In Parkinson's disease pallidal deep brain stimulation speeds up response initiation but has no effect on reactive inhibition.

The fronto-striatal circuits are considered to mediate inhibitory control over action. The aim of this study was to investigate the contribution of the internal segment of the pallidum (GPi), one of the final output pathways from the basal ganglia to the cortex, in inhibition. We examined the effect of deep brain stimulation (DBS) of the GPi (GPi-DBS) in patients with Parkinson's disease who performed a conditional stop signal task, with DBS on and off. Modulation of GPi activity was associated with significantly faster Go reaction times with DBS on than off, but stop signal reaction times were not altered. Application of the drift diffusion model indicated that GPi-DBS was associated with significantly lower response thresholds compared to GPi-DBS off. However, the drift rate was significantly lower than healthy controls with both GPi-DBS on and off. These results suggest that the GPi plays a crucial role in the 'Go' pathway, perhaps facilitating reaching the required threshold to initiate actions. However, GPi-DBS does not alter the functioning of the indirect 'NoGo' pathway, and other basal ganglia nuclei, such as the STN, may play a greater role in reactive response inhibition and conflict resolution.

Effects of pravastatin on thoracic aortic atherosclerosis in patients with heterozygous familial hypercholesterolemia.

Data regarding the effects of plasma lipid lowering on the evolution of thoracic aortic atherosclerosis (TAA) are scarce. In this study, we performed transesophageal echocardiography to characterize TAA in 16 newly diagnosed patients with heterozygous familial hypercholesterolemia and to follow its evolution after 2 years of statin treatment. TAA was graded as follows: grade I = normal intima; grade II = increased intimal echo density without thickening; grade IIIA = increased intimal echo density with single atheromatous plaque < or = 3 mm; grade IIIB = multiple plaques < or = 3mm; grade IV = > or = 1 plaque >3 mm; and grade V = mobile or ulcerated plaques. Baseline aortic intimal morphology was grade I in one patient, grade II in 4, grade IIIA in 6, grade IIIB in 3, and grade IV in 2 patients. Hypolipidemic treatment resulted in significant reductions in plasma total cholesterol and low-density lipoprotein (LDL) cholesterol. Follow-up aortic morphology was grade I in 5 patients, grade II in 2, grade IIIA in 3, grade IIIB in 3, and grade IV in 3 patients. TAA remained stable in 7 patients, progressed in 3, and regressed in 6 patients. TAA evolved in a uniform manner in the ascending aorta, aortic arch, and descending aorta. Patients with TAA regression were younger (39+/-14 vs 52+/-8 years, p=0.038) and had a greater decrease in plasma LDL cholesterol as a result of treatment (138+/-56 vs 73+/-55 mg/dl, p=0.036) than patients with TAA stability or progression. These observations support the hypothesis that hypolipidemic treatment may favorably affect the course of TAA in patients with heterozygous familial hypercholesterolemia.

Identification of patients with coronary artery disease by assessing diastolic abnormalities during isometric exercise.

BACKGROUND: Previous clinical studies using invasive and noninvasive methods have shown handgrip-induced diastolic abnormalities in patients with coronary artery disease (CAD). HYPOTHESIS: The study was undertaken to determine the utility of Doppler echo- and pressocardiography during hand-grip in discriminating patients with coronary artery disease (CAD) and in those with normal coronary arteries. METHODS: Both methods were obtained in 96 patients with suspected CAD within 24 h before coronary angiography. An abnormal handgrip-Doppler was defined by an early (E) to late (A) transmitral flow velocities ratio (E/A) < 1 during handgrip and a positive handgrip pressocardiographic test (HAT) by an abnormal increase in the A wave/total excursion or prolongation of the absolute or relative (heart-rate corrected) total relaxation time during isometric exercise. RESULTS: Of the 96 patients studied, 23 had normal coronary arteries and 73 showed CAD. In patients with normal coronary arteries, handgrip-Doppler showed an abnormal average E/A at rest and during handgrip, whereas all variables of HAT were within normal limits. In patients with CAD, handgrip-Doppler showed only a moderate handgrip-induced increase in average A (+ 19%, p < 0.001), whereas HAT showed a significant (p < 0.001) increase in mean A wave/total excursion (+ 60%) and decrease in the relative total relaxation time (- 17%). Furthermore, handgrip-Doppler and HAT were abnormal in 15 of 23 (65%, specificity 35%) and the HAT in 5 of 23 (22%, specificity 78%) patients with normal coronary arteries, as well as in 57 of 73 (sensitivity 78%) and 69 of 73 (95%) patients with CAD. CONCLUSIONS: Our study demonstrates that these noninvasive stress tests can become a useful new diagnostic modality for detecting patients with unknown or suspected CAD.

Improved detection of coronary artery disease by exercise electrocardiography with the use of right precordial leads.

BACKGROUND: Exercise electrocardiography is an perfect test for the detection of coronary artery disease. We attempted to improve the diagnostic accuracy of exercise testing as a noninvasive method for the detection of coronary artery disease by using a combination of the left and right precordial leads. METHODS: We studied 245 patients (218 men and 27 women) ranging from 32 to 74 years of age (mean [+/-SD], 52+/-8) who underwent treadmill exercise testing, thallium-201 scintigraphy, and coronary arteriography. During exercise testing, each patient had one electrocardiogram recorded with the standard 12 leads and 3 right precordial leads (V3R, V4R, and V5R), with the results for each set of leads recorded and analyzed separately. RESULTS: On the basis of coronary arteriography, 34 patients had normal coronary arteries, 85 had single-vessel disease, 84 had two-vessel disease, and 42 had three-vessel disease. The sensitivities of the standard 12-lead exercise electrocardiogram, exercise electrocardiography incorporating right precordial leads, and thallium-201 scintigraphy were 52 percent, 89 percent, and 87 percent, respectively, for the detection of single-vessel disease; 71 percent, 94 percent, and 96 percent for the detection of two-vessel disease; 83 percent, 95 percent, and 98 percent for the detection of three-vessel disease; and 66 percent, 92 percent, and 93 percent for the detection of any coronary artery disease. The specificities of the three methods for the detection of any coronary artery disease were 88 percent, 88 percent, and 82 percent, respectively. CONCLUSIONS: Use of right precordial leads along with the standard six left precordial leads during exercise electrocardiography greatly improves the sensitivity of exercise testing for the diagnosis of coronary artery disease.