Modulating temporal dynamics of performance across retinotopic locations enhances the generalization of perceptual learning.

Human visual perception can be improved through perceptual learning. However, such learning is often specific to stimulus and learning conditions. Here, we explored how temporal dynamics of performance across conditions impact learning generalization. Participants performed a visual task, with the target at retinotopic location A. Then, the target was presented at location B either immediately after location A (same-session performance) or following a 48h consolidation period (different-session performance). Long-term generalization was measured the following week. Following initial training, both groups demonstrated generalization, consistent with previous accounts of fast learning. However, long-term generalization was enhanced in the same-session performance group. Consistently, improvements at locations A and B were correlated only following same-session performance, implying an integrated learning process across locations. The results support a new account of perceptual learning and generalization dynamics, suggesting that the temporal proximity of learning and consolidation of different conditions may integrate correlated learning processes, facilitating generalized learning.

Initial motor skill performance predicts future performance, but not learning.

People show vast variability in skill performance and learning. What determines a person's individual performance and learning ability? In this study we explored the possibility to predict participants' future performance and learning, based on their behavior during initial skill acquisition. We recruited a large online multi-session sample of participants performing a sequential tapping skill learning task. We used machine learning to predict future performance and learning from raw data acquired during initial skill acquisition, and from engineered features calculated from the raw data. Strong correlations were observed between initial and final performance, and individual learning was not predicted. While canonical experimental tasks developed and selected to detect average effects may constrain insights regarding individual variability, development of novel tasks may shed light on the underlying mechanism of individual skill learning, relevant for real-life scenarios.

Reactivation-induced motor skill modulation does not operate at a rapid micro-timescale level.

Abundant evidence shows that consolidated memories are susceptible to modifications following their reactivation. Processes of memory consolidation and reactivation-induced skill modulation have been commonly documented after hours or days. Motivated by studies showing rapid consolidation in early stages of motor skill acquisition, here we asked whether motor skill memories are susceptible to modifications following brief reactivations, even at initial stages of learning. In a set of experiments, we collected crowdsourced online motor sequence data to test whether post-encoding interference and performance enhancement occur following brief reactivations in early stages of learning. Results indicate that memories forming during early learning are not susceptible to interference nor to enhancement within a rapid reactivation-induced time window, relative to control conditions. This set of evidence suggests that reactivation-induced motor skill memory modulation might be dependent on consolidation at the macro-timescale level, requiring hours or days to occur.

Elevated integration within the reward network underlies vulnerability to distress.

Distress tolerance (DT), the capability to persist under negative circumstances, underlies a range of psychopathologies. It has been proposed that DT may originate from the activity and connectivity in diverse neural networks integrated by the reward system. To test this hypothesis, we examined the link between DT and integration and segregation in the reward network as derived from resting-state functional connectivity data. DT was measured in 147 participants from a large community sample using the Behavioral Indicator of Resiliency to Distress task. Prior to DT evaluation, participants underwent a resting-state functional magnetic resonance imaging scan. For each participant, we constructed a whole-brain functional connectivity network and calculated the degree of reward network integration and segregation based on the extent to which reward network nodes showed functional connections within and outside their network. We found that distress-intolerant participants demonstrated heightened reward network integration relative to the distress-tolerant participants. In addition, these differences in integration were higher relative to the rest of the brain and, more specifically, the somatomotor network, which has been implicated in impulsive behavior. These findings support the notion that increased integration in large-scale brain networks may constitute a risk for distress intolerance and its psychopathological correlates.

Brief memory reactivations induce learning in the numeric domain.

Learning of arithmetic facts such as the multiplication table requires time-consuming, repeated practice. In light of evidence indicating that reactivation of encoded memories can modulate learning and memory processes at the synaptic, system and behavioral levels, we asked whether brief memory reactivations can induce human learning in the numeric domain. Adult participants performed a number-fact retrieval task in which they learned arbitrary numeric facts. Following encoding and a baseline test, 3 passive, brief reactivation sessions of only 40 s each were conducted on separate days. Learning was evaluated in a retest session. Results showed reactivations induced learning, with improved performance at retest relative to baseline test. Furthermore, performance was superior compared to a control group performing test-retest sessions without reactivations, who showed significant memory deterioration. A standard practice group completed active-retrieval sessions on 3 separate days, and showed significant learning gains. Interestingly, while these gains were higher than those of the reactivations group, subjects showing reactivation-induced learning were characterized by superior efficiency relative to standard practice subjects, with higher rate of improvement per practice time. A follow-up long-term retention experiment showed that 30 days following initial practice, weekly brief reactivations reduced forgetting, with participants performing superior to controls undergoing the same initial practice without reactivations. Overall, the results demonstrate that brief passive reactivations induce efficient learning and reduce forgetting within a numerical context. Time-efficient practice in the numeric domain carries implications for enhancement of learning strategies in daily-life settings.

A distinct route for efficient learning and generalization in autism.

Visual skill learning is the process of improving responses to surrounding visual stimuli.1 For individuals with autism spectrum disorders (ASDs), efficient skill learning may be especially valuable due to potential difficulties with sensory processing2 and challenges in adjusting flexibly to changing environments.3,4 Standard skill learning protocols require extensive practice with multiple stimulus repetitions,5-7 which may be difficult for individuals with ASD and create abnormally specific learning with poor ability to generalize.4 Motivated by findings indicating that brief memory reactivations can facilitate skill learning,8,9 we hypothesized that reactivation learning with few stimulus repetitions will enable efficient learning in individuals with ASD, similar to their learning with standard extensive practice protocols used in previous studies.4,10,11 We further hypothesized that in contrast to experience-dependent plasticity often resulting in specificity, reactivation-induced learning would enable generalization patterns in ASD. To test our hypotheses, high-functioning adults with ASD underwent brief reactivations of an encoded visual learning task, consisting of only 5 trials each instead of hundreds. Remarkably, individuals with ASD improved their visual discrimination ability in the task substantially, demonstrating successful learning. Furthermore, individuals with ASD generalized learning to an untrained visual location, indicating a unique benefit of reactivation learning mechanisms for ASD individuals. Finally, an additional experiment showed that without memory reactivations ASD subjects did not demonstrate efficient learning and generalization patterns. Taken together, the results provide proof-of-concept evidence supporting a distinct route for efficient visual learning and generalization in ASD, which may be beneficial for skill learning in other sensory and motor domains.

Breaking the boundaries of interacting with the human brain using adaptive closed-loop stimulation.

The human brain is arguably one of the most complex systems in nature. To understand how it operates, it is essential to understand the link between neural activity and behavior. Experimental investigation of that link requires tools to interact with neural activity during behavior. Human neuroscience, however, has been severely bottlenecked by the limitations of these tools. While invasive methods can support highly specific interaction with brain activity during behavior, their applicability in human neuroscience is limited. Despite extensive development in the last decades, noninvasive alternatives have lacked spatial specificity and yielded results that are commonly fraught with variability and replicability issues, along with relatively limited understanding of the neural mechanisms involved. Here we provide a comprehensive review of the state-of-the-art in interacting with human brain activity and highlight current limitations and recent efforts to overcome these limitations. Beyond crucial technical and scientific advancements in electromagnetic brain stimulation, new frontiers in interacting with human brain activity such as task-irrelevant sensory stimulation and focal ultrasound stimulation are introduced. Finally, we argue that, along with technological improvements and breakthroughs in noninvasive methods, a paradigm shift towards adaptive closed-loop stimulation will be a critical step for advancing human neuroscience.

Neuromodulation of Visual Cortex Reduces the Intensity of Intrusive Memories.

Aversive events can be reexperienced as involuntary and spontaneous mental images of the event. Given that the vividness of retrieved mental images is coupled with elevated visual activation, we tested whether neuromodulation of the visual cortex would reduce the frequency and negative emotional intensity of intrusive memories. Intrusive memories of a viewed trauma film and their accompanied emotional intensity were recorded throughout 5 days. Functional connectivity, measured with resting-state functional magnetic resonance imaging prior to film viewing, was used as predictive marker for intrusions-related negative emotional intensity. Results indicated that an interaction between the visual network and emotion processing areas predicted intrusions' emotional intensity. To test the causal influence of early visual cortex activity on intrusions' emotional intensity, participants' memory of the film was reactivated by brief reminders 1 day following film viewing, followed by inhibitory 1 Hz repetitive transcranial magnetic stimulation (rTMS) over early visual cortex. Results showed that visual cortex inhibitory stimulation reduced the emotional intensity of later intrusions, while leaving intrusion frequency and explicit visual memory intact. Current findings suggest that early visual areas constitute a central node influencing the emotional intensity of intrusive memories for negative events. Potential neuroscience-driven intervention targets designed to downregulate the emotional intensity of intrusive memories are discussed.

Crowdsourcing in Cognitive and Systems Neuroscience.

Behavioral research in cognitive and human systems neuroscience has been largely carried out in-person in laboratory settings. Underpowering and lack of reproducibility due to small sample sizes have weakened conclusions of these investigations. In other disciplines, such as neuroeconomics and social sciences, crowdsourcing has been extensively utilized as a data collection tool, and a means to increase sample sizes. Recent methodological advances allow scientists, for the first time, to test online more complex cognitive, perceptual, and motor tasks. Here we review the nascent literature on the use of online crowdsourcing in cognitive and human systems neuroscience. These investigations take advantage of the ability to reliably track the activity of a participant's computer keyboard, mouse, and eye gaze in the context of large-scale studies online that involve diverse research participant pools. Crowdsourcing allows for testing the generalizability of behavioral hypotheses in real-life environments that are less accessible to lab-designed investigations. Crowdsourcing is further useful when in-laboratory studies are limited, for example during the current COVID-19 pandemic. We also discuss current limitations of crowdsourcing research, and suggest pathways to address them. We conclude that online crowdsourcing is likely to widen the scope and strengthen conclusions of cognitive and human systems neuroscience investigations.

Intrinsic Functional Connectivity of the Anterior Cingulate Cortex Is Associated with Tolerance to Distress.

The ability to adapt under significant adversity, defined as psychological resilience, is instrumental in preventing stress-related disorders. An important aspect of resilience is the capacity to endure affective distress when in pursuit of goals, also known as distress tolerance. Evidence that links intrinsic baseline interactions within large-scale functional networks with performance under distress remains missing. We hypothesized that the anterior cingulate cortex (ACC) may engage in distress tolerance because of its involvement in attention and emotion regulation. Accordingly, we tested whether behavioral performance under distress is associated with baseline resting-state ACC functional connectivity (FC). Distress tolerance was measured in 97 participants using the behavioral indicator of resiliency to distress (BIRD) task. Analyses contrasted participants who quit the task before its designated termination (n = 51) with those who persisted throughout it (n = 46). Seed-based FC analysis indicated greater connectivity between the ACC and dorsolateral prefrontal cortex (DLPFC) in subjects who persisted throughout the task, along with greater FC between the ACC and the precentral gyrus in those who quit before its termination. The results shed light on the mechanisms underlying interindividual differences in the ability to handle distress.

Reactivation-induced motor skill learning.

Learning motor skills commonly requires repeated execution to achieve gains in performance. Motivated by memory reactivation frameworks predominantly originating from fear-conditioning studies in rodents, which have extended to humans, we asked the following: Could motor skill learning be achieved by brief memory reactivations? To address this question, we had participants encode a motor sequence task in an initial test session, followed by brief task reactivations of only 30 s each, conducted on separate days. Learning was evaluated in a final retest session. The results showed that these brief reactivations induced significant motor skill learning gains. Nevertheless, the efficacy of reactivations was not consistent but determined by the number of consecutive correct sequences tapped during memory reactivations. Highly continuous reactivations resulted in higher learning gains, similar to those induced by full extensive practice, while lower continuity reactivations resulted in minimal learning gains. These results were replicated in a new independent sample of subjects, suggesting that the quality of memory reactivation, reflected by its continuity, regulates the magnitude of learning gains. In addition, the change in noninvasive brain stimulation measurements of corticospinal excitability evoked by transcranial magnetic stimulation over primary motor cortex between pre- and postlearning correlated with retest and transfer performance. These results demonstrate a unique form of rapid motor skill learning and may have far-reaching implications, for example, in accelerating motor rehabilitation following neurological injuries.

Indirect modulation of human visual memory.

Conditions in which memories become maladaptive have inspired extensive research geared to modulate memory by targeting it directly and explicitly. Given limitations of direct memory modulation, we asked the following: can the target memories be modulated indirectly? To address this question, we uniquely targeted visual memories, and leveraged a paradigm utilizing instructions to either forget or remember newly encoded memories. We used a multi-domain approach, and applied the instructions to embedded verbal information presented during encoding (words), with the intention to indirectly modulate recognition of the target visual context memory itself (pictures). Accordingly, participants were presented with two lists of words, where each word was preceded and followed by pictures. Participants were instructed to either remember or forget the first list of words. As expected, the instruction to either remember or forget the words differentially influenced word memory strength. Importantly, the instruction regarding the words, indirectly modulated picture memory strength. Better memory for words resulted in reduced picture memory strength and vice versa, with the instruction to remember the words reducing picture memory strength. Together with a negative correlation between word and picture memory strength, the results suggest a competition for shared resources between memory for content and context. These findings may open new avenues to indirectly modulate maladaptive memories.

Early Visual Cortex Stimulation Modifies Well-Consolidated Perceptual Gains.

Perception thresholds can improve through repeated practice with visual tasks. Can an already acquired and well-consolidated perceptual skill be noninvasively neuromodulated, unfolding the neural mechanisms involved? Here, leveraging the susceptibility of reactivated memories ranging from synaptic to systems levels across learning and memory domains and animal models, we used noninvasive brain stimulation to neuromodulate well-consolidated reactivated visual perceptual learning and reveal the underlying neural mechanisms. Subjects first encoded and consolidated the visual skill memory by performing daily practice sessions with the task. On a separate day, the consolidated visual memory was briefly reactivated, followed by low-frequency, inhibitory 1 Hz repetitive transcranial magnetic stimulation over early visual cortex, which was individually localized using functional magnetic resonance imaging. Poststimulation perceptual thresholds were measured on the final session. The results show modulation of perceptual thresholds following early visual cortex stimulation, relative to control stimulation. Consistently, resting state functional connectivity between trained and untrained parts of early visual cortex prior to training predicted the magnitude of perceptual threshold modulation. Together, these results indicate that even previously consolidated human perceptual memories are susceptible to neuromodulation, involving early visual cortical processing. Moreover, the opportunity to noninvasively neuromodulate reactivated perceptual learning may have important clinical implications.

Inhibition of the supplementary motor area affects distribution of effort over time.

In tasks that extend over time, people tend to exert much effort at the beginning and the end, but not in the middle, exhibiting the stuck-in-the-middle pattern (STIM). To date, little is known about the neural mechanisms underlying this effect. As the supplementary motor area (SMA) was previously implicated in coding prospective task-demands, we tested its role in producing the STIM pattern. Participants first underwent an SMA-localization session in which they tapped their fingers repeatedly while fMRI-scanned. In the next two sessions, before playing a 10-min computer game that measured effort-engagement, participants underwent inhibitory 1-Hz repetitive transcranial magnetic stimulation over the SMA, or over a control precuneus location. Three control experiments and a pretest confirmed that this task yields a STIM, which can be eliminated when the task lacks a salient end-point, or is too short. The results of the main experiment showed a more pronounced STIM following inhibitory SMA stimulation compared to control. A control analysis showed that overall level of effort was similar in both conditions, rendering alternative accounts in terms of motor inhibition unlikely. These findings are consistent with the possibility that the SMA may play a role in moment-to-moment coding of effort value, or in related sub-processes, which can cause effort to be distributed more equally over the course of a task.

Intrusive memories: A mechanistic signature for emotional memory persistence.

Memories of negative emotional events persist more over time relative to memories for neutral information. Such persistence has been attributed to heightened encoding and consolidation processes. However, reactivation of the encoded information may also lead to reduced memory decay through rehearsal or a reconsolidation processes. Here, we tested whether involuntary intrusive memories, spontaneously arising following a stressful event and reactivating its memory, function to prevent memory decay, enhancing its persistence. Participants watched a stressful film containing scenes of aversive material. Memory for the film contents was tested immediately post-film using a visual recognition test. In the following five days, participants recorded intrusive memories of the film using a digitized diary. After 5-days, memory for the film contents was retested. Results indicate that in the immediate aftermath of film watching, participant's memory scores were similarly high for scenes that were later experienced as intrusions and scenes that did not intrude, suggesting effective encoding for all scenes. However, persistence of memory for scenes that intruded was preserved relative to memory for scenes that did not intrude, pointing to a mechanism through which negative intrusive memories persist over time. Implications for memory modification interventions in trauma-related psychopathology are discussed.

Mechanisms of offline motor learning at a microscale of seconds in large-scale crowdsourced data.

Performance improvements during early human motor skill learning are suggested to be driven by short periods of rest during practice, at the scale of seconds. To reveal the unknown mechanisms behind these "micro-offline" gains, we leveraged the sampling power offered by online crowdsourcing (cumulative N over all experiments = 951). First, we replicated the original in-lab findings, demonstrating generalizability to subjects learning the task in their daily living environment (N = 389). Second, we show that offline improvements during rest are equivalent when significantly shortening practice period duration, thus confirming that they are not a result of recovery from performance fatigue (N = 118). Third, retroactive interference immediately after each practice period reduced the learning rate relative to interference after passage of time (N = 373), indicating stabilization of the motor memory at a microscale of several seconds. Finally, we show that random termination of practice periods did not impact offline gains, ruling out a contribution of predictive motor slowing (N = 71). Altogether, these results demonstrate that micro-offline gains indicate rapid, within-seconds consolidation accounting for early skill learning.

Explaining Individual Differences in Motor Behavior by Intrinsic Functional Connectivity and Corticospinal Excitability.

Motor performance varies substantially between individuals. This variance is rooted in individuals' innate motor abilities, and should thus have a neural signature underlying these differences in behavior. Could these individual differences be detectable with neural measurements acquired at rest? Here, we tested the hypothesis that motor performance can be predicted by resting motor-system functional connectivity and motor-evoked-potentials (MEPs) induced by non-invasive brain stimulation. Twenty healthy right handed subjects performed structural and resting-state fMRI scans. On a separate day, MEPs were measured using transcranial magnetic stimulation (TMS) over the contrateral primary motor cortex (M1). At the end of the session, participants performed a finger-tapping task using their left non-dominant hand. Resting-state functional connectivity between the contralateral M1 and the supplementary motor area (SMA) predicted motor task performance, indicating that individuals with stronger resting M1-SMA functional connectivity exhibit better motor performance. This prediction was neither improved nor reduced by the addition of corticospinal excitability to the model. These results confirm that motor behavior can be predicted from neural measurements acquired prior to task performance, primarily relying on resting functional connectivity rather than corticospinal excitability. The ability to predict motor performance from resting neural markers, provides an opportunity to identify the extent of successful rehabilitation following neurological damage.

Visual-oculomotor interactions facilitate consolidation of perceptual learning.

Visual skill learning is commonly considered a manifestation of brain plasticity. Following encoding, consolidation of the skill may result in between-session performance gains. A great volume of studies have demonstrated that during the offline consolidation interval, the skill is susceptible to external inputs that modify the preformed representation of the memory, affecting future performance. However, while basic visual perceptual learning is thought to be mediated by sensory brain regions or their higher-order readout pathways, the possibility of visual-oculomotor interactions affecting the consolidation interval and reshaping visual learning remains uncharted. Motivated by findings mapping connections between oculomotor behavior and visual performance, we examined whether visual consolidation can be facilitated by visual-oculomotor interactions. To this aim, we paired reactivation of an oculomotor memory with consolidation of a typical visual texture discrimination task. Importantly, the oculomotor memory was encoded by learning of the pure motor component of the movement, removing visual cues. When brief reactivation of the oculomotor memory preceded the visual task, visual gains were substantially enhanced compared with those achieved by visual practice per se and were strongly related to the magnitude of oculomotor gains, suggesting that the brain utilizes oculomotor memory to enhance basic visual perception.