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Robert A. McGovern and Sameer A. Sheth

OBJECTIVE

Advances in understanding the neurobiological basis of psychiatric disorders will improve the ability to refine neuromodulatory procedures for treatment-refractory patients. One of the core dysfunctions in obsessive-compulsive disorder (OCD) is a deficit in cognitive control, especially involving the dorsal anterior cingulate cortex (dACC). The authors' aim was to derive a neurobiological understanding of the successful treatment of refractory OCD with psychiatric neurosurgical procedures targeting the dACC.

METHODS

First, the authors systematically conducted a review of the literature on the role of the dACC in OCD by using the search terms “obsessive compulsive disorder” and “anterior cingulate.” The neuroscience literature on cognitive control mechanisms in the dACC was then combined with the literature on psychiatric neurosurgical procedures targeting the dACC for the treatment of refractory OCD.

RESULTS

The authors reviewed 89 studies covering topics that included structural and functional neuroimaging and electrophysiology. The majority of resting-state functional neuroimaging studies demonstrated dACC hyperactivity in patients with OCD relative to that in controls, while task-based studies were more variable. Electrophysiological studies showed altered dACC-related biomarkers of cognitive control, such as error-related negativity in OCD patients. These studies were combined with the cognitive control neurophysiology literature, including the recently elaborated expected value of control theory of dACC function. The authors suggest that a central feature of OCD pathophysiology involves the generation of mis-specified cognitive control signals by the dACC, and they elaborate on this theory and provide suggestions for further study.

CONCLUSIONS

Although abnormalities in brain structure and function in OCD are distributed across a wide network, the dACC plays a central role. The authors propose a theory of cognitive control dysfunction in OCD that attempts to explain the therapeutic efficacy of dACC neuromodulation. This theoretical framework should help to guide further research into targeted treatments of OCD and other disorders of cognitive control.

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Saurabh Sinha, Robert A. McGovern and Sameer A. Sheth

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

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Jennifer F. Russo and Sameer A. Sheth

Chronic neuropathic pain is estimated to affect 3%-4.5% of the worldwide population. It is associated with significant loss of productive time, withdrawal from the workforce, development of mood disorders such as depression and anxiety, and disruption of family and social life. Current medical therapeutics often fail to adequately treat chronic neuropathic pain. Deep brain stimulation (DBS) targeting subcortical structures such as the periaqueductal gray, the ventral posterior lateral and medial thalamic nuclei, and the internal capsule has been investigated for the relief of refractory neuropathic pain over the past 3 decades. Recent work has identified the dorsal anterior cingulate cortex (dACC) as a new potential neuromodulation target given its central role in cognitive and affective processing. In this review, the authors briefly discuss the history of DBS for chronic neuropathic pain in the United States and present evidence supporting dACC DBS for this indication. They review existent literature on dACC DBS and summarize important findings from imaging and neurophysiological studies supporting a central role for the dACC in the processing of chronic neuropathic pain. The available neurophysiological and empirical clinical evidence suggests that dACC DBS is a viable therapeutic option for the treatment of chronic neuropathic pain and warrants further investigation.

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Charles B. Mikell, Saurabh Sinha and Sameer A. Sheth

The main objectives of this review were to provide an update on the progress made in understanding specific circuit abnormalities leading to psychotic symptoms in schizophrenia and to propose rational targets for therapeutic deep brain stimulation (DBS). Refractory schizophrenia remains a major unsolved clinical problem, with 10%–30% of patients not responding to standard treatment options. Progress made over the last decade was analyzed through reviewing structural and functional neuroimaging studies in humans, along with studies of animal models of schizophrenia. The authors reviewed theories implicating dysfunction in dopaminergic and glutamatergic signaling in the pathophysiology of the disorder, paying particular attention to neurosurgically relevant nodes in the circuit. In this context, the authors focused on an important pathological circuit involving the associative striatum, anterior hippocampus, and ventral striatum, and discuss the possibility of targeting these nodes for therapeutic neuromodulation with DBS. Finally, the authors examined ethical considerations in the treatment of these vulnerable patients. The functional anatomy of neural circuits relevant to schizophrenia remains of great interest to neurosurgeons and psychiatrists and lends itself to the development of specific targets for neuromodulation. Ongoing progress in the understanding of these structures will be critical to the development of potential neurosurgical treatments of schizophrenia.

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Sameer A. Sheth, Emad N. Eskandar and Mark A. Liker

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Sameer A. Sheth, Jennifer L. Tirino and Robert L. Martuza

Microsurgery via the suboccipital approach is a common treatment option for vestibular schwannomas (VS). The procedure is performed under general anesthesia with cranial nerve monitoring in the supine position. Following suboccipital craniectomy, durotomy, CSF release from the foramen magnum, and identification of cranial nerve position, the tumor is debulked internally. The internal auditory canal is drilled and dissection of the tumor progresses. Following resection, the IAC is waxed and a fat graft placed. A watertight pericranial graft is sewn in and a titanium mesh cranioplasty placed. The muscle and skin are closed in layers.

The video can be found here: http://youtu.be/ialtKy3cuPU.

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Patrick J. Karas, Charles B. Mikell, Eisha Christian, Mark A. Liker and Sameer A. Sheth

Deep brain stimulation (DBS), the practice of placing electrodes deep into the brain to stimulate subcortical structures with electrical current, has been increasing as a neurosurgical procedure over the past 15 years. Originally a treatment for essential tremor, DBS is now used and under investigation across a wide spectrum of neurological and psychiatric disorders. In addition to applying electrical stimulation for clinical symptomatic relief, the electrodes implanted can also be used to record local electrical activity in the brain, making DBS a useful research tool. Human single-neuron recordings and local field potentials are now often recorded intraoperatively as electrodes are implanted. Thus, the increasing scope of DBS clinical applications is being matched by an increase in investigational use, leading to a rapidly evolving understanding of cortical and subcortical neurocircuitry. In this review, the authors discuss recent innovations in the clinical use of DBS, both in approved indications as well as in indications under investigation. Deep brain stimulation as an investigational tool is also reviewed, paying special attention to evolving models of basal ganglia and cortical function in health and disease. Finally, the authors look to the future across several indications, highlighting gaps in knowledge and possible future directions of DBS treatment.

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Brett E. Youngerman, Andrew K. Chan, Charles B. Mikell, Guy M. McKhann and Sameer A. Sheth

OBJECTIVE

Deep brain stimulation (DBS) is an emerging treatment option for an expanding set of neurological and psychiatric diseases. Despite growing enthusiasm, the patterns and implications of this rapid adoption are largely unknown. National trends in DBS surgery performed for all indications between 2002 and 2011 are reported.

METHODS

Using a national database of hospital discharges, admissions for DBS for 14 indications were identified and categorized as either FDA approved, humanitarian device exempt (HDE), or emerging. Trends over time were examined, differences were analyzed by univariate analyses, and outcomes were analyzed by hierarchical regression analyses.

RESULTS

Between 2002 and 2011, there were an estimated 30,490 discharges following DBS for approved indications, 1647 for HDE indications, and 2014 for emerging indications. The volume for HDE and emerging indications grew at 36.1% annually in comparison with 7.0% for approved indications. DBS for emerging indications occurred at hospitals with more neurosurgeons and neurologists locally, but not necessarily at those with the highest DBS caseloads. Patients treated for HDE and emerging indications were younger with lower comorbidity scores. HDE and emerging indications were associated with greater rates of reported complications, longer lengths of stay, and greater total costs.

CONCLUSIONS

DBS for HDE and emerging indications underwent rapid growth in the last decade, and it is not exclusively the most experienced DBS practitioners leading the charge to treat the newest indications. Surgeons may be selecting younger and healthier patients for their early experiences. Differences in reported complication rates warrant further attention and additional costs should be anticipated as surgeons gain experience with new patient populations and targets.

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Nir Lipsman and Andres M. Lozano

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Nader Pouratian, Sameer Sheth, Susan Y. Bookheimer, Neil A. Martin and Arthur W. Toga

Perfusion-dependent brain mapping modalities, such as functional magnetic resonance imaging, positron emission tomography, and optical imaging of intrinsic signals, have become increasingly popular for neurosurgical guidance because they offer a relatively rapid and noninvasive means of mapping brain function. These modalities are unique because they rely on perfusion-related signals that are coupled with neuronal activity to map the brain instead of measuring electrophysiological responses. They consequently present unique challenges to the clinician in terms of understanding the significance and limitations of the maps they produce. In particular, one must be aware of limitations of the modalities with respect to spatial specificity, sensitivity, and reliability of these maps and how the presence of intracranial lesions may further complicate these issues.

The authors review the evolution, interpretation, and limitations of perfusion-based brain mapping techniques, with special attention to clinical implications of the brain maps.