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Biomedical subjects

Stephen M Rao

Publications and source records attributed to Stephen M Rao.

At least 19 recordsLinked to original sources
PubMed2007

Inhibitory control test is a simple method to diagnose minimal hepatic encephalopathy and predict development of overt hepatic encephalopathy.

OBJECTIVES: To compare inhibitory control test (ICT), a simple/rapid test of attention, to a standard psychometric battery (SPT) to diagnose minimal hepatic encephalopathy (MHE) and predict development of overt hepatic encephalopathy (OHE) in cirrhotic patients. METHODS: Fifty nonalcoholic cirrhotics and 50 age/educational-status-matched controls were given ICT and SPT in the same sitting. Performance impaired beyond two standard deviations of controls was considered MHE in cirrhotics. ICT results (lure/target response and lures/person) were compared between controls and cirrhotics and within cirrhotics with/without MHE. Receiver-operating characteristic analysis was used to study ICT for MHE diagnosis. Twenty subjects were administered SPT and ICT twice to assess test-retest reliability. All cirrhotics were followed routinely for the development of OHE. RESULTS: Cirrhotics performed worse than controls on SPT and ICT. Using SPT, 39 cirrhotics had MHE. ICT was administered faster than SPT (15 vs 37 min). Cirrhotics with MHE had significantly higher lure (28%vs 3%) and lower target response (91%vs 96%) compared with those without MHE. Lure/person >5 had 90% sensitivity/specificity for MHE diagnosis. AUC for receiver-operating characteristic for lures alone was 95.8%. Lure and target responses were highly correlated (r= 0.9) between sessions showing high test-retest reliability. Five (10%) patients developed OHE on f/u of 26 +/- 10 months; all five had been diagnosed with MHE using ICT and SPT. None of the five patients with discordant results on SPT and ICT developed OHE. CONCLUSIONS: ICT has good sensitivity/specificity for MHE diagnosis, is reliable and is equivalent to SPT for predicting OHE development.

Attention↗
PubMed2006

Neural and electromyographic correlates of wrist posture control.

In identical experiments in and out of a MR scanner, we recorded functional magnetic resonance imaging and electromyographic correlates of wrist stabilization against constant and time-varying mechanical perturbations. Positioning errors were greatest while stabilizing random torques. Wrist muscle activity lagged changes in joint angular velocity at latencies suggesting trans-cortical reflex action. Drift in stabilized hand positions gave rise to frequent, accurately directed, corrective movements, suggesting that the brain maintains separate representations of desired wrist angle for feedback control of posture and the generation of discrete corrections. Two patterns of neural activity were evident in the blood-oxygenation-level-dependent (BOLD) time series obtained during stabilization. A cerebello-thalamo-cortical network showed significant activity whenever position errors were present. Here, changes in activation correlated with moment-by-moment changes in position errors (not force), implicating this network in the feedback control of hand position. A second network, showing elevated activity during stabilization whether errors were present or not, included prefrontal cortex, rostral dorsal premotor and supplementary motor area cortices, and inferior aspects of parietal cortex. BOLD activation in some of these regions correlated with positioning errors integrated over a longer time-frame consistent with optimization of feedback performance via adjustment of the behavioral goal (feedback setpoint) and the planning and execution of internally generated motor actions. The finding that nonoverlapping networks demonstrate differential sensitivity to kinematic performance errors over different time scales supports the hypothesis that in stabilizing the hand, the brain recruits distinct neural systems for feedback control of limb position and for evaluation/adjustment of controller parameters in response to persistent errors.

Adult↗
PubMed2006

Functional magnetic resonance imaging response to increased verbal working memory demands among patients with multiple sclerosis.

Multiple sclerosis (MS) patients frequently experience impaired verbal working memory (VWM). Functional magnetic resonance imaging (fMRI) may help identify neural mechanisms underlying these deficits. Neuroimaging studies of healthy adults have characterized responses associated with increased VWM demands during the n-Back task, suggesting that this experimental paradigm could help identify neural correlates of VWM deficits among MS patients. Fifteen MS patients and 15 matched control participants completed the n-Back during whole-brain fMRI. Mean signal during adjacent 0-Back blocks was subtracted, on a voxel-wise basis, from mean signal observed during n-Back blocks. Resulting difference scores for 1-, 2-, and 3-Back were compared across groups and difficulty levels. Signal intensity was positively related to difficulty level in anterior regions, including premotor, supplementary motor, and dorsolateral prefrontal cortices. MS patients exhibited significantly greater intensity in these areas compared to controls during the 1-Back, while portions of the left superior frontal gyrus, cingulate, and parahippocampal gyri were relatively less intense at more difficult levels. MS group responses were slower during the 1-Back and tended to be slower during the 3-Back; however, accuracy did not differ at any level. Lesion load was positively related to only 1-Back activity and unrelated to any performance measure. Results suggest that compensatory activity occurs among MS patients matched on performance accuracy. Furthermore, compensatory activity occurs predominantly in regions associated with VWM, and this may decline relative to controls as task demands increase. These findings may help to explain why MS patient performance decreases as a function of effort on neuropsychological tests.

Brain↗
PubMed2006

An FMRI analysis of the human hippocampus: inference, context, and task awareness.

The hippocampus is critical for encoding and retrieving semantic and episodic memories. Animal studies indicate that the hippocampus is also required for relational learning tasks. A prototypical relational learning task, and the one investigated in this experiment, using event-related functional magnetic resonance imaging, is the transitive inference (TI) task. In the TI task, participants were to choose between A and B (A?B) and learned by trial and error to choose A (A > B). There were four such premise pairs during a training (A > B, B > C, C > D, D > E). These can be acquired distinctly or can be organized into a superordinate hierarchy (A > B > C > D > E), which would efficiently represent all the learned relations and allow inferences (e.g., B > D). At test there was no reinforcement: In addition to premise pairs, untrained pairings were introduced (e.g., A?E, B?D). Correctly inferring that B > D is taken as evidence for the formation of a superordinate hierarchy; several alternatives to the superordinate hierarchy hypothesis are considered. Awareness of the formation of this hierarchy was measured by a postscan questionnaire. Four main findings are reported: (1) Inferential performance and task awareness dissociated behaviorally and at the level of hemodynamic response; (2) As expected, performance on the inferred relation, B > D, corresponded to the ability to simultaneously acquire B > C and C > D premise pairs during training; (3) Interestingly, acquiring these "inner pairs" corresponded to greater hippocampal activation than the "outer pairs" (A > B, D > E) for all participants. However, a distinct pattern of hippocampal activity for these inner pairs differentiated those able to perform the inferential discrimination, B > D, at test. Because these inner premise pairs require contextual discrimination (e.g., C is incorrect in the context of B but correct in the context of D), we argue that the TI task is hippocampal-dependent because the premise pair acquisition necessary for inference is hippocampal-dependent; (4) We found B > D related hippocampal activity at test that is anatomically consistent with preconsolidation recall effects shown in other studies.

Adolescent↗
PubMed2005

Age-related functional recruitment for famous name recognition: an event-related fMRI study.

Recent neuroimaging research shows that older adults exhibit recruitment, or increased activation on various cognitive tasks. The current study evaluated whether a similar pattern also occurs in semantic memory by evaluating age-related differences during recognition of Recent (since the 1990s) and Enduring (1950s to present) famous names. Fifteen healthy older and 15 healthy younger adults performed the name recognition task with a high and comparable degree of accuracy, although older adults had slower reaction time in response to Recent famous names. Event-related functional MRI showed extensive networks of activation in the two groups including posterior cingulate, right hippocampus, temporal lobe and left prefrontal regions. The Recent condition produced more extensive activation than the Enduring condition. Older adults had more extensive and greater magnitude of activation in 15 of 20 regions, particularly for the Recent condition (15 of 15; 7 of 15 also differed for Enduring); young adults did not show greater activation magnitude in any region. There were no group differences for non-famous names, indicating that age differences are task-specific. The results support and extend the existing literature to semantic memory tasks, indicating that older adult brains use functional recruitment to support task performance, even when task performance accuracy is high.

Age Factors↗
PubMed2005

Distinct neural systems underlie learning visuomotor and spatial representations of motor skills.

Motor skill learning depends upon acquiring knowledge about multiple features of sequential behaviors, including their visuomotor and spatial properties. To investigate the neural systems that distinguish these representations, we carried out functional magnetic resonance imaging (fMRI) as healthy adults learned to type sequences on a novel keyboard. On the initial training day, learning-related changes in brain activation were found in distributed cortical regions, only a subset of which correlated with improvements in movement time (MT), suggesting their preeminence in controlling movements online. Subjects received extended training on the sequences during the ensuing week, after which they returned to the scanner for another imaging session. Relative to performance at the end of the first training day, continued plasticity was most striking in the inferior parietal cortex and new areas of plasticity were uncovered in the caudate and cerebellum. Plasticity in these regions correlated with reaction time (RT), suggesting their role in planning sequences before movement onset. Two transfer conditions probed for "what" subjects learned. The probe for visuomotor learning produced increased activation in visual analysis (left inferior visual cortex) and advance planning (left caudate) systems. The probe for spatial learning produced increased activation in visuomotor-transformation (left dorsal visual pathway) and retrieval (left precuneus) systems. Increased activity in all of these regions correlated with increased RT, but not MT, indicating that both transfer conditions interfered with the neural representation of plans for the sequences, but not processes that controlled their implementation. These findings demonstrated that neuroanatomically dissociable systems support the acquisition of visuomotor and spatial representations of actions.

Adolescent↗
PubMed2005

Medial temporal lobe activity for recognition of recent and remote famous names: an event-related fMRI study.

Previous neuroimaging studies examining recognition of famous faces have identified activation of an extensive bilateral neural network [Gorno Tempini, M. L., Price, C. J., Josephs, O., Vandenberghe, R., Cappa, S. F., Kapur, N. et al. (1998). The neural systems sustaining face and proper-name processing. Brain, 121, 2103-2118], including the medial temporal lobe (MTL) and specifically the hippocampal complex [Haist, F., Bowden, G. J., & Mao, H. (2001). Consolidation of human memory over decades revealed by functional magnetic resonance imaging. Nature Neuroscience, 4, 1139-1145; Leveroni, C. L., Seidenberg, M., Mayer, A. R., Mead, L. A., Binder, J. R., & Rao, S. M. (2000). Neural systems underlying the recognition of familiar and newly learned faces. Journal of Neuroscience, 20, 878-886]. One model of hippocampal functioning in autobiographical, episodic memory retrieval argues that the hippocampal complex remains active in retrieval tasks regardless of time or age of memory (multiple trace theory, MTT), whereas another proposal posits that the hippocampal complex plays a time-limited role in retrieval of autobiographical memories. The current event-related fMRI study focused on the medial temporal lobe and its response to recognition judgments of famous names from two distinct time epochs (1990s and 1950s) in 15 right-handed healthy older adults (mean age=70 years). A pilot study with an independent sample of young and older subjects ensured that the stimuli were representative of a recent and remote time period. Increased MR signal activity was observed on a bilateral basis for both the hippocampus and parahippocampal gyrus (PHG) during recognition of familiar names from both the recent and remote time periods when compared to non-famous names. However, the impulse response functions in the right hippocampus and right PHG demonstrated a differential response to stimuli from different time epochs, with the 1990s names showing the greatest MR signal intensity change, followed by the 1950s names, followed by foils. The finding that recognition of famous names produced significant bilateral MTL activation regardless of time epoch relative to foils provides support for the MTT model. However, the finding of a temporal gradient in the right MTL also provides support for the HC model, given the greater MTL response associated with recently famous names relative to remotely famous names.

Adult↗
PubMed2004

Comparability of functional MRI response in young and old during inhibition.

When using fMRI to study age-related cognitive changes, it is important to establish the integrity of the hemodynamic response because, potentially, it can be affected by age and disease. However, there have been few attempts to document such integrity and no attempts using higher cognitive rather than perceptual or motor tasks. We used fMRI with 28 healthy young and older adults on an inhibitory control task. Although older and young adults differed in task performance and activation patterns, they had comparable hemodynamic responses. We conclude that activation during cognitive inhibition, which was predominantly increased in elders, was not due to vascular confounds or specific changes in hemodynamic coupling.

Adult↗
PubMed2004

Neural representation of interval encoding and decision making.

Our perception of time depends on multiple psychological processes that allow us to anticipate events. In this study, we used event-related functional magnetic resonance imaging (fMRI) to differentiate neural systems involved in formulating representations of time from processes associated with making decisions about their duration. A time perception task consisting of two randomly presented standard intervals was used to ensure that intervals were encoded on each trial and to enhance memory requirements. During the encoding phase of a trial, activation was observed in the right caudate nucleus, right inferior parietal cortex and left cerebellum. Activation in these regions correlated with timing sensitivity (coefficient of variation). In contrast, encoding-related activity in the right parahippocampus and hippocampus correlated with the bisection point and right precuneus activation was associated with a measure of memory distortion. Decision processes were studied by examining brain activation during the decision phase of a trial that was associated with the difficulty of interval discriminations. Activation in the right parahippocampus was greater for easier than harder discriminations. In contrast, activation was greater for harder than easier discriminations in systems involved in working memory (left middle-frontal and parietal cortex) and auditory rehearsal (left inferior-frontal and superior-temporal cortex). Activity in the auditory rehearsal network correlated with memory distortion. Our results support the independence of systems that mediate interval encoding and decision processes. The results also suggest that distortions in memory for time may be due to strategic processing in cortical systems involved in either encoding or rehearsal.

Acoustic Stimulation↗
PubMed2004

Neural systems supporting timing and chronometric counting: an FMRI study.

At least two strategies are available to humans for estimating multisecond intervals. One depends on an interval timing system that is common to many species. The other is the language-based strategy of chronometric counting. These two strategies are easily distinguished by the psychophysical properties of their behavioral correlates: counting supports substantially more precise estimates than are possible using the more general interval timing system. The present study investigates the neural systems that underlie the execution of these different strategies. Eighteen adults reproduced a 16-s interval either by internally timing or covertly counting the duration. Comparison of counting and timing to a resting baseline suggested that these strategies engage some nonoverlapping neural systems. Counting, but not timing, strongly activated Broca's area, primary motor cortex in the mouth region, and right cerebellum, all of which are associated with internal speech. Counting also activated parts of the medial premotor circuit, including the putamen, supplementary motor area (SMA) proper, and cingulate motor area (CMA), that have been associated with reproducing isochronous and syncopated rhythms of elements lasting hundreds of milliseconds. During timing, only a portion of this circuit, the SMA proper and CMA, was engaged. Both timing and counting interfered with semantic processing during the resting state, evidenced by task-related decreases in the left inferior and middle frontal gyri, right superior frontal gyrus, left angular gyrus, and bilateral posterior cingulate cortex. This study suggests that counting activates a corticostriatal network associated with millisecond, rhythmic timing. In contrast, timing long durations without the benefit of linguistic strategies for subdividing counts reduces activity in this circuitry.

Adult↗
PubMed2004

fMRI of healthy older adults during Stroop interference.

The Stroop interference effect, caused by difficulty inhibiting overlearned word reading, is often more pronounced in older adults. This has been proposed to be due to declines in inhibitory control and frontal lobe functions with aging. Initial neuroimaging studies of inhibitory control show that older adults have enhanced activation in multiple frontal areas, particularly in inferior frontal gyrus, indicative of recruitment to aid with performance of the task. The current study compared 13 younger and 13 older adults, all healthy and well educated, who completed a Stroop test during functional magnetic resonance imaging. Younger adults were more accurate across conditions, and both groups were slower and less accurate during the interference condition. The groups exhibited comparable activation regions, but older adults exhibited greater activation in numerous frontal areas, including the left inferior frontal gyrus. The results support the recruitment construct and suggest, along with previous research, that the inferior frontal gyrus is important for successful inhibition.

Adult↗
PubMed2004

Neural networks underlying endogenous and exogenous visual-spatial orienting.

The orienting of visual-spatial attention is fundamental to most organisms and is controlled through external (exogenous) or internal (endogenous) processes. Exogenous orienting is considered to be reflexive and automatic, whereas endogenous orienting refers to the purposeful allocation of attentional resources to a predetermined location in space. Although behavioral, electrophysiological and lesion research in both primates and humans suggests that separate neural systems control these different modes of orienting, previous human neuroimaging studies have largely reported common neuronal substrates. Therefore, event-related FMRI (ER-FMRI) was used to independently examine different components of the orienting response including endogenous facilitation, exogenous facilitation and inhibition of return (IOR). In contrast to previous studies, endogenous versus exogenous facilitation resulted in widespread cortical activation including bilateral temporoparietal junction, bilateral superior temporal gyrus, right middle temporal gyrus, right frontal eye field and left intraparietal sulcus. Conversely, IOR compared to endogenous facilitation resulted in only a single focus of activation in the left superior temporal gyrus. These findings suggest that endogenous orienting activates a large cortical network to achieve internally generated shifts of attentional resources versus the automatic orienting that occurs with exogenous cues. However, similar networks may mediate endogenous orienting and IOR. The activation of the temporoparietal junction suggests that it is involved in more effortful processes, such as endogenous orienting, as well as in attentional reorienting and locating targets. Current results are discussed in terms of the functional development of the visual-spatial attentional system.

Adult↗
PubMed2004

An event-related fMRI study of exogenous orienting: supporting evidence for the cortical basis of inhibition of return?

This event-related fMRI experiment examined the neural substrates of exogenous visuospatial attention. Exogenous attention produces a biphasic response pattern denoted by facilitation at short cue-target intervals and inhibition of return (IOR) at longer intervals. Whereas the volitional orienting of attention has been well described in the literature, the neural systems that support exogenous facilitation and IOR in humans are relatively unknown. In direct comparisons to valid facilitation trials, valid IOR trials produced unique foci of activation in the right posterior parietal, superior temporal, middle temporal, middle occipital, anterior cingulate, and dorsal medial thalamic areas. Valid IOR trials also resulted in activation of motor exploratory and frontal areas previously associated with inhibition and oculomotor control. In contrast, invalid IOR compared to facilitation trials only activated anterior cortical structures. These results provide support for both attentional and oculomotor theories of IOR and suggest that IOR may be mediated by two networks. One network may mediate the inhibitory bias following an exogenous cue, whereas a separate network may be activated when a response must be made to stimuli that appear in inhibited locations of space.

Adult↗
PubMed2004

Motor sequence complexity and performing hand produce differential patterns of hemispheric lateralization.

Studies in brain damaged patients conclude that the left hemisphere is dominant for controlling heterogeneous sequences performed by either hand, presumably due to the cognitive resources involved in planning complex sequential movements. To determine if this lateralized effect is due to asymmetries in primary sensorimotor or association cortex, whole-brain functional magnetic resonance imaging was used to measure differences in volume of activation while healthy right-handed subjects performed repetitive (simple) or heterogeneous (complex) finger sequences using the right or left hand. Advanced planning, as evidenced by reaction time to the first key press, was greater for the complex than simple sequences and for the left than right hand. In addition to the expected greater contralateral activation in the sensorimotor cortex (SMC), greater left hemisphere activation was observed for left, relative to right, hand movements in the ipsilateral left superior parietal area and for complex, relative to simple, sequences in the left premotor and parietal cortex, left thalamus, and bilateral cerebellum. No such volumetric asymmetries were observed in the SMC. Whereas the overall MR signal intensity was greater in the left than right SMC, the extent of this asymmetry did not vary with hand or complexity level. In contrast, signal intensity in the parietal and premotor cortex was greater in the left than right hemisphere and for the complex than simple sequences. Signal intensity in the caudal anterior cerebellum was greater bilaterally for the complex than simple sequences. These findings suggest that activity in the SMC is associated with execution requirements shared by the simple and complex sequences independent of their differential cognitive requirements. In contrast, consistent with data in brain damaged patients, the left dorsal premotor and parietal areas are engaged when advanced planning is required to perform complex motor sequences that require selection of different effectors and abstract organization of the sequence, regardless of the performing hand.

Adult↗
PubMed2004

"One-thousand one... one-thousand two...": chronometric counting violates the scalar property in interval timing.

Weber's law applied to interval timing is called the scalar property. A hallmark of timing in the seconds-to-minutes range, the scalar property is characterized by proportionality between the standard deviation of a response distribution and the duration being timed. In this temporal reproduction study, we assessed whether the scalar property was upheld when participants chronometrically counted three visually presented durations (8, 16, and 24 sec) as compared with explicitly timing durations without counting. Accuracy for timing and accuracy for counting were similar. However, whereas timing variability showed the scalar property, counting variability did not. Counting variability across intervals was accurately modeled by summing a random variable representing an individual count. A second experiment replicated the first and demonstrated that task differences were not due to presentation order or practice effects. The distinct psychophysical properties of counting and timing behaviors argue for greater attention to participant strategies in timing studies.

Adult↗
PubMed2004

Functional magnetic resonance imaging of working memory among multiple sclerosis patients.

BACKGROUND AND PURPOSE: Verbal working memory (VWM) deficits have been a well-replicated finding among patients with multiple sclerosis (MS). Functional magnetic resonance imaging (FMRI) studies have described a VWM system in healthy samples; however, functional neuroimaging of this system among MS patients is just beginning to appear. METHODS: Fifteen MS patients and 15 sex-, age-, education-, and IQ-matched healthy control (HC) participants completed a 2-Back VWM task as whole-brain FMRI was conducted. RESULTS: Each group exhibited increased brain activity compared to the O-Back control task in regions associated with the 2-Back in previous neuroimaging studies. These included Broca's area, supplementary motor area (SMA), premotor cortices (PMC), and dorsolateral prefrontal cortices (DLPFC). MS patients exhibited greater cortical activity than did HC participants in left primary motor and somatosensory cortices, PMC, DLPFC, anterior cingulate, and bilateral SMA. MS patients exhibited relatively less activation in Broca's area, bilateral cerebellum, and other regions not typically associated with the 2-Back (e.g., right fusiform gyrus, left lingual gyrus, right hippocampus). Performance accuracy and reaction time did not differ between groups. CONCLUSIONS: Normal performance of a challenging VWM task among high-functioning MS patients is associated with a shift toward greater activity in regions related to sensorimotor functions and anterior attentional/executive components of the VWM system. Posterior memory storage systems appeared unaffected, while portions of the visual processing and subvocal rehearsal systems were less active. Although a shift in neural activity was noted relative to HC participants, deviation from regions normally involved in VWM function was not observed in this patient sample.

Adult↗
PubMed2003

Neural basis for impaired time reproduction in Parkinson's disease: an fMRI study.

Studies involving brain-lesioned subjects have used the paced finger tapping (PFT) task to investigate the neural systems that govern motor timing. Patients with Parkinson's disease (PD), for example, demonstrate abnormal performance on the PFT, characterized by decreased accuracy and variability changes, suggesting that the basal ganglia may play a critical role in motor timing. Consistent with this hypothesis, an fMRI study of healthy participants demonstrated that the medial frontostriatal circuit (dorsal putamen, ventrolateral thalamus, SMA) correlated with explicit time-dependent components of the PFT task. In the current fMRI study, PD patients and healthy age-matched controls were imaged while performing the PFT. PD patients underwent 2 imaging sessions, 1 on and the other off dopamine supplementation. Relative to controls, PD patients were less accurate and showed greater variability on the PFT task relative to controls. No PFT performance differences were observed between the on and off medication states despite significantly greater motor symptoms on the Unified Parkinson's Disease Rating Scale (UPDRS) in the off medication state. Functional imaging results demonstrated decreased activation within the sensorimotor cortex (SMC), cerebellum, and medial premotor system in the PD patients compared to controls. With dopamine replacement, an increase in the spatial extent of activation was observed within the SMC, SMA, and putamen in the PD patients. These results indicate that impaired timing reproduction in PD patients is associated with reduced brain activation within motor and medial premotor circuits. Despite a lack of improvement in PFT performance, PD patient's brain activation patterns were partially "normalized" with dopamine supplementation. These findings could not be attributed to greater head movement artifacts or basal ganglia atrophy within the PD group.

Acoustic Stimulation↗