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Nicholas D Schiff

Publications and source records attributed to Nicholas D Schiff.

13 recordsLinked to original sources
PubMed2006

Cognitive enhancement with central thalamic electrical stimulation.

Central thalamic electrical stimulation has been proposed as a method for remediation of acquired cognitive disability. Long-standing experimental and clinical observations indicate a key role for neurons within the central thalamus in maintaining the alert waking state and facilitating attended behaviors. Here, we show that continuous high frequency (100 Hz) electrical stimulation of the central thalamus generates widespread cortical activation of c-fos across all cortical layers and a selective pattern of regulation of zif268 within the supragranular, granular, and infragranular cortical laminae. Significant elevation of both immediate early genes also is seen in the dentate gyrus of the hippocampus. Use of the same stimulation parameters is shown to facilitate untrained goal-directed seeking behavior and object recognition memory in rodents. An overall increase of exploratory motor behaviors and grooming activity also is observed, consistent with a global increase in arousal. Taken together, these studies indicate that electrical stimulation of the central thalamus may enhance cognitive performance through neocortical and hippocampal neuronal activation and specific regulation of gene expression.

Animals↗
PubMed2006

Measurements and models of cerebral function in the severely injured brain.

We review the emerging applications of functional and structural neuroimaging techniques for the assessment of patients with disorders of consciousness. Measurements of brain function from patients in the vegetative state (VS) and minimally conscious state (MCS) are compared, and a conceptual organization is developed that suggests models of brain mechanisms associated with different functional levels of recovery. We emphasize developing strategies to place complex brain injuries on a more equal footing using global and regional quantification of resting or activated brain activity using functional imaging techniques alongside more detailed structural assessments of neuronal integrity and axonal connectivity now available. Preliminary studies from several investigative groups suggest that some MCS patients may harbor a functional reserve in the form of recruitable cerebral networks. These findings support developing systematic characterizations of the severely injured brain and suggest that some patients may benefit from improved diagnostic assessments.

Brain Injuries↗
PubMed2006

How should functional imaging of patients with disorders of consciousness contribute to their clinical rehabilitation needs?

PURPOSE OF REVIEW: We discuss the problems of evidence-based neurorehabilitation in disorders of consciousness, and recent functional neuroimaging data obtained in the vegetative state and minimally conscious state. RECENT FINDINGS: Published data are insufficient to make recommendations for or against any of the neurorehabilitative treatments in vegetative state and minimally conscious state patients. Electrophysiological and functional imaging studies have been shown to be useful in measuring residual brain function in noncommunicative brain-damaged patients. Despite the fact that such studies could in principle allow an objective quantification of the putative cerebral effect of rehabilitative treatment in the vegetative state and minimally conscious state, they have so far not been used in this context. SUMMARY: Without controlled studies and careful patient selection criteria it will not be possible to evaluate the potential of therapeutic interventions in disorders of consciousness. There also is a need to elucidate the neurophysiological effects of such treatments. Integration of multimodal neuroimaging techniques should eventually improve our ability to disentangle differences in outcome on the basis of underlying mechanisms and better guide our therapeutic options in the challenging patient populations encountered following severe acute brain damage.

Brain↗
PubMed2006

Possible axonal regrowth in late recovery from the minimally conscious state.

We used diffusion tensor imaging (DTI) to study 2 patients with traumatic brain injury. The first patient recovered reliable expressive language after 19 years in a minimally conscious state (MCS); the second had remained in MCS for 6 years. Comparison of white matter integrity in the patients and 20 normal subjects using histograms of apparent diffusion constants and diffusion anisotropy identified widespread altered diffusivity and decreased anisotropy in the damaged white matter. These findings remained unchanged over an 18-month interval between 2 studies in the first patient. In addition, in this patient, we identified large, bilateral regions of posterior white matter with significantly increased anisotropy that reduced over 18 months. In contrast, notable increases in anisotropy within the midline cerebellar white matter in the second study correlated with marked clinical improvements in motor functions. This finding was further correlated with an increase in resting metabolism measured by PET in this subregion. Aberrant white matter structures were evident in the second patient's DTI images but were not clinically correlated. We propose that axonal regrowth may underlie these findings and provide a biological mechanism for late recovery. Our results are discussed in the context of recent experimental studies that support this inference.

Adolescent↗
PubMed2005

Modeling the minimally conscious state: measurements of brain function and therapeutic possibilities.

The minimally conscious state (MCS) defines a functional level of recovery following severe brain injuries. Patients in MCS demonstrate unequivocal evidence of response to their environment yet fail to recover the ability to communicate. Drawing on recent functional brain-imaging studies, pathological data, and neurophysiological investigations, models of brain function in MCS are proposed. MCS models are compared and contrasted with models of the vegetative state (VS), a condition characterized by wakeful appearance and unconsciousness. VS reflects a total loss of cognitive function and failure to recover basic aspects of the normal physiologic brain state associated with wakefulness. MCS may represent a recovery of the minimal dynamic architecture required to organize behavioral sets and respond to sensory stimuli. Several pathophysiological mechanisms that might limit further recovery in MCS patients are considered. Implications for future research directions and possible therapeutic strategies are reviewed.

Brain↗
PubMed2004

Brain function in coma, vegetative state, and related disorders.

We review the nosological criteria and functional neuroanatomical basis for brain death, coma, vegetative state, minimally conscious state, and the locked-in state. Functional neuroimaging is providing new insights into cerebral activity in patients with severe brain damage. Measurements of cerebral metabolism and brain activations in response to sensory stimuli with PET, fMRI, and electrophysiological methods can provide information on the presence, degree, and location of any residual brain function. However, use of these techniques in people with severe brain damage is methodologically complex and needs careful quantitative analysis and interpretation. In addition, ethical frameworks to guide research in these patients must be further developed. At present, clinical examinations identify nosological distinctions needed for accurate diagnosis and prognosis. Neuroimaging techniques remain important tools for clinical research that will extend our understanding of the underlying mechanisms of these disorders.

Brain↗
PubMed2003

Analysis of perisaccadic field potentials in the occipitotemporal pathway during active vision.

Eye movement potentials (EMPs) associated with saccades appear in both subcortical and cortical structures of the primate visual system. In this study, EMPs are recorded across sites in the occipitotemporal (OT) pathway of monkeys performing a pattern-recognition task. We characterize pair recordings of saccade-triggered local field potentials (LFPs) in early extrastriate and inferotemporal regions of the ventral visual pathway using time-frequency spectrograms. Parameters of the spectrograms, including the centroids of identified regions of interest in the time-frequency plane, are extracted and analyzed. Comparisons among the distributions of the extracted parameters reveal that the occipital lobe EMPs are largely postsaccadic events centered at 100 ms after saccade onset that are typically not influenced in timing by the direction of the saccade or the appearance of a stimulus transient appearing either before or after the saccade. The occipital lobe EMPs also demonstrate a significant shift in frequency content during their transient time course that is influenced, in a few cases, by saccade direction. Temporal lobe EMPs, on the other hand, may be centered in either the presaccadic or postsaccadic intervals; the time of their appearance is significantly influenced by the direction of the saccade. Temporal lobe EMPs demonstrate less frequency modulation than those recorded in the occipital lobe. The prevalence of EMPs in the OT pathway suggests that many cortical regions important for pattern recognition can be modulated by saccades. The timing and frequency characteristics of these signals suggest that the nature of this perisaccadic modulation varies across the cortex.

Action Potentials↗
PubMed2002

Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain.

This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed a unique metabolic pattern. In three of the five patients, co-registered PET/MRI correlate islands of relatively preserved brain metabolism with isolated fragments of behaviour. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30-40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50-80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioural patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioural fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical- pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients do not appear to represent random survivals of a few neuronal islands; rather they reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains.

Adult↗
PubMed2002

Developing prosthetics to treat cognitive disabilities resulting from acquired brain injuries.

Persistent cognitive disabilities represent the most troublesome consequences of acquired brain injury. Although these problems are widely recognized, few neuroprosthetic efforts have focused on developing therapeutic strategies aimed at improving general cognitive functions such as sustained attention, intention, working memory or awareness. If possible, effective modulation of these neuropsychologic components might improve recovery of interactive behaviors. The emerging field of neuromodulation holds promise that technologies developed to treat other neurological disorders may be adapted to address the cognitive problems of patients suffering from acquired brain injuries. We here discuss initial efforts at neuromodulation in patients in the persistent vegetative state and aspects of recent studies of the underlying neurobiology of PVS and other severe brain injuries. Innovative strategies for open-loop and closed-loop neuromodulation of impaired cognitive function are outlined. We discuss the possibilities of linking neuromodulation techniques to underlying neuronal mechanisms underpinning cognitive rehabilitation maneuvers. Ethical considerations surrounding the development of these strategies are reviewed.

Arousal↗
PubMedDate not supplied

Neurophysiological correlates of persistent vegetative and minimally conscious states.

The evaluation of patients after severe brain injury is a complex process for the clinician, even with the information provided by a detailed neurological examination. The clinical examination often does not provide sufficient information to fully evaluate these patients due to several factors. Limited and inconsistent motor responses may obscure expression of greater cognitive capacities. More importantly, evaluation of the functional integrity of the cerebral cortical, thalamic and basal ganglia system is poorly indicated by the clinical examination in many patients. Neurophysiological studies provide a complementary set of objective data for evaluating brain-injured patients, as well as predicting and following the course of their recovery. This additional information can be of great importance since vegetative patients may be difficult to distinguish clinically from those in the minimally conscious state. This is important because the latter category of patients may have a significantly better prognosis for recovery in the initial phase of injury. Electrodiagnostic and imaging studies can help the practitioner to determine the degree of preserved and recovering neurological function. In this review we will assess the various neurophysiological studies currently at our disposal to evaluate and follow the clinical course of patients who have suffered severe brain injuries.

Cognition Disorders↗
PubMedDate not supplied

Multimodal neuroimaging approaches to disorders of consciousness.

Advances in neuroimaging techniques hold significant promise for improving understanding of disorders of consciousness arising from severe brain injuries. We review neuroimaging studies of the vegetative state (VS) and minimally conscious state (MCS), and findings in an unusual case of late emergence from MCS. Multimodal neuroimaging studies using positron emission tomography techniques, functional magnetic resonance imaging, and quantitative electroencephalography and magnetoencephalography quantify variations of residual cerebral activity across these patient populations. The results suggest models to distinguish the pathophysiologic basis of VS and MCS. Less clear are potential brain mechanisms underlying late recovery of communication in rare MCS patients. Diffusion tensor magnetic resonance imaging studies and recent experimental findings suggest that structural remodeling of the brain following severe injury may play a role in late functional recoveries. More generally, relatively long time courses of recovery following severe brain injury emphasize the need to develop markers for identifying patients who may harbor potential for further meaningful recovery. Introduction of neuroimaging into the clinical evaluation process will require developing frameworks for longitudinal assessments of cerebral function. Although limited in number, available studies already provide important insights into underlying brain mechanisms that may help guide development of such assessment strategies.

Arousal↗