI-rTMS were not accompanied with long lasting changes in brain-derived neurotrophic factor (BDNF) expression or in the expression of plasticity markers at excitatory and inhibitory synapses for either priming or consolidation groups. These results suggest that LI-rTMS can alter specific aspects of skilled motor learning in a manner dependent on the timing of intervention.

Distinct modulation of interhemispheric inhibitory mechanisms during movement preparation reveals the influence of cognition on action control.

When selecting actions based on visual warning stimuli (WS), corticospinal excitability (CSE) is initially suppressed, consistent with a neural mechanism to prevent premature release of the competing responses. Despite being implicated in between-hand movement selection and preparation, the role that interhemispheric inhibition (IHI) may play in this 'impulse control' mechanism is not known. Participants performed a warned, between-hand, choice reaction time (RT) task in which the informativeness of the WS (with regards to which hand would be required to respond) was manipulated. Transcranial magnetic stimulation (TMS) assessed CSE of the right primary motor cortex (M1) and IHI from left to right M1 with 10 (IHI10) and 40 (IHI40) msec interstimulus intervals during movement selection and preparation. Consistent with impulse control, CSE was initially suppressed prior to both left and right hand actions, irrespective of WS informativeness. Subsequent CSE increases occurred in the responding hand which were larger, and occurred earlier, following an informative WS. Importantly, these increases strongly predicted response times. In contrast to the generic CSE suppression, an informative WS permitted a hand-specific release of IHI10 in the responding hand, whereas IHI40 was released in both hands. As releases of IHI cannot explain a simultaneous suppression of CSE, this suggests several distinct movement preparation mechanisms are at play with IHI modulation occurring independently from impulse control. Notably, the findings support the notion that IHI10 and IHI40 between contralateral motor regions are mediated by discrete transcallosal pathways, and are differently modulated by specific motor and cognitive attributes of a rapid choice task.

Influence of Cognitive Functioning on Age-Related Performance Declines in Visuospatial Sequence Learning.

Objectives: The aim of this study was to investigate how age-related performance differences in a visuospatial sequence learning task relate to age-related declines in cognitive functioning. Method: Cognitive functioning of 18 younger and 18 older participants was assessed using a standardized test battery. Participants then undertook a perceptual visuospatial sequence learning task. Various relationships between sequence learning and participants' cognitive functioning were examined through correlation and factor analysis. Results: Older participants exhibited significantly lower performance than their younger counterparts in the sequence learning task as well as in multiple cognitive functions. Factor analysis revealed two independent subsets of cognitive functions associated with performance in the sequence learning task, related to either the processing and storage of sequence information (first subset) or problem solving (second subset). Age-related declines were only found for the first subset of cognitive functions, which also explained a significant degree of the performance differences in the sequence learning task between age-groups. Discussion: The results suggest that age-related performance differences in perceptual visuospatial sequence learning can be explained by declines in the ability to process and store sequence information in older adults, while a set of cognitive functions related to problem solving mediates performance differences independent of age.

Facilitatory non-invasive brain stimulation in older adults: the effect of stimulation type and duration on the induction of motor cortex plasticity.

Despite holding significant promise for counteracting the deleterious effects of ageing on cognitive and motor function, little is known of the effects of facilitatory non-invasive brain stimulation (NBS) techniques on corticospinal excitability (CSE) in older adults. Thirty-three older adults (≥60 years) participated in four NBS sessions on separate days, receiving 10- and 20-min anodal transcranial direct current stimulation (atDCS), and 300 and 600 pulses of intermittent theta burst stimulation (iTBS) over the left M1. Motor-evoked potentials measured in the contralateral hand served as a measure of CSE before and for 30 min following each NBS intervention. At the group level, generalized post-stimulation CSE increases were observed (p < 0.001) with no significant differences between the two durations of each stimulation type (atDCS: p = 0.5; iTBS: p = 0.9). For individuals exhibiting overall facilitatory change to atDCS ('responders', n = 10), 20-min atDCS resulted in longer lasting CSE facilitation than 10 min. No such difference was observed between the two iTBS protocols. Considerable variability was observed inter-individually, where 52-58 % of the cohort exhibited the expected facilitation after each of the NBS protocols-as well as intra-individually, where 45-48 % of the cohort maintained consistent post-stimulation responses across the varying durations and types of stimulation. In conclusion, as shown previously in young adults, older adults demonstrate substantial variability in response to different facilitatory NBS protocols. Studies to assess the intra-individual reliability of these protocols are critical to progress towards translation of appropriate protocols (i.e. those that elicit the greatest response for each individual) into clinical practice.

Design and preliminary evaluation of a wearable device for mass-screening of sleep apnea.

Between 7-18 million Americans suffer from sleep disordered breathing (SDB), including those who suffer from obstructive sleep apnea (OSA). Despite this high prevalence and burden of OSA, existing diagnostic techniques remain impractical for widespread screening. In this study, we introduce a new model for OSA screening and describe an at-home wearable sleep mask (named ARAM) that can robustly track the wearers' sleep patterns. This monitoring is achieved using select sensors that enable screening and monitoring in a form-factor that can be easily self-instrumented. Based on feedback from sleep doctors and technicians, we incorporate the most valuable sensors for OSA diagnosis, while maintaining ease-of-use and comfort for the patient. We discuss the results of preliminary field trials, where both our sleep mask and a commercially available device were worn simultaneously to evaluate our device's robustness. Based on these results, we discuss next steps for the design of the screening system, including analyses techniques that would provide more efficient screening than existing systems.

The Influence of Mirror-Visual Feedback on Training-Induced Motor Performance Gains in the Untrained Hand.

The well-documented observation of bilateral performance gains following unilateral motor training, a phenomenon known as cross-limb transfer, has important implications for rehabilitation. It has recently been shown that provision of a mirror image of the active hand during unilateral motor training has the capacity to enhance the efficacy of this phenomenon when compared to training without augmented visual feedback (i.e., watching the passive hand), possibly via action observation effects [1]. The current experiment was designed to confirm whether mirror-visual feedback (MVF) during motor training can indeed elicit greater performance gains in the untrained hand compared to more standard visual feedback (i.e., watching the active hand). Furthermore, discussing the mechanisms underlying any such MVF-induced behavioural effects, we suggest that action observation and the cross-activation hypothesis may both play important roles in eliciting cross-limb transfer. Eighty participants practiced a fast-as-possible two-ball rotation task with their dominant hand. During training, three different groups were provided with concurrent visual feedback of the active hand, inactive hand or a mirror image of the active hand with a fourth control group receiving no training. Pre- and post-training performance was measured in both hands. MVF did not increase the extent of training-induced performance changes in the untrained hand following unilateral training above and beyond those observed for other types of feedback. The data are consistent with the notion that cross-limb transfer, when combined with MVF, is mediated by cross-activation with action observation playing a less unique role than previously suggested. Further research is needed to replicate the current and previous studies to determine the clinical relevance and potential benefits of MVF for cases that, due to the severity of impairment, rely on unilateral training programmes of the unaffected limb to drive changes in the contralateral affected limb.

Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective.

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.