Jason Carmel

Jason Carmel
Columbia University | CU · Department of Neurology

MD PhD

About

88
Publications
8,923
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1,891
Citations
Citations since 2016
64 Research Items
1245 Citations
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Introduction
I am a child neurologist and motor system neuroscientist interested in central nervous system injury and repair. I direct a a translational research program which models repair strategies in animals with brain and spinal cord injury and then uses those results to design better treatments for patients. The main therapeutic approach of the laboratory is electrical stimulation of brain and spinal cord. Our primary tools are electrophysiology, behavior, and anatomy of neural circuits.

Publications

Publications (88)
Article
While epidural stimulation of the lumbar spinal cord has emerged as a powerful modality for recovery of movement, how it should be targeted to the cervical spinal cord to activate arm and hand muscles is not well-understood, particularly in humans. We sought to map muscle responses to posterior epidural cervical spinal cord stimulation in humans. W...
Article
Full-text available
Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects. In addition, the targeted circuits are inferred, rather than tested directly. In contrast, we sought to target the strong convergence between motor and sensor...
Article
Full-text available
After sensory information is encoded into neural signals at the periphery, it is processed through multiple brain regions before perception occurs (i.e., sensory processing). Recent work has begun to tease apart how neuromodulatory systems influence sensory processing. Vagus nerve stimulation (VNS) is well-known as an effective and safe method of a...
Preprint
Full-text available
While epidural stimulation of the lumbar spinal cord has emerged as a powerful modality for recovery of movement, how it should be targeted to the cervical spinal cord to activate arm and hand muscles is not well-understood, particularly in humans. We sought to map muscle responses to posterior epidural cervical spinal cord stimulation in humans. W...
Article
Full-text available
The central nervous system (CNS) integrates sensory and motor information to acquire skilled movements, known as sensory-motor integration (SMI). The reciprocal interaction of the sensory and motor systems is a prerequisite for learning and performing skilled movement. Injury to various nodes of the sensorimotor network causes impairment in movemen...
Article
Full-text available
Transcutaneous spinal cord stimulation (TSCS) has demonstrated potential to beneficially modulate spinal cord motor and autonomic circuitry. We are interested in pairing cervical TSCS with other forms of nervous system stimulation to enhance synaptic plasticity in circuits serving hand function. We use a novel configuration for cervical TSCS in whi...
Article
Polymer toughness is preserved at chronic timepoints in a new class of modulus-changing bioelectronics, which hold promise for commercial chronic implant components such as spinal cord stimulation leads. The underlying ester-free chemical network of the polymer substrate enables device rigidity during implantation, soft, compliant, conforming struc...
Article
Purpose: To conduct a pilot study to assess the feasibility and effectiveness of an intensive bimanual intervention on upper limb function in children who have undergone hemispherectomy. Methods: Thirteen children received 90 hours of intensive bimanual training (Hand-Arm Bimanual Intensive Therapy, HABIT). The Jebsen-Taylor Test of Hand Functio...
Article
AIM To determine which patients with cerebral palsy (CP) should undergo genetic testing, we compared the rate of likely causative genetic variants from whole-exome sequencing in individuals with and without environmental risk factors. METHOD Patients were part of a convenience and physician-referred cohort recruited from a single medical center, an...
Article
Full-text available
Background/Objectives: Intensive training of the more affected upper extremity (UE) has been shown to be effective for children with unilateral spastic cerebral palsy (USCP). Two types of UE training have been particularly successful: Constraint-Induced Movement Therapy (CIMT) and Bimanual training. Reorganization of the corticospinal tract (CST) e...
Preprint
Full-text available
Associative plasticity occurs when two stimuli converge on a common neural target. We sought to use the strong convergence between motor and sensory systems in the spinal cord to restore movement after spinal cord injury (SCI). We developed a paired motor cortex and dorsal spinal cord stimulation protocol to target this interaction called spinal co...
Article
Background. Variability in hand function among children with unilateral cerebral palsy (UCP) might reflect the type of brain injury and resulting anatomical sequelae. Objective. We used atlas-based analysis of structural images to determine whether children with periventricular (PV) versus middle cerebral artery (MCA) injuries might exhibit unique...
Article
Full-text available
We report a novel posteroanterior approach to cervical spinal stimulation. This approach easily activates arm and hand muscles on both sides simultaneously. A mix of afferent and efferent nerve roots is activated across stimulus intensities. a b s t r a c t Objective: We aim to non-invasively facilitate activation of spared neural circuits after ce...
Poster
Full-text available
Pairs of stimuli engage associative learning mechanisms to change the nervous system. We developed a paired stimulation approach that relies on proper timing of motor cortex and spinal cord stimulation to alter spinal sensorimotor circuits. When pairing is performed repeatedly, there is a lasting and robust increase in cortical and spinal excitabil...
Article
Background and Purpose— Lacunar strokes are subcortical infarcts with small size and high disability rates, largely due to injury of the corticospinal tract in the internal capsule (IC). Current rodent models of lacunar infarcts are created based on stereotactic coordinates. We tested the hypothesis that better understanding of the somatotopy of th...
Article
Date Presented 04/05/19 We examined whether an OT regimen that combines modified constraint-induced unimanual therapy with bimanual therapy can improve hand function in children with unilateral brain injury. We also examined the optimal order of each therapy type. We found that combined unimanual and bimanual intensive OT improves motor and functio...
Article
Rodent tests of function have advanced our understanding of movement, largely through the human training and testing and manual assessment. Tools such as reaching and grasping of a food pellet have been widely adopted because they are effective and simple to use. However, these tools are time-consuming, subjective, and often qualitative. Automation...
Article
Cervical spinal cord injury (SCI) impairs arm and hand function largely by interrupting descending tracts. Most SCI spare some axons at the lesion, including the corticospinal tract (CST), which is critical for voluntary movement. We targeted descending motor connections with paired electrical stimulation of motor cortex and cervical spinal cord in...
Article
Full-text available
Stimulating the nervous system and measuring muscle response offers a unique opportunity to interrogate motor system function. Often, this is performed by stimulating motor cortex and recording muscle activity with electromyography; the evoked response is called the motor evoked potential (MEP). To understand system dynamics, MEPs are typically rec...
Article
Full-text available
The contrast sensitivity function (CSF) is an informative measure of visual function, but current tools for assessing it are limited by the attentional, motor, and communicative abilities of the participant. Impairments in these abilities can prevent participants from engaging with tasks or following an experimenter's instructions. Here, we describ...
Article
Full-text available
After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each mot...
Article
Objective: We sought to develop a cervical spinal cord stimulator for the rat that is durable, stable, and does not perturb the underlying spinal cord. Approach: We created a softening spinal cord stimulation (SCS) array made from shape memory polymer (SMP)-based flexible electronics. We developed a new photolithographic process to pattern high...
Data
Transcranial Direct Current Stimulation (tDCS) Risk Mitigation.
Data
Transcranial Magnetic Stimulation (TMS) Risk Mitigation.
Article
Background: In many children with unilateral spastic cerebral palsy (USCP), the corticospinal tract to the affected hand atypically originates in the hemisphere ipsilateral to the affected hand. Such ipsilateral connectivity is on average a predictor of poor hand function. However, there is high variability in hand function in these children, whic...
Article
Objective: We tested the hypothesis that somatosensory system injury would more strongly affect movement than motor system injury in children with unilateral cerebral palsy (USCP). This hypothesis was based on how somatosensory and corticospinal circuits adapt to injury during development: while the motor system can maintain connections to the imp...
Article
Full-text available
Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Auto...
Chapter
In this chapter we describe how injury and development interact in neonates. Since infants born prematurely have unique patterns of brain injury, we have divided the chapter into injuries that are common to both term and pre-term and those that are specific to preterm infants. We first describe the abnormalities that can occur in term and pre-term...
Article
Full-text available
Key points: Pairing motor cortex stimulation and spinal cord epidural stimulation produced large augmentation in motor cortex evoked potentials if they were timed to converge in the spinal cord. The modulation of cortical evoked potentials by spinal cord stimulation was largest when the spinal electrodes were placed over the dorsal root entry zone...
Article
Date Presented 3/31/2017 This study examined the efficacy of modified constraint-induced movement therapy, with progressive introduction of bimanual therapy to improve hand functions in children with unilateral brain injury participating in an intensive occupational therapy program. Primary Author and Speaker: Ka Lai Kelly Au Contributing Authors:...
Article
Background Hand function is critical for independence, and neurological injury often impairs dexterity. To measure hand function in people or forelimb function in animals, sensors are employed to quantify manipulation. These sensors make assessment easier and more quantitative and allow automation of these tasks. While automated tasks improve objec...
Article
Full-text available
Introduction We report a case of hypertrophic olivary degeneration due to pontine hemorrhage. A 59-year-old male with untreated hypertension suffered a primary pontine hemorrhage, which caused horizontal eye-movement limitation. Progressive neurological deterioration with involuntary eye and palatal movements began months after hemorrhage. This was...
Data
Clinical assessments during the year following hemorrhage. (00:00-00:18) Horizontal Pursuit 3.0 Months. The range-of-movement is limited in both eyes when looking to the left or right 3 months after hemorrhage. Nystagmus is present in the left eye during leftward gaze and in the right eye during rightward gaze. (00:18-00:28) Horizontal Saccades 6.5...
Article
Background: 4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. Objective: To determine if 4-AP at clinically relevant levels alters the excitability of intact m...
Data
Figure S1. A representative participant with discrepant findings between diffusion tensor imaging (DTI) tractography (A, B) and TMS motor mapping (C1).
Data
Appendix S1. Transcranial magnetic stimulation (TMS) motor mapping details.
Chapter
Brain stimulation holds the promise of being able to target specific circuits for assessment or repair. In order to fulfill this promise, we need to know which neural circuits can restore lost function after injury and how electrical stimulation interacts with those circuits. To this end, we present three examples of how brain stimulation interacts...
Chapter
Neuromodulation encompasses a variety of methods by which brain function can be monitored or influenced using non-invasive brain stimulation (NIBS). As the use of NIBS becomes more common in pediatric populations, it is essential to consider and optimize the safety and ethical application of these techniques. In this chapter, we discuss the safety...
Article
Background: Reorganization of the corticospinal tract (CST) can occur in unilateral spastic cerebral palsy (USCP). The affected hand can be controlled via (1) typical contralateral projections from the lesioned hemisphere, (2) ipsilateral projections from the nonlesioned hemisphere, and (3) a combination of contralateral and ipsilateral projection...
Article
Full-text available
After injury, electrical stimulation of the nervous system can augment plasticity of spared or latent circuits through focal modulation. Pairing stimulation of two parts of a spared circuit can target modulation more specifically to the intended circuit. We discuss 3 kinds of paired stimulation in the context of the corticospinal system, because of...
Article
Background: Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not m...
Article
Full-text available
Aim: To determine whether diffusion tensor imaging (DTI) can be an independent assessment for identifying the corticospinal tract (CST) projecting from the more-affected motor cortex in children with unilateral spastic cerebral palsy (CP). Method: Twenty children with unilateral spastic CP participated in this study (16 males, four females; mean...
Article
Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury, but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training...
Article
Full-text available
Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses...
Article
Background: Neurological injuries or disease can impair the function of motor circuitry controlling forearm supination, and recovery is often limited. Preclinical animal models are essential tools for developing therapeutic interventions to improve motor function after neurological damage. Here we describe the supination assessment task, an automa...
Article
Background: Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective: We hypothesized that structured skill training...
Article
Full-text available
Poor regeneration of severed axons in the central nervous system (CNS) limits functional recovery. Regeneration failure involves interplay of inhibitory environmental elements and the growth state of the neuron. To find internal changes in gene expression that might overcome inhibitory environmental cues, we compared several paradigms that allow gr...
Article
Full-text available
The adult CNS does not spontaneously regenerate after injury, due in large part to myelin-associated inhibitors such as myelin-associated glycoprotein (MAG), Nogo-A and oligodendrocyte-myelin glycoprotein. All three inhibitors can interact with either the Nogo receptor complex or paired immunoglobulin-like receptor B. A conditioning lesion of the s...
Article
Background: Advanced age is a leading risk factor for stroke and is associated with worse recovery. The goal of post-stroke rehabilitative therapies is to enhance neuroplasticity to support the recovery of motor function. Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitative training drives robust plasticity and resu...
Article
Full-text available
Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing param...
Article
Full-text available
Objective: To determine feasibility of a home-based, intensive bimanual intervention with children with unilateral spastic cerebral palsy. Methods: Eleven children (aged 29-54 months) received 90 hours of home hand-arm bimanual intensive therapy (H-HABIT) provided by their trained caregivers. Parenting stress levels and compliance were monitored...