Biomedical subjects

Andrew J Butler

Publications and source records attributed to Andrew J Butler.

16 recordsLinked to original sources

PubMed2006

Variability of motor potentials evoked by transcranial magnetic stimulation depends on muscle activation.

The purpose of this research was to determine whether motor cortex excitability assessed using transcranial magnetic stimulation (TMS) is less variable when subjects maintain a visually controlled low-level contraction of the muscle of interest. We also examined the dependence of single motor evoked potential (MEP) amplitude on stimulation intensity and pre-stimulus muscle activation level using linear and non-linear multiple regression analysis. Eight healthy adult subjects received single pulse TMS over the left motor cortex at a point where minimal stimulation intensity was required to produce MEPs in extensor digitorum communis (EDC). Voluntary activation of the muscle was controlled by visual display of a target force (indicated by a stable line on an oscilloscope) and the isometric force produced as the subject attempted to extend the fingers (indicated by a line on the oscilloscope representing the finger extension force) while subjects were instructed to: exert zero extension force (0%) and produce forces equal to 5 and 10% of maximum voluntary finger extension under separate conditions. Relative variability (coefficient of variation) of single MEPs at a constant stimulus intensity and of pre-stimulus muscle EMG was lower during maintained 5 and 10% contractions than at 0% contraction levels. Therefore, maintaining a stable low intensity contraction helps stabilize cortical and spinal excitability. Multiple regression analyses showed that a linear dependence of single MEPs on stimulation intensity and pre-stimulus muscle activation level produced similar fits to those for a non-linear dependence on stimulus intensity and a linear dependence on pre-stimulus EMG. Thus, a simple linear method can be used to assess dependence of single MEP amplitudes on both stimulus intensity (to characterize slope of the recruitment curve) and low intensity background muscle activation level.

Adult↗

PubMed2006

Mental practice with motor imagery: evidence for motor recovery and cortical reorganization after stroke.

OBJECTIVES: To measure the efficacy of a program combining mental and physical practice with the efficacy of a program composed of only constraint-induced movement therapy (CIMT) or only mental practice on stroke patients' levels of upper-extremity impairment and upper-extremity functional outcomes and to establish the relationship between changes in blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging response during a specific motor or imagery task and improvement in motor function between intervention groups. DESIGN: Case series. SETTING: Licensed, 56-bed, freestanding, university-affiliated rehabilitation hospital. PARTICIPANTS: Three men and 1 woman with moderate upper-limb hemiparesis after stroke were randomized. INTERVENTIONS: Two patients received mental practice and CIMT, 1 patient received only mental practice, and 1 received only CIMT. MAIN OUTCOME MEASURES: Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), Sirigu break test, Movement Imagery Questionnaire-Revised, and Vividness of Movement Imagery Questionnaire. RESULTS: The mental practice intervention alone led to slight improvement in certain functional and mental imagery measures (Sirigu, MAL, WMFT) but did not result in a clinically meaningful improvement with notable right cerebellar hemisphere activation that was not present before intervention. After CIMT, only the single patient showed clinically meaningful improvement of his affected hand as exhibited by decreased times on the MAL and WMFT. The patient showed increased bilateral cortical activation in both the motor and premotor areas during execution of a finger flexion and extension task. In contrast, during a second task, which was an imagined flexion and extension task, motor, occipital, and inferior parietal activation mainly in the contralateral hemisphere were observed. After 2 weeks of CIMT plus mental practice a patient with a lesion restricted to the parietal cortex showed little improvement in upper-extremity function and mental imagery in comparison with the patient with damage to nonparietal areas, who showed clinically meaningful improvement. The pattern of activation after 2 weeks of CIMT plus mental practice in the patient with nonparietal damage led to more focal contralateral activation in primary motor cortex when executing a voluntary flexion and extension task. CONCLUSIONS: The case series indicates that for these patients with chronic, moderate upper-extremity impairment after stroke, a 2-week regimen of CIMT or CIMT plus mental practice only (in 1 case) resulted in modest changes occurring as a decrease in impairment, with functional improvement. Mental practice alone did not result in a clinically meaningful improvement in upper-limb impairment. We describe how these interventions may elicit "plastic" changes in the brain. Further investigations to determine the appropriate delivery and dosing of both physical and mental practice, as well as to determine whether mental practice-induced changes positively correlate with distinct patterns of cortical activation, should be undertaken before the efficacy of their use can be ascertained among patients with limitations comparable with these participants.

Aged↗

PubMed2005

Finger extensor variability in TMS parameters among chronic stroke patients.

BACKGROUND: This study determined the reliability of topographic motor cortical maps and MEP characteristics in the extensor digitorum communis (EDC) evoked by single-pulse TMS among patients with chronic stroke. METHODS: Each of ten patients was studied on three occasions. Measures included location of the EDC hotspot and center of gravity (COG), threshold of activation and average amplitude of the hotspot, number of active sites, map volume, and recruitment curve (RC) slope. RESULTS: Consistent intrahemispheric measurements were obtained for the three TMS mapping sessions for all measured variables. No statistically significant difference was observed between hemispheres for the number of active sites, COG distance or the RC slope. The magnitude and range of COG movement between sessions were similar to those reported previously with this muscle in able-bodied individuals. The average COG movement over three sessions in both hemispheres was 0.90 cm. The average COG movement in the affected hemisphere was 1.13 (+/- 0.08) cm, and 0.68 (+/- 0.04) cm) for the less affected hemisphere. However, significant interhemispheric variability was seen for the average MEP amplitude, normalized map volume, and resting motor threshold. CONCLUSION: The physiologic variability in some TMS measurements of EDC suggest that interpretation of TMS mapping data derived from hemiparetic patients in the chronic stage following stroke should be undertaken cautiously. Irrespective of the muscle, potential causes of variability should be resolved to accurately assess the impact of pharmacological or physical interventions on cortical organization as measured by TMS among patients with stroke.

Journal Article↗

PubMed2005

Intra- and intersubject reliability of abductor pollicis brevis muscle motor map characteristics with transcranial magnetic stimulation.

OBJECTIVE: To determine consistency in motor maps of the abductor pollicis brevis (APB) muscle using transcranial magnetic stimulation (TMS) with conventional and close-spaced surface electrode recording placements. DESIGN: Nonrandom convenience sample. SETTING: TMS laboratory. PARTICIPANTS: Eleven participants without any known neurologic disorders. INTERVENTIONS: The left hemisphere of right-hand-dominant subjects was mapped using TMS at each of 2 sessions, separated by 1 to 8 weeks. MAIN OUTCOME MEASURES: Measurements at each session included the resting motor threshold, active site locations and average motor response amplitude for active sites, normalized map volume, and center of gravity (COG) for both electrode array configurations. RESULTS: The normalized map volume was larger for the conventional electrode placement than for the close electrode placement (4.23 cm2 vs 3.44 cm2, P=.010). Resting motor threshold was higher for the close-spaced than for the conventional-spaced electrodes (48.36% vs 46.59%, P=.028). No statistical difference was found between sessions and within electrode placements for the normalized map volume, for resting motor threshold, or for the mean motor amplitude of the most active site for each map. No statistical difference was observed for the COG distance between electrode placements. CONCLUSIONS: This study revealed differences between close-spaced and conventional-spaced surface electrode placement for TMS motor map volumes and for resting motor thresholds. The motor maps for the APB muscle were reliably reproducible between sessions for each electrode array.

Adult↗

PubMed2005

Contemporary linkages between EMG, kinetics and stroke rehabilitation.

EMG and kinetic measures have been primary tools in the study of movement and have provided the foundation for much of the work presented in this journal. Recently, novel ways of combining these tools have provided opportunities to examine elements of motor learning and brain plasticity. This presentation reviews the quantification of EMG within the context of transcranial magnetic stimulation. This vehicle permits acquisition of measures that are fundamental to examining prospects for cortical reorganization among patients with stroke and employs a therapeutic approach called "constraint induced therapy" as a model to demonstrate the interpretation of changes in EMG measures among patients with stroke. Moreover, interfacing novel uses of kinetic measurements during functional task performances is highlighted to illustrate how EMG and kinetics can provide further insight into mechanisms related to reacquisition of movement and concomitant changes in plasticity. Clinicians and researchers interested in expanding their use of these measurement tools are encouraged to learn more about application possibilities.

Brain↗

PubMed2005

Evidence of macrophage receptors capable of direct recognition of xenogeneic epitopes without opsonization.

BACKGROUND: We have previously demonstrated that porcine livers perfused with human blood remove most of the erythrocytes from three units of human blood over the course of a 72-h extracorporeal perfusion. Red blood cell loss did not appear to involve classical complement pathway-mediated hemolysis, but instead resulted from porcine Kupffer cell phagocytosis. METHODS: We developed a method incorporating collagenase digestion and metrizamide separation to isolate and maintain porcine Kupffer cells in primary culture. An in vitro rosetting assay was used to assess the binding of human and porcine erythrocytes to porcine Kupffer cells. Immunohistochemistry was used to confirm the presence of porcine macrophages. The rosetting assay was quantified using 51Cr-labeling of erythrocytes to assay for both rosette formation and phagocytosis. RESULTS: Porcine Kupffer cells were successfully isolated and maintained in primary culture. The presence of porcine macrophages was confirmed using the monoclonal antibody 74-22-15A. Human, but not porcine, erythrocytes were bound in an in vitro rosetting assay as confirmed by immunohistochemistry, electron microscopy and 51Cr-quantitation. Porcine Kupffer cells bound human erythrocytes regardless of the presence of opsonizing antibody. Approximately 70% of the isolated porcine Kupffer cells demonstrated the capacity to bind non-opsonized human erythrocytes. Phagocytosis was not observed. CONCLUSIONS: Using primary porcine Kupffer cell cultures, we have demonstrated that a subpopulation of porcine macrophages has the ability to recognize specifically xenogeneic human erythrocyte epitopes without the need for prior opsonization. The possibility is discussed that lectin-mediated carbohydrate binding plays a role in the cellular and humoral recognition and rejection of xenografts.

Animals↗

PubMed2004

Classical pathway complement destruction is not responsible for the loss of human erythrocytes during porcine liver perfusion.

BACKGROUND: Porcine livers perfused with human blood destroy 85% of human erythrocytes (red blood cells [RBC]) during prolonged extracorporeal perfusion, raising the possibility of a complement-mediated graft-versus-host effect. METHODS: Isolated porcine livers were perfused with fresh human blood. Plasma samples were analyzed for complement production by reverse CH50 analysis and porcine immunoglobulin class and specificity by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Anti-CD59 and anti-decay accelerating factor (DAF) monoclonal antibody were used to investigate whether human complement regulatory proteins inhibit porcine complement. RESULTS: After 64 hr of perfusion of porcine livers with human blood, mean complement activity in the perfusate was 95% of the starting value and increasing, whereas perfusion in the absence of a liver showed a falling complement activity of 28.7%. ELISA demonstrated porcine immunoglobulin (Ig) G and IgM in the xenoperfused human plasma. Whereas in a previous study flow cytometry demonstrated porcine antibodies specific for antigens on human T lymphocytes, in this study, anti-human RBC antibodies were not found. Xenoperfused human plasma did not lyse fresh human RBC. Human complement was consistently more efficient at lysing porcine RBC than was porcine complement at lysing human RBC, and human plasma inhibited the ability of porcine plasma to lyse human RBC, raising the possibility of cross-species complement regulation. Complement regulatory proteins on human RBC were blocked using mouse monoclonal anti-human CD59 and DAF. Blocking CD59, but not DAF, augmented lysis of human RBC by porcine complement. CONCLUSIONS: Human CD59 inhibits porcine complement. The production of porcine complement from xenoperfused porcine livers is unlikely to result in clinically significant injury mediated through the classical pathway of complement activation.

Animals↗

PubMed2004

Neural mechanisms underlying reaching for remembered targets cued kinesthetically or visually in left or right hemispace.

Reaching for a target involves integrative coordinate transformation processes between the representation of the target location, the sensorimotor information of limb of reach, and body space. Although right hemisphere dominance for visuospatial information processing is well established, corresponding right hemisphere dominance for kinesthetic spatial information processing remains to be demonstrated. We explored neural mechanisms of encoding target locations using 15O-butanol positron emission tomography (PET) in normal volunteers in a factorial experiment, where modality (visual/kinesthetic) and hemispace of target presentation (left/right of midsagittal plane) were varied systematically. After target presentation, subjects reached to the encoded target location. PET data analysis using SPM99 showed increased neural activity (P < 0.05, corrected) associated with left hemispace target presentation in right hemisphere areas (sensorimotor, anterior cingulate, insular, and temporo-occipital cortex) only. By contrast, right hemispace target presentation activated bilateral temporo-occipital cortex, which extended into the right temporo-parietal cortex and left sensorimotor cortex. A significant interaction of hemispace and modality of target presentation observed in right temporo-parietal cortex resulted from an increase in neural activity with kinesthetic target presentation in right hemispace. The data support an important role for the right temporo-parietal area in visuospatial processing and suggest a specific role of the right hemisphere in kinesthetic spatial processing.

Adult↗

PubMed2004

Intra-subject reliability of parameters contributing to maps generated by transcranial magnetic stimulation in able-bodied adults.

OBJECTIVE: This study evaluated the reliability of several parameters contributing to topographic motor cortical maps of the extensor digitorum communis (EDC) within able-bodied participants, across 3 sessions and from both hemispheres with greater precision than previously reported. METHODS: Nine healthy right-handed males aged 44-75 years were studied at 3 separate sessions, spaced 7-14 days apart. Transcranial magnetic stimulation (TMS) was used to elicit motor evoked potentials (MEP) in the contralateral EDC. Closely spaced surface electrodes were used to record the MEPs. RESULTS: TMS-related parameters did not demonstrate a significant difference within participants across sessions and between hemispheres, with the exception of the hotspot distance, center of gravity distance, and normalized map volume. Hotspot and COG distances were determined from the Euclidean equation to calculate the distance in x,y coordinates traveled over sessions: one to two (distance A) and two to three (distance B). The hotspot distance, center of gravity distance and normalized map volume demonstrated a significant difference between right and left hemispheres, within participants. Adjusting for time and examining mean changes for hemispheres across sessions revealed that there was a 9-fold greater movement over sessions in the left hemisphere among these variables. CONCLUSIONS: TMS-related parameters are reliable within participants across 3 sessions. These data should be useful for planning and interpreting TMS studies using a healthy or patient population before and after an intervention.

Adult↗

PubMed2004

Changes in serial optical topography and TMS during task performance after constraint-induced movement therapy in stroke: a case study.

The authors examined serial changes in optical topography in a stroke patient performing a functional task, as well as clinical and physiologic measures while undergoing constraint-induced therapy (CIT). A 73-year-old right hemiparetic patient, who had a subcortical stroke 4 months previously, received 2 weeks of CIT. During the therapy, daily optical topography imaging using near-infrared light was measured serially while the participant performed a functional key-turning task. Clinical outcome measures included the Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and functional key grip test. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were also used to map cortical areas and hemodynamic brain responses, respectively. Optical topography measurement showed an overall decrease in oxy-hemoglobin concentration in both hemispheres as therapy progressed and the laterality index increased toward the contralateral hemisphere. An increased TMS motor map area was observed in the contralateral cortex following treatment. Posttreatment fMRI showed bilateral primary motor cortex activation, although slightly greater in the contralateral hemisphere, during affected hand movement. Clinical scores revealed marked improvement in functional activities. In one patient who suffered a stroke, 2 weeks of CIT led to improved function and cortical reorganization in the hemisphere contralateral to the affected hand.

Aged↗

PubMed2004

The effects of constraint-induced therapy on precision grip: a preliminary study.

OBJECTIVE: This preliminary study examines the effects of a 2-week constraint-induced therapy (CIT) intervention on the force-producing capabilities of the hemiparetic hand during the performance of a functional dexterous manipulation task. METHODS: A 6-degree-of-freedom force/torque transducer that was embedded into the handle of a key allowed for the quantification of grasping forces and torques produced during the performance of a functional key-turning task. Clinical and kinetic data were collected from 10 subacute patients (3-9 months poststroke) who were participating in an ongoing national clinical study (EXCITE trial) examining the effects of CIT on upper extremity motor performance. Investigators were blinded to treatment designation. Five patients receiving treatment immediately completed 2 weeks of intensive CIT, whereas a group randomized to treatment 1 year later did not receive any therapy during a similar 2-week span. RESULTS: . Results indicated that 4 of the 5 patients in the CIT group, compared to the delayed group, showed significant clinical improvements in hand function, increased maximum precision grip force, improved force and torque regulation, and reduced variability in rate of force production during task performance. CONCLUSIONS: Improved force control may be a mechanism contributing to the observed improvements in dexterous function in those patients undergoing CIT.

Chronic Disease↗

PubMed2003

Transcranial magnetic stimulation to assess cortical plasticity: a critical perspective for stroke rehabilitation.

Transcranial magnetic stimulation has gained increasing visibility as an evaluative and interventional tool during the past 15 years. Within the context of rehabilitation, transcranial magnetic stimulation has been applied to differentiate excitatory and inhibitory mechanisms and to assess cortical reorganization following specific interventions. This article reviews some of the more salient features of transcranial magnetic stimulation applications relevant to stroke rehabilitation, highlighting the strengths and weaknesses in this approach. Data derived from such studies may be profoundly over-interpreted. Information is provided showing the importance of utilizing fundamental principles of electrode placement and kinesiological electromyography to more accurately reflect and interpret data emerging from transcranial magnetic stimulation mapping studies, particularly as they apply to the interpretation of cortical reorganization following application of neurorehabilitative procedures.

Brain Mapping↗

PubMed2002

Porcine livers perfused with human blood mount a graft-versus-"host" reaction.

BACKGROUND: A major focus of xenotransplantation research is the interaction between human immune effector mechanisms and porcine tissues. We present evidence that a transplanted porcine organ might also mount a significant immune response to a human recipient. METHODS: Isolated porcine livers were perfused with fresh human blood. Plasma samples were analyzed for complement production by reverse CH50 analysis. ELISA was used to determine the amount and class of porcine immunoglobulin in human blood after xenoperfusion. Flow cytometry was used to determine the specificity and class of porcine immunoglobulin in human blood after xenoperfusion and to determine whether porcine immunoglobulins had bound to the human lymphocytes in the blood perfusing the porcine livers. Electron microscopy was used to evaluate the interaction of porcine Kupffer cells and human erythrocytes. RESULTS: Over the course of 72 hr of extracorporeal perfusion of porcine livers with human blood, the hematocrit fell progressively to as low as 2.5% of starting values, a phenomenon not seen in experiments using porcine blood. We have demonstrated both porcine complement and immunoglobulin in the human blood after xenoperfusion. The porcine antibodies in the human blood have specificity for human lymphocyte antigens. In fact, with increasing duration of perfusion, 40% of the xenoperfusions showed increasing titers of porcine antibodies with specificity for human lymphocyte antigens suggesting a response by primed porcine lymphocytes. However, the majority of erythrocytes are extracted directly by Kupffer cells in the liver. CONCLUSIONS: These data demonstrate the ability of porcine livers to generate both a humoral and cellular graft versus host response to human cells.

Animals↗

PubMed2002

Prolonged function of extracorporeal hDAF transgenic pig livers perfused with human blood.

BACKGROUND: The development of genetically modified pigs has renewed interest in the use of porcine liver perfusion in the treatment of acute liver failure. METHOD: A previously developed model of extracorporeal perfusion has been used to test the function of porcine livers transgenic for human decay accelerating factor when perfused with fresh, whole, human blood. Three experimental groups were studied: alloperfusions (normal pig livers perfused with pig blood) and xenoperfusions of both unmodified and transgenic pig livers with human blood. All livers were perfused for up to 72 hr. RESULTS: Alloperfusion resulted in the maintenance of good function and histological structure. Stable hemodynamic, synthetic, and metabolic parameters were demonstrated in both unmodified and transgenic liver xenoperfusions; hyperacute rejection was not seen. In both groups, however, the measured parameters of liver function deteriorated toward the end of the 72 hr perfusion period; deterioration was more marked in the nontransgenic group. Xenoperfusions were characterized by a progressive and marked decrease in hematocrit of the circulating blood. Histologically, patchy necrosis was noted in both groups and more retained erythrocytes were seen in the sinusoids of nontransgenic livers, but no other consistent differences were apparent. CONCLUSIONS: These studies have demonstrated that porcine liver xenoperfusions can be performed for prolonged periods while maintaining good liver function. The use of organs from animals transgenic for a human complement regulator protein confers improvement in some measures of liver function. This preclinical model provides evidence that extracorporeal liver xenoperfusion may be effective in temporary liver support for patients in acute liver failure.

Animals↗

PubMed2002

Successful extracorporeal porcine liver perfusion for 72 hr.

BACKGROUND: Improvements in extracorporeal perfusion technology and the production of transgenic pigs resistant to hyperacute rejection have stimulated several groups to re-explore the possibility of supporting patients in hepatic failure with extracorporeal porcine livers. The success of organ transplantation has also stimulated interest in using extracorporeal perfusion as a means of organ preservation and resuscitation of organs from marginal donors. The present study describes a method by which livers can be maintained in a viable condition for a minimum of 72 hr of normothermic, extracorporeal perfusion. METHODS: Five extracorporeal porcine liver perfusions were performed, each with a duration of 72 hr. Hepatectomy was performed, followed by cold preservation, cannulation of vessels, and initiation of perfusion with normothermic, oxygenated porcine blood. Organ viability was assessed by metabolic, synthetic, hemodynamic, and histologic parameters. RESULTS: After 72 hr of normothermic, extracorporeal perfusion, the isolated livers demonstrated maintenance of normal physiological levels of pH and electrolytes. Continued hepatic protein synthesis (complement and factor V) was maintained throughout the perfusion. Hemodynamic parameters remained within normal physiological range. Histology demonstrated good preservation of the liver with no overall architectural change. CONCLUSION: It is possible to maintain a liver in a viable condition for a minimum of 72 hr of extracorporeal perfusion. This technique has been developed primarily as a preclinical model of extracorporeal liver support with the intention of proceeding to a clinical trial in patients with fulminant liver failure. However, it also has potential applications in organ preservation or resuscitation before transplantation and in the experimental study of isolated liver physiology.

Animals↗

PubMed2002

Repetitive task practice: a critical review of constraint-induced movement therapy in stroke.

BACKGROUND: Constraint-induced (CI) movement therapy (also called forced use by some investigators and clinicians) has gained increasing popularity as a treatment mode for restoring function in the upper extremities of patients with stroke. The purpose of this article is to review the concept of constraint-induced movement therapy and provide a critical analysis of the existing data. REVIEW SUMMARY: The evidence to date offers encouragement for the application of this procedure for patients who have some movement recovery out of synergy. Success may be contingent on patient cooperation and intense repetitive use with applications of retraining through practice and shaping. The extent to which each of the latter elements influences the magnitude of recovery is still unclear. However, task novelty and challenge seem important to recovery of function. There are several methods used to map cortical changes after stroke. At this time, transcranial magnetic stimulation is the primary vehicle used to assess motor cortical reorganization after CI therapy in humans. CONCLUSIONS: Accumulating data indicate that the size of a cortical area representative of a muscle does expand and its center of gravity does change with CI therapy.

Journal Article↗