Alexander Li Cohen

Boston Children's Hospital ·  Department of Neurology

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and d...

Freely available software, derived from the past 2 decades of neuroimaging research, is significantly more flexible for research purposes than presently available clinical tools. Here, we describe and demonstrate the utility of rapidly deployable analysis software to facilitate trainee-driven translational neuroimaging research. A recipe and video...

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis was first described in young women with ovarian teratoma. Typical presentations include subacute onset of neuropsychiatric symptoms, seizures, altered awareness, movement disorders, and autonomic dysfunction. Growing evidence indicates that anti-NMDAR encephalitis is one of the most commo...

The cerebral cortex is anatomically organized at many physical scales starting at the level of single neurons and extending up to functional systems. Current functional magnetic resonance imaging (fMRI) studies often focus at the level of areas, networks, and systems. Except in restricted domains, (e.g., topographically-organized sensory regions),...

The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MR...

Introduction: Predicting individual outcomes post-stroke with the highest possible accuracy is a crucial steppingstone in the realization of precision medicine. We here evaluated various types of lesion information in their capacity to predict stroke severity in a large cohort of patients with acute ischemic stroke. Methods: A total of 1,075 patien...

Background: Emotion regulation has been linked to specific brain networks based on functional neuroimaging, but networks causally involved in emotion regulation remain unknown. Methods: We studied patients with focal brain damage (n=167) who completed the "managing emotion" subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT...

Objective: Tuberous Sclerosis Complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms. Methods: We delineated tuber locations for 115 TSC participants with ASD (n = 31) a...

Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2...

A wide variety of model systems and experimental techniques can provide insight into the structure and function of the human brain in typical development and in neurodevelopmental disorders. Unfortunately, this work, whether based on manipulation of animal models or observational and correlational methods in humans, has a high attrition rate in tra...

Emotion regulation has been linked to specific brain networks based on functional neuroimaging. We found that damage to these networks was associated with emotion regulation impairment in patients following focal brain injury (n = 167). Next, we used this lesion dataset to derive a de novo brain network for emotion regulation, which was defined by...

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity...

Face-processing deficits, while not required for the diagnosis of autism spectrum disorder (ASD), have been associated with impaired social skills—a core feature of ASD; however, the strength and prevalence of this relationship remains unclear. Across 445 participants from the NIMH Data Archive, we examined the relationship between Benton Face Reco...

Introduction: Understanding the relations between lesions and outcomes is a particularly promising avenue to support tailored stroke care. We here employed a novel Bayesian framework integrating lesion location and functional lesion connectivity, i.e., lesion network mapping data, aiming to augment the prediction of stroke severity and the interpre...

Background and Objectives Disorders of consciousness, EEG background suppression and epileptic seizures are associated with poor outcome after cardiac arrest. Our objective was to identify the distribution of diffusion MRI-measured anoxic brain injury after cardiac arrest and to define the regional correlates of disorders of consciousness, EEG back...

Objective Blindsight is a disorder where brain injury causes loss of conscious but not unconscious visual perception. Prior studies have produced conflicting results regarding the neuroanatomical pathways involved in this unconscious perception. Methods We performed a systematic literature search to identify lesion locations causing visual field l...

Functional MRI (fMRI) is widely used to study the functional organization of normal and pathological brains. However, the fMRI signal may be contaminated by subject motion artifacts that are only partially mitigated by motion correction strategies. These artifacts lead to distance-dependent biases in the inferred signal correlations. To mitigate th...

Background and Purpose: Functional MRI neurofeedback (fMRI-nf) leverages the brain's ability to self-regulate its own activity. However, self-regulation processes engaged during fMRI-nf are incompletely understood. Here, we used matched feedback in an fMRI-nf experimental protocol to investigate whether brain processes recognize true neurofeedback...

Background Over 80% of the global population consider themselves religious with even more identifying as spiritual, but the neural substrates of spirituality and religiosity remain unresolved. Methods In two independent brain lesion datasets (N1=88; N2=105), we apply lesion network mapping to test whether lesion locations associated with spiritual...

Introduction Disorders of consciousness, EEG background suppression and epileptic seizures are associated with poor outcome after cardiac arrest. The underlying patterns of anoxic brain injury associated with each remain unknown. Our objective was to identify the distribution of anoxic brain injury after cardiac arrest, as measured with diffusion M...

Objective Approximately 50% of patients with Tuberous Sclerosis Complex develop infantile spasms, a sudden‐onset epilepsy syndrome associated with poor neurological outcomes. While an increased burden of tubers confers an elevated risk of infantile spasms, it remains unknown whether some tuber locations confer higher risk than others. Here, we test...

BACKGROUND Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets. METHODS Lesion locations associated with mania were identified using a systematic literature search (n = 41) and ma...

Inconsistent findings from migraine neuroimaging studies have limited attempts to localize migraine symptomatology. Novel brain network mapping techniques offer a new approach for linking neuroimaging findings to a common neuroanatomical substrate and localizing therapeutic targets. In this study, we attempted to determine whether neuroanatomically...

Brain lesions can provide unique insight into the neuroanatomical substrate of human consciousness. For example, brainstem lesions causing coma map to a specific region of the tegmentum. Whether specific lesion locations outside the brainstem are associated with loss of consciousness (LOC) remains unclear. Here, we investigate the topography of cor...

Damage to the right fusiform face area can disrupt the ability to recognize faces, a classic example of how damage to a specialized brain region can disrupt a specialized brain function. However, similar symptoms can arise from damage to other brain regions, and face recognition is now thought to depend on a distributed brain network. The extent of...

Objective: To evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS). Methods: The postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individual...

We characterized the blood oxygenation level dependent (BOLD) signal in humans and macaque monkeys by comparing the response in visual cortex to a single checkerboard or two checkerboards, spaced 1.5, 3.0, or 4.5 s apart. We found that the magnitude and shape of the BOLD response to a single checkerboard was similar in the two species. In addition,...

Background: The dynamin 1-like gene ( DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature. Results: A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifoc...

Study Objective To assess comorbidities in a community-based cohort of narcolepsy. Methods A 2000-2014 community-based narcolepsy cohort was identified in Olmsted County, Minnesota. Records were reviewed by a certified sleep specialist for accuracy of diagnosis and comorbidities were extracted and analyzed. Comorbidities in narcolepsy subjects, bo...

A young man with normal neurodevelopment presented with 3 years of medically refractory, progressive epilepsy and myoclonus. Initial examination included neuroimaging, electroencephalography, and biochemical analyses, all of which were unremarkable except for mildly enlarged ventricles. Over the following year, the patient experienced rapid cogniti...

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and d...

Abstract: Objective - The past two decades have seen tremendous advances in neuroimaging capabilities as well as maturation of freely available software for neurologic research. While not FDAapproved for clinical use, these have capabilities that are often more flexible than those available in day-to-day clinical practice. Using this software, howe...

We describe methods for parcellating an individual subject's cortical and subcortical brain structures using resting-state functional correlations (RSFCs). Inspired by approaches from social network analysis, we first describe the application of snowball sampling on RSFC data (RSFC-Snowballing) to identify the centers of cortical areas, subdivision...

Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks...

A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-...

Connectivity Map of the Brain The growing appreciation that clinically abnormal behaviors in children and adolescents may be influenced or perhaps even initiated by developmental miscues has stoked an interest in mapping normal human brain maturation. Several groups have documented changes in gray and white matter using structural and functional ma...

The parietal lobe has long been viewed as a collection of architectonic and functional subdivisions. Though much parietal research has focused on mechanisms of visuospatial attention and control-related processes, more recent functional neuroimaging studies of memory retrieval have reported greater activity in left lateral parietal cortex (LLPC) wh...

Studies in non-human primates and humans reveal that discrete regions (henceforth, "divisions") in the basal ganglia are intricately interconnected with regions in the cerebral cortex. However, divisions within basal ganglia nuclei (e.g., within the caudate) are difficult to identify using structural MRI. Resting-state functional connectivity MRI (...

In humans, the anterior insula (aI) has been the topic of considerable research and ascribed a vast number of functional properties by way of neuroimaging and lesion studies. Here, we argue that the aI, at least in part, plays a role in domain-general attentional control and highlight studies (Dosenbach et al. 2006; Dosenbach et al. 2007) supportin...

The parietal lobe has long been viewed as a collection of architectonic and functional subdivisions. Though much parietal research has focused on mechanisms of visuospatial attention and control-related processes, more recent functional neuroimaging studies of memory retrieval have reported greater activity in left lateral parietal cortex (LLPC) wh...

Diffuse optical tomography (DOT) is a portable functional neuroimaging technique that is able to simultaneously measure both oxy- and deoxyhemoglobin responses to brain activity. Herein, we demonstrate a technique for mapping functional connections in the brain by measuring the spatial distribution of temporal correlations in resting brain activity...

Diffuse optical tomography (DOT) is a portable functional neuroimaging technique that is able to simultaneously measure both oxy- and deoxyhemoglobin responses to brain activity. Herein, we demonstrate a technique for mapping functional connections in the brain by measuring the spatial distribution of temporal correlations in resting brain activity...

The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MR...

Scatterplot of modularity as a function of age. Each point in the graph represents the modularity calculated for each individual subject. A threshold of r≥0.1 was applied to each subject's matrices before calculations were performed and denotes connected versus non-connected region pairs (see Materials and Methods). (0.35 MB TIF)

An extended version of Figure 5, which includes a visualization of these connections represented on a semi-transparent brain. (4.69 MB TIF)

Modularity remains relatively high across age and does not differ between children and adults across differing thresholds. Blue dots represent modularity and red dots represent graph connectedness. A graph in which there is a path between all nodes represents 100% graph connectedness, whereas a fragmented network in which some nodes cannot reach th...

Reducing the boxcar size does not substantially alter community assignments over age. The same procedure as presented in Figure 4 with the boxcar reduced to (A) 40 subjects and (B) 20 subjects. (4.65 MB TIF)

Clustering coefficients and path lengths do not differ between children and adults across differing thresholds with respect to comparable lattice and random graphs. For children all parameters across thresholds were calculated from the first 60 subjects in age order (i.e., subjects 1–60, average age 8.48). For adults, all parameters across threshol...

Connection strength as a function of distance for all possible connections is similar between children and adults. The relationship of correlation as a function of distance is described by the inverse square law, r∼1/D2, as reported in [85] for all possible connections in children (blue) and adults (red). (0.71 MB TIF)

Over age, the graph architecture matures from a “local” organization to a “distributed” organization. This movie shows the dynamic development and interaction of positive correlations between the two task control networks, the default network, and cerebellar network using spring embedding. The figure highlights the segregation of local, anatomicall...

Variation of information (VOI) in observed and equivalent random networks subjected to perturbation alpha. VOI is a measure of how much information is not shared between two sets of community assignments and allows for the quantification of network robustness (see [95] and [96]). Values of 0 indicate identical community assignments, and values of 1...

Reducing the boxcar size to 40 subjects does not change qualitative patterns observed with the 60 subject boxcar. The same procedure as presented in Figure 3 and Video S1 is presented here with the boxcar reduced to 40 subjects. (9.62 MB MPG)

Mapping resting-state networks allows insight into the brain's functional architecture and physiology and has rapidly become important in contemporary neuroscience research. Diffuse optical tomography (DOT) is an emerging functional neuroimaging technique with the advantages, relative to functional magnetic resonance imaging (fMRI), of portability...

Tourette syndrome (TS) is a developmental disorder characterized by unwanted, repetitive behaviours that manifest as stereotyped movements and vocalizations called 'tics'. Operating under the hypothesis that the brain's control systems may be impaired in TS, we measured resting-state functional connectivity MRI (rs-fcMRI) between 39 previously defi...

In recent years, the brain's “default network,” a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a “default mode” of brain function. In early studies, investigators...

Complex systems ensure resilience through multiple controllers acting at rapid and slower timescales. The need for efficient information flow through complex systems encourages small-world network structures. On the basis of these principles, a group of regions associated with top-down control was examined. Functional magnetic resonance imaging sho...

In recent years, the brain's "default network," a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a "default mode" of brain function. In early studies, investigators...

Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to s...

Control regions in the brain are thought to provide signals that configure the brain's moment-to-moment information processing. Previously, we identified regions that carried signals related to task-control initiation, maintenance, and adjustment. Here we characterize the interactions of these regions by applying graph theory to resting state funct...

Resting state functional connectivity MRI (fcMRI) has become a particularly useful tool for studying regional relationships in typical and atypical populations. Because many investigators have already obtained large data sets of task-related fMRI, the ability to use this existing task data for resting state fcMRI is of considerable interest. Two cl...

alpha-Dystrobrevin (DB), a cytoplasmic component of the dystrophin-glycoprotein complex, is found throughout the sarcolemma of muscle cells. Mice lacking alphaDB exhibit muscular dystrophy, defects in maturation of neuromuscular junctions (NMJs) and, as shown here, abnormal myotendinous junctions (MTJs). In normal muscle, alternative splicing produ...