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Biomedical subjects

Robert Chen

Publications and source records attributed to Robert Chen.

At least 55 records · Page 3Linked to original sources
PubMed2003

An automated method to determine the transcranial magnetic stimulation-induced contralateral silent period.

BACKGROUND: The transcranial magnetic stimulation (TMS)-induced contralateral silent period (CSP) refers to a period of interruption of voluntary muscle activity measured in tonically active muscles. The length of the CSP is generally interpreted to reflect cortical inhibition. The determination of the return of voluntary motor activity is typically accomplished via visual inspection of the electromyography (EMG) waveform and may be subject to inaccuracy on the part of the rater. OBJECTIVE: To present and evaluate an automated method (AM) to determine the CSP. METHODS: The CSP of 11 healthy controls was recorded using stimulus intensities 20 and 50% above the resting motor threshold (RMT). The mean CSP duration obtained by the two raters using visual inspection and our automated approach were compared. RESULTS: The interclass correlation coefficient (ICC) between the two raters and the AM was 0.99 at 150% of RMT and was 0.97 at 120% of RMT. The level of pre-stimulus EMG amplitude and sampling rate did not affect agreement between the AM and more conventional visually guided methods. CONCLUSIONS: Our study demonstrates that this AM is a simple, objective and reliable approach for CSP determination. SIGNIFICANCE: The CSP is an important neurophysiological measure of cortical inhibition and its determination by our AM provides a more objective and automated approach compared to visually guided methods.

Adult↗
PubMed2003

Plasticity of the human motor system following muscle reconstruction: a magnetic stimulation and functional magnetic resonance imaging study.

OBJECTIVE: Although motor system plasticity in response to neuromuscular injury has been documented, few studies have examined recovered and functioning muscles in the human. We examined brain changes in a group of patients who had a muscle transfer. METHODS: Transcranial magnetic stimulation (TMS) was used to study a unique group of 9 patients who had upper extremity motor function restored using microneurovascular transfer of the gracilis muscle. The findings from the reconstructed muscle were compared to the homologous muscle of the intact arm. One patient was also studied with functional magnetic resonance imaging (fMRI). RESULTS: TMS showed that the motor threshold and short interval intracortical inhibition was reduced on the transplanted side while at rest but not during muscle activation. The difference in motor threshold decreased with the time since surgery. TMS mapping showed no significant difference in the location and size of the representation of the reconstructed muscle in the motor cortex compared to the intact side. In one patient with reconstructed biceps muscle innervated by the intercostal nerves, both TMS mapping and fMRI showed that the upper limb area rather than the trunk area of the motor cortex controlled the reconstructed muscle. CONCLUSIONS: Plasticity occurs in cortical areas projecting to functionally relevant muscles. Changes in the neuronal level are not necessarily accompanied by changes in motor representation. Brain reorganization may involve multiple processes mediated by different mechanisms and continues to evolve long after the initial injury. SIGNIFICANCE: Central nervous system plasticity following neuromuscular injury may have functional relevance.

Adolescent↗
PubMed2003

Constraint-induced therapy in stroke: magnetic-stimulation motor maps and cerebral activation.

Constraint-induced movement therapy (CI), a standardized intensive rehabilitation intervention, was given to patients a year or more following stroke. The goal was to determine if CI was more effective than a less-intensive control intervention in changing motor function and/or brain physiology and to gain insight into the mechanisms underlying this recovery process. Subjects were recruited and randomized more than 1 year after a single subcortical infarction. Clinical assessments performed before and after the intervention and at 6 months postintervention included the Wolf Motor Function Test (WMFT), the Motor Activity Log (MAL), and the Assessment of Motor and Process Skills (AMPS). Transcranial magnetic stimulation was used to map the motor cortex. Positron emission tomography was used to measure changes in motor task-related activation due to the intervention. MAL increased by 1.08 after CI therapy and decreased by 0.01 after control therapy. The difference between groups was significant (P < 0.001). Changes in WMFT and AMPS were not significantly different between groups. Cerebral activation during a motor task decreased significantly, and motor map size increased in the affected hemisphere motor cortex in CI patients but not in control patients. Both changes may reflect improved ability of upper motor neurons to produce movement.

Adult↗
PubMed2003

Efficacy and safety of HLA-B7/beta-2 microglobulin plasmid DNA/lipid complex (Allovectin-7) in patients with metastatic melanoma.

Human leukocyte antigen (HLA)-B7/beta-2 microglobulin plasmid DNA/lipid complex, otherwise known as Allovectin-7 (Vical, Inc., San Diego, CA, USA), has been developed as a non-viral gene delivery product. After multiple laboratory and human trials, it appears that the concept of gene transfer has established itself as a clinical reality. While the manifestations of the gene transfer have not been as dramatic as one might have hoped, HLA-B7/beta-2 microglobulin plasmid DNA/lipid complex appears to be a promising agent with an extremely safe toxicity profile. Ongoing trials are further investigating potential clinical uses of Allovectin-7.

Animals↗
PubMed2003

Prostate cancer on the internet: impact on patients and how technology helps physicians and researchers.

The Internet is a repository of information unparalleled in history. The abundance of published material about prostate cancer has never been greater. Couple this with burgeoning pharmaceutical public-relations budgets and the result is a bewildering maze of hundreds of thousands of prostate cancer-oriented Internet pages. Our purposes are to help practitioners understand the profound handicap that patients are faced with when they attempt to search the Internet for information about their newly diagnosed disease and to succinctly evaluate the presence or absence of key aspects of prostate cancer on some of the most easily accessible sites. Part two of this paper will then discuss 4 of the most valuable Web sites for the prostate cancer specialist. Surfing the World Wide Web can be frustrating and time-consuming, but it can also be rewarding and informative.

Humans↗
PubMed2003

Using electrodiagnostic machine to study movement rhythm variation.

BACKGROUND: Hand movement constitutes the most common daily activities in our life. Hand dexterity is often impaired in patients with neurological disease. We developed an adjunct method, based upon the electrodiagnostic software, for study of motor control and hand dexterity. METHODS: Thirty-two normal subjects, 2 stroke patients and 2 Parkinson patients were included in the study. All of them were right-handed, and were asked to pace rhythmic finger tapping at a comfortable rate without cue or any external stimuli. A trigger kit was designed to transform the finger tapping. After using the triggering mode and adjusting the sweep speed, 2 tapping signals were simultaneously displayed on the screen. The first signal was the triggering potential, and the variation in timing of the second signal represented the variation in timing of the inter-response interval. Twenty sweeps were recorded, superimposed and measured on the screen. Movement rhythm variation (MRV) was defined as b/a x 100 (b = [maximal interval of finger tapping - minimal interval of finger tapping]; a = [maximal interval of finger tapping + minimal interval of finger tapping]/2). Each subject started with right hand and then left hand. RESULTS: MRV measurement showed excellent intrarater (r = 0.97) and interrater (r = 0.97) reliability. In normal right-handed subjects, the MRV was better in right hand than in left hand (right 16.5 +/- 4.1% and left 21.0 +/- 7.6%; p < 0.05). The MRV improved in stroke patients along with the recovery and improved in Parkinson patients after levodopa treatment. CONCLUSIONS: MRV was a good method to provide quantitative data for assessment of hand dexterity. Our study also showed the potential role of MRV in motor control study.

Adult↗
PubMed2002

The Brighton Collaboration: addressing the need for standardized case definitions of adverse events following immunization (AEFI).

UNLABELLED: To further scientific progress of immunization safety, comparability of data from clinical trials and surveillance systems is essential. Comparability requires the availability of standardized case definitions for adverse events following immunization (AEFI) and guidelines for case determination, recording and data presentation. METHOD: International collaborative working groups, consisting of professional volunteers from developed and developing countries, conduct systematic literature reviews to develop 50-100 AEFI definitions. Case definitions are finalized after a comment period by a reference group consisting of organizations concerned with immunization safety, and will be disseminated via the world-wide-web and other means for free world-wide use. RESULTS: Literature reviews yielded substantial diversity in data collection and presentation. We have developed standardized case definitions together with guidelines for use in clinical trials and surveillance systems. CONCLUSIONS: Diversity in safety methods leads to considerable loss of scientific information. We have built the necessary international network of currently about 300 participants from patient care, public health, scientific, pharmaceutical, regulatory and professional organizations to develop and assess standardized AEFI case definitions and guidelines. Evaluation studies, global implementation, ongoing definition development and a continuously growing network will be essential for the success of the collaboration.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002.

This report updates CDC's recommendations for using yellow fever vaccine (CDC. Yellow Fever Vaccine: Recommendations of the Advisory Committee on Immunizations Practices: MMWR 1990;39[No. RR-6]1-6). The 2002 recommendations include new or updated information regarding 1) reports of yellow fever vaccine-associated viscerotropic disease (previously reported as febrile multiple organ system failure); 2) use ofyellow fever vaccine for pregnant women and persons infected with human immunodeficiency virus (HIV); and 3) concurrent use of yellow fever vaccine with other vaccines. A link to this report and other information related to yellow fever can be accessed at the website for Travelers' Health, Division of Global Migration and Quarantine, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/travel/index.htm, and through the website for the Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, CDC, at http://www.cdc.gov/ncidod/ dvbid/yellowfever/index.htm.

Adolescent↗
PubMed2002

Organization of ipsilateral excitatory and inhibitory pathways in the human motor cortex.

Motor cortex stimulation has both excitatory and inhibitory effects on ipsilateral muscles. Excitatory effects can be assessed by ipsilateral motor-evoked potentials (iMEPs). Inhibitory effects include an interruption of ipsilateral voluntary muscle activity known as the silent period (iSP) and a reduction in corticospinal excitability evoked by conditioning stimulation of the contralateral motor cortex (interhemispheric inhibition, IHI). Both iSP and IHI may be mediated by transcallosal pathways. Their relationship to the contralateral corticospinal projection and whether iSP and IHI represent the same phenomenon remain unclear. The neuronal population activated by transcranial magnetic stimulation (TMS) is highly dependent on the direction of the induced current in the brain. We examined the relationship among iMEP, iSP, IHI, and the contralateral corticospinal system by examining the effects of different stimulus intensities and current directions. Surface electromyography (EMG) was recorded from both first dorsal interosseous (FDI) muscles. The iSP in the right FDI muscle was obtained by right motor cortex stimulation during voluntary muscle contraction. IHI was examined by conditioning stimulation of the right motor cortex followed by test stimulation of the left motor cortex at interstimulus intervals (ISIs) of 2-80 ms. The induced current directions tested in the right motor cortex were anterior medial (AM), posterior medial (PM), posterior lateral, and anterior lateral (AL). Contralateral MEPs (cMEPs) had the lowest threshold with the AM direction and the shortest latency with the PM direction. iMEPs were present in 8 of 10 subjects. Both iMEP and IHI did not show significant directional preference. iSP was observed in all subjects with the highest threshold for the AL direction and the longest duration for the AM direction. cMEP, iSP, and IHI all increased with stimulus intensity up to approximately 75% stimulator output. Target muscle activation decreased IHI at 8-ms ISI but had little effect on IHI at 40-ms ISI. iSP and IHI at 8-ms ISI did not correlate at any stimulus intensities and current directions tested, and factor analysis showed that they are explained by different factors. However, active IHI at 40-ms ISI was explained by the same factor as iSP. The different directional preference for cMEP compared with iMEP and IHI suggests that these ipsilateral effects are mediated by populations of cortical neurons that are different from those activating the corticospinal neurons. iSP and IHI do not represent the same phenomenon and should be considered complementary measures of ipsilateral inhibition.

Adult↗
PubMed2002

Effects of peripheral sensory input on cortical inhibition in humans.

Cortical inhibitory systems play an important role in motor output. The motor cortex can be inhibited by intracortical mechanisms and by peripheral sensory inputs. We examined whether cortical inhibition from peripheral sensory input is mediated through previously identified intracortical inhibitory systems and how these inhibitory systems interact. Two types of intracortical inhibition were assessed by paired-pulse transcranial magnetic stimulation (TMS). Short-interval intracortical inhibition (SICI) was determined with a subthreshold conditioning stimulus (CS) followed by a test stimulus 2 ms later and long-interval intracortical inhibition (LICI) with suprathreshold conditioning and test stimuli 100 ms apart. Cortical inhibition from peripheral sensory input was induced by median nerve stimulation (MNS) of the right hand and followed by a suprathreshold TMS over the left motor cortex 200 ms later. The first set of experiments tested the effects of different test stimulus intensities on SICI, LICI and cortical inhibition induced by median nerve stimulation (MNSI). With higher test stimulus intensities, LICI and MNSI decreased whereas SICI showed a trend towards an increase. The extent of SICI, LICI and MNSI did not correlate. The second experiment assessed the interaction between MNSI and LICI. The results of applying MNSI and LICI simultaneously were compared with MNSI and LICI alone. MNSI was virtually abolished in the presence of LICI and LICI was also significantly decreased in the presence of MNSI. Thus, the effects of MNSI and LICI when applied together were much less than their expected additive effects when applied alone. The degree of interaction between MNSI and LICI was related to the combined strength of MNSI and LICI but not to the strength of LICI alone. The third experiment investigated the interaction between SICI and MNSI. MNSI and SICI were applied together and the results were compared with MNSI and SICI alone. SICI remained unchanged in the presence of MNSI. We conclude that MNSI is mediated by circuits distinct from those mediating LICI or SICI. The MNSI circuits seem to have an inhibitory interaction with the LICI circuits, whereas the SICI and MNSI circuits do not seem to interact.

Adult↗
PubMed2002

The mechanisms of interhemispheric inhibition in the human motor cortex.

Transcranial magnetic stimulation can be used to non-invasively study inhibitory processes in the human motor cortex. Interhemispheric inhibition can be measured by applying a conditioning stimulus to the motor cortex resulting in inhibition of the contralateral motor cortex. Transcranial magnetic stimulation can also be used to demonstrate ipsilateral cortico-cortical inhibition in the motor cortex. At least two different ipsilateral cortico-cortical inhibitory processes have been identified: short interval intracortical inhibition and long interval intracortical inhibition. However, the relationship between interhemispheric inhibition and ipsilateral cortico-cortical inhibition remains unclear. This study examined the relationship between interhemispheric inhibition, short interval intracortical inhibition and long interval intracortical inhibition. First, the effect of test stimulus intensity on each inhibitory process was studied. Second, the effects of interhemispheric inhibition on short interval intracortical inhibition and long interval intracortical inhibition on interhemispheric inhibition were examined. Motor evoked potentials were recorded from the right first dorsal interosseous muscle in 11 right-handed healthy volunteers. For interhemispheric inhibition, conditioning stimuli were applied to the right motor cortex and test stimuli to the left motor cortex. For short interval intracortical inhibition and long interval intracortical inhibition, both conditioning stimuli and test stimuli were applied to the left motor cortex. With increasing test stimulus intensities, long interval intracortical inhibition and interhemispheric inhibition decreased, while short interval intracortical inhibition increased. Moreover, short interval intracortical inhibition was significantly reduced in the presence of interhemispheric inhibition. Interhemispheric inhibition was significantly reduced in the presence of long interval intracortical inhibition when matched for test motor evoked potential amplitude but the difference was not significant when matched for test pulse intensity. These findings suggest that both interhemispheric inhibition and long interval intracortical inhibition are predominately mediated by low threshold cortical neurons and may share common inhibitory mechanisms. In contrast, the mechanisms mediating short interval intracortical inhibition are probably different from those mediating long interval intracortical inhibition and interhemispheric inhibition although these systems appear to interact.

Adult↗
PubMed2002

Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation.

BACKGROUND: Cortical inhibition (CI) deficits have been proposed as a pathophysiologic mechanism in schizophrenia. This study employed 3 transcranial magnetic stimulation (TMS) paradigms to assess CI in patients with schizophrenia. Paired-pulse TMS involves stimulating with a lower-intensity pulse a few milliseconds before a higher-intensity pulse, thereby inhibiting the size of the motor evoked potential produced by the higher-intensity pulse. In the cortical silent period paradigm, inhibition is reflected by the silent period duration (ie, the duration of electromyographic activity cessation following a TMS-induced motor evoked potential). Transcallosal inhibition involves stimulation of the contralateral motor cortex several milliseconds prior to stimulation of the ipsilateral motor cortex, inhibiting the size of the motor evoked potential produced by ipsilateral stimulation. METHODS: We measured CI using these 3 paradigms in 15 unmedicated patients with schizophrenia (14 medication-naive and 1 medication-free for longer than 1 year) (13 were in the transcallosal inhibition paradigm), 15 medicated patients with schizophrenia (11 taking olanzapine, 1 risperidone, 1 quetiapine, 1 methotrimeprazine + perphenazine, 1 quetiapine + loxapine), and 15 healthy controls. RESULTS: Unmedicated patients demonstrated significant CI deficits compared with healthy controls across all inhibitory paradigms whereas medicated patients did not (at all inhibitory intervals, paired-pulse TMS: controls = 59.9%, medicated = 44.3%, unmedicated = 28.7%; cortical silent period: controls = 55.0 milliseconds, medicated = 60.4 milliseconds, unmedicated = 39.7 milliseconds; transcallosal inhibition: controls = 33.6%, medicated = 23.7%, unmedicated = 10.4%; P<.05). CONCLUSIONS: These results suggest that schizophrenia is associated with deficits in CI and that antipsychotic medications may increase CI.

Adult↗
PubMed2002

Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation.

Recovery of function after acute injury to the central nervous system may be controlled by the availability of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cerebral cortex. Acute lesions as well as manipulation of sensory inputs can lead to rapid reorganization of the cerebral cortex, occurring within minutes to hours. Reduction of cortical inhibitory tone through a decrease in the availability of GABA has been suggested as a possible mechanism; however, the degree and temporal course of the changes in brain GABA are not known. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy showed that GABA levels in the human sensorimotor cortex are quickly reduced within minutes of deafferentation. This finding strongly supports the view that the release of latent corticocortical projections from tonic inhibition through decreased GABA availability is a mechanism of rapid cortical plasticity. Reduction of brain GABA can play a pivotal role in regulating the extent of rapid cortical reorganization after lesions or changes in sensory input.

Adult↗
PubMed2002

Effects of apomorphine on flexor reflex and periodic limb movement.

It has been suggested that periodic leg movements (PLM) and spinal flexor reflex (FR) share common mechanisms. Although dopaminergic agents improve PLM in humans and strongly influence spinal FR circuitry in animal studies, its effects on FR have not been documented in humans. We describe a 65-year-old man with PLM after overnight withdrawal of dopaminergic agents. The electromyographic pattern of spontaneous PLM closely resembled that of the FR elicited by medial plantar nerve stimulation. Thirty minutes after subcutaneous injection of apomorphine, both PLM and FR were completely abolished. These findings demonstrate that dopaminergic agents can suppress exaggerated FR in humans, and support the hypothesis of common mechanisms for PLM and FR.

Aged↗
PubMed2002

Synthesis of (-)-5,8-dihydroxy-3R-methyl-2R-(dipropylamino)-1,2,3,4-tetrahydronaphthalene: an inhibitor of beta-amyloid(1-42) aggregation.

A concise synthesis of the beta-amyloid(1-42 )aggregation inhibitor (-)-5,8-dihydroxy-3R-methyl-2R-(dipropylamino)-1,2,3,4-tetrahydronaphthalene [(-)-2] has been developed. The key step is a regio- and diastereoselective hydroboration-amination sequence to convert alkene into amine. Enantiomeric resolution was achieved by recrystallization of amine as the dibenzoyl-D-tartaric acid salt. Hydroquinone is a potent inhibitor of the fibrillar aggregation of beta-amyloid as determined in two different assay systems.

Amyloid beta-Peptides↗
PubMed2002

Intensity-dependent effects of 1 Hz rTMS on human corticospinal excitability.

OBJECTIVES: This study explored whether the effects of repetitive transcranial magnetic stimulation (rTMS) on corticospinal excitability are dependent on the stimulation intensity and examined the effect of rTMS on inhibitory function. METHODS: Nine normal volunteers received 15min of 1Hz rTMS at 85 and 115% of the resting motor threshold (RMT). Cortical excitability was measured before and after rTMS. RESULTS: rTMS at both intensities produced an increase in the RMT but only 115% stimulation reduced the size of motor evoked potentials (MEPs). rTMS had no effects on the cortical silent period or cortical inhibition measured with paired pulse TMS. CONCLUSIONS: The effects of 1Hz rTMS on motor cortex excitability are partially dependent on stimulus intensity and the effects of rTMS on motor thresholds and MEP size may differ.

Adult↗
PubMed2002

Deep brain stimulation for Parkinson's disease: disrupting the disruption.

Many people are disabled by Parkinson's disease (PD) despite the drug treatments that are currently available. For these patients, neurosurgery has the potential to help restore their function. The most effective neurosurgical procedures to date use electrical stimulation--deep brain stimulation (DBS)--of small targets in the brain by use of a pacemaker-like device to deliver constant stimulation. Although these operations can produce striking results, the mechanism by which delivery of electrical stimulation to targets deep in the brain can restore function in the motor system is not clear. This type of surgery probably works by interfering with and shutting down abnormal brain activity in areas where the current is delivered, such as the thalamus, globus pallidus, or the subthalamic nucleus. With this abnormal neuronal activity neutralised, motor areas of the brain can resume their function and normal movements are reinstated. Current research is aimed at elucidating how DBS works and using this information to develop better treatments for patients with PD and other neurological disorders.

Animals↗