Iowa Brain-Behavior Modeling Toolkit: An Open-Source MATLAB Tool for Inferential and Predictive Modeling of Imaging-Behavior and Lesion-Deficit Relationships.

The traditional analytical framework taken by neuroimaging studies in general, and lesion-behavior studies in particular, has been inferential in nature and has focused on identifying and interpreting statistically significant effects within the sample under study. While this framework is well-suited for hypothesis testing approaches, achieving the modern goal of precision medicine requires a different framework that is predictive in nature and that focuses on maximizing the predictive power of models and evaluating their ability to generalize beyond the data that were used to train them. However, few tools exist to support the development and evaluation of predictive models in the context of neuroimaging or lesion-behavior research, creating an obstacle to the widespread adoption of predictive modeling approaches in the field. Further, existing tools for lesion-behavior analysis are often unable to accommodate categorical outcome variables and often impose restrictions on the predictor data. Researchers therefore often must use different software packages and analytical approaches depending on whether they are addressing a classification vs. regression problem and on whether their predictor data correspond to binary lesion images, continuous lesion-network images, connectivity matrices, or other data modalities. To address these limitations, we have developed a MATLAB software toolkit that supports both inferential and predictive modeling frameworks, accommodates both classification and regression problems, and does not impose restrictions on the modality of the predictor data. The toolkit features both a graphical user interface and scripting interface, includes implementations of multiple mass-univariate, multivariate, and machine learning models, features built-in and customizable routines for hyper-parameter optimization, cross-validation, model stacking, and significance testing, and automatically generates text-based descriptions of key methodological details and modeling results to improve reproducibility and minimize errors in the reporting of methods and results. Here, we provide an overview and discussion of the toolkit's features and demonstrate its functionality by applying it to the question of how expressive and receptive language impairments relate to lesion location, structural disconnection, and functional network disruption in a large sample of patients with left hemispheric brain lesions. We find that impairments in expressive vs. receptive language are most strongly associated with left lateral prefrontal and left posterior temporal/parietal damage, respectively. We also find that impairments in expressive vs. receptive language are associated with partially overlapping patterns of fronto-temporal structural disconnection, and that the associated functional networks are also similar. Importantly, we find that lesion location and lesion-derived network measures are highly predictive of both types of impairment, with predictions from models trained on these measures explaining ~30-40% of the variance on average when applied to data from patients not used to train the models. We have made the toolkit publicly available, and we have included a comprehensive set of tutorial notebooks to support new users in applying the toolkit in their studies.

Sensing, feeling and regulating: investigating the association of focal brain damage with voluntary respiratory and motor control.

Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal or limbic regions on the sensation and regulation of breathing patterns. Participants performed a respiratory regulation task across regular and irregular frequencies ranging from 6 to 60 breaths per minute (bpm), with a counterbalanced hand motor control task. Interoceptive and affective states induced by each condition were assessed via questionnaire, and autonomic signals were indexed via skin conductance. Participants with focal lesions to the bilateral frontal lobe, right insula/basal ganglia and left medial temporal lobe showed reduced performance relative to individually matched healthy comparisons during the breathing and motor tasks. They also reported significantly higher anxiety during the 60 bpm regular and irregular breathing trials, with anxiety correlating with difficulty in rapid breathing specifically within this group. This study demonstrates that damage to frontal, temporal or limbic regions is associated with abnormal voluntary respiratory and motor regulation and tachypnoea-related anxiety, highlighting the role of the forebrain in affective and motor responses during breathing. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Neuroanatomy of cerebellar mutism syndrome: the role of lesion location.

Approximately 25% of paediatric patients who undergo cerebellar tumour resection develop cerebellar mutism syndrome. Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with an increased risk of cerebellar mutism syndrome. Here, we tested whether these findings replicate in an independent cohort. We evaluated the relationship between lesion location and the development of cerebellar mutism syndrome in an observational study of 56 paediatric patients ranging from five months to 14 years of age who underwent cerebellar tumour resection. We hypothesized that individuals who developed cerebellar mutism syndrome after surgery, relative to those who did not, would have lesions that preferentially intersect with: (i) the cerebellar outflow pathway and (ii) a previously generated 'lesion-symptom map' of cerebellar mutism syndrome. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). We found supporting evidence for both hypotheses. Compared to patients who did not develop cerebellar mutism syndrome, patients with cerebellar mutism syndrome (n = 10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d = 0.73, P = 0.05), and the cerebellar mutism syndrome lesion-symptom map (Cohen's d = 1.1, P = 0.004). These results strengthen the association of lesion location with the risk of developing cerebellar mutism syndrome and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to paediatric cerebellar tumours.

Network localization of pediatric lesion-induced dystonia.

Objective: Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia. Methods: Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia. Results: Multivariate lesion-symptom mapping showed that lesions of the putamen (stroke: r = 0.50, p <0.01; hypoxia, r = 0.64, p <0.001) and globus pallidus (kernicterus, r = 0.61, p <0.01) were associated with dystonia. Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular and somato-cognitive-action networks. Interpretation: We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is involved in higher order coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention.

Cortical and subcortical functional connectivity and cognitive impairment in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson's Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We focus on canonical cortical networks linked to cognition, including the salience network (SAL), frontoparietal network (FPN), and default mode network (DMN), as well as a subcortical basal ganglia network (BGN). We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. In 82 PD patients, we found that lower MoCA scores were linked with lower intra-network connectivity of the FPN. We also found that lower MoCA scores were linked with lower inter-network connectivity between the SAL and the BGN, the SAL and the DMN, as well as the FPN and the DMN. These data elucidate the relationship of cortical and subcortical functional connectivity with cognitive impairments in PD.

Effects of transcranial magnetic stimulation on the human brain recorded with intracranial electrocorticography.

Transcranial magnetic stimulation (TMS) is increasingly used as a noninvasive technique for neuromodulation in research and clinical applications, yet its mechanisms are not well understood. Here, we present the neurophysiological effects of TMS using intracranial electrocorticography (iEEG) in neurosurgical patients. We first evaluated safety in a gel-based phantom. We then performed TMS-iEEG in 22 neurosurgical participants with no adverse events. We next evaluated intracranial responses to single pulses of TMS to the dorsolateral prefrontal cortex (dlPFC) (N = 10, 1414 electrodes). We demonstrate that TMS is capable of inducing evoked potentials both locally within the dlPFC and in downstream regions functionally connected to the dlPFC, including the anterior cingulate and insular cortex. These downstream effects were not observed when stimulating other distant brain regions. Intracranial dlPFC electrical stimulation had similar timing and downstream effects as TMS. These findings support the safety and promise of TMS-iEEG in humans to examine local and network-level effects of TMS with higher spatiotemporal resolution than currently available methods.

Sensing, Feeling, and Regulating: Investigating the Association of Focal Brain Damage with Voluntary Respiratory and Motor Control.

Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal, or limbic regions on the sensation and regulation of breathing patterns. Participants performed a respiratory regulation task across regular and irregular frequencies ranging from 6 to 60 breaths per minute (bpm), with a counterbalanced hand motor control task. Interoceptive and affective states induced by each condition were assessed via questionnaire and autonomic signals were indexed via skin conductance. Participants with focal lesions to the bilateral frontal lobe, right insula/basal ganglia, and left medial temporal lobe showed reduced performance than individually matched healthy comparisons during the breathing and motor tasks. They also reported significantly higher anxiety during the 60-bpm regular and irregular breathing trials, with anxiety correlating with difficulty in rapid breathing specifically within this group. This study demonstrates that damage to frontal, temporal, or limbic regions is associated with abnormal voluntary respiratory and motor regulation and tachypnea-related anxiety, highlighting the role of the forebrain in affective and motor responses during breathing. Highlights: Impaired human respiratory regulation is associated with cortical/subcortical brain lesionsFrontolimbic/temporal regions contribute to rhythmic breathing and hand motor controlFrontolimbic/temporal damage is associated with anxiety during tachypnea/irregular breathingThe human forebrain is vital for affective and interoceptive experiences during breathing.

Anterolateral temporal lobe localization of dysnomia after temporal lobe epilepsy surgery.

Objectives: To evaluate what factors influence naming ability after temporal lobectomy in patients with drug-resistant epilepsy. Methods: 85 participants with drug-resistant epilepsy who underwent temporal lobe (TL) resective surgery were retrospectively identified (49 left TL and 36 right TL). Naming ability was assessed before and >3 months post-surgery using the Boston Naming Test (BNT).Multivariate lesion-symptom mapping was performed to evaluate whether lesion location related to naming deficits. Multiple regression analyses were conducted to examine if other patient characteristics were significantly associated with pre-to post-surgery changes in naming ability. Results: Lesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy ( p = 0.015) while a decrement in performance was observed following left temporal lobectomy ( p = 0.002). Lesion-symptom mapping showed the decline in naming performance was associated with surgical resection of the anterior left middle temporal gyrus (Brodmann area 21, r =0.41, p = <.001). For left hemisphere surgery, later onset of epilepsy was associated with a greater reduction in post-surgical naming performance ( p = 0.01). Significance: There is a wide range of variability in outcomes for naming ability after temporal lobectomy, from significant improvements to decrements observed. If future studies support the association of left anterior middle temporal gyrus resection and impaired naming this may help in surgical planning and discussions of prognosis.

Salience network and cognitive impairment in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson's Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We tested the hypothesis that cognitive impairments in PD involve altered connectivity of the salience network (SN), a key cortical network that detects and integrates responses to salient stimuli. We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. We report two major results. First, in 82 PD patients we found significant relationships between lower intra-network connectivity of the frontoparietal network (FPN; comprising the dorsolateral prefrontal and posterior parietal cortices bilaterally) with lower MoCA scores. Second, we found significant relationships between lower inter-network connectivity between the SN and the basal ganglia network (BGN) and the default mode network (DMN) with lower MoCA scores. These data support our hypothesis about the SN and provide new insights into the brain networks contributing to cognitive impairments in PD.

Functional geometry of auditory cortical resting state networks derived from intracranial electrophysiology.

Understanding central auditory processing critically depends on defining underlying auditory cortical networks and their relationship to the rest of the brain. We addressed these questions using resting state functional connectivity derived from human intracranial electroencephalography. Mapping recording sites into a low-dimensional space where proximity represents functional similarity revealed a hierarchical organization. At a fine scale, a group of auditory cortical regions excluded several higher-order auditory areas and segregated maximally from the prefrontal cortex. On mesoscale, the proximity of limbic structures to the auditory cortex suggested a limbic stream that parallels the classically described ventral and dorsal auditory processing streams. Identities of global hubs in anterior temporal and cingulate cortex depended on frequency band, consistent with diverse roles in semantic and cognitive processing. On a macroscale, observed hemispheric asymmetries were not specific for speech and language networks. This approach can be applied to multivariate brain data with respect to development, behavior, and disorders.

Neuropsychiatric outcomes following strokes involving the cerebellum: a retrospective cohort study.

Introduction: Given the wide-ranging involvement of cerebellar activity in motor, cognitive, and affective functions, clinical outcomes resulting from cerebellar damage can be hard to predict. Cerebellar vascular accidents are rare, comprising less than 5% of strokes, yet this rare patient population could provide essential information to guide our understanding of cerebellar function. Methods: To gain insight into which domains are affected following cerebellar damage, we retrospectively examined neuropsychiatric performance following cerebellar vascular accidents in cases registered on a database of patients with focal brain injuries. Neuropsychiatric testing included assessment of cognitive (working memory, language processing, and perceptual reasoning), motor (eye movements and fine motor control), and affective (depression and anxiety) domains. Results: Results indicate that cerebellar vascular accidents are more common in men and starting in the 5th decade of life, in agreement with previous reports. Additionally, in our group of twenty-six patients, statistically significant performance alterations were not detected at the group level an average of 1.3 years following the vascular accident. Marginal decreases in performance were detected in the word and color sub-scales of the Stroop task, the Rey Auditory Verbal Learning Test, and the Lafayette Grooved Pegboard Test. Discussion: It is well established that the acute phase of cerebellar vascular accidents can be life-threatening, largely due to brainstem compression. In the chronic phase, our findings indicate that recovery of cognitive, emotional, and affective function is likely. However, a minority of individuals may suffer significant long-term performance impairments in motor coordination, verbal working memory, and/or linguistic processing.

Neuroanatomy of Cerebellar Mutism Syndrome: The Role of Lesion Location.

Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar deep nuclei and superior cerebellar peduncles, which we refer to as the cerebellar outflow pathway, is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated 'lesion-symptom map' of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). We found supporting evidence for both hypotheses. Compared with CMS- patients, CMS + patients (n = 10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d = .73, p = .05), and the CMS lesion-symptom map (Cohen's d = 1.1, p = .004). These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.

High-dimensional multivariate autoregressive model estimation of human electrophysiological data using fMRI priors.

Multivariate autoregressive (MVAR) model estimation enables assessment of causal interactions in brain networks. However, accurately estimating MVAR models for high-dimensional electrophysiological recordings is challenging due to the extensive data requirements. Hence, the applicability of MVAR models for study of brain behavior over hundreds of recording sites has been very limited. Prior work has focused on different strategies for selecting a subset of important MVAR coefficients in the model to reduce the data requirements of conventional least-squares estimation algorithms. Here we propose incorporating prior information, such as resting state functional connectivity derived from functional magnetic resonance imaging, into MVAR model estimation using a weighted group least absolute shrinkage and selection operator (LASSO) regularization strategy. The proposed approach is shown to reduce data requirements by a factor of two relative to the recently proposed group LASSO method of Endemann et al (Neuroimage 254:119057, 2022) while resulting in models that are both more parsimonious and more accurate. The effectiveness of the method is demonstrated using simulation studies of physiologically realistic MVAR models derived from intracranial electroencephalography (iEEG) data. The robustness of the approach to deviations between the conditions under which the prior information and iEEG data is obtained is illustrated using models from data collected in different sleep stages. This approach allows accurate effective connectivity analyses over short time scales, facilitating investigations of causal interactions in the brain underlying perception and cognition during rapid transitions in behavioral state.

Localization of a Medial Temporal Lobe-Precuneus Network for Time Orientation.

OBJECTIVE: Time orientation is a fundamental cognitive process in which one's personal sense of time is matched with a universal reference. Time orientation is commonly assessed through mental status examination, yet its neural correlates remain unclear. Large lesions have been associated with deficits in time orientation, but the regional anatomy implicated in time disorientation is not well established. The current study investigates the anatomy of time disorientation and its network correlates in patients with focal brain lesions. METHODS: Time orientation was assessed 3 months or more after lesion onset using the Benton Temporal Orientation Test (BTOT) in 550 patients with acquired, focal brain lesions, 39 of whom were impaired. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with time disorientation. Performance on a variety of neuropsychological tests was compared between the time oriented and time disoriented group. RESULTS: Lesion-symptom mapping showed that lesions of the precuneus, medial temporal lobes (MTL), and occipito-temporal cortex were associated with time disorientation (r = 0.264, p < 0.001). Lesion network mapping using normative connectome data demonstrated that these regional findings occurred along a network that includes white and gray matter connecting the precuneus and MTL. There was a strong behavioral and anatomical association of time disorientation with memory impairment, such that the 2 processes could not be fully disentangled. INTERPRETATION: We interpret these findings as novel evidence for a network involving the precuneus and the medial temporal lobe in supporting time orientation. ANN NEUROL 2023;94:421-433.

White matter disconnection of left multiple demand network is associated with post-lesion deficits in cognitive control.

Cognitive control modulates other cognitive functions to achieve internal goals and is important for adaptive behavior. Cognitive control is enabled by the neural computations distributed over cortical and subcortical areas. However, due to technical challenges in recording neural activity from the white matter, little is known about the anatomy of white matter tracts that coordinate the distributed neural computations that support cognitive control. Here, we leverage a large sample of human patients with focal brain lesions (n = 643) and investigate how lesion location and connectivity profiles account for variance in cognitive control performance. We find that lesions in white matter connecting left frontoparietal regions of the multiple demand network reliably predict deficits in cognitive control performance. These findings advance our understanding of the white matter correlates of cognitive control and provide an approach for incorporating network disconnection to predict deficits following lesions.

Investigating lesion location in relation to cerebellar mutism following pediatric tumor resection.

Background and Objectives: Approximately 25% of pediatric patients who undergo cerebellar tumor resection develop cerebellar mutism syndrome (CMS). Our group recently showed that damage to the cerebellar outflow pathway is associated with increased risk of CMS. Here, we tested whether these findings replicate in an independent cohort. Methods: We evaluated the relationship between lesion location and the development of CMS in an observational study of 56 pediatric patients who underwent cerebellar tumor resection. We hypothesized that individuals that developed CMS after surgery (CMS+), relative to those that did not (CMS-) would have lesions that preferentially intersected with: 1) the cerebellar outflow pathway, and 2) a previously generated 'lesion-symptom map' of CMS. Analyses were conducted in accordance with pre-registered hypotheses and analytic methods (https://osf.io/r8yjv/). Results: We found supporting evidence for both hypotheses. Compared with CMS- patients, CMS+ patients (n=10) had lesions with greater overlap with the cerebellar outflow pathway (Cohen's d=.73, p=.05), and the CMS lesion-symptom map (Cohen's d=1.1, p=.004). Discussion: These results strengthen the association of lesion location with risk of developing CMS and demonstrate generalizability across cohorts. These findings may help to inform the optimal surgical approach to pediatric cerebellar tumors.

Posterior Fossa Sub-Arachnoid Cysts Observed in Patients with Bipolar Disorder: a Retrospective Cohort Study.

Posterior fossa arachnoid cysts (PFACs) are rare congenital abnormalities observed in 0.3 to 1.7% of the population and are traditionally thought to be benign. While conducting a neuroimaging study investigating cerebellar structure in bipolar disorder, we observed a higher incidence of PFACs in bipolar patients (5 of 75; 6.6%) compared to the neuronormative control group (1 of 54; 1.8%). In this report, we detail the cases of the five patients with bipolar disorder who presented with PFACs. Additionally, we compare neuropsychiatric measures and cerebellar volumes of these patients to neuronormative controls and bipolar controls (those with bipolar disorder without neuroanatomical abnormalities). Our findings suggest that patients with bipolar disorder who also present with PFACs may have a milder symptom constellation relative to patients with bipolar disorder and no neuroanatomical abnormalities. Furthermore, our observations align with prior literature suggesting an association between PFACs and psychiatric symptoms that warrants further study. While acknowledging sample size limitations, our primary aim in the present work is to highlight a connection between PFACs and BD-associated symptoms and encourage further study of cerebellar abnormalities in psychiatry.

Large-scale lesion symptom mapping of depression identifies brain regions for risk and resilience.

Understanding neural circuits that support mood is a central goal of affective neuroscience, and improved understanding of the anatomy could inform more targeted interventions in mood disorders. Lesion studies provide a method of inferring the anatomical sites causally related to specific functions, including mood. Here, we performed a large-scale study evaluating the location of acquired, focal brain lesions in relation to symptoms of depression. Five hundred and twenty-six individuals participated in the study across two sites (356 male, average age 52.4 ± 14.5 years). Each subject had a focal brain lesion identified on structural imaging and an assessment of depression using the Beck Depression Inventory-II, both obtained in the chronic period post-lesion (>3 months). Multivariate lesion-symptom mapping was performed to identify lesion sites associated with higher or lower depression symptom burden, which we refer to as 'risk' versus 'resilience' regions. The brain networks and white matter tracts associated with peak regional findings were identified using functional and structural lesion network mapping, respectively. Lesion-symptom mapping identified brain regions significantly associated with both higher and lower depression severity (r = 0.11; P = 0.01). Peak 'risk' regions include the bilateral anterior insula, bilateral dorsolateral prefrontal cortex and left dorsomedial prefrontal cortex. Functional lesion network mapping demonstrated that these 'risk' regions localized to nodes of the salience network. Peak 'resilience' regions include the right orbitofrontal cortex, right medial prefrontal cortex and right inferolateral temporal cortex, nodes of the default mode network. Structural lesion network mapping implicated dorsal prefrontal white matter tracts as 'risk' tracts and ventral prefrontal white matter tracts as 'resilience' tracts, although the structural lesion network mapping findings did not survive correction for multiple comparisons. Taken together, these results demonstrate that lesions to specific nodes of the salience network and default mode network are associated with greater risk versus resiliency for depression symptoms in the setting of focal brain lesions.

Frontoparietal network activation is associated with motor recovery in ischemic stroke patients.

Strokes cause lesions that damage brain tissue, disrupt normal brain activity patterns and can lead to impairments in motor function. Although modulation of cortical activity is central to stimulation-based rehabilitative therapies, aberrant and adaptive patterns of brain activity after stroke have not yet been fully characterized. Here, we apply a brain dynamics analysis approach to study longitudinal brain activity patterns in individuals with ischemic pontine stroke. We first found 4 commonly occurring brain states largely characterized by high amplitude activations in the visual, frontoparietal, default mode, and motor networks. Stroke subjects spent less time in the frontoparietal state compared to controls. For individuals with dominant-hand CST damage, more time spent in the frontoparietal state from 1 week to 3-6 months post-stroke was associated with better motor recovery over the same time period, an association which was independent of baseline impairment. Furthermore, the amount of time spent in brain states was linked empirically to functional connectivity. This work suggests that when the dominant-hand CST is compromised in stroke, resting state configurations may include increased activation of the frontoparietal network, which may facilitate compensatory neural pathways that support recovery of motor function when traditional motor circuits of the dominant-hemisphere are compromised.