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Transcranial magnetic stimulation, causal structure-function mapping and networks of functional relevance.

Transcranial magnetic stimulation is now a well-established tool for inducing transient changes in brain activity non-invasively in conscious human volunteers. During the past couple of years, the ability to actively interfere with neural processing during behavioral performance has been used increasingly for the investigation of causal brain-behavior relationships in higher cognitive functions. The simultaneous combination of transcranial magnetic stimulation with methods of functional brain imaging, however, promises to be of especially great value for our understanding of the human brain, as it provides the opportunity to stimulate brain circuits while simultaneously monitoring changes in brain activity and behavior. Such an approach could help us to identify brain networks of functional relevance, and might enable causal brain-behavior inferences across the entire brain.

Behavior↗

Improved papillary muscle function attenuates functional mitral regurgitation in patients with dilated cardiomyopathy after cardiac resynchronization therapy.

BACKGROUND: Functional mitral valve regurgitation attenuation after cardiac resynchronization therapy (CRT) in patients with severe heart failure has been attributed to both the increased rate of left ventricular systolic pressure increase and to papillary muscle (PM) recoordinated contraction. We hypothesized that an increase in systolic deformation of the PMs or the adjacent myocardial wall may in part account for this effect, by preventing their outward displacement during systole. METHODS: We studied by echocardiography 22 patients with moderate/severe functional mitral valve regurgitation and a mean ejection fraction of 18 +/- 4% at baseline and after implantation of a CRT system. RESULTS: CRT induced a significant reduction of the effective regurgitant orifice area (0.18 +/- 0.11 vs 0.35 +/- 0.17 mm2, P < .001). Strain improved in both PMs and their adjacent walls, although this improvement was significant only in anterolateral PM (-16 +/- 4.7 vs -11 +/- 4.3%, P = .02) and posteromedial PM adjacent wall (-16 +/- 10 vs -8 +/- 4.6%, P = .01). CONCLUSIONS: CRT acutely reduces the severity of functional mitral valve regurgitation in patients with heart failure and this effect may be in part attributed to improved strain of PM or adjacent wall.

Aged↗

Functional effects of cocaine self-administration in primate brain regions regulating cardiovascular function.

Cocaine abuse is associated with autonomic dysregulation, such as altered blood pressure and heart rate. Both central and peripheral mechanisms have been implicated in mediating these changes, however, to date, no study has examined functional changes in activity within central autonomic-associated brain regions in response to cocaine in non-human primates. The aim of the present study was to measure local cerebral glucose utilization, in selected autonomic brain regions, in rhesus monkeys that had self-administered cocaine (0.3 mg/kg/infusion) for 5 days (initial) or 100 days (chronic). Measurements were compared with control monkeys, in which responding was maintained by food reinforcement. In general, decreased rates of glucose utilization were observed in targeted areas following both 5 and 100 days of cocaine self-administration compared to control values. However, after initial stages of cocaine exposure, significant reductions in the forebrain were restricted to the bed nucleus of stria terminalis and in the brainstem to the nucleus tractus solitarius and dorsomotor nucleus of the vagus nerve. The pattern of significantly altered functional activity induced by chronic 100-day cocaine self-administration extended within the forebrain to include the paraventricular hypothalamic nucleus, and in the brainstem to include additional autonomic-related nuclei, the nucleus ambiguus and locus coeruleus. These results suggest that even at the initial stages of cocaine self-administration, functional changes in activity occur in autonomic and reward-related brain regions. These alterations progress with prolonged cocaine exposure, and therefore may be involved in mediating changes in central autonomic control and the neuroadaptations reported to result from chronic drug abuse.

Animals↗

Functional assessment of pediatric pain patients: psychometric properties of the functional disability inventory.

The Functional Disability Inventory (FDI; Walker LS, Greene JW. The functional disability inventory: measuring a neglected dimension of child health status. J Pediatr Psychol 1991;16:39-58) assesses activity limitations in children and adolescents with a variety of pediatric conditions. This study evaluated the psychometric properties of the FDI in pediatric pain patients. Participants included 596 patients with chronic abdominal pain, ages 8-17, and a subset of their parents (n = 151) who completed the FDI and measures of pain, limitations in school activities, and somatic and depressive symptoms at a clinic visit. Test-retest reliability was high at 2 weeks (child report, .74; parent-report, .64) and moderate at 3 months (child report, .48; parent report, .39). Internal consistency reliability was excellent, ranging from .86 to .91. Validity was supported by significant correlations of child- and parent-report FDI scores with measures of school-related disability, pain, and somatic symptoms. Study results add to a growing body of empirical literature supporting the reliability and validity of the FDI for functional assessment of pediatric patients with chronic pain.

Activities of Daily Living↗

Is the functional decline of Parkinson's disease similar to the functional decline of Alzheimer's disease?

Since many Parkinson's disease (PD) subjects develop dementia, we determined whether the correlation between functional and cognitive decline seen in Alzheimer's disease (AD) is seen in PD. Seventy-five PD subjects with and without dementia and 103 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), the UPDRS motor portion, and the MMSE. In AD/MCI subjects, changes in FAST and GDS scores correlated with MMSE (rho=-0.814, P<0.001; rho=-0.840, P<0.001, respectively). In PD subjects, the FAST and GDS also correlated with MMSE (rho=-0.675, P<0.001; rho=-0.647, P<0.001, respectively). The UPDRS correlated with the GDS and FAST more closely in PD than in AD. Similar to AD, functional declines in PD correlates with cognitive decline and may be influenced by motor disability in PD.

Activities of Daily Living↗

The behavioral function of feeding problems as assessed by the questions about behavioral function (QABF).

Differences in subscale scores on the questions about behavioral function (QABF) were assessed for participants identified with pica, rumination, food stealing, food refusal, and mealtime behavior problems (e.g., aggression, self-injurious behavior). The QABF was administered to informants for 125 individuals identified with problematic feeding behaviors and mental retardation primarily in the severe to profound range. Results of the nonparametric analyses yielded significant differences across the escape, nonsocial, physical, and tangible subscales of the QABF. Behavior functions most commonly associated with problematic feeding behaviors were identified. The results extend upon previous literature describing behavioral function of feeding problems for those with mental retardation.

Adolescent↗

Luteal function and conception in lactating cows and some factors influencing luteal function after first insemination.

The objective of this study was to investigate the types and incidence of luteal sub-function in lactating cows after artificial insemination (AI) and their relationship with pregnancy, and to clarify the relationship between luteal function and parity, body condition score (BCS), milk yield, and dietary intake. In 19 cows, milk samples were collected daily from AI to confirmation of pregnancy. Milk progesterone concentrations were determined by EIA. Based on peak progesterone concentration and the day of onset of luteal phase, 15 of 30 progesterone profiles (50%) were normal, with progesterone concentration reaching 1.0 ng/ml within 5 days after insemination and > or =2.0 ng/ml thereafter. In addition, 6 (20%) were insufficient, (progesterone concentration remained < 2.0 ng/ml), 5 (17%) were delayed (progesterone reached 1.0 ng/ml after 5 days), 2 (7%) were both delayed and insufficient, one (3%) was short (progesterone >1.0 ng/ml for only 7 days), and one (3%) remained basal. Cows with a normal profile had a higher (P < 0.05) pregnancy rate than those with an abnormal profile (87% versus 33%, respectively). The amount of progesterone secreted in milk after first AI, as indicated by progesterone area under curve (AUC), was negatively correlated with milk yield (r = -0.83, P < 0.01), dry matter intake (r = -0.81, P < 0.05), total digestible nutrients (r = -0.82, P< 0.05), and digestible crude protein (r = -0.79, P <0.05). Cows that produced more milk and consumed more dry matter had less progesterone during the luteal phase. In conclusion, abnormal luteal function was associated with reduced pregnancy rates and high milk production and increased dietary intake during breeding were associated with reduced progesterone concentrations.

Animals↗

The function, composition and analysis of cerebrospinal fluid in companion animals: part I - function and composition.

Cerebrospinal fluid (CSF) is a clear, colourless ultrafiltrate of plasma with low protein content and few cells. The CSF is mainly produced by the choroid plexus, but also by the ependymal lining cells of the brain's ventricular system. CSF flows through the ventricular system and then into the subarachnoid space and it is subsequently absorbed through the subarachnoid villi into the venous system. CSF has several functions in the nervous system. It protects the brain during blood pressure fluctuations, regulates the chemical environment of the central nervous system and it is a vehicle for intracerebral transport. This two-part article reviews CSF function, physiology, analytical techniques and interpretations in disease states of companion animals. This first part will address the function and composition of CSF in companion animals.

Animals↗

Mitral valve repair is superior to valve replacement for the early preservation of cardiac function: relation of ventricular geometry to function.

The immediate effect or mitral valve repair (MVP) or replacement (MVR) on cardiac function was compared in patients with mitral regurgitation in relation to the changes in left ventricular (LV) function and geometry by using intraoperative transesophageal echocardiography in 29 patients with MVP and 21 patients with MVR, before and immediately after cardiopulmonary bypass. The LV volumes, ejection fraction, and long-axis and short-axis lengths and eccentricity index (ratio of long axis to short axis) at end-systole and end-diastole were measured. After both MVP and MVR, there were significant decreases in LV end-diastolic volume (p < 0.0001). However, the ejection fraction did not change after MVP, whereas it decreased after MVR (p < 0.0001). After MVP, there was an increase in eccentricity index at end-systole (p < 0.0001). After MVR, there was no decrease in end-systolic volume, and the eccentricity index was lower than that after MVP (p < 0.0001). The change in LV ejection fraction correlated with the changes in eccentricity index at end-systole (r = 0.55; p < 0.0001) and end-diastole (r = 0.42; p < 0.0003). Immediate intraoperative LV function is preserved after MVP but is depressed after MVR for mitral regurgitation. The changes in ejection fraction correlate with changes in ventricular geometry.

Aged↗

Pindolol and propranolol in patients with angina pectoris and normal or near-normal ventricular function. Lack of influence of intrinsic sympathomimetic activity on global and segmental left ventricular function assessed by radionuclide ventriculography.

To investigate the role of intrinsic sympathomimetic activity on left ventricular (LV) function during antianginal therapy with beta-adrenoreceptor antagonists, 23 patients with chronic, exercise-induced angina pectoris and normal or near normal LV function underwent radionuclide ventriculography at rest and during exercise, during 3 randomly allocated periods: (a) treatment with oral propranolol, a drug without intrinsic sympathomimetic activity, 40 to 80 mg 4 times a day; (2) treatment with pindolol, a drug with marked intrinsic sympathomimetic activity, 5 to 10 mg 2 times a day; and (3) a control period. During the control period, the LV ejection fraction decreased from rest (58.9 +/- 8.2%) to exercise (54.3 +/- 10.7%), and the wall motion score decreased from 0.57 +/- 1.08 at rest to 2.39 +/- 2.10 during exercise, p less than 0.001. After propranolol, the ejection fraction did not change significantly at rest (57.2 +/- 8.1%) but improved during exercise (56.8 +/- 11.8%), compared with control values. After pindolol, the ejection fraction did not change at rest (57.9 +/- 8.6%) but improved during exercise (56.9 +/- 8.1%), compared with control values. Similarly, the wall motion score after administration of both agents did not change significantly at rest, but improved during exercise (p less than 0.001). The number of anginal episodes, nitroglycerin tablets consumed, and magnitude of S-T segment depression decreased significantly with both pindolol and propranolol. With both drugs, a similar improvement in exercise tolerance and a similar decrease in exercise heart rate and blood pressure were obtained. It is concluded that pindolol and propranolol, beta-adrenoreceptor antagonists with and without intrinsic sympathomimetic activity, respectively, have similar effects on global and regional LV function in patients with angina pectoris, at doses producing equal suppression of exercise heart rate and similar antianginal effect.

Adult↗

Comparison of three-dimensional echocardiographic assessment of volume, mass, and function in children with functionally single left ventricles with two-dimensional echocardiography and magnetic resonance imaging.

Diminished systolic function or inappropriate hypertrophy are considered risk factors for outcome following the Fontan procedure. These parameters are difficult to assess in univentricular hearts that do not conform to the uniform shapes prescribed by conventional 2-dimensional imaging volume algorithms. Three-dimensional echocardiography requires no geometric assumptions and has been validated in both normal and distorted left ventricles. To assess the feasibility and accuracy of this technique in patients with univentricular hearts, we compared 2- and 3-dimensional echocardiographic estimates of ventricular volume, ejection fraction, and mass in patients with functionally single left ventricles with results obtained by magnetic resonance imaging (MRI). Twelve patients with functionally single left ventricles (6 months to 22 years) underwent examination by all 3 modalities. Correlation and agreement with MRI were calculated for volumes, ejection fraction, and mass. Three-dimensional echocardiographic comparison with MRI yielded a bias of 3.4 +/- 5.5 ml and 14.2 +/- 8.3 ml for systolic and diastolic volumes, respectively. Agreement analysis for mass showed a bias of 5.8 +/- 8.4 grams. Two-dimensional echocardiography showed less agreement for both volumes and mass (bias of -2.9 +/- 8.1, 2.9 +/- 10.4 ml and -8.3 +/- 12.0 g for volume and mass, respectively, p >0.05). Ejection fraction by 3-dimensional echocardiography showed significantly closer agreement with MRI (bias of 4.4 +/- 5.3%) than 2-dimensional echocardiography (bias of 8.5 +/- 10.3%, p = 0.04). Thus, 3-dimensional echocardiography provides estimates of ventricular volumes, ejection fraction, and mass that are comparable to MRI in this select group of patients with single ventricles of left ventricular morphology.

Adolescent↗

Intermodal agreement of follow-up telephone functional assessment using the Functional Independence Measure in patients with stroke.

OBJECTIVE: To examine the intermodal agreement of Functional Independence Measure (FIM) ratings when obtained by two commonly used approaches: telephone interview and in-person assessment of functional performance. DESIGN: A random sample of 40 persons with hemiparesis was tested by two registered nurses trained in FIM definitions and telephone interview techniques. The two assessments occurred within 5 days of each other. The raters were blind to previous assessments. The administration of assessments was alternated to minimize bias and order effects. SETTING: All subjects were assessed at home, between 3 and 10 months after discharge from rehabilitation. PATIENTS: The criteria for inclusion were: (1) diagnosis of cerebral vascular accident (CVA); (2) completion of a minimum of 2 weeks in an acute rehabilitation program; (3) currently living at home; (4) living within a 30-mile radius of the hospital; and (5) cognitive and verbal skills adequate to complete a telephone interview. From a population of 103 patients, 40 subjects were randomly selected, 18 women and 22 men ranging in age from 37 to 90 years. MAIN OUTCOME MEASURES: The intermodal agreement between FIM ratings obtained by telephone interview and in-person assessment was examined using the intraclass correlation (ICC). FIM item scores were analyzed for agreement using the Kappa coefficient. The stability of the responses was determined by computing the coefficient of variation and plotting the data to visually examine the relationship between the two methods of administration. RESULTS: Data analysis revealed that there was no statistically significant difference (p > .05) between the two methods of administration for total FIM score. The total FIM ICC was .97. ICC values for FIM subscales ranged from .85 to .98, except for social cognition. Kappa scores for noncognitive items ranged from .49 (bowel movement) to .93 (grooming). The coefficient of variation computed to examine cognitive and communication items with reduced variability indicated good stability across all items. CONCLUSION: The results indicated good intermodal agreement for follow-up telephone assessment using the Functional Independence Measure. The findings were limited to persons with effective communication skills.

Activities of Daily Living↗

Functional measures of first-stroke rehabilitation inpatients: usefulness of the Functional Independence Measure total score with a clinical rationale.

OBJECTIVE: The Functional Independence Measure (FIM) was used to measure function in first-stroke patients on admission to and discharge from a rehabilitation center, and to determine gain; all data were analyzed by a clinically oriented approach. DESIGN: All patients admitted after a first supratentorial stroke to a comprehensive rehabilitation facility over a 2-year period were examined prospectively with the FIM. Diagnosis was determined by neuroimaging. Data were collected continuously and stored in the departmental database. For analysis of data, the patients were divided by side of lesion (right or left hemisphere), main clinical syndrome (presence or absence of neglect or aphasic syndromes in those with damage to the right or left hemisphere, respectively), type of lesion (ischemic, hemorrhagic, etc), and site of lesion (cortical or subcortical). SETTING: Neurological rehabilitation ward. PATIENTS: The study population included 151 patients of average age 60.8 years; 60% were men. All were admitted an average of 28.9 days after stroke and rehabilitated for 109.3 days. MAIN OUTCOME MEASURE: The raw FIM total score was determined at 48 to 72 hours after admission and at discharge. FIM gain was calculated by subtracting the FIM discharge score from the FIM admission score for each individual. Length of stay was also recorded. RESULTS: There was no difference in average total FIM scores when patients were divided by side of damage (right or left hemisphere). Significant findings were obtained for the various parameters when the clinical criterion was applied. Patients with neglect or aphasia syndromes showed significantly higher gains despite their lower FIM admission scores, but they had a much longer in-hospital stay. CONCLUSION: The raw FIM total score is a simple, practical, and efficient measure of function in first-stroke patients on admission for rehabilitation, provided an appropriate clinical approach is used during data analysis. Results can be used for comparison with similar measures, determination of admission and discharge policy, and program evaluation. The presence of neglect and aphasic syndromes has a significant effect on the various measures. Length of stay in rehabilitation is also of paramount importance in stroke patients with special clinical syndromes.

Cerebrovascular Disorders↗

Discharge destination and motor function outcome in severe stroke as measured by the functional independence measure/function-related group classification system.

OBJECTIVES: Function-related groups based on the Functional Independence Measure have been proposed as a model for a prospective payment system for medical rehabilitation. This study describes discharge destination and motor function outcomes in a sample of patients with stroke from the FIM-FRG STR1 classification. STUDY DESIGN: A retrospective review of 293 cases of stroke from the years 1993 to 1995. The demographic and outcome characteristics of this sample were described. RESULTS/CONCLUSIONS: Forty-five percent of the patients were discharged to home after a mean length of stay of 23.8 days in acute medical rehabilitation. Patients who were discharged home had higher admission and discharge motor FIM scores than those discharged to a subacute facility or long-term care facility, although the correlation between motor FIM score and discharge destination was low to moderate. Median discharge motor FIM scores indicate considerable residual disability in this classification after rehabilitation. Research problems that address methods to improve the usefulness of the FIM-FRG system in a prospective payment system are discussed.

Activities of Daily Living↗

Functional adaptation and ingrowth of bone vary as a function of hip implant stiffness.

The purpose of the present study was to test the hypothesis that cortical bone loss, trabecular bone density and the amount of bone ingrowth vary as a function of stem stiffness in a canine cementless hip replacement model. The study was motivated by the problem of cortical bone atrophy in the proximal femur following cementless total hip replacement. Two stem stiffnesses were used and both designs were identical in external geometry and porous coating placement. The high stiffness stem caused approximately 26% cortical bone stress-shielding and the low stiffness stem caused approximately 7.5% stress-shielding, as assessed by beam theory. Each group included nine adult, male canines who received unilateral arthroplasties for a period of six months. The animals with the low stiffness stems tended to lose less proximal cortical bone than the animals with high stiffness stems (4% +/- 9 as opposed to 11% +/- 14), but the difference was not statistically significant (p = 0.251). However, the patterns of bone ingrowth into the implant and change in medullary bone density adjacent to the implant were fundamentally different as a function of stem stiffness (p < 0.01). Most importantly, while the high stiffness group had peaks in these variables at the distal end of the stem, the low stiffness group had peak values proximally. These different patterns of functional adaptation are consistent with the idea that reduced stem stiffness enhances proximal load transfer.

Adaptation, Physiological↗

Compensating for executive function impairments after TBI: a single case study of functional intervention.

UNLABELLED: The purpose of this study was to demonstrate the effectiveness of compensatory strategies for impairments in executive function. The strategies were designed to enable a client with traumatic brain injury (TBI) to obtain professional employment. In a series of individual speech-language therapy sessions, compensatory strategies were developed, refined, and trained in mock-interview situations. Significant improvements were noted in report-writing accuracy and self-reported stress during report-writing. The client was able to obtain and maintain competitive employment in his chosen profession. The results support the use of strategies aimed at supporting executive function to improve performance on verbal tasks, and were informative regarding the effects of self-perceived efficacy and stress on performance after TBI. They illustrate that intervention based on real-life supports may be effective even many years post-TBI. LEARNING OUTCOMES: At the conclusion of this article, readers will: (1) identify aspects of executive function that relate to communication in the workplace, (2) describe the steps in considering intervention within a single subject research design framework, and (3) consider the effects of stress and perceived self-efficacy on performance of communication tasks.

Brain Injuries↗

Physiologic functional imaging in "functional" visual loss.

Neuroimaging with nuclear medicine techniques permits assessment of brain function by measurement of metabolism or blood flow. Such studies complement the anatomic information derived from computed tomography (CT) or magnetic resonance imaging (MRI). We describe two patients with occipital lesions who were initially diagnosed with functional visual loss. Neither CT scan nor MRI adequately demonstrated the source of visual dysfunction; however, single proton emission tomography (SPECT) scanning in a patient with carbon monoxide poisoning and positron emission tomography (PET) scanning in a patient with post-hypoxic delayed encephalopathy were helpful in confirming the organic substrate of their visual impairment. Functional imaging techniques such as SPECT and PET should be considered in patients with suspected cortical visual loss and normal CT or MR scans.

Adult↗

Endogenous RGS proteins regulate presynaptic and postsynaptic function: functional expression of RGS-insensitive Galpha subunits in central nervous system neurons.

Regulators of G-protein signaling (RGS)-insensitive (RGSi) G-protein alpha subunits can be used to indirectly determine the function of endogenous RGS proteins in native cells. This article describes the application of RGSi Galpha subunits to the study of endogenous RGS function in central nervous system (CNS) neurons. Presynaptic inhibition of neurotransmitter release was reconstituted in primary neurons using RGSi Galpha(i/o) subunits, whereas postsynaptic regulation of potassium channels was reconstituted using RGSi chimeras of Galpha(q) and Galpha(i). These studies have shown that endogenous RGS proteins are essential for the rapid termination of some G-protein-mediated signals in CNS neurons, whereas these proteins are much less important for the regulation of other signals. Together, these techniques have helped reveal the complexity of RGS regulation of CNS function.

Adenoviridae↗