When a stable memory is reactivated it becomes transiently labile and requires restabilization, a process known as reconsolidation. Animal studies have convincingly demonstrated that during reconsolidation memories are modifiable and can be erased when reactivation is followed by an interfering intervention. Few studies have been conducted in humans, however, and results are inconsistent regarding the extent to which a memory can be degraded. We used a motor sequence learning paradigm to show that the length of reactivation constitutes a crucial boundary condition determining whether human motor memories can be degraded. In our first experiment, we found that a short reactivation (less than 60 sec) renders the memory labile and susceptible to degradation through interference, while a longer reactivation does not. In our second experiment, we reproduce these results and show a significant linear relationship between the length of memory reactivation and the detrimental effect of the interfering task performed afterwards, i.e., the longer the reactivation, the smaller the memory loss due to interference. Our data suggest that reactivation via motor execution activates a time-dependent process that initially destabilizes the memory, which is then followed by restabilization during further practice.

Neurodevelopmental disconnections have been assumed to cause behavioral alterations in autism spectrum disorders (ASDs). Here, we combined measurements of intrinsic functional connectivity (iFC) from resting-state functional magnetic resonance imaging (fMRI) with task-based fMRI to explore whether altered activity and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched-controls underwent resting-state and task-based fMRI, during which participants discriminated emotional states from point light displays (PLDs). Intrinsic FC of the right pSTS was further examined using 584 (278 ASD/306 controls) resting-state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with ASD were less accurate than controls in recognizing emotional states from PLDs. Analyses revealed pronounced ASD-related reductions both in task-based activity and resting-state iFC of the right pSTS with fronto-parietal areas typically encompassing the action observation network (AON). Notably, pSTS-hypo-activity was related to pSTS-hypo-connectivity, and both measures were predictive of emotion recognition performance with each measure explaining a unique part of the variance. Analyses with the large independent ABIDE dataset replicated reductions in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are linked to the social deficits characteristic of ASD.

The multiple memory systems hypothesis posits that dorsal striatum and hippocampus are central nodes in independent memory systems, supporting response-based and place-based learning, respectively. Although our understanding of the function of hippocampus within this framework is relatively well established, the contribution of dorsal striatum is less clear. This in part seems to be due to the heterogeneous nature of dorsal striatum, which receives extensive topographically organized projections from higher cortical areas. Here we quantified neural activity in the intact brain while mice and humans acquired analogous versions of the Morris water maze. We found that dorsomedial striatum and medial prefrontal cortex support the initial acquisition of what is typically considered a hippocampus-dependent spatial learning task. We suggest that the circuit involving dorsomedial striatum and medial prefrontal cortex identified here plays a more task-independent role in early learning than currently thought. Furthermore, our results demonstrate that dorsomedial and dorsolateral striatum serve fundamentally different roles during place learning. The remarkably high degree of anatomical overlap in brain function between mouse and human observed in our study emphasizes the extent of convergence achievable with a well-matched multilevel approach.functional MRI | immediate early gene | navigation T he multiple memory systems hypothesis posits that hippocampus and dorsal striatum are central nodes in independent memory systems, each supporting different aspects of learning and memory formation (1-4). In the context of spatial learning, the hippocampus supports place-based behavioral strategies relying on learning the general layout of the environment, whereas the dorsal striatum supports response-based behavioral strategies driven by task-specific stimuli (5-12). Although the dorsal striatum is often referred to as a unitary structure within the multiple memory systems framework, there is considerable evidence in rodents and humans that it is composed of functional subdivisions that support different aspects of learning (13-20).Here we conducted parallel experiments in mouse and human to test whether dorsomedial and dorsolateral striatum make distinct contributions during early (initial acquisition) and late (overtraining) phases of place learning in the intact brain. Subjects performed the classic hippocampus-dependent hidden platform version of the Morris water maze, which was matched between species with respect to behavioral processing demands (9). This widely used paradigm has served a critical role in the study of neurobiological aspects of learning and memory over the past 25 years (21,22).Although it is well established that hippocampus supports the spatial processing demands of the water maze, much less is known about the precise contribution of dorsomedial and dorsolateral striatum during the early and late phases of learning in the hiddenplatform version of the task. If dorsomedial striatum plays a general role in ...

Sex differences in humans on virtual water maze navigation are well established when overall performance is measured, e.g., by the total time taken to find the hidden platform, total path length, or quadrant dwell time during probe trials. Currently, it is unknown whether males are better spatial learners than females, or if overall performance differences reflect other aspects of the task unrelated to spatial memory. Here, males and females were tested on a virtual analogue of the Morris water maze. We devised a novel method of analysis in which each trial was divided into an initial trajectory phase and search phase. We also implemented a new measure of spatial learning during early and late training, by including trials in which subjects were only required to indicate where they thought the hidden target zone was located. Consistent with previous reports, males outperformed females on overall measures of task performance. Males also performed significantly better on all initial trajectory phase variables. Interestingly, only small (non-significant) differences were observed during the search phase and when spatial learning was tested without the constraints of a typical water maze trial. Our results suggest that spatial knowledge regarding the location of the hidden target zone is not the main factor responsible for overall sex differences in virtual water maze performance. Instead, the largest sex differences were observed during the initial trajectory phase of the trial, which is thought to depend on effective processing of distal features of the environment.

Studies examining dual adaptation to opposing novel environments have yielded contradictory results, with previous evidence supporting both successful dual adaptation and interference leading to poorer adaptive performance. Whether or not interference is observed during dual adaptation appears to be dependent on the method used to allow the performer of the task to distinguish between two novel environments. This experiment tested if colour cues, a separation in workspace, and presentation schedule, could be used to distinguish between two opposing visuomotor rotations and enable dual adaptation. Through the use of a purpose designed manipulandum, each visuomotor rotation was either presented in the same region of workspace and associated with colour cues (Group 1), different regions of workspace in addition to colour cues (Groups 2 and 3) or different regions of workspace only (Groups 4 and 5). We also assessed the effectiveness of the workspace separation with both randomised and alternating presentation schedules (Groups 4 and 5). The results indicated that colour cues were not effective at enabling dual adaptation when each of the visuomotor rotations was associated with the same region of workspace. When associated with different regions of workspace, however, dual adaptation to the opposing rotations was successful regardless of whether colour cues were present or the type of presentation schedule.

Both increases and decreases in resting state functional connectivity have been previously observed within the motor network during aging. Moreover, the relationship between altered functional connectivity and age-related declines in bimanual coordination remains unclear. Here, we explored the developmental dynamics of the resting brain within a task-specific motor network in a sample of 128 healthy participants, aged 18-80 years. We found that age-related increases in functional connectivity between interhemispheric dorsal and ventral premotor areas were associated with poorer performance on a novel bimanual visuomotor task. Additionally, a control analysis performed on the default mode network confirmed that our age-related increases in functional connectivity were specific to the motor system. Our findings suggest that increases in functional connectivity within the resting state motor network with aging reflect a loss of functional specialization that may not only occur in the active brain but also in the resting brain.

Chronic wrist impairment is frequent following stroke and negatively impacts everyday life. Rehabilitation of the dysfunctional limb is possible but requires extensive training and motivation. Wearable training devices might offer new opportunities for rehabilitation. However, few devices are available to train wrist extension even though this movement is highly relevant for many upper limb activities of daily living. As a proof of concept, we developed the eWrist, a wearable one degree-of-freedom powered exoskeleton which supports wrist extension training. Conceptually one might think of an electric bike which provides mechanical support only when the rider moves the pedals, i.e. it enhances motor activity but does not replace it. Stroke patients may not have the ability to produce overt movements, but they might still be able to produce weak muscle activation that can be measured via surface electromyography (sEMG). By combining force and sEMG-based control in an assist-as-needed support strategy, we aim at providing a training device which enhances activity of the wrist extensor muscles in the context of daily life activities, thereby, driving cortical reorganization and recovery. Preliminary results show that the integration of sEMG signals in the control strategy allow for adjustable assistance with respect to a proxy measurement of corticomotor drive.

Reaching to visual targets engages the nervous system in a series of transformations between sensory information and motor commands. That which remains to be determined is the extent to which the processes that mediate sensorimotor adaptation to novel environments engage neural circuits that represent the required movement in joint-based or muscle-based coordinate systems. We sought to establish the contribution of these alternative representations to the process of visuomotor adaptation. To do so we applied a visuomotor rotation during a center-out isometric torque production task that involved flexion/extension and supination/pronation at the elbow-joint complex. In separate sessions, distinct half-quadrant rotations (i.e., 45 degrees ) were applied such that adaptation could be achieved either by only rescaling the individual joint torques (i.e., the visual target and torque target remained in the same quadrant) or by additionally requiring torque reversal at a contributing joint (i.e., the visual target and torque target were in different quadrants). Analysis of the time course of directional errors revealed that the degree of adaptation was lower (by approximately 20%) when reversals in the direction of joint torques were required. It has been established previously that in this task space, a transition between supination and pronation requires the engagement of a different set of muscle synergists, whereas in a transition between flexion and extension no such change is required. The additional observation that the initial level of adaptation was lower and the subsequent aftereffects were smaller, for trials that involved a pronation-supination transition than for those that involved a flexion-extension transition, supports the conclusion that the process of adaptation engaged, at least in part, neural circuits that represent the required motor output in a muscle-based coordinate system.