Sameer A Sheth

Baylor College of Medicine | BCM · Department of Neurosurgery

Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative ph...

Object: Obsessive-compulsive disorder (OCD) is a common and disabling psychiatric illness, and in a significant proportion of patients with OCD the disease is refractory to conventional pharmacotherapy and psychotherapy. For more than half a century, patients with severe, treatment-resistant OCD have been treated with stereotactic limbic system le...

We use rules to extend learned behavior beyond specific instances to general scenarios. The prefrontal cortex (PFC) is thought to play an important role in representing rules, as evidenced by subjects who have difficulty in following rules after PFC damage and by animal studies demonstrating rule sensitivity of individual PFC neurons. How rules are...

The ability to optimize behavioural performance when confronted with continuously evolving environmental demands is a key element of human cognition. The dorsal anterior cingulate cortex (dACC), which lies on the medial surface of the frontal lobes, is important in regulating cognitive control. Hypotheses about its function include guiding reward-b...

Linking values to actions and evaluating expectations relative to outcomes are both central to reinforcement learning and are thought to underlie financial decision-making. However, neurophysiology studies of these processes in humans remain limited. Here, we recorded the activity of single human nucleus accumbens neurons while subjects performed a...

OBJECTIVE Deep brain stimulation (DBS) is an effective neurosurgical option for patients with treatment-resistant obsessive-compulsive disorder (OCD). Despite being more costly than neuroablative procedures of comparable efficacy, DBS has gained popularity over the years for its reversibility and adjustability. Although the cost-effectiveness of DB...

Alteration of responses to salient stimuli occurs in a wide range of brain disorders and may be rooted in pathophysiological brain state dynamics. Specifically, tonic and phasic modes of activity in the reticular activating system (RAS) influence, and are influenced by, salient stimuli, respectively. The RAS influences the spectral characteristics...

It is becoming more broadly accepted that human-based models are needed to better understand the complexities of the human nervous system and its diseases. The recently developed human brain organotypic culture model is one highly promising model that requires the involvement of neurosurgeons and neurosurgical patients. Studies have investigated th...

Natural vision is an active sensing process that entails frequent eye movements to sample the environment. Nonetheless vision is often studied using passive viewing with eye position held constant. Using closed-loop eye-tracking, with saccade-contingent stimulation and simultaneous intracranial recordings in surgical epilepsy patients, we tested th...

In this paper, we provide an overview and analysis of the BRAIN Initiative data-sharing ecosystem. First, we compare and contrast the characteristics of the seven BRAIN Initiative data archives germane to data sharing and reuse, namely data submission and access procedures and aspects of interoperability. Second, we discuss challenges, benefits, an...

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of en...

BACKGROUND Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions) performed to relieve distress related to the obsessions. For patients with severe illness refractory to first-line pharmacotherapy and psychotherapy, neurosurgical treatments suc...

Single pulse electrical stimulation experiments produce pulse-evoked potentials used to infer brain connectivity. The choice of recording reference for intracranial electrodes remains non-standardized and can significantly impact data interpretation. When the reference electrode is affected by stimulation or evoked brain activity, it can contaminat...

This proof-of-concept study uses individualized functional magnetic resonance imaging neuromodulation (iNM) to explore the mechanisms that enhance BOLD signals in visuospatial perception (VP) networks that are crucial for navigation. Healthy participants (n = 8) performed a VP up- and down-direction discrimination task at full and subthreshold cohe...

To develop reliable, valid, and efficient measures of obsessive-compulsive disorder (OCD) severity, comorbid depression severity, and total electrical energy delivered (TEED) by deep brain stimulation (DBS), we trained and compared random forests regression models in a clinical trial of participants receiving DBS for refractory OCD. Six participant...

Background Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear. Methods In this study, we used sequential single-cell transcriptomics on 144,678 and spectral cytometry on over two million immune cells en...

Understanding the neural basis of major depressive disorder (MDD) is vital to guiding neuromodulatory treatments. The available evidence supports the hypothesis that MDD is fundamentally a disease of cortical disinhibition, where breakdowns of inhibitory neural systems lead to diminished emotion regulation and intrusive ruminations. Recent research...

BACKGROUND AND OBJECTIVES Directional deep brain stimulation (DBS) enables treatment optimization by current steering using segmented leads. Identification of the lead's rotational orientation is critical to guide programming decisions. Orientation is often assessed during or immediately after implant, but the degree of lead rotation in the followi...

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by...

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy (NCT05915741). We develop...

Despite abundant evidence of functional networks in the human brain, their neuronal underpinnings, and relationships to real-time behavior have been challenging to resolve. Analyzing brain-wide intracranial-EEG recordings with video monitoring, acquired in awake subjects during clinical epilepsy evaluation, we discovered the tendency of each brain...

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thi...

In daily life, we must recognize others' emotions so we can respond appropriately. This ability may rely, at least in part, on neural responses similar to those associated with our own emotions. We hypothesized that the insula, a cortical region near the junction of the temporal, parietal, and frontal lobes, may play a key role in this process. We...

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this...

Epilepsy affects over 70 million people globally. One-third of people with focal epilepsy have drug-resistant epilepsy. Identification and removal of the site of onset of seizures, termed the epileptogenic zone (EZ), is the most successful treatment to stop seizures in these people. Implanting electrodes into the brain with intracranial electroence...

To develop reliable, valid, and efficient measures of obsessive-compulsive disorder (OCD) severity, comorbid depressionseverity, and total electrical energy delivered (TEED) by deep brain stimulation (DBS), we trained and compared random forestsregression models in a clinical trial of participants receiving DBS for refractory OCD. Six participants...

Disrupted cortical and peripheral neural responses to salient stimuli occur in neural disease states, which may be rooted in pathophysiological neuromodulatory system dynamics. Although low-frequency oscillatory activity is the canonical measure of cortical neuromodulatory state, aperiodic 1/f slope encapsulates the balance between low-frequency an...

Miniaturized neuromodulation systems could improve the safety and reduce the invasiveness of bioelectronic neuromodulation. However, as implantable bioelectronic devices are made smaller, it becomes difficult to store enough power for long-term operation in batteries. Here, we present a battery-free epidural cortical stimulator that is only 9 milli...

BACKGROUND AND OBJECTIVES Recent advances in stereotactic and functional neurosurgery have brought forth the stereo-electroencephalography approach which allows deeper interrogation and characterization of the contributions of deep structures to neural and affective functioning. We argue that this approach can and should be brought to bear on the n...

INTRODUCTION Responsive neurostimulation (RNS) is an FDA-approved therapy for focal drug-resistant epilepsy (DRE). Emerging evidence supports a role for RNS in DRE with regional, multifocal, or non-resectable seizure onset zones. The centromedian nucleus of the thalamus (CMT) is a promising target, although descriptions of predictors of longer-term...

INTRODUCTION Despite the success of DBS for the treatment of refractory OCD, there are currently no robust neural signatures for obsessive-compulsive (OC) symptoms or initial mood and energy improvements associated with DBS. This gap may be due to limited opportunities available for conducting intracranial electrophysiological recordings during nat...

INTRODUCTION Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) improves symptoms in ∼66% of patients with treatment-resistant obsessive-compulsive disorder (OCD). However, a common adverse effect of VC/VS DBS is hypomania, marked by decreased need for sleep and increased risk-taking behaviors. Modern DBS devices have enab...

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9–11, 2023 in Gainesville, Florida with the theme of “Pushing the Forefront of Neuromodulation”. The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gord...

Neuromodulation through implantable pulse generators (IPGs) represents an important treatment approach for neurological disorders. While the field has observed the success of state-of-the-art interventions, such as deep brain stimulation (DBS) or responsive neurostimulation (RNS), implantable systems face various technical challenges, including the...

To develop reliable, valid, and efficient measures of severity of OCD and comorbid depression and electrical deep brain stimulation (DBS), we trained and compared random forests regression models in a clinical trial of participants receiving DBS for refractory OCD. Six participants were recorded during open-ended interviews at pre- and post-surgery...

There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity wa...

Prefrontal circuits in the human brain play an important role in cognitive and affective processing. Neuromodulation therapies delivered to certain key hubs within these circuits are being used with increasing frequency to treat a host of neuropsychiatric disorders. However, the detailed neurophysiological effects of stimulation to these hubs are l...

Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation’s behavioral and physiological effec...

A reliable physiological biomarker for Major Depressive Disorder (MDD) is necessary to improve treatment success rates by shoring up variability in outcome measures. In this study, we establish a passive biomarker that tracks with changes in mood on the order of minutes to hours. We record from intracranial electrodes implanted deep in the brain –...

Background Single-pulse electrical stimulation (SPES) is an established technique used to map functional effective connectivity networks in treatment-refractory epilepsy patients undergoing intracranial-electroencephalography monitoring. While the connectivity path between stimulation and recording sites has been explored through the integration of...

Background Connectomic modeling studies are expanding understanding of the brain networks that are modulated by deep brain stimulation (DBS) therapies. However, explicit integration of these modeling results into prospective neurosurgical planning is only beginning to evolve. One challenge of employing connectomic models in patient-specific surgica...

Background Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. Objective /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challen...

Minimally invasive neural interfaces can be used to diagnose, manage, and treat many disorders with substantially reduced risks of surgical complications. Endovascular neural interfaces implanted in the veins or arteries is one approach, but it requires prescriptions of anti-thrombotic medication and are likely not explantable after endothelializat...

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. It subserves self-referential thinking, recollection of the past, mind wandering, and creativity. Knowledge about the electrophysiology underlying DMN activity is scarce, due to the difficulty to simultane...

The neuromodulation effect of low-intensity focused ultrasound (LIFU) is highly target-specific. Unintended off-target neuronal excitation can be elicited when the beam focusing accuracy and resolution are limited, whereas the resulted side effect has not been evaluated quantitatively. There is also a lack of methods addressing the minimization of...

The relationship between clinically accessible epileptic biomarkers and neuronal activity underlying the seizure transition is complex, potentially leading to imprecise delineation of epileptogenic brain areas. In particular, the pattern of interneuronal firing at seizure onset remains under debate, with some studies demonstrating increased firing...

Direct electrical stimulation of the brain, when applied or optimized in a closed-loop manner, can lead to improvements in memory (Ezzyat et al., 2018) and mood (Scangos et al., 2021a). In these approaches, brain states control the timing of stimulation or the choice of parameters, which build off the notion that stimulation's neural and behavioral...

Background Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for pati...

Emotion is represented in limbic and prefrontal brain areas herein termed the Affective Salience Network (ASN). Within the ASN, there are substantial unknowns about how valence and emotional intensity are processed - specifically, which nodes are associated with affective bias (a phenomenon in which participants interpret emotions in a manner consi...

p>Reliable, valid, efficient measurement of symptom severity in internalizing disorders is critical to gauge treatment response. Self-report and clinical interview are subjective and difficult to standardize, impose patient burden, and lack granularity. We tested the hypothesis that comprehensive sampling of audio and visual modalities during open-...

Objective: Despite advances in the treatment of psychiatric diseases, currently available therapies do not provide sufficient and durable relief for as many as 30-40% of patients. Neuromodulation, including deep brain stimulation (DBS), has emerged as a potential therapy for persistent disabling disease, however it has not yet gained widespread ad...

Objective Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo‐EEG) may miss seizure onset elsewhere...