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In JoVE (1)

Other Publications (10)

Articles by Richard L. Hoffman in JoVE

 JoVE Clinical and Translational Medicine

Utilizing Transcranial Magnetic Stimulation to Study the Human Neuromuscular System

1Ohio Musculoskeletal and Neurological Institute (OMNI) and the Department of Biomedical Sciences, Ohio University


JoVE 3387

Transcranial magnetic stimulation (TMS) is a non-invasive tool to gain insight on the physiology and function of the human nervous system. Here, we present our TMS techniques to study cortical excitability of the upper limb and lumbar musculature.

Other articles by Richard L. Hoffman on PubMed

Cloning the Schizosaccharomyces Pombe Lys2+ Gene and Construction of New Molecular Genetic Tools

Molecular genetic analyses in Schizosaccharomyces pombe rely on selectable markers that are used in cloning vectors or to mark targeted gene deletions and other integrated constructs. In this study, we used genetic mapping data and genomic sequence information to predict the identity of the S. pombe lys2(+) gene, which is homologous to Saccharomyces cerevisiae LYS4(+). We confirmed this prediction, showing that the cloned SPAC343.16 gene can complement a lys2-97 mutant allele, and constructed the lys2(+)-based cloning vector pRH3. In addition, we deleted the S. pombe his7(+) gene with a lys2(+) -marked polymerase chain reaction (PCR) product and the S. pombe lys2(+) gene with a his7(+)-marked PCR product. Strains carrying these deletions of lys2(+) or his7(+) serve as relatively efficient hosts for the deletion of the ade6(+) gene by lys2(+)-- or his7(+)--marked PCR products when compared with hosts carrying lys2 or his7 point mutations. Therefore, these studies provide plasmids and strains allowing the use of lys2(+) as a selectable marker, along with improved strains for the use of his7(+) to mark gene deletions.

Immobilization-induced Increase in Fatigue Resistance is Not Explained by Changes in the Muscle Metaboreflex

Immobilization has been reported to enhance fatigability, which is paradoxical in light of the metabolic and molecular alterations that occur in atrophied muscles. We examined whether the immobilization-induced enhancement in fatigability was associated with attenuation in the muscle metaboreflex response. Ten subjects were examined after 3 weeks of hand-forearm immobilization. The time to task failure of a handgrip contraction (20% intensity) was determined along with heart rate (HR) and mean arterial pressure (MAP) at rest, during the task and during a 2-min postexercise muscle ischemia (PEMI) test that continues to stimulate the metaboreflex. Immobilization decreased strength by 25% (P<0.01) and increased the time to task failure by 21% (P=0.03). However, no changes were observed for the HR and MAP responses to the exercise task or during PEMI (P>0.05). These findings indicate that the augmentation of time to task failure with immobilization is not associated with changes in the pressor or metaboreflex responses.

Neuromuscular Plasticity During and Following 3 Wk of Human Forearm Cast Immobilization

Prolonged reductions in muscle activity results in alterations in neuromuscular properties; however, the time course of adaptations is not fully understood, and many of the specific adaptations have not been identified. This study evaluated the temporal evolution of adaptations in neuromuscular properties during and following 3 wk of immobilization. We utilized a combination of techniques involving nerve stimulation and transcranial magnetic stimulation to assess changes in central activation of muscle, along with spinal (H reflex) and corticospinal excitability [i.e., motor-evoked potential (MEP) amplitude, silent period (SP)] and contractile properties in 10 healthy humans undergoing 3 wk of forearm immobilization and 9 control subjects. Immobilization induced deficits in central activation (85 +/- 3 to 67 +/- 7% ) that returned to baseline levels 1 wk after cast removal. The flexor carpii radialis MEP amplitude increased greater than twofold after the first week of immobilization and remained elevated throughout immobilization and 1 wk after cast removal. Additionally, we observed a prolongation of the SP 1 wk after cast removal compared with baseline (78.5 +/- 7.1 to 98.2 +/- 8.7 ms). The contractile properties were also altered, since the rate of evoked force relaxation was slower following immobilization (-14.5 +/- 1.4 to -11.3 +/- 1.0% peak force/ms), and remained depressed 1 wk after cast removal (-10.5 +/- 0.8% peak force/ms). These observations detail the time course of adaptations in corticospinal and contractile properties associated with disuse and illustrate the profound effect of immobilization on the human neuromuscular system as evidenced by the alterations in corticospinal excitability persisting 1 wk following cast removal.

Quantification of the Corticospinal Silent Period Evoked Via Transcranial Magnetic Stimulation

A magnetic pulse to the cortex during a muscle contraction produces a motor evoked potential (MEP) followed by electrical quiescence before activity resumes that is indicative of corticospinal inhibition and commonly referred to as the corticospinal slient period (SP). The purpose of the present study was to determine the effect of stimulus intensity and quantification method on the between-visit variability of the SP in healthy individuals. On two occasions we recorded the SP from 9 humans at 3 stimulus intensities (10, 20 and 30% above active motor threshold [AMT]) and quantified the SP based on 8 common criteria. We evaluated the effect of stimulus intensity on reliability by using the limits of agreement, and this analysis revealed that the lower stimulus intensities (10 and 20% AMT) exhibited heteroscedasticity, which indicates the amount of random error increases as the silent period increases. The 30% AMT intensity was homoscedastic. We used both visual and mathematical approaches to quantify the SP, and observed that the between-visit coefficient of variation (CV) was less for the visual methods, and that the CV was reduced when the SP onset was earliest in the temporal occurrence of events (i.e. MEP onset to EMG return CV=12%). Inter-rater reliability for the visual analyses were high (r=0.91-0.99). These results suggest that SPs evoked with a stimulus intensity >or=30% AMT and quantified visually by defining the start of the SP at stimulus delivery or the start of the MEP be utilized to decrease the between visit variability.

Delayed-onset Muscle Soreness Induced by Low-load Blood Flow-restricted Exercise

We performed two experiments to describe the magnitude of delayed-onset muscle soreness (DOMS) associated with blood flow restriction (BFR) exercise and to determine the contribution of the concentric (CON) versus eccentric (ECC) actions of BFR exercise on DOMS. In experiment 1, nine subjects performed three sets of unilateral knee extension BFR exercise at 35% of maximal voluntary contraction (MVC) to failure with a thigh cuff inflated 30% above brachial systolic pressure. Subjects repeated the protocol with the contralateral limb without flow restriction. Resting soreness (0-10 scale) and algometry (pain-pressure threshold; PPT) were assessed before and 24, 48 and 96 h post-exercise. Additionally, MVC and vastus lateralis cross-sectional area (CSA) were measured as indices of exercise-induced muscle damage. At 24-h post-exercise, BFR exercise resulted in more soreness than exercise without BFR (2.8 +/- 0.3 vs 1.7 +/- 0.5) and greater reductions in PPT (15.2 +/- 1.7 vs. 20 +/- 2.3 N) and MVC (14.1 +/- 2.5% decrease vs. 1.5 +/- 4.5% decrease) (p

Restoration of Voluntary Muscle Strength After 3 Weeks of Cast Immobilization is Suppressed in Women Compared with Men

To investigate sex-related differences in the loss and recovery of voluntary muscle strength after immobilization.

Cast Immobilization Increases Long-interval Intracortical Inhibition

Immobilization reduces muscle performance, and despite these performance losses being associated with neural impairments little is known regarding adaptations in cortical properties. We utilized transcranial magnetic stimulation to assess changes in flexor carpi radialis (FCR) intracortical facilitation (ICF), and short- and long-interval intracortical inhibition (SICI and LICI) in healthy humans undergoing 3 weeks of immobilization. Measurements were obtained at rest and during contraction (15% intensity). Central activation and the Hoffman reflex (H-reflex) were also assessed. Strength decreased 43.2% +/- 6.1% following immobilization, and central activation also decreased (97.5% +/- 2.4% to 73.2% +/- 8.3%). No changes in ICF, SICI, or LICI were observed at rest; however, LICI was increased during contraction (67.5% +/- 6.9% to 53.1% +/- 6.7% of unconditioned response). The increase in LICI correlated with the loss of strength (r = -0.63). The H-reflex increased following immobilization. These findings suggest that immobilization increases intracortical inhibition during contraction, and this increase is primarily mediated by GABA(B) receptors.

Older Adults Exhibit More Intracortical Inhibition and Less Intracortical Facilitation Than Young Adults

Aging results in decreased neuromuscular function, which is likely associated with neurologic alterations. At present little is known regarding age-related changes in intracortical properties.

Men and Women Exhibit a Similar Time to Task Failure for a Sustained, Submaximal Elbow Extensor Contraction

Sex differences in muscle fatigue-resistance have been observed in a variety of muscles and under several conditions. This study compared the time to task failure (TTF) of a sustained isometric elbow extensor (intensity 15% of maximal strength) contraction in young men (n = 12) and women (n = 11), and examined if their neurophysiologic adjustments to fatigue differed. Motor-evoked potential amplitude (MEP), silent period duration, interference electromyogram (EMG) amplitude, maximal muscle action potential (M (max)), heart rate, and mean arterial pressure were measured at baseline, during the task, and during a 2-min ischemia period. Men and women did not differ in TTF (478.2 +/- 31.9 vs. 500.4 +/- 41.3 s; P = 0.67). We also performed an exploratory post hoc cluster analysis, and classified subjects as low (n = 15) or high endurance (n = 8) based on TTF (415.3 +/- 16.0 vs. 626.7 +/- 25.8 s, respectively). The high-endurance group exhibited a lower MEP and EMG at baseline (MEP 16.3 +/- 4.1 vs. 37.2 +/- 3.0% M (max), P < 0.01; EMG 0.98 +/- 0.18 vs. 1.85 +/- 0.26% M (max), P = 0.03). These findings suggest no sex differences in elbow extensor fatigability, in contrast to observations from other muscle groups. The cluster analyses results indicated that high- and low-endurance groups displayed neurophysiologic differences at baseline (before performing the fatigue task), but that they did not differ in fatigue-induced changes in their neurophysiologic adjustments to the task.

Neurophysiologic Effects of Spinal Manipulation in Patients with Chronic Low Back Pain

While there is growing evidence for the efficacy of SM to treat LBP, little is known on the mechanisms and physiologic effects of these treatments. Accordingly, the purpose of this study was to determine whether SM alters the amplitude of the motor evoked potential (MEP) or the short-latency stretch reflex of the erector spinae muscles, and whether these physiologic responses depend on whether SM causes an audible joint sound.

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