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Biomedical subjects

V Menon

Publications and source records attributed to V Menon.

At least 37 records · Page 2Linked to original sources

Neural correlates of timbre change in harmonic sounds.

Timbre is a major structuring force in music and one of the most important and ecologically relevant features of auditory events. We used sound stimuli selected on the basis of previous psychophysiological studies to investigate the neural correlates of timbre perception. Our results indicate that both the left and right hemispheres are involved in timbre processing, challenging the conventional notion that the elementary attributes of musical perception are predominantly lateralized to the right hemisphere. Significant timbre-related brain activation was found in well-defined regions of posterior Heschl's gyrus and superior temporal sulcus, extending into the circular insular sulcus. Although the extent of activation was not significantly different between left and right hemispheres, temporal lobe activations were significantly posterior in the left, compared to the right, hemisphere, suggesting a functional asymmetry in their respective contributions to timbre processing. The implications of our findings for music processing in particular and auditory processing in general are discussed.

Adult↗

New heparin dosing recommendations for patients with acute coronary syndromes.

Despite major innovations in antithrombotic and antiplatelet therapy, unfractionated intravenous heparin is widely used to treat acute coronary syndromes. Recommendations for unfractionated heparin dosing in acute myocardial infarction and unstable angina have been issued in two recent American College of Cardiology/American Heart Association guidelines. An initial heparin bolus of 60 U/kg (maximum, 4000 U) followed by a 12-U/kg/h infusion (maximum 1000 U/h) is recommended with alteplase for ST-elevation myocardial infarction. When intravenous heparin is administered for myocardial infarction with non-ST elevation and unstable angina, an initial bolus of 60 to 70 U/kg (maximum, 5000 U) followed by a 12- to 15-U/kg/h infusion is recommended. The goal is to achieve an activated partial thromboplastin time of 50 to 70 seconds. Here, we review these new dosing regimens and explain the rationale for their use. We also review the risk of bleeding with heparin, especially when administered concurrently with aspirin, thrombolytic agents, and glycoprotein IIb/IIIa antagonists, and the relationship between activated partial thromboplastin time and cardiac events.

Angina, Unstable↗

Preliminary evidence of widespread morphological variations of the brain in dyslexia.

The MR images of 16 men with dyslexia and 14 control subjects were compared using a voxel-based analysis. Evidence of decreases in gray matter in dyslexic subjects, most notably in the left temporal lobe and bilaterally in the temporoparietooccipital juncture, but also in the frontal lobe, caudate, thalamus, and cerebellum, was found. Widely distributed morphologic differences affecting several brain regions may contribute to the deficits associated with dyslexia.

Adolescent↗

One-year survival following early revascularization for cardiogenic shock.

CONTEXT: Cardiogenic shock (CS) is the leading cause of death for patients hospitalized with acute myocardial infarction (AMI). OBJECTIVE: To assess the effect of early revascularization (ERV) on 1-year survival for patients with AMI complicated by CS. DESIGN: The SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) Trial, an unblinded, randomized controlled trial from April 1993 through November 1998. SETTING: Thirty-six referral centers with angioplasty and cardiac surgery facilities. PATIENTS: Three hundred two patients with AMI and CS due to predominant left ventricular failure who met specified clinical and hemodynamic criteria. INTERVENTIONS: Patients were randomly assigned to an initial medical stabilization (IMS; n = 150) group, which included thrombolysis (63% of patients), intra-aortic balloon counterpulsation (86%), and subsequent revascularization (25%), or to an ERV group (n = 152), which mandated revascularization within 6 hours of randomization and included angioplasty (55%) and coronary artery bypass graft surgery (38%). MAIN OUTCOME MEASURES: All-cause mortality and functional status at 1 year, compared between the ERV and IMS groups. RESULTS: One-year survival was 46.7% for patients in the ERV group compared with 33.6% in the IMS group (absolute difference in survival, 13.2%; 95% confidence interval [CI], 2.2%-24.1%; P<.03; relative risk for death, 0.72; 95% CI, 0.54-0.95). Of the 10 prespecified subgroup analyses, only age (<75 vs >/= 75 years) interacted significantly (P<.03) with treatment in that treatment benefit was apparent only for patients younger than 75 years (51.6% survival in ERV group vs 33.3% in IMS group). Eighty-three percent of 1-year survivors (85% of ERV group and 80% of IMS group) were in New York Heart Association class I or II. CONCLUSIONS: For patients with AMI complicated by CS, ERV resulted in improved 1-year survival. We recommend rapid transfer of patients with AMI complicated by CS, particularly those younger than 75 years, to medical centers capable of providing early angiography and revascularization procedures.

Aged↗

Error-related brain activation during a Go/NoGo response inhibition task.

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.

Adolescent↗

Functional neuroanatomy of visuo-spatial working memory in Turner syndrome.

Turner syndrome (TS), a genetic disorder characterized by the absence of an X chromosome in females, has been associated with cognitive and visuo-spatial processing impairments. We utilized functional MRI (fMRI) to investigate the neural substrates that underlie observed deficits in executive functioning and visuo-spatial processing. Eleven females with TS and 14 typically developing females (ages 7-20) underwent fMRI scanning while performing 1-back and 2-back versions of a standard visuo-spatial working memory (WM) task. On both tasks, TS subjects performed worse than control subjects. Compared with controls, TS subjects showed increased activation in the left and right supramarginal gyrus (SMG) during the 1-back task and decreased activation in these regions during the 2-back task. In addition, decreased activation in the left and right dorsolateral prefrontal cortex (DLPFC) and caudate nucleus was observed during the 2-back task in TS subjects. Activation differences localized to the SMG, in the inferior parietal lobe, may reflect deficits in visuo-spatial encoding and WM storage mechanisms in TS. In addition, deficits in the DLPFC and caudate may be related to deficits in executive function during WM performance. Together these findings point to deficits in frontal-striatal and frontal-parietal circuits subserving multiple WM functions in TS.

Adolescent↗

Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms.

Functional brain imaging studies of working memory (WM) in schizophrenia have yielded inconsistent results regarding deficits in the dorsolateral prefrontal (DLPFC) and parietal cortices. In spite of its potential importance in schizophrenia, there have been few investigations of WM deficits using auditory stimuli and no functional imaging studies have attempted to relate brain activation during auditory WM to positive and negative symptoms of schizophrenia. We used a two-back auditory WM paradigm in a functional MRI study of men with schizophrenia (N = 11) and controls (N = 13). Region of interest analysis was used to investigate group differences in activation as well as correlations with symptom scores from the Brief Psychiatric Rating Scale. Patients with schizophrenia performed significantly worse and were slower than control subjects in the WM task. Patients also showed decreased lateralization of activation and significant WM related activation deficits in the left and right DLPFC, frontal operculum, inferior parietal, and superior parietal cortex but not in the anterior cingulate or superior temporal gyrus. These results indicate that in addition to the prefrontal cortex, parietal cortex function is also disrupted during WM in schizophrenia. Withdrawal-retardation symptom scores were inversely correlated with frontal operculum activation. Thinking disturbance symptom scores were inversely correlated with right DLPFC activation. Our findings suggest an association between thinking disturbance symptoms, particularly unusual thought content, and disrupted WM processing in schizophrenia.

Adult↗

Reorganization of frontal systems used by alcoholics for spatial working memory: an fMRI study.

Chronic alcoholism is associated with impairment in sustained attention and visual working memory. Thus, alcoholics have reduced ability, but not necessarily inability, to perform these executive tasks, assumed to be subserved by regions of prefrontal cortex. To identify neural substrates associated with this impairment, we used functional MRI (fMRI) to determine whether alcoholics invoke the same or different brain systems as controls when engaged in working memory tasks that the two groups were able to perform at equivalent levels. The fMRI spatial working memory paradigm instructed subjects to respond with a button press when a target position was either in the center of the field (match to center) or matched the spatial position of one presented two items previously (match 2-back) or to rest. Using whole-brain fMRI, alcoholics showed diminished activation frontal cortical systems compared to controls (bilateral dorsolateral prefrontal cortex) when responding 2-back vs rest. In the center vs rest contrast, the control group compared with the alcoholic group activated a large expanse of prefrontal cortex (including Brodmann areas 9, 10, and 45), whereas there was significantly greater activation by the alcoholic group relative to the control group localized more posteriorly and inferiorly in the frontal cortex (area 47). Examination of within group activation patterns revealed two different patterns of activation: the control group exhibited activation of the dorsal ("Where?") stream for visual spatial working memory processing, whereas the alcoholic group exhibited activation of the ventral ("What?") stream and declarative memory systems to accomplish the spatial working memory task. The differences in the pattern of brain activations exhibited by the alcoholic and control groups, despite equivalence in behavioral performance, is consistent with a functional reorganization of the brain systems invoked by alcoholic individuals or invocation of an inappropriate brain system when engaged in a visual spatial task requiring working memory.

Adult↗

Left superior parietal cortex involvement in writing: integrating fMRI with lesion evidence.

Writing is a uniquely human skill that we utilize nearly everyday. Lesion studies in patients with Gerstmann's syndrome have pointed to the parietal cortex as being critical for writing. Very little information is, however, available about the precise anatomical location of brain regions subserving writing in normal healthy individuals. In this study, we used functional magnetic resonance imaging (fMRI) to investigate parietal lobe function during writing to dictation. Significant clusters of activation were observed in left superior parietal lobe (SPL) and the dorsal aspects of the inferior parietal cortex (IPC) bordering the SPL. Localized clusters of activation were also observed in the left premotor cortex, sensorimotor cortex and supplementary motor area. No activation cluster was observed in the right hemisphere. These results clearly indicate that writing appears to be primarily organized in the language-dominant hemisphere. Further analysis revealed that within the parietal cortex, activation was significantly greater in the left SPL, compared to left IPC. Together with lesion studies, findings from the present study provide further evidence for the essential role of the left SPL in writing. Deficits to the precise left hemisphere parietal cortex regions identified in the present study may specifically underlie disorders of writing observed in Gerstmann's syndrome and apractic agraphia.

Adolescent↗

Event-related brain potential evidence of spared knowledge in Alzheimer's disease.

The authors recorded event-related brain potentials (ERPs) to picture primes and word targets (picture-name verification task) in patients with Alzheimer's disease (AD) and in elderly and young participants. N400 was more negative to words that did not match pictures than to words that did match pictures in all groups: In the young, this effect was significant at all scalp sites; in the elderly, it was only at central-parietal sites; and in AD patients, it was limited to right central-parietal sites. Among AD patients pretested with a confrontation-naming task to identify pictures they could not name, neither the N400 priming effect nor its scalp distribution was affected by ability to name pictures correctly. This ERP evidence of spared knowledge of these items was complemented by 80% performance accuracy. Thus, although the name of an item may be inaccessible in confrontation naming, N400 shows that knowledge is intact enough to prime cortical responses.

Adult↗

Trends in cardiogenic shock: report from the SHOCK Study. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

AIMS: We analysed time trends in patient characteristics, management, and outcomes of cardiogenic shock complicating acute myocardial infarction in the international, prospective SHOCK Trial Registry and pre-study Registry. BACKGROUND: Despite therapeutic advances in its management, the incidence and high mortality of this complication has remained unchanged for decades. However, in recent years mortality was reported to decrease in one community concomitant with increasing use of revascularization. METHODS: Thirty-six centres registered 1380 patients with suspected cardiogenic shock complicating acute myocardial infarction from January 1992 to August 1997. Patient and myocardial infarction characteristics, haemodynamics, medications, procedure use, and vital status at discharge were recorded. RESULTS: In all, 79% of patients had shock due to predominant pump failure (non-mechanical aetiology). The aetiology, patient profile, and clinical characteristics of cardiogenic shock did not differ over time, except for increases in the incidence of prior bypass surgery (P=0.054) and transfers to tertiary centres (P=0.008). In all, 44% underwent revascularization (n=485), with angioplasty performed more often than bypass surgery (69% vs 31%). The revascularization rate increased over time (P=0.006) with a significant decrease in the time to revascularization (P=0.033). The use of Swan-Ganz catheterization decreased over time (P=0.018), as did the mean length of hospitalization (P=0.034). Overall in-hospital mortality was high (63%) but decreased over time in all patients (P=0.004) and those with pump failure (P=0.018). Mortality was lower for patients who underwent revascularization compared to those who were not revascularized (41% vs 79%, P<0.001). CONCLUSIONS: Cardiogenic shock complicating acute myocardial infarction is associated with a high mortality rate, but mortality decreased significantly from 1992 to 1997. This partly reflects the greater use of revascularization, which was associated with better outcomes. The reported international trend towards shorter admissions for myocardial infarction was also observed in this cohort.

Adult↗

The late open artery hypothesis--a decade later.

BACKGROUND: Early reperfusion after myocardial infarction has been proved to preserve left ventricular function and reduce mortality. However, a significant number of patients have persistent occlusion of the infarct-related artery late (days to weeks) after myocardial infarction because of ineligibility for thrombolytic therapy, failure of reperfusion, or reocclusion. METHODS: In this report we review the data on the potential mechanisms and benefits of late reperfusion and present prospective data on the incidence of and current practice patterns for the management of persistently occluded infarct-related arteries late after myocardial infarction. RESULTS: Although several studies have associated late patency of the infarct-related artery with improved long-term clinical outcome, they were nonrandomized and reflect selection bias. Furthermore, data on late patency from the largest study, Global Utilization of Steptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO-I), failed to confirm independent benefits of an open infarct-related artery 1 year after myocardial infarction. The randomized data on the effects of percutaneous transluminal coronary angioplasty for occluded infarct-related arteries late after myocardial infarction are limited and inconclusive. CONCLUSIONS: The hypothesis that late reperfusion by percutaneous coronary intervention days to weeks after myocardial infarction results in improved long-term clinical outcomes in asymptomatic patients with occluded infarct-related artery is currently being tested in the randomized, multicenter Occluded Artery Trial.

Clinical Trials as Topic↗

Postischemic apoptosis and functional recovery after angiotensin II type 1 receptor blockade in isolated working rat hearts.

OBJECTIVE: To determine whether chronic angiotensin (AngII) type I receptor (AT1R) blockade inhibits cardiomyocyte (CM) apoptosis and attenuates left ventricular (LV) dysfunction after ischemia-reperfusion (IR) in the isolated working rat heart. METHODS: Postischemic recovery of LV developed pressure, the apoptotic index (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labeling or TUNEL assay), and changes in expression of apoptotic markers Bcl-2, Bax, p53 and caspase-3 (Western immunoblots) were measured after IR (50 min aerobic perfusion; 25 min global ischemia; 40 min reperfusion) in working rat hearts that were randomized to five groups of six each along 1 week or 3 week pretreatment arms: sham (no drug, no perfusion); no drug, aerobic perfusion; and oral AT1R blockers losartan (30 mg/kg per day) or UP269-6 (3 mg/kg per day), or no drug before IR. RESULTS: Compared to the no drug group after IR, losartan (not UP269-6) preserved functional recovery in 1 and 3 week groups. However, both losartan and UP269-6 reduced the apoptotic index and normalized the increase in Bax, decrease in Bcl-2 and increase in p53 and caspase-3 after IR. A bell-shaped relation between apoptosis and functional recovery after IR was flattened by AT1R blockade. CONCLUSION: The results indicate that IR is associated with LV dysfunction and CM apoptosis involving activation of p53, caspase-3, and increased Bax/Bcl-2 ratio in the working rat heart. Importantly, chronic AT1R blockade inhibited the apoptosis and changes in expression of the markers without improving functional recovery, implying that decrease in apoptosis does not necessarily translate into decreased LV dysfunction.

Angiotensin Receptor Antagonists↗

Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia.

OBJECTIVE: This study was an examination of basal ganglia dysfunction in schizophrenia using functional magnetic resonance imaging (fMRI). METHOD: The authors used a motor sequencing task to investigate activation of the caudate, anterior putamen plus globus pallidus, and posterior putamen plus globus pallidus in eight subjects with schizophrenia and 12 group-matched comparison subjects. Differences in activation of the thalamus, the target of direct output from the globus pallidus, were also examined. RESULTS: The schizophrenia subjects showed significant bilateral deficits in the posterior putamen, globus pallidus, and thalamus but not the anterior putamen plus globus pallidus or caudate. Functional connectivity analysis revealed that the deficits in thalamic activation were related to deficits in posterior putamen and globus pallidus activation. CONCLUSIONS: These results provide fMRI evidence for basal ganglia dysfunction in subjects with schizophrenia and suggest that this deficit results in disrupted outflow to the thalamus. These deficits may underlie the behavioral impairments in goal-directed action observed in schizophrenia.

Adult↗

Functional neuroanatomy of visuospatial working memory in fragile X syndrome: relation to behavioral and molecular measures.

OBJECTIVE: Fragile X syndrome is a neurogenetic disorder that is the most common known heritable cause of neurodevelopmental disability. This study examined the neural substrates of working memory in female subjects with fragile X syndrome. Possible correlations among behavioral measures, brain activation, and the FMR1 gene product (FMRP expression), as well as between IQ and behavioral measures, were investigated. METHOD: Functional magnetic resonance imaging was used to examine visuospatial working memory in 10 female subjects with fragile X syndrome and 15 typically developing female subjects (ages 10-23 years). Subjects performed standard 1-back and 2-back visuospatial working memory tasks. Brain activation was examined in four regions of the cortex known to play a critical role in visuospatial working memory. Correlations between behavioral, neuroimaging, and molecular measures were examined. RESULTS: Relative to the comparison group, subjects with fragile X syndrome performed significantly worse on the 2-back task but not on the 1-back task. In a region-of-interest analysis focused on the inferior frontal gyrus, middle frontal gyrus, superior parietal lobule, and supramarginal gyrus, comparison subjects showed significantly increased brain activation between the 1-back and 2-back tasks, but subjects with fragile X syndrome showed no change in activation between the two tasks. Significant correlations were found in comparison subjects between activation in the frontal and parietal regions and the rate of correct responses on the 2-back task, but not on the 1-back task. In subjects with fragile X syndrome, significant correlations were found during the 2-back task between FMRP expression and activation in the right inferior and bilateral middle frontal gyri and the bilateral supramarginal gyri. CONCLUSIONS: Subjects with fragile X syndrome are unable to modulate activation in the prefrontal and parietal cortex in response to an increasing working memory load, and these deficits are related to a lower level of FMRP expression in fragile X syndrome subjects than in normal comparison subjects. The observed correlations between biological markers and brain activation provide new evidence for links between gene expression and cognition.

Adolescent↗

Effect of chronic AT(1) receptor antagonism on postischemic functional recovery and AT(1)/AT(2) receptor proteins in isolated working rat hearts.

To determine whether chronic angiotensin II (Ang II) type I receptor (AT(1)R) antagonism improves recovery of left ventricular (LV) function after ischemia-reperfusion (IR) and increases AT(1)R and Ang II type 2 receptor (AT(2)R) protein expression in isolated working rat hearts, rats were randomized to pretreatment with either losartan (30 mg/kg/day) or UP269-6 (3 mg/kg/day), or no drug (control), for 1 week or 3 weeks before IR (50 min perfusion, 25 min ischemia, 40 min reperfusion). In vitro LV work and power and ex vivo AT(1)R and AT(2)R proteins (immunoblots) were measured. Compared to baseline perfusion, LV work and power showed variable recovery in control, losartan, and UP269-6 groups. Compared to control, losartan preserved recovery of LV work and power while UP269-6 showed less recovery after IR at both 1 week and 3 weeks. Both antagonists increased AT(2)R but not AT(1)R protein. The duration of pretreatment did not affect the expression of AT(1)R or AT(2)R proteins. The results indicate that chronic AT(1)R blockade over 1 or 3 weeks increases AT(2)R (not AT(1)R) protein expression and may preserve but not improve postischemic functional recovery compared to controls in isolated working rat hearts.

Analysis of Variance↗