William F. Brown

McMaster University, Hamilton, Ontario, Canada

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Publications (43)74.01 Total impact

  • William F. Brown · Anh X. Nguyen · Bradley V. Watson ·
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    ABSTRACT: The physiological consequences of demyelination depend on the extent and severity of the demyelination as well as the types of nerve fibers involved. Demyelination impairs the transmission of impulses by changing the biophysical properties of the paranodal and internodal membranes and has been studied in single nerve fibers. For example, loss of the myelin sheath increases the capacitance and diminishes the transverse resistance in the paranodal and internodal regions. Demyelination in the paranodal region is especially critical for three reasons. First, retraction of the myelin sheath and Schwann cell processes increases the available nodal membrane area, thereby diluting the available depolarizing current over a larger membrane surface. Second, potassium channels that are normally present in the nearby paranodal–axolemmal membrane become exposed and as a result the membrane becomes hyperpolarized, thereby reducing the safety factor for transmission in the region. Third, the (sodium ion) Na+, (potassium ion) K+-ATPase electrogenic pump in the nodal region tends to drive the membrane toward the K+ equilibrium potential, further increasing the load on the internal longitudinal current (ILC) available for generating an action potential at the next nodal region in line.
    Handbook of Clinical Neurophysiology 12/2006; 7. DOI:10.1016/S1567-4231(09)70065-6
  • Bradley V Watson · William F Brown · Timothy J Doherty ·
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    ABSTRACT: Frequency-dependent conduction block (FDB) across segments of demyelination in response to high-frequency nerve stimulation has been well demonstrated in animals and has been explored in humans. However, attempts to demonstrate this phenomenon in sensory fibers involved in entrapment neuropathies have been unsuccessful. Therefore, we investigated the effects of high-frequency nerve stimulation in the median motor nerve in patients with carpal tunnel syndrome (CTS) with moderate to severely increased distal motor terminal latencies (MTL). As a group, the mean decrease in negative peak amplitude (npAmp) during 20 stimuli at 30-HZ frequency was significantly greater in CTS subjects (-11.3%) than in controls (+7.9%). The degree of FDB was greater when MTL was more prolonged (i.e., -4.9% at 5.0 ms and -25.3% at 9.4 ms) and FDB was more pronounced at higher stimulation frequencies (20 and 30 HZ). Our results suggest that the safety margin for impulse transmission is impaired in the motor axons of patients with a focal demyelinating lesion. These findings may correlate with the observation of weakness in the absence of conduction block in patients with entrapment neuropathies.
    Muscle & Nerve 05/2006; 33(5):619-26. DOI:10.1002/mus.20513 · 2.28 Impact Factor
  • Shaun G Boe · Daniel W Stashuk · William F Brown · Timothy J Doherty ·
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    ABSTRACT: Decomposition-based quantitative electromyography (DQEMG) allows for the collection of motor unit potentials (MUPs) over a broad range of force levels. Given the size principle of motor unit recruitment, it may be necessary to control for force when using DQEMG for the purpose of deriving a motor unit number estimate (MUNE). Therefore, this study was performed to examine the effect of force on the physiological characteristics of concentric needle- and surface-detected MUPs and the subsequent impact on MUNEs obtained from the first dorsal interosseous (FDI) muscle sampled using DQEMG. Maximum M waves were elicited in 10 subjects with supramaximal stimulation of the ulnar nerve at the wrist. Intramuscular and surface-detected EMG signals were collected simultaneously during 30-s voluntary isometric contractions performed at specific percentages of maximal voluntary contraction (MVC). Decomposition algorithms were used to identify needle-detected MUPs and their individual MU firing times. These MU firing times were used as triggers to extract their corresponding surface-detected MUPs (S-MUPs) using spike-triggered averaging. A mean S-MUP was then calculated, the size of which was divided into the maximum M-wave size to derive a MUNE. Increased levels of contraction had a significant effect on needle- and surface-detected MUP size, firing rate, and MUNE. These results suggest that force level is an important factor to consider when performing quantitative EMG, including MUNEs with this method.
    Muscle & Nerve 03/2005; 31(3):365-73. DOI:10.1002/mus.20266 · 2.28 Impact Factor
  • Timothy J. Doherty · Daniel W. Stashuk · William F. Brown ·
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    ABSTRACT: Both MPS and the F-response techniques provide what appears to be a representative sample of S-MUPs from which to derive a MUNE. While MPS in its basic form can be carried out on any EMG system, specialized software that allows for template subtraction and the calculation of an average S-MUP waveform are important additions and improve efficiency and validity, respectively. Future work is required to determine the reliability and precision of MPS in specific clinical conditions - both of which are important in order for MPS or any other MUNE method to be accepted as useful clinical outcomes.
    Supplements to Clinical neurophysiology 12/2003; 55. DOI:10.1016/S1567-424X(02)55004-2
  • Timothy J. Doherty · Daniel W. Stashuk · William F. Brown ·
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    ABSTRACT: Percutaneous electrical stimulation is capable of exciting single motor axons and obtaining an unbiased sample of S-MUPs from which to derive a MUNE. Alternation, recognized at the outset by McComas and colleagues, has been problematic for the IS technique. This has prompted the development of other techniques including an automated IS method that tests statistically for alternation, the MPS technique and its modifications, the STA technique, and a statistical technique. Further investigation is required regarding the extent to which the above arguments hold true in pathologic disorders affecting the MU, especially ALS.
    Supplements to Clinical neurophysiology 12/2003; 55. DOI:10.1016/S1567-424X(02)55002-9
  • Timothy J. Doherty · Daniel W. Stashuk · William F. Brown ·
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    ABSTRACT: Aging is associated with significant declines in muscle strength, which are for the most part secondary to losses of muscle mass. The loss of muscle mass is mainly accounted for by losses of muscle fibers which appear secondary to MU losses. MUNE has significantly contributed to our understanding of the extent to which the MU pool is altered and adapts to aging. In general, proximal and distal muscles appear to have significantly fewer, but larger MUs. On balance, average MUNE values in groups over 60 years of age show reductions of about 50% in comparison to younger controls. Whether this decline is modifiable or an inherent age-related process will require well-planned longitudinal study.
    Supplements to Clinical neurophysiology 01/2003; 55. DOI:10.1016/S1567-424X(02)55017-0
  • Daniel W. Stashuk · Timothy J. Doherty · William F. Brown ·
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    ABSTRACT: In summary DE-STA is a very useful technique for obtaining MUNEs. It can be performed easily and quickly, it is well tolerated by the subject and operator and is suitably repeatable. Furthermore, it can also provide potentially useful additional information about the size, structure and behaviour of individual MUs. For it to be widely used however, it must be implemented on a wider variety of commercially available systems. In addition, standards for the acceptance or rejection of "noisy" S-MUPs and for the alignment of S-MUPs for the calculation of the mS-MUP need to be developed.
  • K. Ming Chan · William F. Brown ·

    Supplements to Clinical neurophysiology 01/2003; 55. DOI:10.1016/S1567-424X(02)55025-X
  • William F. Brown · Bradley V. Watson ·

    Neuromuscular Function and Disease: Basic, Clinical and Electrodiagnostic Aspects, Edited by Brown WF, Bolton CF, Aminoff MJ, 01/2002: chapter Recording of electrical activity in nerve trunks and conduction in human sensory and motor nerve fibers: pages 21-55; W.B. Saunders Company., ISBN: 0-7216-8922-1
  • William F. Brown · Bradley V. Watson ·

    Neuromuscular Function and Disease: Basic, Clinical, and Electrodiagnostic Aspects, Edited by Brown WF, Bolton CF, Aminoff Mj, 01/2002: chapter Volume Conduction: pages 96-101; W.B. Saunders Company., ISBN: 0-7216-8922-1
  • William F. Brown · Bradley V. Watson ·

    Neuromuscular Function and Disease: Basic, Clinical, and Electrodiagnostic Aspects, Edited by Brown WF, Bolton CF, Aminoff MJ, 01/2002: chapter Pathophysiology of conduction in peripheral neuropathies: pages 56-95; W.B. Saunders Company., ISBN: 0-7216-8922-1
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    ABSTRACT: We have studied the relationship between genotype, clinical phenotype, and pathology in 13 families with dominant X-linked Charcot-Marie-Tooth (CMT) neuropathy. Connexin32 (Cx32) gene mutations were spread throughout the coding region and included eight missense mutations, one 8-bp deletion/4-bp insertion frame shifting mutation, two nonsense mutations, and one deletion of the entire coding sequence. One hundred sixteen affected CMTX patients (53 males and 63 females) and 63 unaffected, at-risk individuals were compared by neurological and electrophysiological examinations and analyzed by gender; nerve biopsies were available from seven index cases. It was found that mutations within all regions of the Cx32 gene coding sequence caused an identical clinical phenotype. Male CMTX patients were affected more severely and showed an age-dependent progression of clinical signs and of the pathology; there was, however, variability in the severity of disease expression, irrespective of age, among males within families of defined genotype. All but 10% of female CMTX patients had only mild signs. Motor nerve conduction velocities were moderately slowed (median nerve MNCV: males 34.5 +/- 6.2 m/sec; females 45.8 +/- 7.3 m/sec), and motor and sensory nerve amplitudes were reduced (median nerve CMAP: males 3.7 +/- 3.7 mV; females 7.8 +/- 3.4 mV), with electromyographic evidence of chronic denervation. Differences were significant between gender and between affected and unaffected individuals. In agreement with the electrophysiological observations, pathological studies showed evidence of paranodal demyelination and of a length-related axonal degeneration in motor and sensory nerve fibers. Correlations between genotype and clinical phenotype suggested that missense mutations located within the second transmembrane domain and/or cytoplasmic loop might be associated with milder clinical phenotype, and therefore might be less disruptive of connexin32 gap junction function. Missense, chain-terminating, or deletion mutations in all other locations of the connexin32 protein caused severe forms of CMTX and disease onset in the first decade. Observed variability of disease severity among males within kinships suggests the influence of other modifying factors.
    Annals of the New York Academy of Sciences 10/1999; 883(1 CHARCOT-MARIE):366-82. DOI:10.1111/j.1749-6632.1999.tb08598.x · 4.38 Impact Factor
  • K. Ming Chan · Leonard P. Andres · Yelena Polykovskaya · William F. Brown ·
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    ABSTRACT: The relative impact of training on motor units (MUs) with differing physiological characteristics remains controversial. To examine this issue, we longitudinally tracked the contractile and electrical characteristics of six human thenar MUs in 2 young healthy subjects before, during, and following an intermittent, high-frequency electrical stimulation program. Responses of MUs with differing baseline physiological characteristics varied widely. While the twitch and maximal tetanic tensions of the slower and fatigue-resistant MUs increased, tensions of the faster and more fatigable MUs declined. The fatigue resistance of the faster and more fatigable MUs, on the other hand, increased while that of the slower MUs remained unchanged. Although electrical stimulation of individual MUs allowed their training to be precisely controlled, it will be of practical importance to determine whether similar divergent MU contractile changes also occur with voluntary training.
    Muscle & Nerve 02/1999; 22(2):186-95. DOI:10.1002/(SICI)1097-4598(199902)22:2<186::AID-MUS6>3.0.CO;2-I · 2.28 Impact Factor
  • K. Ming Chan · Daniel W. Stashuk · William F. Brown ·
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    ABSTRACT: The sequence of pathophysiological changes in amyotrophic lateral sclerosis (ALS) at the single motor unit (MU) level is not well understood. Using a recently described technique, a comprehensive range of physiological properties in two thenar MUs in ALS were intensively studied. In the first MU, despite a marked decline in the ability of the subject to voluntarily recruit the MU, the physiological properties of this MU remained remarkably stable over a 2-year period. In contrast, the physiological properties of the other MU declined rapidly over 5 months despite the fact that this MU could be recruited with ease throughout the study period. These differences between the progressively dysfunctional changes in these two MUs illustrates the value of such longitudinal studies of specific MUs in improving our understanding of the evolution of changes in single motoneurons in ALS. The broader application of longitudinally tracking the pathophysiological changes of the surviving MUs may prove to be a sensitive measure of disease progression and in evaluating the effectiveness of treatments.
    Muscle & Nerve 01/1999; 21(12):1714-23. DOI:10.1002/(SICI)1097-4598(199812)21:123.0.CO;2-8 · 2.28 Impact Factor
  • K. Ming Chan · Leonard P. Andres · Yelena Polykovskaya · William F. Brown ·
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    ABSTRACT: The surface EMG area often exhibits progressive enlargement during a submaximal fatiguing contraction, but the underlying reasons still remain uncertain. Fatigue-induced changes in the surface-detected motor unit action potentials (S-MUAPs) of 10 human thenar motor units (MUs) with widely differing physiological properties were examined. After 2 min of repetitive 40-Hz stimulation, the size of the S-MUAPs of all MUs increased, the magnitude of which was negatively correlated with their tetanic tension changes. These findings suggest that during muscle fatigue, in addition to reflecting recruitment of new MUs and increases in firing rates of the active MUs, the surface EMG may also be markedly influenced by changes in the S-MUAPs, especially in fast fatigable muscles.
    Muscle & Nerve 01/1999; 21(12):1786-9. DOI:10.1002/(SICI)1097-4598(199812)21:12<1786::AID-MUS25>3.0.CO;2-I · 2.28 Impact Factor
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    ABSTRACT: Electromyographic signals detected from the quadriceps femoris during various constant force contractions were decomposed to identify individual motor unit discharges and mean firing rates (FRs). Subject and group mean FRs were calculated for each force level. Mean FR values and FR variability increased with force. Individual, subject, and group mean FRs showed slight increases until 30% of maximum voluntary contraction and larger increases thereafter. Findings are discussed in relation to motor unit recruitment, frequency modulation, and fatigue.
    Muscle & Nerve 11/1998; 21(10):1338-40. DOI:10.1002/(SICI)1097-4598(199810)21:10<1338::AID-MUS17>3.0.CO;2-Y · 2.28 Impact Factor
  • K. Ming Chan · Shanker Nasathurai · Jeffrey M. Chavin · William F. Brown ·
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    ABSTRACT: Cervical spondylytic myelopathy (CSM) is common. Magnetic resonance imaging (MRI), although sensitive, often reveals extensive and sometimes clinically irrelevant findings. The purpose of this study was to investigate the usefulness of central motor conduction studies in localizing the rostral level of cord involvement in 6 patients with CSM. Central motor conduction was assessed using high-voltage stimulation for the spinal roots and magnetoelectrical stimulation for the motor cortex, recording from "marker muscles" innervated by successively higher cervical cord segments. Abnormal central motor conduction affected all subjects at C8-T1, 5 subjects at C7, but none at the C5-C6 levels. The MRI showed abnormalities at multiple levels as high as C4. Our results suggest that central motor conduction studies are helpful in localizing the clinically relevant levels of spinal cord compression in CSM and correlate well with motor abnormalities on clinical examination.
    Muscle & Nerve 10/1998; 21(9):1220-3. DOI:10.1002/(SICI)1097-4598(199809)21:93.3.CO;2-I · 2.28 Impact Factor
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    ABSTRACT: Serial motor unit number estimates have shed important light on the extent and rates of motoneuron losses in aging and amyotrophic lateral sclerosis. However, the estimates alone provide few clues to the health and functional status of surviving motor units. A reliable means for assessing the functional status of the surviving motor units would therefore by a welcome addition to our present tools for studying motor units. Examining the physiological properties of samples of motor units drawn at intervals during the course of a motoneuronal disease suffers from the important limitation that the samples may not be representative of one another. The latter problem could be circumvented by serially studying the same motor units. This study describes a noninvasive technique capable of longitudinally tracking the contractile and electrical properties of specific single thenar motor units in healthy subjects, in some instances over several years. The technique proved to be reasonably reliable and provided information on a wide range of contractile and electrical properties of motor units. Such an approach could serve as a potentially powerful and sensitive means of studying the life histories of single motor units in aging, diseases of the motoneuron, and in the latter instances, the responses of the motoneurons to treatment.
    Muscle & Nerve 08/1998; 21(7):839-49. DOI:10.1002/(SICI)1097-4598(199807)21:73.0.CO;2-7 · 2.28 Impact Factor
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    ABSTRACT: Decomposition-enhanced spike-triggered averaging (DE-STA) was applied to the vastus medialis muscle to examine size distributions of surface-detected motor-unit action potentials (S-MUAPs) at various force levels. Using DE-STA, 15-20 S-MUAPs were identified during 5%, 10%, 20%, and 30% of maximum voluntary contraction. Average S-MUAPs showed increase in peak to peak (and negative peak) amplitude with force (In microV): 5% = 37.9 +/- 6.1 (16.6 +/- 2.5), 10% = 44.0 +/- 4.0 (20.4 +/- 1.8), 20% = 80.7 +/- 9.3 (41.3 +/- 4.5), and 30% = 102.5 +/- 10.3 (53.6 +/- 5.0). Test-retest variability of peak to peak (and negative peak amplitude) between repeated trials was 0.10 (0.14), 0.14 (0.14), 0.17 (0.15), and 0.21 (0.20) at 5%, 10%, 20%, and 30% respectively. A relationship was found between the S-MUAP amplitude and force (r2 = 0.78, df = 90, F = 160, P < 0.001). Increase in average S-MUAP amplitude with force suggests that STA performed only at low levels of contraction may result in a biased sampling and small average S-MUAP amplitudes.
    Muscle & Nerve 08/1997; 20(8):976-82. DOI:10.1002/(SICI)1097-4598(199708)20:83.0.CO;2-3 · 2.28 Impact Factor
  • William F. Brown · K. Ming Chan ·

    Muscle & Nerve 02/1997; 5(S5):S70-3. DOI:10.1002/(SICI)1097-4598(1997)5+<70::AID-MUS17>3.0.CO;2-2 · 2.28 Impact Factor

Publication Stats

1k Citations
74.01 Total Impact Points


  • 2005-2006
    • McMaster University
      • Division of Neurology
      Hamilton, Ontario, Canada
  • 2003
    • Boston University
      • Department of Neurology
      Boston, Massachusetts, United States
  • 1994-2003
    • Tufts University
      • Department of Neurology
      Бостон, Georgia, United States
  • 1993-1999
    • New England Baptist Hospital
      Boston, Massachusetts, United States
  • 1996
    • The University of Western Ontario
      London, Ontario, Canada
  • 1992
    • University of Waterloo
      • Department of Systems Design Engineering
      Waterloo, Quebec, Canada