Distinct patterns of cortical manifold expansion and contraction underlie human sensorimotor adaptation.

Sensorimotor learning is a dynamic, systems-level process that involves the combined action of multiple neural systems distributed across the brain. Although much is known about the specialized cortical systems that support specific components of action (such as reaching), we know less about how cortical systems function in a coordinated manner to facilitate adaptive behavior. To address this gap, our study measured human brain activity using functional MRI (fMRI) while participants performed a classic sensorimotor adaptation task and used a manifold learning approach to describe how behavioral changes during adaptation relate to changes in the landscape of cortical activity. During early adaptation, areas in the parietal and premotor cortices exhibited significant contraction along the cortical manifold, which was associated with their increased covariance with regions in the higher-order association cortex, including both the default mode and fronto-parietal networks. By contrast, during Late adaptation, when visuomotor errors had been largely reduced, a significant expansion of the visual cortex along the cortical manifold was associated with its reduced covariance with the association cortex and its increased intraconnectivity. Lastly, individuals who learned more rapidly exhibited greater covariance between regions in the sensorimotor and association cortices during early adaptation. These findings are consistent with a view that sensorimotor adaptation depends on changes in the integration and segregation of neural activity across more specialized regions of the unimodal cortex with regions in the association cortex implicated in higher-order processes. More generally, they lend support to an emerging line of evidence implicating regions of the default mode network (DMN) in task-based performance.

Whole-brain dynamics of human sensorimotor adaptation.

Humans vary greatly in their motor learning abilities, yet little is known about the neural processes that underlie this variability. We identified distinct profiles of human sensorimotor adaptation that emerged across 2 days of learning, linking these profiles to the dynamics of whole-brain functional networks early on the first day when cognitive strategies toward sensorimotor adaptation are believed to be most prominent. During early learning, greater recruitment of a network of higher-order brain regions, involving prefrontal and anterior temporal cortex, was associated with faster learning. At the same time, greater integration of this "cognitive network" with a sensorimotor network was associated with slower learning, consistent with the notion that cognitive strategies toward adaptation operate in parallel with implicit learning processes of the sensorimotor system. On the second day, greater recruitment of a network that included the hippocampus was associated with faster learning, consistent with the notion that declarative memory systems are involved with fast relearning of sensorimotor mappings. Together, these findings provide novel evidence for the role of higher-order brain systems in driving variability in adaptation.

Human Variation in Error-Based and Reinforcement Motor Learning Is Associated With Entorhinal Volume.

Error-based and reward-based processes are critical for motor learning and are thought to be mediated via distinct neural pathways. However, recent behavioral work in humans suggests that both learning processes can be bolstered by the use of cognitive strategies, which may mediate individual differences in motor learning ability. It has been speculated that medial temporal lobe regions, which have been shown to support motor sequence learning, also support the use of cognitive strategies in error-based and reinforcement motor learning. However, direct evidence in support of this idea remains sparse. Here we first show that better overall learning during error-based visuomotor adaptation is associated with better overall learning during the reward-based shaping of reaching movements. Given the cognitive contribution to learning in both of these tasks, these results support the notion that strategic processes, associated with better performance, drive intersubject variation in both error-based and reinforcement motor learning. Furthermore, we show that entorhinal cortex volume is larger in better learning individuals-characterized across both motor learning tasks-compared with their poorer learning counterparts. These results suggest that individual differences in learning performance during error and reinforcement learning are related to neuroanatomical differences in entorhinal cortex.

Motor Planning Modulates Neural Activity Patterns in Early Human Auditory Cortex.

It is well established that movement planning recruits motor-related cortical brain areas in preparation for the forthcoming action. Given that an integral component to the control of action is the processing of sensory information throughout movement, we predicted that movement planning might also modulate early sensory cortical areas, readying them for sensory processing during the unfolding action. To test this hypothesis, we performed 2 human functional magnetic resonance imaging studies involving separate delayed movement tasks and focused on premovement neural activity in early auditory cortex, given the area's direct connections to the motor system and evidence that it is modulated by motor cortex during movement in rodents. We show that effector-specific information (i.e., movements of the left vs. right hand in Experiment 1 and movements of the hand vs. eye in Experiment 2) can be decoded, well before movement, from neural activity in early auditory cortex. We find that this motor-related information is encoded in a separate subregion of auditory cortex than sensory-related information and is present even when movements are cued visually instead of auditorily. These findings suggest that action planning, in addition to preparing the motor system for movement, involves selectively modulating primary sensory areas based on the intended action.

Muting, not fragmentation, of functional brain networks under general anesthesia.

Changes in resting-state functional connectivity (rs-FC) under general anesthesia have been widely studied with the goal of identifying neural signatures of consciousness. This work has commonly revealed an apparent fragmentation of whole-brain network structure during unconsciousness, which has been interpreted as reflecting a break-down in connectivity and a disruption of the brain's ability to integrate information. Here we show, by studying rs-FC under varying depths of isoflurane-induced anesthesia in nonhuman primates, that this apparent fragmentation, rather than reflecting an actual change in network structure, can be simply explained as the result of a global reduction in FC. Specifically, by comparing the actual FC data to surrogate data sets that we derived to test competing hypotheses of how FC changes as a function of dose, we found that increases in whole-brain modularity and the number of network communities - considered hallmarks of fragmentation - are artifacts of constructing FC networks by thresholding based on correlation magnitude. Taken together, our findings suggest that deepening levels of unconsciousness are instead associated with the increasingly muted expression of functional networks, an observation that constrains current interpretations as to how anesthesia-induced FC changes map onto existing neurobiological theories of consciousness.

Dynamic Reconfiguration, Fragmentation, and Integration of Whole-Brain Modular Structure across Depths of Unconsciousness.

General anesthetics are routinely used to induce unconsciousness, and much is known about their effects on receptor function and single neuron activity. Much less is known about how these local effects are manifest at the whole-brain level nor how they influence network dynamics, especially past the point of induced unconsciousness. Using resting-state functional magnetic resonance imaging (fMRI) with nonhuman primates, we investigated the dose-dependent effects of anesthesia on whole-brain temporal modular structure, following loss of consciousness. We found that higher isoflurane dose was associated with an increase in both the number and isolation of whole-brain modules, as well as an increase in the uncoordinated movement of brain regions between those modules. Conversely, we found that higher dose was associated with a decrease in the cohesive movement of brain regions between modules, as well as a decrease in the proportion of modules in which brain regions participated. Moreover, higher dose was associated with a decrease in the overall integrity of networks derived from the temporal modules, with the exception of a single, sensory-motor network. Together, these findings suggest that anesthesia-induced unconsciousness results from the hierarchical fragmentation of dynamic whole-brain network structure, leading to the discoordination of temporal interactions between cortical modules.

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

Blast-related mild traumatic brain injury: a Bayesian random-effects meta-analysis on the cognitive outcomes of concussion among military personnel.

Throughout their careers, many soldiers experience repeated blasts exposures from improvised explosive devices, which often involve head injury. Consequentially, blast-related mild Traumatic Brain Injury (mTBI) has become prevalent in modern conflicts, often occuring co-morbidly with psychiatric illness (e.g., post-traumatic stress disorder [PTSD]). In turn, a growing body of research has begun to explore the cognitive and psychiatric sequelae of blast-related mTBI. The current meta-analysis aimed to evaluate the chronic effects of blast-related mTBI on cognitive performance. A systematic review identified 9 studies reporting 12 samples meeting eligibility criteria. A Bayesian random-effects meta-analysis was conducted with cognitive construct and PTSD symptoms explored as moderators. The overall posterior mean effect size and Highest Density Interval (HDI) came to d = -0.12 [-0.21, -0.04], with executive function (-0.16 [-0.31, 0.00]), verbal delayed memory (-0.19 [-0.44, 0.06]) and processing speed (-0.11 [-0.26, 0.01]) presenting as the most sensitive cognitive domains to blast-related mTBI. When dividing executive function into diverse sub-constructs (i.e., working memory, inhibition, set-shifting), set-shifting presented the largest effect size (-0.33 [-0.55, -0.05]). PTSD symptoms did not predict cognitive effects sizes, ß PTSD = -0.02 [-0.23, 0.20]. The results indicate a subtle, but chronic cognitive impairment following mTBI, especially in set-shifting, a relevant aspect of executive attention. These findings are consistent with past meta-analyses on multiple mTBI and correspond with past neuroimaging research on the cognitive correlates of white matter damage common in mTBI. However, all studies had cross-sectional designs, which resulted in universally low quality ratings and limited the conclusions inferable from this meta-analysis.

The unity and diversity of executive functions: A systematic review and re-analysis of latent variable studies.

Confirmatory factor analysis (CFA) has been frequently applied to executive function measurement since first used to identify a three-factor model of inhibition, updating, and shifting; however, subsequent CFAs have supported inconsistent models across the life span, ranging from unidimensional to nested-factor models (i.e., bifactor without inhibition). This systematic review summarized CFAs on performance-based tests of executive functions and reanalyzed summary data to identify best-fitting models. Eligible CFAs involved 46 samples (N = 9,756). The most frequently accepted models varied by age (i.e., preschool = one/two-factor; school-age = three-factor; adolescent/adult = three/nested-factor; older adult = two/three-factor), and most often included updating/working memory, inhibition, and shifting factors. A bootstrap reanalysis simulated 5,000 samples from 21 correlation matrices (11 child/adolescent; 10 adult) from studies including the three most common factors, fitting seven competing models. Model results were summarized as the mean percent accepted (i.e., average rate at which models converged and met fit thresholds: CFI ≥ .90/RMSEA ≤ .08) and mean percent selected (i.e., average rate at which a model showed superior fit to other models: ΔCFI ≥ .005/.010/ΔRMSEA ≤ -.010/-.015). No model consistently converged and met fit criteria in all samples. Among adult samples, the nested-factor was accepted (41-42%) and selected (8-30%) most often. Among child/adolescent samples, the unidimensional model was accepted (32-36%) and selected (21-53%) most often, with some support for two-factor models without a differentiated shifting factor. Results show some evidence for greater unidimensionality of executive function among child/adolescent samples and both unity and diversity among adult samples. However, low rates of model acceptance/selection suggest possible bias toward the publication of well-fitting but potentially nonreplicable models with underpowered samples. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Manipulating the Alpha Level Cannot Cure Significance Testing.

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.

Executive functions and intraindividual variability following concussion.

UNLABELLED: The long-term outcomes of executive functions and intraindividual variability (IIV; i.e., trial-to-trial or across-task variability in cognitive performance) following concussion are unclear due to inconsistent and limited research findings, respectively. OBJECTIVE: Responding to these gaps in scientific understanding, the current study aimed to assess the utility of both executive functions and IIV at predicting concussion history. METHOD: Altogether 138 self-identified athletes (Mage = 19.9 ± 1.91 years, 60.8% female, 19.6% with one concussion, 18.1% with two or more concussions) completed three executive-related cognitive tasks (i.e., n-back, go/no-go, global-local). Ordinal logistic regression analyses examined the joint effect of person-mean and IIV as predictors of concussion status. RESULTS: Only mean response time for the global-local task predicted the number of past concussions, while no IIV variables reached unique significance. CONCLUSIONS: IIV research on concussion remains limited; however, the preliminary results do not indicate any additional value of IIV indices above mean performances at predicting past concussion. For executive functions, shifting appears most sensitive at detecting concussion group differences, with past researchers identifying post concussion impairment in attentional processing.

The neuropsychological outcomes of concussion: a systematic review of meta-analyses on the cognitive sequelae of mild traumatic brain injury.

UNLABELLED: Mild Traumatic Brain Injury (mTBI), also known as concussion, has become a growing public health concern, prevalent in both athletic and military settings. Many researchers have examined post-mTBI neuropsychological outcomes, leading to multiple meta-analyses amalgamating individual study results. OBJECTIVE: Considering the plethora of meta-analytic findings, the next logical step stands as a systematic review of meta-analyses, effectively reporting key moderators that predict post-mTBI neuropsychological outcomes. METHOD: A systematic review of reviews yielded 11 meta-analyses meeting inclusion criteria (i.e., English-language systematic reviews/meta-analyses covering post-mTBI observational cognitive research on late adolescents/adults), with their findings qualitatively synthesized based on moderator variables (i.e., cognitive domain, time since injury, past head injury, participant characteristics, comparison group, assessment technique, and persistent symptoms). RESULTS: The overall effect sizes ranged for both general (range: .07-.61) and sports-related mTBI (range: .40-.81) and differed both between and within cognitive domains, with executive functions appearing most sensitive to multiple mTBI. Cognitive domains varied in recovery rates, but overall recovery occurred by 90 days postinjury for most individuals and by 7 days postinjury for athletes. Greater age/education and male gender produced smaller effects sizes, and high school athletes suffered the largest deficits post-mTBI. Control-group comparisons yielded larger effects than within-person designs, and assessment techniques had limited moderating effects. CONCLUSIONS: Overall, meta-analytic review quality remained low with few studies assessing publication or study quality bias. Meta-analyses consistently identified adverse acute mTBI-related effects and fairly rapid symptom resolution. Future meta-analyses should better operationally define cognitive constructs to produce more consistent effect estimates across domains.

An empirical comparison of the therapeutic benefits of physical exercise and cognitive training on the executive functions of older adults: a meta-analysis of controlled trials.

UNLABELLED: A robust body of aging-related research has established benefits of both physical exercise (PE) and cognitive training (CT) on executive functions related to the activities of daily living of older adults; however, no meta-analysis has compared these treatments. OBJECTIVE: The current quantitative review involved a comparison of the overall effect sizes of PE and CT interventions on executive functions (Morris, 2008; pre-post-controlled effect size: d(ppc)), while also exploring contextual moderators of treatment outcomes. METHOD: A systematic review identified 46 studies (23 PE, 21 CT, and 2 both) meeting inclusion criteria (i.e., controlled interventions, executive-related outcomes, mean ages 65+, information to calculate d(ppc)). RESULTS: The weighted mean dppc values came to 0.12 (p < .01) for PE and 0.24 (p < .01) for CT. Treatment effects differed based on executive constructs for CT, with problem solving presenting the highest d(ppc) (0.47, p < .01). Notably, PE produced similar effect sizes across distinct executive functions. Treatment characteristics (e.g., session length/frequency) did not predict effect sizes. CT had a significant benefit on healthy participants (0.26, p < .01), but cognitively impaired samples did not experience a significant effect. CONCLUSIONS: Both treatments improved executive functions, but CT presented a potential advantage at improving executive functions. Improvements in executive functions differed depending on construct for CT, whereas each construct produced similar, modest effect sizes for PE. Publication bias and study quality variability potentially bias these conclusions, as lower quality studies likely produced inflated effect sizes.