Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Left anterior supramarginal gyrus activity during tool use action observation after extensive tool use training.

The advanced use of complex tools is considered a primary characteristic of human evolution and technological advancement. However, questions remain regarding whether humans possess unique underlying brain networks that support advanced tool-using abilities. Specifically, previous studies have demonstrated the presence of a structurally and functionally unique region in the left anterior supramarginal gyrus (aSMG), that is consistently active during tool use action observation. This region has been proposed as a primary hub for integrating semantic and technical information to form action plans with tools. However, it is still largely unknown how tool use motor learning affects left aSMG activation or connectivity with other brain regions. To address this, participants with little experience using chopsticks observed an experimenter using chopsticks to perform a novel task while undergoing two functional magnetic resonance imaging (fMRI) scans. Between the scans, participants underwent four weeks of behavioral training where they learned to use chopsticks and achieve proficiency in the observed task. Results demonstrated a significant change in effective connectivity between the left aSMG and the left anterior intraparietal sulcus (aIPS), a region involved in object affordances and planning grasping actions. These findings suggest that during unfamiliar tool use, the left aSMG integrates semantic and technical information to communicate with regions involved with grasp selection, such as the aIPS. This communication then allows appropriate grasps to be planned based on the physical properties of the objects involved and their potential interactions.

Sensorimotor control of object manipulation following middle cerebral artery (MCA) stroke.

Methods for assessing the loss of hand function post-stroke examine limited aspects of motor performance and are not sensitive to subtle changes that can cause deficits in everyday object manipulation tasks. Efficiently lifting an object entails a prediction of required forces based on intrinsic features of the object (sensorimotor integration), short-term updates in the forces required to lift objects that are poorly predicted (sensorimotor memory), as well as the ability to modulate distal fingertip forces, which are not measured by existing assessment tools used in clinics for both diagnostic and rehabilitative purposes. The presented research examined these three components of skilled object manipulation in 60 chronic, unilateral middle cerebral artery stroke participants. Performance was compared to age-matched control participants, and linear regressions were used to predict performance based on clinical scores. Most post-stroke participants performed below control levels in at least one of the tasks. Post-stroke participants presented with combinations of deficits in each of the tasks performed, regardless of the hemisphere damaged by the stroke. Surprisingly, the ability to modulate distal forces was impaired in those patients with damage ipsilateral (right hemisphere) to the hand being used. Sensorimotor integration was also impaired in patients with right hemisphere damage, though they performed at control levels in later lifts, whereas left-hemisphere-damaged patients did not. Lastly, during a task requiring sensorimotor memory, neither patient group performed outside of control ranges on initial lifts, with patients with right hemisphere damage showing impaired performance in later lifts suggesting they were unable to learn the mapping novel mapping of color and mass of the objects. The presented research demonstrates unilateral MCA stroke patients can have deficits in one or more components required for the successful manipulation of hand-held objects and that skillful object lifting requires intact bilateral systems. Further, this information may be used in future studies to aid efforts that target rehabilitation regimens to a stroke survivor's specific pattern of deficits.

Methylation of genes and regulation of inflammatory processes on emotional response in young adults with alcoholic parents.

Many Americans are adult children of an alcoholic parent (ACoA), which can confer an increased risk of trauma and hazardous alcohol use, as well as heritable and environmental genetic influence. Psychological health and related neural activity can be influenced by inflammation responses, but it is not clear how these factors interact regarding risk or resilience to hazardous alcohol use. The goals of this study were to better understand the relationships between current alcohol use and inflammation, how these are modified by single nucleotide polymorphisms (SNPs) and/or epigenetic modifications of inflammation-associated genes; and how these alter neural reactivity to emotionally-salient stimuli. To do so, ACoA participants were dichotomized as resilient (not engaged in hazardous alcohol use) or vulnerable (currently engaged in hazardous alcohol use). Measures of blood-oxygen-level-dependent (BOLD) activity within regions of interest (ROIs), SNPs and DNA methylation of specific inflammation regulatory genes, and biological markers of inflammation were compared between these groups. Vulnerable ACoAs exhibited higher plasma C-reactive protein (CRP) and greater BOLD activity in the right hippocampus and ventral anterior cingulate cortex in response to emotional cues as well as reduced methylation of CRP and glucocorticoid-related genes. Path analysis revealed significant relationships between alcohol use, SNPs, DNA methylation of inflammatory-related genes, CRP levels, and BOLD activity to emotional stimuli. Taken together, these findings suggest a complex association related to hazardous alcohol use in ACoAs that may predict current inflammation and neural reactivity to emotional stimuli. A better understanding of these associations could direct the future of individual treatment options.

A Comparative Study of Body Lice and Bed Bugs Reveals Factors Potentially Involved in Differential Vector Competence for the Relapsing Fever Spirochete Borrelia recurrentis.

Borrelia recurrentis is the causative agent of louse-borne relapsing fever and the only Borrelia species transmitted by an insect rather than a tick vector. While bed bugs (Cimex lectularius L.) are not established vectors of any human pathogens, a recent study reported that they may be competent vectors of B. recurrentis. However, many aspects of infection and transmission remain unclear in this possible secondary vector. Here, we carried out several quantitative laboratory studies to gain a better understanding of the host suitability of bed bugs relative to the established body louse vector as well as the factors that may affect the ability of bed bugs to transmit the pathogen. We fed bed bugs B. recurrentis and estimated the level and duration of infection in the hemolymph using live imaging. We performed quantitative PCR (qPCR) to examine whole-body spirochete levels and the occurrence of vertical transmission to progeny. We also developed an assay to compare the amounts of force required to release infectious hemolymph from recently engorged bed bugs and body lice. Finally, we analyzed humoral antibacterial activity in the hemolymph, hemolymph pH, and hemocyte activity in both insect species. Our results confirm that within 24 h of ingestion, B. recurrentis can penetrate the midgut epithelium of bed bugs and enter the hemolymph, overcoming a major host barrier, as in body lice. Once in the hemolymph, spirochetes remain visible for at least 4 days. Moreover, we show that bed bugs are more physically susceptible to crushing than body lice, suggesting that crushing is a feasible route for the natural dissemination of B. recurrentis from the hemolymph of bed bugs, as for body lice. Nonetheless, our data also indicate that bed bugs are suboptimal hosts for B. recurrentis, as the bacterium does not appear to proliferate to high levels or stably colonize the hemolymph and exhibits pleomorphism in this environment. In particular, our data suggest that hemolymph pH and unique cellular immune responses, rather than humoral effectors, may be involved in limiting spirochete survival in bed bugs. Notably, we document the formation of extracellular DNA traps by bed bug hemocytes for the first time. For these reasons, while bed bugs may be capable of limited transmission given their ecology, vector competence is probably minimal relative to body lice. Additional mechanistic studies of human pathogen infection of bed bugs may provide much-needed insight into the biological factors that restrict their ability to act as vectors and may reveal novel mechanisms of immunity.

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium.

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1300 PTSD cases and >2000 trauma-exposed control subjects (ages 6.2-85.2 years) by the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta Analysis-Psychiatric Genomics Consortium) PTSD working group. Cortical regions in the network were rank ordered by the effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2-148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared with the mean SC of 5000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD control subjects, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex, and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The SC networks that are perturbed in PTSD comport with converging evidence from resting-state functional connectivity networks and networks affected by inflammatory processes and stress hormones in PTSD.

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Relationships between Freezing of Gait Severity and Cognitive Deficits in Parkinson's Disease.

Freezing of gait (FOG) is one of the most debilitating motor symptoms experienced by patients with Parkinson's disease (PD), as it can lead to falls and a reduced quality of life. Evidence supports an association between FOG severity and cognitive functioning; however, results remain debatable. PD patients with (PDFOG+, n = 41) and without FOG (PDFOG-, n = 39) and control healthy subjects (n = 41) participated in this study. The NIH toolbox cognition battery, the Montreal Cognitive Assessment (MoCA), and the interval timing task were used to test cognitive domains. Measurements were compared between groups using multivariable models and adjusting for covariates. Correlation analyses, linear regression, and mediation models were applied to examine relationships among disease duration and severity, FOG severity, and cognitive functioning. Significant differences were observed between controls and PD patients for all cognitive domains. PDFOG+ and PDFOG- exhibited differences in Dimensional Change Card Sort (DCCS) test, interval timing task, and MoCA scores. After adjusting for covariates in two different models, PDFOG+ and PDFOG- differed in both MoCA and DCCS scores. In addition, significant relationships between FOG severity and cognitive function (MoCA, DCCS, and interval timing) were also found. Regression models suggest that FOG severity may be a predictor of cognitive impairment, and mediation models show the effects of cognitive impairment on the relationship between disease severity and FOG severity. Overall, this study provides insight into the relationship between cognitive and FOG severity in patients with PD, which could aid in the development of therapeutic interventions to manage both.

Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

Altered Cerebellar Oscillations in Parkinson's Disease Patients during Cognitive and Motor Tasks.

Structural and functional abnormalities in the cerebellar region have been shown in patients with Parkinson's disease (PD). Since the cerebellar region has been associated with cognitive and lower-limb motor functions, it is imperative to study cerebellar oscillations in PD. Here, we evaluated cerebellar electroencephalography (EEG) during cognitive processing and lower-limb motor performances in PD. Cortical and cerebellar EEG were collected from 74 PD patients and 37 healthy control subjects during a 7-second interval timing task, 26 PD patients and 13 controls during a lower-limb pedaling task, and 23 PD patients during eyes-open/closed resting conditions. Analyses were focused on the mid-cerebellar Cbz electrode and further compared to the mid-occipital Oz and mid-frontal Cz electrodes. Increased alpha-band power was observed during the eyes-closed resting-state condition over Oz, but no change in alpha power was observed over Cbz. PD patients showed higher dispersion when performing the 7-second interval timing cognitive task and executed the pedaling motor task with reduced speed compared to controls. PD patients exhibited attenuated cue-triggered theta-band power over Cbz during both the interval timing and pedaling motor tasks. Connectivity measures between Cbz and Cz showed theta-band differences, but only during the pedaling motor task. Cbz oscillatory activity also differed from Oz across multiple frequency bands in both groups during both tasks. Our cerebellar EEG data along with previous magnetoencephalography and animal model studies clearly show alterations in cerebellar oscillations during cognitive and motor processing in PD.

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Neural and psychological characteristics of college students with alcoholic parents differ depending on current alcohol use.

A significant proportion of college students are adult children of an alcoholic parent (ACoA), which can confer greater risk of depression, poor self-esteem, alcohol and drug problems, and greater levels of college attrition. However, some ACoA are resilient to these negative outcomes. The goal of this study was to better understand the psychobiological factors that distinguish resilient and vulnerable college-aged ACoAs. To do so, scholastic performance and psychological health were measured in ACoA college students not engaged in hazardous alcohol use (resilient) and those currently engaged in hazardous alcohol use (vulnerable). Neural activity (as measured by functional magnetic resonance imaging) in response to performing working memory and emotion-based tasks were assessed. Furthermore, the frequency of polymorphisms in candidate genes associated with substance use, risk taking and stress reactivity were compared between the two ACoA groups. College ACoAs currently engaged in hazardous alcohol use reported more anxiety, depression and posttraumatic stress symptoms, and increased risky nicotine and marijuana use as compared to ACoAs resistant to problem alcohol use. ACoA college students with current problem alcohol showed greater activity of the middle frontal gyrus and reduced activation of the posterior cingulate in response to visual working memory and emotional processing tasks, which may relate to increased anxiety and problem alcohol and drug behaviors. Furthermore, polymorphisms of cholinergic receptor and the serotonin transporter genes also appear to contribute a role in problem alcohol use in ACoAs. Overall, findings point to several important psychobiological variables that distinguish ACoAs based on their current alcohol use that may be used in the future for early intervention.

Resource forecasting: Differential effects of glucose taste and ingestion on delay discounting and self-control.

We tested a novel hypothesis that glucose taste acts as a signal for resource acquisition, motivating preference for immediate rewards while actual glucose ingestion prompts resource conservation, promoting future-orientated self-regulation. In Study 1, participants were engaged in a delay-discounting task and a grip-control task before and after a beverage intervention (glucose drink, water drink, or glucose mouth-rinse). Glucose ingestion decreased delay discounting, making larger-and-later rewards more attractive. In contrast, glucose rinse increased delay discounting. Water ingestion had none of the effects. In the grip-control task, only glucose ingestion improved the performance. Study 2 using fMRI revealed that glucose rinse and glucose ingestion resulted in distinct brain activational patterns. Compared to glucose rinse, glucose ingestion deactivated a few brain regions (e.g., the anterior cingulate gyrus and inferior frontal gyrus) that are previously shown to be more active when making more difficult intertemporal choices, suggesting that glucose ingestion eases the process of making intertemporal choice. In sum, our behavioral and neuroimaging findings together suggest a dual signaling role of glucose sensation and ingestion in regulating delay discounting and self-control.

Getting a handle on virtual tools: An examination of the neuronal activity associated with virtual tool use.

Tool use is associated with three visual streams-dorso-dorsal, ventro-dorsal, and ventral visual streams. These streams are involved in processing online motor planning, action semantics, and tool semantics features, respectively. Little is known about the way in which the brain represents virtual tools. To directly assess this question, a virtual tool paradigm was created that provided the ability to manipulate tool components in isolation of one another. During functional magnetic resonance imaging (fMRI), adult participants performed a series of virtual tool manipulation tasks in which vision and movement kinematics of the tool were manipulated. Reaction time and hand movement direction were monitored while the tasks were performed. Functional imaging revealed that activity within all three visual streams was present, in a similar pattern to what would be expected with physical tool use. However, a previously unreported network of right-hemisphere activity was found including right inferior parietal lobule, middle and superior temporal gyri and supramarginal gyrus - regions well known to be associated with tool processing within the left hemisphere. These results provide evidence that both virtual and physical tools are processed within the same brain regions, though virtual tools recruit bilateral tool processing regions to a greater extent than physical tools.

Rapid Automatic Motor Encoding of Competing Reach Options.

Mounting neural evidence suggests that, in situations in which there are multiple potential targets for action, the brain prepares, in parallel, competing movements associated with these targets, prior to implementing one of them. Central to this interpretation is the idea that competing viewed targets, prior to selection, are rapidly and automatically transformed into corresponding motor representations. Here, by applying target-specific, gradual visuomotor rotations and dissociating, unbeknownst to participants, the visual direction of potential targets from the direction of the movements required to reach the same targets, we provide direct evidence for this provocative idea. Our results offer strong empirical support for theories suggesting that competing action options are automatically represented in terms of the movements required to attain them. The rapid motor encoding of potential targets may support the fast optimization of motor costs under conditions of target uncertainty and allow the motor system to inform decisions about target selection.

Representing multiple object weights: competing priors and sensorimotor memories.

When lifting an object, individuals scale lifting forces based on long-term priors relating external object properties (such as material and size) to object weight. When experiencing objects that are poorly predicted by priors, people rapidly form and update sensorimotor memories that can be used to predict an object's atypical size-weight relation in support of predictively scaling lift forces. With extensive experience in lifting such objects, long-term priors, assessed with weight judgments, are gradually updated. The aim of the present study was to understand the formation and updating of these memory processes. Participants lifted, over multiple days, a set of black cubes with a normal size-weight mapping and green cubes with an inverse size-weight mapping. Sensorimotor memory was assessed with lifting forces, and priors associated with the black and green cubes were assessed with the size-weight illusion (SWI). Interference was observed in terms of adaptation of the SWI, indicating that priors were not independently adjusted. Half of the participants rapidly learned to scale lift forces appropriately, whereas reduced learning was observed in the others, suggesting that individual differences may be affecting sensorimotor memory abilities. A follow-up experiment showed that lifting forces are not accurately scaled to objects when concurrently performing a visuomotor association task, suggesting that sensorimotor memory formation involves cognitive resources to instantiate the mapping between object identity and weight, potentially explaining the results of experiment 1 These results provide novel insight into the formation and updating of sensorimotor memories and provide support for the independent adjustment of sensorimotor memory and priors.

Cognitive attribution of the source of an error in object-lifting results in differences in motor generalization.

To lift an object, the motor system must predict the weight of the object and use this information to program appropriate lifting forces. If this prediction is erroneous, people may assign blame for the error to either themselves or an external source-a process called credit assignment. In the present study, we explored the role of credit assignment on weight predictions during a lifting task. Participants were told that the EMG surface electrodes attached to their lifting hand were either part of a "passive" system that recorded muscular activity, or part of an "active" system that would apply energy to the muscle, influencing weight perception. Participants performed 90 lifts of the training blocks, followed by 10 lifts of a newly encountered larger test block. In between training and test trials, the experimenter turned off the recording system and removed the surface electrodes for participants in the "active" group. For each lift, we determined the initial peak rate of change of vertical load force rate and load-phase duration, estimates of predicted object weight. Analysis of the first 10 training lifts and the last 10 training lifts revealed no effect of Active versus Passive EMG on weight predictions. However, after removing the EMG equipment, participants in the "active" group failed to scale their predictive load forces in the same manner as those in the "passive" condition when lifting a novel block. We conclude that cognitive information may play a role in credit assignment, influencing weight prediction when lifting novel objects.