Cardiac-sympathetic contractility and neural alpha-band power: cross-modal collaboration during approach-avoidance conflict.

As evidence mounts that the cardiac-sympathetic nervous system reacts to challenging cognitive settings, we ask if these responses are epiphenomenal companions or if there is evidence suggesting a more intertwined role of this system with cognitive function. Healthy male and female human participants performed an approach-avoidance paradigm, trading off monetary reward for painful electric shock, while we recorded simultaneous electroencephalographic (EEG) and cardiac-sympathetic signals. Participants were reward sensitive, but also experienced approach-avoidance "conflict" when the subjective appeal of the reward was near equivalent to the revulsion of the cost. Drift-diffusion model parameters suggested that participants managed conflict in part by integrating larger volumes of evidence into choices (wider decision boundaries). Late alpha-band (neural) dynamics were consistent with widening decision boundaries serving to combat reward-sensitivity and spread attention more fairly to all dimensions of available information. Independently, wider boundaries were also associated with cardiac "contractility" (an index of sympathetically mediated positive inotropy). We also saw evidence of conflict-specific "collaboration" between the neural and cardiac-sympathetic signals. In states of high conflict, the alignment (i.e., product) of alpha dynamics and contractility were associated with a further widening of the boundary, independent of either signal's singular association. Cross-trial coherence analyses provided additional evidence that the autonomic systems controlling cardiac-sympathetics might influence the assessment of information streams during conflict by disrupting or overriding reward processing. We conclude that cardiac-sympathetic control might play a critical role, in collaboration with cognitive processes, during the approach-avoidance conflict in humans.Significance statement Complex behavior likely involves coordination across multiple branches of the human nervous system. We know much of how cortical systems of the brain adapt to cognitive challenges. In parallel, we are beginning to understand that autonomic mediated responses in peripheral organ (cardiac-sympathetic) systems might also play an adaptive role in cognition, particularly complex decisions. We probed if such signals have separate or collaborative associations with behavior, using computational models of decision behavior, brain (electroencephalography) and cardiac-sympathetic (contractility) data. Our evidence suggests that these systems might work together, as humans attend to all available information when resolving particularly conflicting decisions. The cardiac-sympathetic system may be part of a coordinated response that helps balance the human tendency to overly focus on rewards.

Menstrual cycle-driven hormone concentrations co-fluctuate with white and gray matter architecture changes across the whole brain.

Cyclic fluctuations in hypothalamic-pituitary-gonadal axis (HPG-axis) hormones exert powerful behavioral, structural, and functional effects through actions on the mammalian central nervous system. Yet, very little is known about how these fluctuations alter the structural nodes and information highways of the human brain. In a study of 30 naturally cycling women, we employed multidimensional diffusion and T1-weighted imaging during three estimated menstrual cycle phases (menses, ovulation, and mid-luteal) to investigate whether HPG-axis hormone concentrations co-fluctuate with alterations in white matter (WM) microstructure, cortical thickness (CT), and brain volume. Across the whole brain, 17ß-estradiol and luteinizing hormone (LH) concentrations were directly proportional to diffusion anisotropy (µFA; 17ß-estradiol: ß1 = 0.145, highest density interval (HDI) = [0.211, 0.4]; LH: ß1 = 0.111, HDI = [0.157, 0.364]), while follicle-stimulating hormone (FSH) was directly proportional to CT (ß1 = 0 .162, HDI = [0.115, 0.678]). Within several individual regions, FSH and progesterone demonstrated opposing relationships with mean diffusivity (Diso) and CT. These regions mainly reside within the temporal and occipital lobes, with functional implications for the limbic and visual systems. Finally, progesterone was associated with increased tissue (ß1 = 0.66, HDI = [0.607, 15.845]) and decreased cerebrospinal fluid (CSF; ß1 = -0.749, HDI = [-11.604, -0.903]) volumes, with total brain volume remaining unchanged. These results are the first to report simultaneous brain-wide changes in human WM microstructure and CT coinciding with menstrual cycle-driven hormone rhythms. Effects were observed in both classically known HPG-axis receptor-dense regions (medial temporal lobe, prefrontal cortex) and in other regions located across frontal, occipital, temporal, and parietal lobes. Our results suggest that HPG-axis hormone fluctuations may have significant structural impacts across the entire brain.

Corticospinal premotor fibers facilitate complex motor control after stroke.

OBJECTIVE: The corticospinal tract (CST) is considered the most important motor output pathway comprising fibers from the primary motor cortex (M1) and various premotor areas. Damage to its descending fibers after stroke commonly leads to motor impairment. While premotor areas are thought to critically support motor recovery after stroke, the functional role of their corticospinal output for different aspects of post-stroke motor control remains poorly understood. METHODS: We assessed the differential role of CST fibers originating from premotor areas and M1 in the control of basal (single-joint muscle synergies and strength) and complex motor control (involving inter-joint coordination and visuomotor integration) using a novel diffusion imaging approach in chronic stroke patients. RESULTS: While M1 sub-tract anisotropy was positively correlated with basal and complex motor skills, anisotropy of PMd, PMv, and SMA sub-tracts was exclusively associated with complex motor tasks. Interestingly, patients featuring persistent motor deficits showed an additional positive association between premotor sub-tract integrity and basal motor control. INTERPRETATION: While descending M1 output seems to be a prerequisite for any form of upper limb movements, complex motor skills critically depend on output from premotor areas after stroke. The additional involvement of premotor tracts in basal motor control in patients with persistent deficits emphasizes their compensatory capacity in post-stroke motor control. In summary, our findings highlight the pivotal role of descending corticospinal output from premotor areas for motor control after stroke, which thus serve as prime candidates for future interventions to amplify motor recovery.

Active reinforcement learning versus action bias and hysteresis: control with a mixture of experts and nonexperts.

Active reinforcement learning enables dynamic prediction and control, where one should not only maximize rewards but also minimize costs such as of inference, decisions, actions, and time. For an embodied agent such as a human, decisions are also shaped by physical aspects of actions. Beyond the effects of reward outcomes on learning processes, to what extent can modeling of behavior in a reinforcement-learning task be complicated by other sources of variance in sequential action choices? What of the effects of action bias (for actions per se) and action hysteresis determined by the history of actions chosen previously? The present study addressed these questions with incremental assembly of models for the sequential choice data from a task with hierarchical structure for additional complexity in learning. With systematic comparison and falsification of computational models, human choices were tested for signatures of parallel modules representing not only an enhanced form of generalized reinforcement learning but also action bias and hysteresis. We found evidence for substantial differences in bias and hysteresis across participants-even comparable in magnitude to the individual differences in learning. Individuals who did not learn well revealed the greatest biases, but those who did learn accurately were also significantly biased. The direction of hysteresis varied among individuals as repetition or, more commonly, alternation biases persisting from multiple previous actions. Considering that these actions were button presses with trivial motor demands, the idiosyncratic forces biasing sequences of action choices were robust enough to suggest ubiquity across individuals and across tasks requiring various actions. In light of how bias and hysteresis function as a heuristic for efficient control that adapts to uncertainty or low motivation by minimizing the cost of effort, these phenomena broaden the consilient theory of a mixture of experts to encompass a mixture of expert and nonexpert controllers of behavior.

Stress affects navigation strategies in immersive virtual reality.

There are known individual differences in both the ability to learn the layout of novel environments and the flexibility of strategies for navigating known environments. However, it is unclear how navigational abilities are impacted by high-stress scenarios. Here we used immersive virtual reality (VR) to develop a novel behavioral paradigm to examine navigation under dynamically changing situations. We recruited 48 participants (24 female; ages 17-32) to navigate a virtual maze (7.5 m × 7.5 m). Participants learned the maze by moving along a fixed path past the maze's landmarks (paintings). Subsequently, participants experienced either a non-stress condition, or a high-stress condition tasking them with navigating the maze. In the high-stress condition, their initial path was blocked, the environment was darkened, threatening music was played, fog obstructed more distal views of the environment, and participants were given a time limit of 20 s with a countdown timer displayed at the top of their screen. On trials where the path was blocked, we found self-reported stress levels and distance traveled increased while trial completion rate decreased (as compared to non-stressed control trials). On unblocked stress trials, participants were less likely to take a shortcut and consequently navigated less efficiently compared to control trials. Participants with more trait spatial anxiety reported more stress and navigated less efficiently. Overall, our results suggest that navigational abilities change considerably under high-stress conditions.

A practical evaluation of measures derived from compressed sensing diffusion spectrum imaging.

Diffusion Spectrum Imaging (DSI) using dense Cartesian sampling of q-space has been shown to provide important advantages for modeling complex white matter architecture. However, its adoption has been limited by the lengthy acquisition time required. Sparser sampling of q-space combined with compressed sensing (CS) reconstruction techniques has been proposed as a way to reduce the scan time of DSI acquisitions. However prior studies have mainly evaluated CS-DSI in post-mortem or non-human data. At present, the capacity for CS-DSI to provide accurate and reliable measures of white matter anatomy and microstructure in the living human brain remains unclear. We evaluated the accuracy and inter-scan reliability of 6 different CS-DSI schemes that provided up to 80% reductions in scan time compared to a full DSI scheme. We capitalized on a dataset of 26 participants who were scanned over eight independent sessions using a full DSI scheme. From this full DSI scheme, we subsampled images to create a range of CS-DSI images. This allowed us to compare the accuracy and inter-scan reliability of derived measures of white matter structure (bundle segmentation, voxel-wise scalar maps) produced by the CS-DSI and the full DSI schemes. We found that CS-DSI estimates of both bundle segmentations and voxel-wise scalars were nearly as accurate and reliable as those generated by the full DSI scheme. Moreover, we found that the accuracy and reliability of CS-DSI was higher in white matter bundles that were more reliably segmented by the full DSI scheme. As a final step, we replicated the accuracy of CS-DSI in a prospectively acquired dataset (n = 20, scanned once). Together, these results illustrate the utility of CS-DSI for reliably delineating in vivo white matter architecture in a fraction of the scan time, underscoring its promise for both clinical and research applications.

Diffusion MRI head motion correction methods are highly accurate but impacted by denoising and sampling scheme.

Head motion correction is particularly challenging in diffusion-weighted MRI (dMRI) scans due to the dramatic changes in image contrast at different gradient strengths and directions. Head motion correction is typically performed using a Gaussian Process model implemented in FSL's Eddy. Recently, the 3dSHORE-based SHORELine method was introduced that does not require shell-based acquisitions, but it has not been previously benchmarked. Here we perform a comprehensive evaluation of both methods on realistic simulations of a software fiber phantom that provides known ground-truth head motion. We demonstrate that both methods perform remarkably well, but that performance can be impacted by sampling scheme and the extent of head motion and the denoising strategy applied before head motion correction. Furthermore, we find Eddy benefits from denoising the data first with MP-PCA. In sum, we provide the most extensive known benchmarking of dMRI head motion correction, together with extensive simulation data and a reproducible workflow. PRACTITIONER POINTS: Both Eddy and SHORELine head motion correction methods performed quite well on a large variety of simulated data. Denoising with MP-PCA can improve head motion correction performance when Eddy is used. SHORELine effectively corrects motion in non-shelled diffusion spectrum imaging data.

ReeBundle: A Method for Topological Modeling of White Matter Pathways Using Diffusion MRI.

Tractography can generate millions of complex curvilinear fibers (streamlines) in 3D that exhibit the geometry of white matter pathways in the brain. Common approaches to analyzing white matter connectivity are based on adjacency matrices that quantify connection strength but do not account for any topological information. A critical element in neurological and developmental disorders is the topological deterioration and irregularities in streamlines. In this paper, we propose a novel Reeb graph-based method "ReeBundle" that efficiently encodes the topology and geometry of white matter fibers. Given the trajectories of neuronal fiber pathways (neuroanatomical bundle), we re-bundle the streamlines by modeling their spatial evolution to capture geometrically significant events (akin to a fingerprint). ReeBundle parameters control the granularity of the model and handle the presence of improbable streamlines commonly produced by tractography. Further, we propose a new Reeb graph-based distance metric that quantifies topological differences for automated quality control and bundle comparison. We show the practical usage of our method using two datasets: (1) For International Society for Magnetic Resonance in Medicine (ISMRM) dataset, ReeBundle handles the morphology of the white matter tract configurations due to branching and local ambiguities in complicated bundle tracts like anterior and posterior commissures; (2) For the longitudinal repeated measures in the Cognitive Resilience and Sleep History (CRASH) dataset, repeated scans of a given subject acquired weeks apart lead to provably similar Reeb graphs that differ significantly from other subjects, thus highlighting ReeBundle's potential for clinical fingerprinting of brain regions.

Interhemispheric Structural Connectivity Underlies Motor Recovery after Stroke.

OBJECTIVE: Although ample evidence highlights that the ipsilesional corticospinal tract (CST) plays a crucial role in motor recovery after stroke, studies on cortico-cortical motor connections remain scarce and provide inconclusive results. Given their unique potential to serve as structural reserve enabling motor network reorganization, the question arises whether cortico-cortical connections may facilitate motor control depending on CST damage. METHODS: Diffusion spectrum imaging (DSI) and a novel compartment-wise analysis approach were used to quantify structural connectivity between bilateral cortical core motor regions in chronic stroke patients. Basal and complex motor control were differentially assessed. RESULTS: Both basal and complex motor performance were correlated with structural connectivity between bilateral premotor areas and ipsilesional primary motor cortex (M1) as well as interhemispheric M1 to M1 connectivity. Whereas complex motor skills depended on CST integrity, a strong association between M1 to M1 connectivity and basal motor control was observed independent of CST integrity especially in patients who underwent substantial motor recovery. Harnessing the informational wealth of cortico-cortical connectivity facilitated the explanation of both basal and complex motor control. INTERPRETATION: We demonstrate for the first time that distinct aspects of cortical structural reserve enable basal and complex motor control after stroke. In particular, recovery of basal motor control may be supported via an alternative route through contralesional M1 and non-crossing fibers of the contralesional CST. Our findings help to explain previous conflicting interpretations regarding the functional role of the contralesional M1 and highlight the potential of cortico-cortical structural connectivity as a future biomarker for motor recovery post-stroke. ANN NEUROL 2023;94:785-797.

Decision heuristics in contexts integrating action selection and execution.

Heuristics can inform human decision making in complex environments through a reduction of computational requirements (accuracy-resource trade-off) and a robustness to overparameterisation (less-is-more). However, tasks capturing the efficiency of heuristics typically ignore action proficiency in determining rewards. The requisite movement parameterisation in sensorimotor control questions whether heuristics preserve efficiency when actions are nontrivial. We developed a novel action selection-execution task requiring joint optimisation of action selection and spatio-temporal skillful execution. State-appropriate choices could be determined by a simple spatial heuristic, or by more complex planning. Computational models of action selection parsimoniously distinguished human participants who adopted the heuristic from those using a more complex planning strategy. Broader comparative analyses then revealed that participants using the heuristic showed combined decisional (selection) and skill (execution) advantages, consistent with a less-is-more framework. In addition, the skill advantage of the heuristic group was predominantly in the core spatial features that also shaped their decision policy, evidence that the dimensions of information guiding action selection might be yoked to salient features in skill learning.

Within-subject reproducibility varies in multi-modal, longitudinal brain networks.

Network neuroscience provides important insights into brain function by analyzing complex networks constructed from diffusion Magnetic Resonance Imaging (dMRI), functional MRI (fMRI) and Electro/Magnetoencephalography (E/MEG) data. However, in order to ensure that results are reproducible, we need a better understanding of within- and between-subject variability over long periods of time. Here, we analyze a longitudinal, 8 session, multi-modal (dMRI, and simultaneous EEG-fMRI), and multiple task imaging data set. We first confirm that across all modalities, within-subject reproducibility is higher than between-subject reproducibility. We see high variability in the reproducibility of individual connections, but observe that in EEG-derived networks, during both rest and task, alpha-band connectivity is consistently more reproducible than connectivity in other frequency bands. Structural networks show a higher reliability than functional networks across network statistics, but synchronizability and eigenvector centrality are consistently less reliable than other network measures across all modalities. Finally, we find that structural dMRI networks outperform functional networks in their ability to identify individuals using a fingerprinting analysis. Our results highlight that functional networks likely reflect state-dependent variability not present in structural networks, and that the type of analysis should depend on whether or not one wants to take into account state-dependent fluctuations in connectivity.

The role of corticospinal and extrapyramidal pathways in motor impairment after stroke.

Anisotropy of descending motor pathways has repeatedly been linked to the severity of motor impairment following stroke-related damage to the corticospinal tract. Despite promising findings consistently tying anisotropy of the ipsilesional corticospinal tract to motor outcome, anisotropy is not yet utilized as a biomarker for motor recovery in clinical practice as several methodological constraints hinder a conclusive understanding of degenerative processes in the ipsilesional corticospinal tract and compensatory roles of other descending motor pathways. These constraints include estimating anisotropy in voxels with multiple fibre directions, sampling biases and confounds due to ageing-related atrophy. The present study addressed these issues by combining diffusion spectrum imaging with a novel compartmentwise analysis approach differentiating voxels with one dominant fibre direction (one-directional voxels) from voxels with multiple fibre directions. Compartmentwise anisotropy for bihemispheric corticospinal and extrapyramidal tracts was compared between 25 chronic stroke patients, 22 healthy age-matched controls, and 24 healthy young controls and its associations with motor performance of the upper and lower limbs were assessed. Our results provide direct evidence for Wallerian degeneration along the entire length of the ipsilesional corticospinal tract reflected by decreased anisotropy in descending fibres compared with age-matched controls, while ageing-related atrophy was observed more ubiquitously across compartments. Anisotropy of descending ipsilesional corticospinal tract voxels showed highly robust correlations with various aspects of upper and lower limb motor impairment, highlighting the behavioural relevance of Wallerian degeneration. Moreover, anisotropy measures of two-directional voxels within bihemispheric rubrospinal and reticulospinal tracts were linked to lower limb deficits, while anisotropy of two-directional contralesional rubrospinal voxels explained gross motor performance of the affected hand. Of note, the relevant extrapyramidal structures contained fibres crossing the midline, fibres potentially mitigating output from brain stem nuclei, and fibres transferring signals between the extrapyramidal system and the cerebellum. Thus, specific parts of extrapyramidal pathways seem to compensate for impaired gross arm and leg movements incurred through stroke-related corticospinal tract lesions, while fine motor control of the paretic hand critically relies on ipsilesional corticospinal tract integrity. Importantly, our findings suggest that the extrapyramidal system may serve as a compensatory structural reserve independent of post-stroke reorganization of extrapyramidal tracts. In summary, compartment-specific anisotropy of ipsilesional corticospinal tract and extrapyramidal tracts explained distinct aspects of motor impairment, with both systems representing different pathophysiological mechanisms contributing to motor control post-stroke. Considering both systems in concert may help to develop diffusion imaging biomarkers for specific motor functions after stroke.

Reinforcement learning with associative or discriminative generalization across states and actions: fMRI at 3 T and 7 T.

The model-free algorithms of "reinforcement learning" (RL) have gained clout across disciplines, but so too have model-based alternatives. The present study emphasizes other dimensions of this model space in consideration of associative or discriminative generalization across states and actions. This "generalized reinforcement learning" (GRL) model, a frugal extension of RL, parsimoniously retains the single reward-prediction error (RPE), but the scope of learning goes beyond the experienced state and action. Instead, the generalized RPE is efficiently relayed for bidirectional counterfactual updating of value estimates for other representations. Aided by structural information but as an implicit rather than explicit cognitive map, GRL provided the most precise account of human behavior and individual differences in a reversal-learning task with hierarchical structure that encouraged inverse generalization across both states and actions. Reflecting inference that could be true, false (i.e., overgeneralization), or absent (i.e., undergeneralization), state generalization distinguished those who learned well more so than action generalization. With high-resolution high-field fMRI targeting the dopaminergic midbrain, the GRL model's RPE signals (alongside value and decision signals) were localized within not only the striatum but also the substantia nigra and the ventral tegmental area, including specific effects of generalization that also extend to the hippocampus. Factoring in generalization as a multidimensional process in value-based learning, these findings shed light on complexities that, while challenging classic RL, can still be resolved within the bounds of its core computations.

Single-case disconnectome lesion-symptom mapping: Identifying two subtypes of limb apraxia.

Influential theories of skilled action posit that distinct cognitive mechanisms and neuroanatomic substrates support meaningless gesture imitation and tool use pantomiming, and poor performance on these tasks are hallmarks of limb apraxia. Yet prior research has primarily investigated brain-behavior relations at the group level; thus, it is unclear whether we can identify individuals with isolated impairments in meaningless gesture imitation or tool use pantomiming whose performance is associated with a distinct neuroanatomic lesion profile. The goal of this study was to test the hypothesis that individuals with disproportionately worse performance in meaningless gesture imitation would exhibit cortical damage and white matter disconnection in left fronto-parietal brain regions, whereas individuals with disproportionately worse performance in tool use pantomiming would exhibit cortical damage and white matter disconnection in left temporo-parietal brain regions. Fifty-eight participants who experienced a left cerebrovascular accident took part in a meaningless gesture imitation task, a tool use pantomiming task, and a T1 structural MRI. Two participants were identified who had relatively small lesions and disproportionate impairments on one task relative to the other, as well as below-control-level performance on one task and not the other. Using these criteria, one participant was disproportionately impaired at meaningless gesture imitation, and the other participant was disproportionately impaired at pantomiming tool use. Graph theoretic analysis of each participant's structural disconnectome demonstrated that disproportionately worse meaningless gesture imitation performance was associated with disconnection among the left inferior parietal lobule, the left superior parietal lobule, and the left middle and superior frontal gyri, whereas disproportionately worse tool use pantomiming performance was associated with disconnection between left temporal and parietal regions. Our results demonstrate that relatively focal lesions to specific portions of the Tool Use Network can be associated with distinct limb apraxia subtypes.

Habituation of the stress response multiplex to repeated cold pressor exposure.

Humans show remarkable habituation to aversive events as reflected by changes of both subjective report and objective measures of stress. Although much experimental human research focuses on the effects of stress, relatively little is known about the cascade of physiological and neural responses that contribute to stress habituation. The cold pressor test (CPT) is a common method for inducing acute stress in human participants in the laboratory; however, there are gaps in our understanding of the global state changes resulting from this stress-induction technique and how these responses change over multiple exposures. Here, we measure the stress response to repeated CPT exposures using an extensive suite of physiologic measures and state-of-the-art analysis techniques. In two separate sessions on different days, participants underwent five 90 s CPT exposures of both feet and five warm water control exposures, while electrocardiography (ECG), impedance cardiography, continuous blood pressure, pupillometry, scalp electroencephalography (EEG), salivary cortisol and self-reported pain assessments were recorded. A diverse array of adaptive responses are reported that vary in their temporal dynamics within each exposure as well as habituation across repeated exposures. During cold-water exposure there was a cascade of changes across several cardiovascular measures (elevated heart rate (HR), cardiac output (CO) and Mean Arterial Pressure (MAP) and reduced left ventricular ejection time (LVET), stroke volume (SV) and high-frequency heart rate variability (HF)). Increased pupil dilation was observed, as was increased power in low-frequency bands (delta and theta) across frontal EEG electrode sites. Several cardiovascular measures also habituated over repeated cold-water exposures (HR, MAP, CO, SV, LVET) as did pupil dilation and alpha frequency activity across the scalp. Anticipation of cold water induced stress effects in the time-period immediately prior to exposure, indexed by increased pupil size and cortical disinhibition in the alpha and beta frequency bands across central scalp sites. These results provide comprehensive insight into the evolution of a diverse array of stress responses to an acute noxious stressor, and how these responses adaptively contribute to stress habituation.

Combining Repetition Suppression and Pattern Analysis Provides New Insights into the Role of M1 and Parietal Areas in Skilled Sequential Actions.

How does the brain change during learning? In functional magnetic resonance imaging (fMRI) studies, both multivariate pattern analysis (MVPA) and repetition suppression (RS) have been used to detect changes in neuronal representations. In the context of motor sequence learning, the two techniques have provided discrepant findings: pattern analysis showed that only premotor and parietal regions, but not primary motor cortex (M1), develop a representation of trained sequences. In contrast, RS suggested trained sequence representations in all these regions. Here, we applied both analysis techniques to a five-week finger sequence training study, in which participants executed each sequence twice before switching to a different sequence. Both RS and pattern analysis indicated learning-related changes for parietal areas, but only RS showed a difference between trained and untrained sequences in M1. A more fine-grained analysis, however, revealed that the RS effect in M1 reflects a fundamentally different process than in parietal areas. On the first execution, M1 represents especially the first finger of each sequence, likely reflecting preparatory processes. This effect dramatically reduces during the second execution. In contrast, parietal areas represent the identity of a sequence, and this representation stays relatively stable on the second execution. These results suggest that the RS effect does not reflect a trained sequence representation in M1, but rather a preparatory signal for movement initiation. More generally, our study demonstrates that across regions RS can reflect different representational changes in the neuronal population code, emphasizing the importance of combining pattern analysis and RS techniques.SIGNIFICANCE STATEMENT Previous studies using pattern analysis have suggested that primary motor cortex (M1) does not represent learnt sequential actions. However, a study using repetition suppression (RS) has reported M1 changes during motor sequence learning. Combining both techniques, we first replicate the discrepancy between them, with learning-related changes in M1 in RS, but not pattern dissimilarities. We further analyzed the representational changes with repetition, and found that the RS effects differ across regions. M1's activity represents the starting finger of the sequence, an effect that vanishes with repetition. In contrast, activity patterns in parietal areas exhibit sequence dependency, which persists with repetition. These results demonstrate the importance of combining RS and pattern analysis to understand the function of brain regions.

QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data.

Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.

Ventromedial Prefrontal Cortex Activity and Sympathetic Allostasis During Value-Based Ambivalence.

Anxiety is characterized by low confidence in daily decisions, coupled with high levels of phenomenological stress. Ventromedial prefrontal cortex (vmPFC) plays an integral role in maladaptive anxious behaviors via decreased sensitivity to threatening vs. non-threatening stimuli (fear generalization). vmPFC is also a key node in approach-avoidance decision making requiring two-dimensional integration of rewards and costs. More recently, vmPFC has been implicated as a key cortical input to the sympathetic branch of the autonomic nervous system. However, little is known about the role of this brain region in mediating rapid stress responses elicited by changes in confidence during decision making. We used an approach-avoidance task to examine the relationship between sympathetically mediated cardiac stress responses, vmPFC activity and choice behavior over long and short time-scales. To do this, we collected concurrent fMRI, EKG and impedance cardiography recordings of sympathetic drive while participants made approach-avoidance decisions about monetary rewards paired with painful electric shock stimuli. We observe first that increased sympathetic drive (shorter pre-ejection period) in states lasting minutes are associated with choices involving reduced decision ambivalence. Thus, on this slow time scale, sympathetic drive serves as a proxy for "mobilization" whereby participants are more likely to show consistent value-action mapping. In parallel, imaging analyses reveal that on shorter time scales (estimated with a trial-to-trial GLM), increased vmPFC activity, particularly during low-ambivalence decisions, is associated with decreased sympathetic state. Our findings support a role of sympathetic drive in resolving decision ambivalence across long time horizons and suggest a potential role of vmPFC in modulating this response on a moment-to-moment basis.

Dynamic community detection reveals transient reorganization of functional brain networks across a female menstrual cycle.

Sex steroid hormones have been shown to alter regional brain activity, but the extent to which they modulate connectivity within and between large-scale functional brain networks over time has yet to be characterized. Here, we applied dynamic community detection techniques to data from a highly sampled female with 30 consecutive days of brain imaging and venipuncture measurements to characterize changes in resting-state community structure across the menstrual cycle. Four stable functional communities were identified, consisting of nodes from visual, default mode, frontal control, and somatomotor networks. Limbic, subcortical, and attention networks exhibited higher than expected levels of nodal flexibility, a hallmark of between-network integration and transient functional reorganization. The most striking reorganization occurred in a default mode subnetwork localized to regions of the prefrontal cortex, coincident with peaks in serum levels of estradiol, luteinizing hormone, and follicle stimulating hormone. Nodes from these regions exhibited strong intranetwork increases in functional connectivity, leading to a split in the stable default mode core community and the transient formation of a new functional community. Probing the spatiotemporal basis of human brain-hormone interactions with dynamic community detection suggests that hormonal changes during the menstrual cycle result in temporary, localized patterns of brain network reorganization.

Motor adaptation via distributional learning.

Objective. Both artificial and biological controllers experience errors during learning that are probabilistically distributed. We develop a framework for modeling distributions of errors and relating deviations in these distributions to neural activity.Approach. The biological system we consider is a task where human subjects are required to learn to minimize the roll of an inverted T-shaped object with an unbalanced weight (i.e. one side of the object is heavier than the other side) during lift. We also collect BOLD activity during this process. For our experimental setup, we define the state of the system to be the maximum magnitude roll of the object after lift onset and give subjects the goal of achieving the zero state.Main Results. We derive a model for this problem from a variant of Temporal Difference Learning. We then combine this model with Distributional Reinforcement Learning (DRL), a framework that involves defining a value distribution by treating the reward as stochastic. This model transforms the goal of the controller from achieving a target state, to achieving a distribution over distances from the target state. We call it a Distributional Temporal Difference Model (DTDM). The DTDM allows us to model errors in unsuccessfully minimizing object roll using deviations in the value distribution when the center of mass of the unbalanced object is changed. We compute deviations in global neural activity and show that they vary continuously with deviations in the value distribution. Different aspects might contribute to this global shift or signal difference, including a difference in grasp and lift force at lift onset, as well as sensory feedback of error/roll after lift onset. We predict that there exists a coordinated, global response to errors that incorporates all of this information, which is encoding the DTDM objective and used on subsequent trials enabling success. We validate the utility of the DTDM as a model for biological adaptation by using it to engineer a robotic controller to solve a similar problem.Significance. We develop a novel theoretical framework and show that it can be used to model a non-trivial motor learning task. Because this theoretical framework is consistent with state-of-the-art reinforcement learning, we can also use it to program a robot to perform a similar task. These results suggest a way to model the multiple subsystems composing global neural activity in a way that transfers well to engineering artificial intelligence.