Biomedical subjects

S M Rao

Publications and source records attributed to S M Rao.

At least 37 records · Page 2Linked to original sources

PubMed1999

Development of a multiple sclerosis functional composite as a clinical trial outcome measure.

The primary clinical outcome measure for evaluating multiple sclerosis in clinical trials has been Kurtzke's expanded disability status scale (EDSS). New therapies appear to favourably impact the course of multiple sclerosis and render continued use of placebo control groups more difficult. Consequently, future trials are likely to compare active treatment groups which will most probably require increased sample sizes in order to detect therapeutic efficacy. Because more responsive outcome measures will be needed for active arm comparison studies, the National Multiple Sclerosis Society's Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis appointed a Task Force that was charged with developing improved clinical outcome measures. This Task Force acquired contemporary clinical trial and historical multiple sclerosis data for meta-analyses of primary and secondary outcome assessments to provide a basis for recommending a new outcome measure. A composite measure encompassing the major clinical dimensions of arm, leg and cognitive function was identified and termed the multiple sclerosis functional composite (MSFC). The MSFC consists of three objective quantitative tests of neurological function which are easy to administer. Change in this MSFC over the first year of observation predicted subsequent change in the EDSS, suggesting that the MSFC is more sensitive to change than the EDSS. This paper provides details concerning the development and testing of the MSFC.

Clinical Trials as Topic↗

PubMed1999

Conceptual processing during the conscious resting state. A functional MRI study.

Localized, task-induced decreases in cerebral blood flow are a frequent finding in functional brain imaging research but remain poorly understood. One account of these phenomena postulates processes ongoing during conscious, resting states that are interrupted or inhibited by task performance. Psychological evidence suggests that conscious humans are engaged almost continuously in adaptive processes involving semantic knowledge retrieval, representation in awareness, and directed manipulation of represented knowledge for organization, problem-solving, and planning. If interruption of such 'conceptual' processes accounts for task-induced deactivation, tasks that also engage these conceptual processes should not cause deactivation. Furthermore, comparisons between conceptual and nonconceptual tasks should show activation during conceptual tasks of the same brain areas that are 'deactivated' relative to rest. To test this model, functional magnetic resonance imaging data were acquired during a resting state, a perceptual task, and a semantic retrieval task. A network of left-hemisphere polymodal cortical regions showed higher signal values during the resting state than during the perceptual task but equal values during the resting and semantic conditions. This result is consistent with the proposal that perceptual tasks interrupt processes ongoing during rest that involve many of the same brain areas engaged during semantic retrieval. As further evidence for this model, the same network of brain areas was activated in two direct comparisons between semantic and perceptual processing tasks. This same 'conceptual processing' network was also identified in several previous studies that contrasted semantic and perceptual tasks or resting and active states. The model proposed here offers a unified account of these findings and may help to explain several unanticipated results from prior studies of semantic processing.

Adolescent↗

PubMed1999

Neural basis of endogenous and exogenous spatial orienting. A functional MRI study.

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80% of the time), exogenous (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.

Adult↗

PubMed1998

Anomalous origin of the right coronary artery from the main pulmonary artery: diagnosis and management.

Anomalous origin of the right coronary artery (ARCA) from the main pulmonary artery (MPA) is a rare congenital anomaly, with only 18 reported cases in the pediatric age group. More than half of these had associated cardiac anomalies that masked the presence of ARCA. Conversely, in many patients with ARCA as an isolated anomaly, the diagnosis has been missed during lifetime. The only patient with an isolated ARCA who was diagnosed in infancy presented with congestive heart failure. Asymptomatic infants with ARCA from the MPA have not been previously reported. Three additional cases, two infants and a child with ARCA from the MPA, are reported in this paper. The diagnostic dilemmas and the prognosis are discussed and management is recommended.

Child, Preschool↗

PubMed1998

Nicotine-induced limbic cortical activation in the human brain: a functional MRI study.

OBJECTIVE: Nicotine is a highly addictive substance, and cigarette smoking is a major cause of premature death among humans. Little is known about the neuropharmacology and sites of action of nicotine in the human brain. Such knowledge might help in the development of new behavioral and pharmacological therapies to aid in treating nicotine dependence and to improve smoking cessation success rates. METHOD: Functional magnetic resonance imaging, a real-time imaging technique, was used to determine the acute CNS effects of intravenous nicotine in 16 active cigarette smokers. An injection of saline followed by injections of three doses of nicotine (0.75, 1.50, and 2.25 mg/70 kg of weight) were each administered intravenously over 1-minute periods in an ascending, cumulative-dosing paradigm while whole brain gradient-echo, echo-planar images were acquired every 6 seconds during consecutive 20-minute trials. RESULTS: Nicotine induced a dose-dependent increase in several behavioral parameters, including feelings of "rush" and "high" and drug liking. Nicotine also induced a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes. Activation in these structures is consistent with nicotine's behavior-arousing and behavior-reinforcing properties in humans. CONCLUSIONS: The identified brain regions have been previously shown to participate in the reinforcing, mood-elevating, and cognitive properties of other abused drugs such as cocaine, amphetamine, and opiates, suggesting that nicotine acts similarly in the human brain to produce its reinforcing and dependence properties.

Adolescent↗

PubMed1998

The development, standardization, and initial validation of the Chicago Multiscale Depression Inventory.

Current self-report depression scales may overestimate depression symptoms in medical patients by including items measuring symptoms inherent to many medical conditions. They may therefore reflect a patient's medical rather than psychological state. We present the Chicago Multiscale Depression Inventory (CMDI), a factorially derived self-report depression scale that includes Mood, Evaluative, and Vegetative subscales. The CMDI and its subscales were designed to be used separately or combined; we posit that the nonvegetative CMDI subscales are the most accurate means of examining depression in medical patients. In this study we outline the development, standardization, and initial validation of the CMDI, a multistep process that required a total sample of 1,062 adults. We show the CMDI and each of its subscales to be internally consistent, reliable, and valid. Confirmatory factor analysis supports the CMDI factor structure. Finally, we report standardization scores for each of the CMDI scales, derived from an age-, race- and gender-stratified standardization sample of 420 adults.

Adult↗

PubMed1997

Distributed neural systems underlying the timing of movements.

Timing is essential to the execution of skilled movements, yet our knowledge of the neural systems underlying timekeeping operations is limited. Using whole-brain functional magnetic resonance imaging, subjects were imaged while tapping with their right index finger in synchrony with tones that were separated by constant intervals [Synchronization (S)], followed by tapping without the benefit of an auditory cue [Continuation (C)]. Two control conditions followed in which subjects listened to tones and then made pitch discriminations (D). Both the S and the C conditions produced equivalent activation within the left sensorimotor cortex, the right cerebellum (dorsal dentate nucleus), and the right superior temporal gyrus (STG). Only the C condition produced activation of a medial premotor system, including the caudal supplementary motor area (SMA), the left putamen, and the left ventrolateral thalamus. The C condition also activated a region within the right inferior frontal gyrus (IFG), which is functionally interconnected with auditory cortex. Both control conditions produced bilateral activation of the STG, and the D condition also activated the rostral SMA. These results suggest that the internal generation of precisely timed movements is dependent on three interrelated neural systems, one that is involved in explicit timing (putamen, ventrolateral thalamus, SMA), one that mediates auditory sensory memory (IFG, STG), and another that is involved in sensorimotor processing (dorsal dentate nucleus, sensorimotor cortex).

Adolescent↗

PubMed1997

Functional MRI evidence for subcortical participation in conceptual reasoning skills.

Lesions involving the dorsolateral prefrontal lobes may produce deficits on conceptual reasoning (CR) tasks in humans. Such deficits can also occur with subcortical lesions involving the basal ganglia, thalamus, or cerebellum, suggesting a common, yet widespread, neural network supporting this executive function. Here we report the results of a whole brain functional magnetic resonance imaging (fMRI) experiment in healthy volunteers while performing a CR task. Compared to a sensorimotor control condition, the CR task resulted in discrete subcortical activation sites primarily involving the right basal ganglia, right thalamus and left lateral cerebellum. Cortical activation was present in multiple systems, including the dorsolateral prefrontal and inferior frontal/insular areas; posterior parietal, superior extrastriate, and premotor areas; inferior extrastriate and middle temporal regions; and midline pre-supplementary motor and anterior cingulate regions. Our findings provide strong evidence that CR is mediated by interacting neural systems involving the cerebral cortex, basal ganglia, thalamus, and cerebellum.

Adult↗

PubMed1997

Human brain language areas identified by functional magnetic resonance imaging.

Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact human brain. Language was defined broadly to include both phonological and lexical-semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving perceptual analysis of nonlinguistic sounds. Functional maps of the entire brain were obtained from 30 right-handed subjects. These maps were averaged in standard stereotaxic space to produce a robust "average activation map" that proved reliable in a split-half analysis. As predicted from classical models of language organization based on lesion data, cortical activation associated with language processing was strongly lateralized to the left cerebral hemisphere and involved a network of regions in the frontal, temporal, and parietal lobes. Less consistent with classical models were (1) the existence of left hemisphere temporoparietal language areas outside the traditional "Wernicke area," namely, in the middle temporal, inferior temporal, fusiform, and angular gyri; (2) extensive left prefrontal language areas outside the classical "Broca area"; and (3) clear participation of these left frontal areas in a task emphasizing "receptive" language functions. Although partly in conflict with the classical model of language localization, these findings are generally compatible with reported lesion data and provide additional support for ongoing efforts to refine and extend the classical model.

Adolescent↗

PubMed1997

Executive functions in multiple sclerosis: an analysis of temporal ordering, semantic encoding, and planning abilities.

Previous studies have consistently demonstrated impairments in conceptual reasoning and set-shifting abilities in patients with multiple sclerosis (MS). Other executive functions have been less frequently examined. We compared 44 MS patients and 48 demographically matched controls on a temporal-ordering and semantic-encoding task and on a test of planning (Tower of Hanoi). Compared with controls, MS patients experienced deficient semantic encoding and planning but unimpaired temporal-order memory. For both tasks, post hoc analyses indicated that chronic-progressive MS patients contributed most to the group differences. A combination of poor planning and slowed information-processing speed was hypothesized to have contributed to MS patients' impaired Tower of Hanoi performance. Further research is needed to explore the possible relationship between semantic-encoding and planning deficits in MS and social and occupational disabilities.

Cues↗

PubMed1997

Relationship between confabulation and measures of memory and executive function.

Confabulation has traditionally been attributed to a combination of memory impairment and executive dysfunction, but recent models propose that confabulation can result from executive dysfunction alone. One hundred and ten patients with diverse neurologic and psychiatric diagnoses were subdivided into high-, low-, and non-confabulator groups based upon the ratio of confabulations to total responses produced during story recall. Consistent with the combined deficit model, high-confabulators performed significantly worse than the low- and non-confabulators on measures of memory and measures of executive function that assess sustained attention, mental tracking, and set-shifting ability. However, there were no differences between groups on measures of problem-solving, concept formation, and verbal fluency, suggesting a dissociation in executive functions that contribute to confabulation.

Attention↗

PubMed1996

White matter disease and dementia.

Dementia is a common occurrence in patients with disorders affecting cerebral hemispheric white matter. Relatively little is known, however, about the specific pattern of neurobehavioral changes associated with abnormal white matter function. This review examines in detail the neurobehavioral features of a common white matter disease, multiple sclerosis (MS). The neuropsychological characteristics of MS-related dementia are compared and contrasted with those observed in three other white matter disorders (acquired immune deficiency syndrome, Binswanger's disease, and closed head injury) to determine if "white matter dementia" should be recognized as a unique diagnostic entity distinct from other dementing conditions. Finally, possible mechanisms by which white matter disease affects behavior are proposed.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Function of the left planum temporale in auditory and linguistic processing.

Previous research suggests that the human left planum temporale (PT) plays an important role in language. To test this hypothesis, functional MRI (fMRI) data were collected from 12 normal right-handed subjects during passive and active listening to words and tone sequences. Several left hemisphere areas, including the superior temporal sulcus, middle temporal gyrus, angular gyrus and lateral frontal lobe showed stronger activation during the word conditions. This was not true of the PT, which responded equally to tones and words during passive listening and more strongly to tones during active listening. The PT is likely to be involved in early auditory processing, while specifically linguistic functions are mediated by multimodal association areas distributed elsewhere in the left hemisphere.

Adult↗

PubMed1996

Relationship between finger movement rate and functional magnetic resonance signal change in human primary motor cortex.

Functional magnetic resonance imaging (FMRI) is a noninvasive technique for mapping regional brain changes in response to sensory, motor, or cognitive activation tasks. Interpretation of these activation experiments may be confounded by more elementary task parameters, such as stimulus presentation or movement rates. We examined the effect of movement rate on the FMRI response recorded from the contralateral primary motor cortex. Four right-handed healthy subjects performed flexion-extension movements of digits 2-5 of the right hand at rates of 1, 2, 3, 4, or 5 Hz. Results of this study indicated a positive linear relationship between movement rate and FMRI signal change. Additionally, the number of voxels demonstrating functional activity increased significantly with faster movement rates. The magnitude of the signal change at each movement rate remained constant over the course of three 8-min scanning series. These findings are similar to those of previous rate studies of the visual and auditory system performed with positron emission tomography (PET) and FMRI.

Adult↗

PubMed1996

Determination of language dominance using functional MRI: a comparison with the Wada test.

We performed functional MRI (FMRI) in 22 consecutive epilepsy patients undergoing intracarotid amobarbital (Wada) testing and compared language lateralization measures obtained with the two procedures. FMRI used a single-word semantic decision task previously shown to activate lateralized language areas in normal adults. Correlation between the two tests was highly significant (r = 0.96; 95% CIs 0.90 to 0.98; p < 0.0001). These results validate the FMRI technique and suggest that "active" areas observed with this semantic processing task correspond to those underlying hemispheric dominance for language. This strong correlation observed supports the view that language lateralization is a continuous rather than a dichotomous variable. In addition to lateralization information, FMRI consistently demonstrated focal regions of activity in lateral frontal and temporo-parieto-occipital cortex. These functional maps may be helpful in defining the boundaries of surgical excisions.

Adolescent↗

PubMed1996

Conduction aphasia in multiple sclerosis: a case report with MRI findings.

Aphasia is an uncommon manifestation of MS, which is somewhat surprising because various disconnection syndromes, such as conduction aphasia, would be expected to occur with some regularity in this white matter disease. We present a case study of an MS patient with conduction aphasia associated with a large white matter lesion underlying the left supramarginal gyrus.

Adult↗

PubMed1995

Lateralized human brain language systems demonstrated by task subtraction functional magnetic resonance imaging.

OBJECTIVE: To develop a procedure for noninvasive measurement of language lateralization with functional magnetic resonance imaging (MRI). DESIGN: Functional neuroimaging using time-series echo-planar MRI. SETTING: University medical center research facility. SUBJECTS: Five healthy, right-handed, young adults. MAIN OUTCOME MEASURES: Number of MRI voxels in left and right hemispheres showing task-related signal increases during two contrasting auditory processing tasks. The nonlinguistic task involved processing of pure tones, while the linguistic task involved processing of single words based on semantic content. RESULTS: The pure-tone processing task activated temporal lobe auditory areas and dorsolateral frontal regions bilaterally. Using this task as a control condition, the semantic processing task resulted in lateralized activity in distributed regions of the left hemisphere. A significant effect of task on intrahemispheric activity pattern was demonstrated in every subject. Results were reproduced in preliminary studies of test-retest reliability. CONCLUSIONS: The results demonstrate the lateralized anatomy of semantic linguistic systems in contrast to non-linguistic auditory sensory processors and introduce a task subtraction technique adapted for functional MRI as a noninvasive measure of language lateralization.

Adult↗

PubMed1995

Mood disturbance versus other symptoms of depression in multiple sclerosis.

We administered the Multiscale Depression Inventory (MDI) and the Beck Depression Inventory (BDI) to 84 multiple sclerosis (MS) patients, 101 patients diagnosed with major depression and 87 nonmedical, nonpsychiatric controls. The MDI consists of three separate depression scales measuring mood, vegetative, and evaluative symptoms. We found that: (a) MS patients did not significantly differ from the controls in mood symptoms, (b) the depression prevalence rate in MS patients was significantly lower when measured by the mood scale (17.7%) than by the BDI (30.5%) or MDI total score (26.6%), and (c) MS patients showed significantly less mood disturbance than a non-MS comparison group matched on BDI measured depression severity. We suggest that the inclusion of nonmood symptoms in self-report depression scales may artificially raise both prevalence rates and severity ratings of MS related depression and that the most valid measure of depression in MS is mood disturbance.

Adult↗