Pratik Mukherjee

• MD, PhD
• Professor (Full) at University of California, San Francisco

Sensory processing disorders (SPDs) affect up to 16% of school-aged children, and contribute to cognitive and behavioral deficits impacting affected individuals and their families. While sensory processing differences are now widely recognized in children with autism, children with sensory-based dysfunction who do not meet autism criteria based on...

Diffusion tensor imaging (DTI) studies of human brain development have consistently shown widespread, but nonlinear increases in white matter anisotropy through childhood, adolescence, and into adulthood. However, despite its sensitivity to changes in tissue microstructure, DTI lacks the specificity to disentangle distinct microstructural features...

The structural connectome has emerged as a powerful tool to characterize the network architecture of the human brain and shows great potential for generating important new biomarkers for neurologic and psychiatric disorders. The edges of the cerebral graph traverse white matter to interconnect cortical and subcortical nodes, although the anatomic e...

Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment is now included in the DSM-5 diagnostic criteria. However, there are children with sensory processing differences who do not meet an ASD diagno...

Copy number variants (CNVs) of the chromosomal locus 16p11.2, consisting of either deletions or duplications, have been implicated in autism, schizophrenia, epilepsy, and other neuropsychiatric disorders. Since abnormal white matter microstructure can be seen in these more broadly defined clinical disorders, we used diffusion magnetic resonance ima...

Neuroimaging screening and surveillance is one of the first frontline diagnostic tools leveraged in the acute assessment (first 24 h postinjury) of patients suspected to have traumatic brain injury (TBI). While imaging, in particular computed tomography, is used almost universally in emergency departments worldwide to evaluate possible features of...

The hierarchical modular functional structure in the human brain has not been adequately depicted by conventional functional magnetic resonance imaging (fMRI) acquisition techniques and traditional functional connectivity reconstruction methods. Fortunately, rapid advancements in fMRI scanning techniques and deep learning methods open a novel front...

Structural similarity has emerged as a promising tool in mapping the network organization of an individual, living human brain. Here, we propose diffusion similarity networks (DSNs), which employ rotationally invariant spherical harmonic features derived from diffusion magnetic resonance imaging (dMRI), to map gray matter structural organization. C...

INTRODUCTION Systemic and neuroinflammatory responses mediate secondary injuries after traumatic brain injury (TBI), which lead to adverse outcomes. Identifying biomarkers of secondary injury may enable early recognition of patients at risk of clinical decline and delineate targets for therapeutic modulation. METHODS The 18-center TRACK-TBI Study...

INTRODUCTION Neuroworsening, commonly defined as a declining Glasgow Coma Scale motor score (GCS-M), indicates injury progression and is a component of traumatic brain injury (TBI) intensive care guidelines. The utility of assessing neuroworsening in emergency department (ED) settings requires examination. METHODS Adult subjects from the 18-center...

Blood-based glial fibrillary acidic protein (GFAP) level within 24 h of traumatic brain injury (TBI) has been inversely associated with post-traumatic stress disorder at 6 months in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. We sought to assess the relationship between day-of-injury GFAP and cumula...

Background Acute intoxication is common in patients evaluated for traumatic brain injury (TBI). However, the effect of elevated blood alcohol levels (BALs) on the diagnostic accuracy of FDA‐cleared biomarkers for evaluating traumatic intracranial injury on computed tomography (CT) scan, namely, glial fibrillary acidic protein (GFAP) and ubiquitin c...

Background Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Method...

Children with autism and other neurodevelopmental concerns (NDC) frequently exhibit an array of sensory processing dysfunction phenotypes, posing a significant challenge their adaptive development. Additionally, these children often encounter difficulties with self-regulation, including emotion dysregulation, anxiety, and symptoms associated with a...

Exogenous (outward-directed) and endogenous (inward-directed) neural systems are essential for cognition and behavior. However, how they are altered in neurodiverse (ND) children remains unanswered in part due to heterogeneity. Sensory over-responsivity (SOR) serves as a quintessential paradigm to investigate the interaction between exogenous and e...

Background Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. Methods The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014–2018; ClinicalTrials.gov #NCT02119182) enrolled su...

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal...

Despite advances in diffusion MRI, which have led to remarkable progress in mapping white matter of the living human brain, the understanding of cerebral cortical microstructure in vivo and its relationship to macrostructure, myeloarchitecture, cytoarchitecture, chemoarchitecture, metabolism, and function lag far behind. We present neuromaps of 21...

Objectives An estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prosp...

Background and purpose Traumatic brain injury (TBI) is a major source of health loss and disability worldwide. Accurate and timely diagnosis of TBI is critical for appropriate treatment and management of the condition. Neuroimaging plays a crucial role in the diagnosis and characterization of TBI. Computed tomography (CT) is the first-line diagnost...

We use generative AI to enable rapid diffusion MRI (dMRI) with high fidelity, reproducibility, and generalizability across clinical and research settings. We employ a Swin UNEt Transformers (SWIN) model, trained on Human Connectome Project (HCP) data (n = 1021) and conditioned on registered T1 scans, to perform generalized dMRI denoising. We also q...

Autism is traditionally diagnosed behaviorally but has a strong genetic basis. A genetics-first approach could transform understanding and treatment of autism. However, isolating the gene-brain-behavior relationship from confounding sources of variability is a challenge. We demonstrate a novel technique, 3D transport-based morphometry (TBM), to ext...

INTRODUCTION Traumatic brain injury (TBI) patients are at risk for subsequent TBIs. Research on the longitudinal impact of repetitive TBI is limited. METHODS The 18-center TRACK-TBI study enrolled subjects who presented to hospital and received head computed tomography (CT) within 24-hours of TBI between 2014-2018. Subjects were interviewed regard...

INTRODUCTION The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomisation After Significant Head Injury (CRASH) prognostic models for mortality and functional outcome in traumatic brain injury (TBI) were developed using historical data from 1984-2004. METHODS The prospec...

INTRODUCTION Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) is often regarded as a “mild” injury, with reduced need for additional workup. However, tSAH is also a predictor of unfavorable outcomes. Magnetic resonance imaging (MRI) and blood-based biomarkers may improve the diagn...

Background and objectives: Insomnia affects about one-third of patients with traumatic brain injury and is associated with worsened outcomes after injury. We hypothesized that higher levels of plasma neuroinflammation biomarkers at the time of TBI would be associated with worse 12-month insomnia trajectories. Methods: Participants were prospecti...

Objective: The International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization After Significant Head Injury (CRASH) prognostic models for mortality and outcome after traumatic brain injury (TBI) were developed using data from 1984 to 2004. This study examined IMPACT and CRASH...

Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) scan is often regarded as a "mild" injury, with reduced need for additional workup. However, tSAH is also a predictor of incomplete recovery and unfavorable outcome. This study aimed to evaluate the characteristics of CT-occult intr...

Large-scale diffusion MRI tractography remains a significant challenge. Users must orchestrate a complex sequence of instructions that requires many software packages with complex dependencies and high computational costs. We developed MaPPeRTrac, an edge-centric tractography pipeline that simplifies and accelerates this process in a wide range of...

Research aimed at understanding how baseline clinical and demographic characteristics influence outcomes over time is critically important to inform individualized therapeutic programs for children with neurodevelopmental differences. This study characterizes adaptive behavior trajectories in children receiving medical and behavioral therapy within...

Neuroimaging shows volumetric alterations of gray matter in attention-deficit hyperactivity disorder (ADHD); however, results are conflicting. This may be due to heterogeneous phenotypic sampling and limited sensitivity of volumetric analysis. Creating more homogenous cohorts and investigating gray matter microstructure may yield meaningful biomark...

Introduction: While some brain arteriovenous malformations (bAVM) demonstrate long-term stability, others demonstrate dynamic changes (new aneurysms or venous outflow stenosis) that confer higher rupture risk even after apparent cure. The objective of this study is to evaluate the feasibility and efficacy of 4D Flow MRI to quantitatively assess the...

Introduction: Structural changes following intracerebral hemorrhage (ICH) caused by ruptured brain vascular malformations (VMs) remain poorly understood. We conducted a longitudinal study to examine changes across ipsilesional and contralesional hemispheres after unilateral ICH, mainly in the temporoparietal area. Methods: Brain MRI was acquired in...

Blood levels of glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1) within 12h of suspected traumatic brain injury (TBI) have been approved by the Food and Drug administration to aid in determining the need for a brain computed tomography (CT) scan. The current study aimed to determine whether this context o...

Background Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging...

Background Traumatic brain injury (TBI) increases risk for cognitive decline and Alzheimer’s disease/related dementias (ADRD), and Veterans may be at increased risk of both TBI and cognitive decline due to combat/training related exposures and other risk factors. However, it is unknown whether older Veterans are more likely to experience a poor cog...

Objective Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training that targets difficulties with executive control functions. Prior research has found that GOALS training improves executive function, functional outcomes, and PTSD symptoms in Veterans with comorbid PTSD and TBI. The objective of this study is to asse...

Introduction Autism spectrum disorder (ASD) is associated with both functional and microstructural connectome disruptions. We deployed a novel methodology using functionally defined nodes to guide white matter (WM) tractography and identify ASD-related microstructural connectome changes across the lifespan. Methods We used diffusion tensor imaging...

Impaired attention is one of the most common, debilitating, and persistent consequence of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal...

Importance One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited. Objective To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years....

Children with autism and other neurodevelopmental concerns (NDC) present an array of sensory processing patterns and frequently encounter challenges with self-regulation, including emotion dysregulation, anxiety, and ADHD symptoms. Adopting a transdiagnostic perspective within the Research Domain Criteria (RDoC) framework, this study examined the r...

Background: Over the past 5 decades, advances in neuroimaging have yielded insights into the pathophysiologic mechanisms that cause disorders of consciousness (DoC) in patients with severe brain injuries. Structural, functional, metabolic, and perfusion imaging studies have revealed specific neuroanatomic regions, such as the brainstem tegmentum,...

Background and purpose: Very preterm infants (VPIs, <32 weeks gestational age at birth) are prone to long-term neurological deficits. While the effects of birth weight and postnatal growth on VPIs' neurological outcome are well established, the neurobiological mechanism behind these associations remains elusive. In this study, we utilized diffusio...

Study objectives: To describe the association between five previously identified trajectories of insomnia (each defined by a distinct pattern of insomnia severity over 12 months following TBI) and trajectories of mental health and neurocognitive outcomes during the 12 months after TBI. Methods: N=2,022 adults from the Federal Inter-agency Trauma...

Introduction Sensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tens...

Mild traumatic brain injury (mTBI) can have lasting consequences on cognitive functioning and well-being. Goal-Oriented Attentional Self-Regulation (GOALS) training has been shown to improve attention and executive functioning, as well as emotional functioning, in veterans with chronic TBI. An ongoing clinical trial (NCT02920788) is further evaluat...

Objective: We applied 7 Tesla phase sensitive imaging to evaluate the impact of brain iron levels on depression severity and cognitive function in individuals with major depressive disorder (MDD) treated with mindfulness-based cognitive therapy (MBCT). Methods: Seventeen unmedicated MDD participants underwent MRI, evaluation of depression severi...

Diffusion tensor imaging (DTI) studies have demonstrated white matter microstructural differences between the left and right hemispheres of the brain. However, the basis of these hemispheric asymmetries is not yet understood in terms of the biophysical properties of white matter microstructure, especially in children. There are reports of altered h...

The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrol...

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's Disease and Alzheimer's Disease Related Dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD...

Introduction: Neuroworsening may be a sign of progressive brain injury and is a factor for treatment of traumatic brain injury (TBI) in intensive care settings. The implications of neuroworsening for clinical management and long-term sequelae of TBI in the emergency department (ED) require characterization. Methods: Adult TBI subjects from the p...

Dr Hutchinson raises some important points regarding the imaging evaluation of acute mild TBI (mTBI). We agree that attrition is an important consideration in longitudinal studies and the effects of attrition can be assessed by the CONSORT diagram we provided in our study1. We also agree that most acute mTBI patients experience substantial recovery...

Many patients with mild traumatic brain injury (mTBI) are at risk for mental health problems such as posttraumatic stress disorder (PTSD). The objective of this study was to determine whether the polygenic risk for PTSD (or for related mental health disorders or traits including major depressive disorder [MDD] and neuroticism [NEU]) was associated...

We are delighted to present you the Proceedings of the 2022 CNS meeting. The CNS meeting encourages approaches that combine theoretical, computational, and experimental work in the neurosciences, and provides an opportunity for participants to share their views. The abstracts corresponding to speakers' talks and posters are what you find collected...

Older adults have the highest incidence of traumatic brain injury globally. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of age and time post-injury. Several reports have suggested lower accuracy for blood-based biomarkers in older adults, and there is a paucity of data beyond day-1 post-injury...

Magnetoencephalography, the extracranial detection of tiny magnetic fields emanating from intracranial electrical activity of neurons, and its source modeling relation, magnetic source imaging, represent a powerful functional neuroimaging technique, able to detect and localize both spontaneous and evoked activity of the brain in health and disease....

Sensory Over-Responsivity (SOR) is an increasingly recognized challenge among children with neurodevelopmental concerns (NDC). To investigate, we characterized the incidence of auditory and tactile over-responsivity (AOR, TOR) among 82 children with NDC. We found that 70% of caregivers reported concern for their child’s sensory reactions. Direct as...

There has been increasing evidence of White Matter (WM) microstructural disintegrity and connectome disruption in Autism Spectrum Disorder (ASD). We evaluated the effects of age on WM microstructure by examining Diffusion Tensor Imaging (DTI) metrics and connectome Edge Density (ED) in a large dataset of ASD and control patients from different age...

Background The prognostic value of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) as day-of-injury predictors of functional outcome after traumatic brain injury is not well understood. GFAP is a protein found in glial cells and UCH-L1 is found in neurons, and these biomarkers have been cleared to aid in decisi...

Background Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI...

Importance: Mild traumatic brain injury (mTBI) may impair the ability to work. Strategies to facilitate return to work are understudied. Objective: To assess employment and economic outcomes for employed, working-age adults with mTBI in the 12 months after injury and the association between return to work and employer assistance. Design, settin...

Several proteins have proven useful as blood-based biomarkers to assist in evaluation and management of traumatic brain injury (TBI). The objective of this study was to determine whether two day-of-injury blood-based biomarkers are predictive of posttraumatic stress disorder (PTSD). We used data from 1143 individuals with mild TBI (mTBI; defined as...

DTI literature on single-center studies contains conflicting results regarding acute effects of mTBI on WM microstructure and their prognostic significance. This larger-scale multicenter DTI study aimed to determine how acute mTBI affects WM microstructure over time and how early WM changes affect long-term outcome. From TRACK-TBI, a cohort study a...

The anatomic validity of structural connectomes remains a significant uncertainty in neuroimaging. Edge-centric tractography reconstructs streamlines in bundles between each pair of cortical or subcortical regions. Although edge bundles provides a stronger anatomic embedding than traditional connectomes, calculating them for each region-pair requir...

Background After severe traumatic brain injury (sTBI), physicians use long-term prognostication to guide acute clinical care yet struggle to predict outcomes in comatose patients. Purpose To develop and evaluate a prognostic model combining deep learning of head CT scans and clinical information to predict long-term outcomes after sTBI. Materials a...

INTRODUCTION Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery. METHODS Adult subjects from the prospective multicenter TRACK-TBI Pilot study with mTBI (GCS 13-15) who were employed at baseline, with completed three-and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extract...

Background Frailty is known to be associated with poorer outcomes in individuals admitted to hospital for medical conditions requiring intensive care. However, little evidence is available for the effect of frailty on patients’ outcomes after traumatic brain injury. Many frailty indices have been validated for clinical practice and show good perfor...

Following traumatic brain injury (TBI), cognitive impairments manifest through interactions between microscopic and macroscopic changes. On the microscale, a neurometabolic cascade alters neurotransmission, while on the macroscale diffuse axonal injury impacts the integrity of long-range connections. Large-scale brain network modeling allows us to...

Importance: Insomnia is common after traumatic brain injury (TBI) and contributes to morbidity and long-term sequelae. Objective: To identify unique trajectories of insomnia in the 12 months after TBI. Design, setting, and participants: In this prospective cohort study, latent class mixed models (LCMMs) were used to model insomnia trajectories...

Importance Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological...

This study aimed to elucidate the structure of the Rivermead Postconcussion Symptoms Questionnaire (RPQ) and evaluate its longitudinal and group variance. Factor structures were developed and compared in 1,011 patients with mild traumatic brain injury (mTBI; i.e., Glasgow Coma Scale score 13-15) from the Transforming Research and Clinical Knowledge...

Purpose fMRI is increasingly used for presurgical language mapping, but lack of standard methodology has made it difficult to combine/compare data across institutions or determine the relative efficacy of different approaches. Here, we describe a quantitative analytic framework for determining language laterality in clinical fMRI that addresses the...

White matter microstructures have been studied most commonly using diffusion tensor imaging (DTI) that models diffusivity in each voxel of diffusion MRI images as a tensor. Classic DTI parameters (e.g., mean diffusivity or MD, fractional anisotropy or FA) derived from the eigenvalues of tensors have been widely used to describe white matter propert...

Background Traumatic brainstem injury has yet to be incorporated into widely used imaging classification systems for traumatic brain injury (TBI), and questions remain regarding prognostic implications for this TBI subgroup. To address this, retrospective data on patients from the multicenter prospective Transforming Research and Clinical Knowledge...

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15)...