M Hallett

University of Washington Seattle, Seattle, WA, United States

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Publications (489)2669.61 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To study the temporal dynamics of tissue impedance after deep brain stimulation (DBS). DBS therapy commonly employs a constant voltage approach, and current delivery to the tissue is a function of electrode-tissue impedance. It is presumed that impedance fluctuates early postimplantation, with implications for variations in current delivery and therapeutic efficacy. We hypothesised that the largest variation will be recorded early after surgery, followed by stabilisation. Review of impedance checks of implanted DBS systems at standard parameters during the first five months postimplantation. All measurement time points were binned into 1-week periods, and we used repeated measures analysis of variance with Tukey pairwise multiple comparisons correction. The analysis was repeated after normalising impedance values for each subject to that patient's baseline value. There was an initial (non-significant) drop in impedance at week 1, followed by significant increase at week 3 (p=0.0002). There were no further significant differences in impedance values at subsequent time points. Analysis of normalised data showed a significant difference between the initial measurement in postoperative week 1 (normalised value 1) and week 3 (normalised value 1.73, p<0.0001), with no further difference among the subsequent weekly points during the 5-month follow-up. No significant hourly variations were found at any time points. We found major changes in impedance within the first month postimplantation, with no further variation. This is an important confirmation in patients of this temporal dynamics of the impedance of implanted DBS hardware, with potential therapeutic implications.
    Journal of neurology, neurosurgery, and psychiatry 11/2013; · 4.87 Impact Factor
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    Toxicon 01/2013; · 2.92 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Injectable botulinum neurotoxin (BoNT) is the principal effective treatment for blepharospasm (BSP). This trial explores the safety and efficacy of topical acetyl hexapeptide-8 (AH8), a competitive SNAP25 inhibitor, as a potential new therapy in BSP. METHODS: Double-blind, placebo-controlled, randomized trial of daily topical application of AH8 in 24 patients with BSP. The primary outcome was time to return to baseline Jankovic Rating Scale (JBRS) after a BoNT injection simultaneously with the initiation of AH8. Patients displaying a strictly regular pattern of response to 3-monthly injections of BoNT were included. RESULTS: There were no significant adverse events. There was a trend for longer time until return to baseline JBRS after injection in the active group compared to placebo (3.7 months vs. 3.0 months), and for better scores in the active group. One-third (4/12) of the patients in the active group had a considerable extension of symptom control after BoNT (range: 3.3-7.1 months). CONCLUSIONS: Topical AH8 is safe and promising for extending the duration of action of BoNT therapy for BSP.
    European Journal of Neurology 11/2012; · 4.16 Impact Factor
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    ABSTRACT: Subthalamic nucleus deep brain stimulation (STN DBS) is an effective surgical treatment for Parkinson's disease (PD). Recent studies demonstrated that pathological oscillations are seen largely within the dorsolateral portion of the STN, which is the same location that predicts optimal therapeutic benefit with DBS; however, the precise nature of the relationship between these two phenomena remains unclear. The purpose of this study was to explore localization of oscillatory activity in relation to the optimal contacts of DBS which results in the best motor improvement. We studied 23 PD patients who underwent electrode implantation into the STN for motor symptoms. Microelectrode recordings were taken from the STN during surgery and neuronal activity was analyzed offline. Spectral characteristics were calculated. Clinical outcomes were evaluated pre- and post-STN DBS implantation using the Unified Parkinson's Disease Rating Scale (UPDRS III). The position of optimal electrode contacts was assessed by postoperative magnetic resonance imaging (MRI) and was compared to the location of oscillatory activity within the STN as well as its dorsal margin (where STN neuronal activity was first detected). Of the total 188 neurons obtained, 51 (27.1%) neurons showed significant oscillatory activity. Of those, 47 (92.2%) were localized in the dorsal portion of the STN. Furthermore, there was no significant difference between the averaged coordinates of the position of 40 optimal contacts and the coordinates of the dorsal margin of the STN. The data indicate that the positions of the best contacts correlate with the locations of the oscillatory neurons supporting the prediction that stimulation of the dorsolateral oscillatory region leads to an effective clinical outcome for STN DBS surgery.
    Parkinsonism & Related Disorders 09/2012; · 3.27 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) is a highly promising therapy for Parkinson's disease (PD). However, most patients do not get full therapeutic benefit from DBS, due to its critical dependence on electrode location in the Subthalamic Nucleus (STN). For this reason, we believe that the development of a novel surgical tool for DBS placement, i.e., an automated intraoperative closed-loop DBS localization system, is essential. In this paper, we analyze single unit spiking activity of 120 neurons in different STN locations collected from 4 PD patients. Specifically, for each neuron, we estimate a point process model (PPM) of the spiking activity for different depths within the STN by which we are able to detect pathological bursting and oscillations. Our results suggest that these signatures are more prominent in the dorsolateral part of the STN. Therefore, accurately placing the DBS electrode in this target may result in maximal therapeutic benefit with less power effort required by DBS. Furthermore, PPMs might be an effective tool for modeling of the STN neuronal activities as a function of location within the STN, which may pave the way towards developing a closed-loop navigation tool for optimal DBS electrode placement.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:2539-42.
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    ABSTRACT: Deep brain stimulation (DBS) is a highly promising therapy for Parkinson's disease (PD). However, most patients do not get full therapeutic benefit from DBS yet, due to its critical dependence on electrode location. For this reason, we believe that the investigation of a neural modeling, estimation and control framework for the STN is an interesting research problem. This would pave the way for the development of a novel surgical tool for the DBS placement standardization, i.e., an automated intraoperative closed-loop DBS localization system. A fundamental problem to be solved for the realization of a such framework is the neurophysiologic characterization of the STN activity. Indeed, this would allow to understand if the modeling of the sweet spot is feasible. In this paper an effort towards the modeling of the neuronal activity near the stimulation target is made: first we analyze single unit spiking activity of 120 STN neurons collected from four PD patients at different distances from the sweet spot and, for each neuron, we estimate a point process model (PPM). Then, we see that PPMs capture the stochastic effects of the distance from the sweet spot on the STN spiking activity, and characterize the impact of local neuronal networks on the single neurons. Our results suggest that PPMs might be an effective tool for modeling of the STN neuronal activities accounting for the depth within it.
    Control Applications (CCA), 2012 IEEE International Conference on; 01/2012
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    ABSTRACT: Valid assessment of apraxia in usually non-apraxic Parkinson's disease helps to delineate atypical parkinsonism frequently associated with apraxia. Furthermore, in a subgroup of late Parkinson's disease apraxia, typically the ideomotor subtype, may gradually superimpose onto parkinsonian motor symptoms contributing to defective manual skill. Here we evaluate the utility of a brief, standardized test, the apraxia screen of TULIA (AST). Seventy five Parkinson's disease patients were tested with the AST. Parkinsonian motor deficits were measured using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III and difficulties in activities of daily living (ADL) by modified MDS-UPDRS part II (eating, dressing, personal hygiene, and writing). No association was found between the AST and MDS-UPDRS part III, indicating that AST discriminates well (discriminative validity) between apraxia and parkinsonism. Furthermore, AST was associated with ADL and Hoehn & Yahr stage (convergent validity). AST is a short and valid test to rule out or detect apraxia in Parkinson's disease.
    Parkinsonism & Related Disorders 12/2011; 18(4):348-50. · 3.27 Impact Factor
  • Erik Corthout, Mark Hallett, Alan Cowey
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    ABSTRACT: It is known that TMS can induce blinking, but it is unknown to what extent and at what time TMS-induced blinking can cover the pupil. We applied single-pulse TMS with a leftward and rightward monophasic current through a round coil over the occipital pole in 8 healthy subjects, using high-speed video to monitor left or right eye with a spatial resolution of 0.1 mm and a temporal resolution of 2 ms. We plotted eyelid position relative to upper and lower pupil borders as a function of time after TMS for each subject and current direction. We found 2 blinks in every subject, an isolated late blink with one current direction and a superimposed early and late blink with the other current direction, in accordance with our previously reported association between a leftward and rightward lower coil rim current and an early blink in right and left eye, respectively. Blink extent varied, but 4 subjects showed total pupil covering with both current directions. Blink timing varied, but pupil covering was initiated as early as 32 ms after TMS and pupil uncovering was completed as late as 200 ms after TMS. We found no saccades. We conclude that TMS can cause an important optical disruption of visual perception.
    Experimental Brain Research 03/2011; 210(2):243-50. · 2.22 Impact Factor
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    ABSTRACT: To characterize patients with benign essential blepharospasm (BEB) by diagnosis, environmental risk factors, and family history. Two hundred and forty patients with BEB were evaluated through a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for the development of blepharospasm and family history of dystonia and other neurological conditions. Benign essential blepharospasm was more commonly found in women (2.8:1) and 93% of the patients were Caucasian. Fifty percent had pure BEB, 31% had BEB/Meige's syndrome, and 4% had BEB and eyelid opening apraxia (+/- Meige's syndrome). A minority of patients reported preceding photophobia (25%) or other eye conditions (22%). The majority were non-smokers, had no exposure to anti-emetic or antipsychotic agents, had a normal birth history, and had no history of head trauma. Seventy-two percent did report a stressful event immediately prior to the development of symptoms. Treatments reported included botulinum toxin (BoNT), oral medications, surgical procedures, and acupuncture. Thirty-two percent of patients reported a family history of focal dystonia, and BEB was the most commonly reported. This study confirms previous reports of usual age, sex, caffeine and tobacco use, and family history in patients with blepharospasm. New findings include a report on occupation, lower reports of preceding eye conditions and photophobia, and higher reported stressful events. Further, this study shows a change in treatment with an increase in BoNT use and decrease in surgical procedures.
    European Journal of Neurology 03/2011; 18(3):382-6. · 4.16 Impact Factor
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    ABSTRACT: To investigate the safety and efficacy of intermittent theta-burst stimulation (iTBS) in the treatment of motor symptoms in Parkinson disease (PD). Progression of PD is characterized by the emergence of motor deficits, which eventually respond less to dopaminergic therapy and pose a therapeutic challenge. Repetitive transcranial magnetic stimulation (rTMS) has shown promising results in improving gait, a major cause of disability, and may provide a therapeutic alternative. iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS. In this randomized, double-blind, sham-controlled study, we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks (evidence Class I). Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia, Unified Parkinson's Disease Rating Scale (UPDRS), and additional clinical, neuropsychological, and neurophysiologic measures. We investigated 26 patients with mild to moderate PD: 13 received iTBS and 13 sham stimulation. We found beneficial effects of iTBS on mood, but no improvement of gait, bradykinesia, UPDRS, and other measures. EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity. Few reported discomfort or pain and one experienced tinnitus during real stimulation. iTBS of the motor and prefrontal cortices appears safe and improves mood, but failed to improve motor performance and functional status in PD. Classification of evidence: This study provides Class I evidence that iTBS was not effective for gait, upper extremity bradykinesia, or other motor symptoms in PD.
    Neurology 02/2011; 76(7):601-9. · 8.30 Impact Factor
  • Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2011; 122.
  • Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2011; 122.
  • S Bohlhalter, E Abela, M Hallett
    Experimental Neurology 11/2010; 227(1):24-5. · 4.65 Impact Factor
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    G Kranz, E A Shamim, P T Lin, M Hallett
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    ABSTRACT: Benign essential blepharospasm (BEB) is a common form of focal dystonia. Besides pathology in the basal ganglia, accumulating evidence suggests pathologic changes in the anterior cingulate cortex (ACC). This is a randomized, sham-controlled, observer-blinded prospective study. In 12 patients with BEB, we evaluated the effects of a 15-minute session of low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) over the ACC with stimulation intensities at 100% active motor threshold with 3 stimulation coils: a conventional circular coil (C-coil), a sham coil (S-coil), and a Hesed coil (H-coil, which allows stimulation of deeper brain regions. Primary outcome was the clinical effects on BEB (blink rate, number of spasms rated by a blinded physician and patient rating before, immediately after, and 1 hour after stimulation); secondary outcome was the blink reflex recovery curve. Subjective stimulation comfort was similar for each coil with no stimulation-associated adverse events. Stimulation with the H- and C-coils resulted in a significant improvement in all 3 outcome measures and was still detectable in physician rating and patient rating 1 hour after stimulation. S-coil stimulation had no effects. The active motor threshold was significantly lower for the H-coil compared to the other 2 coils. rTMS could be used as a therapeutic tool in BEB. Further studies will be necessary to show whether repeated stimulation applications result in lasting clinical effects. Classification of evidence: This study provides Class II evidence that for patients with BEB, H- and C-coil rTMS is safe and improves clinical symptoms of BEB immediately and 1 hour after stimulation.
    Neurology 10/2010; 75(16):1465-71. · 8.30 Impact Factor
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    ABSTRACT: What makes a movement feel voluntary, and what might make it feel involuntary? Motor conversion disorders are characterized by movement symptoms without a neurologic cause. Conversion movements use normal voluntary motor pathways, but the symptoms are paradoxically experienced as involuntary, or lacking in self-agency. Self-agency is the experience that one is the cause of one's own actions. The matched comparison between the prediction of the action consequences (feed-forward signal) and actual sensory feedback is believed to give rise to self-agency and has been in part associated with the right inferior parietal cortex. Using fMRI, we assessed the correlates of self-agency during conversion tremor. We used a within-subject fMRI block design to compare brain activity during conversion tremor and during voluntary mimicked tremor in 8 patients. The random effects group analysis showed that conversion tremor compared with voluntary tremor had right temporoparietal junction (TPJ) hypoactivity (p < 0.05 family-wise error whole brain corrected) and lower functional connectivity between the right TPJ, sensorimotor regions (sensorimotor cortices and cerebellar vermis), and limbic regions (ventral anterior cingulate and right ventral striatum). The right TPJ has been implicated as a general comparator of internal predictions with actual events. We propose that the right TPJ hypoactivity and lower TPJ and sensorimotor cortex interactions may reflect the lack of an appropriate sensory prediction signal. The lack of a match for the proprioceptive feedback would lead to the perception that the conversion movement is not self-generated.
    Neurology 01/2010; 74(3):223-8. · 8.30 Impact Factor
  • P. Zhuang, M. Hallett, Y.-J. Li
    Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2010; 121.
  • Parkinsonism & Related Disorders - PARKINSONISM RELAT DISORD. 01/2010; 16.
  • Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2010; 121.
  • Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2010; 121.
  • E. Houdayer, R. Kayal, J. Chu, M. Hallett
    Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2010; 121.

Publication Stats

31k Citations
2,669.61 Total Impact Points


  • 2013
    • University of Washington Seattle
      • Department of Neurology
      Seattle, WA, United States
  • 2011
    • Universitätsspital Basel
      • Neurobiology Unit
      Basel, BS, Switzerland
  • 1999–2011
    • University of Oxford
      • Department of Experimental Psychology
      Oxford, ENG, United Kingdom
    • Bulgarian Academy of Sciences
      • Institute of Neurobiology
      Sofia, Oblast Sofiya-Grad, Bulgaria
    • Crozer Chester Medical Center
      Upland, Pennsylvania, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 1988–2011
    • National Institutes of Health
      • Division of Intramural Research (Dental Research)
      Maryland, United States
    • Boston Children's Hospital
      • Children's Hospital Primary Care Center
      Boston, MA, United States
  • 2010
    • Inselspital, Universitätsspital Bern
      • Department of Neurology
      Bern, BE, Switzerland
  • 2009
    • Medical University of Vienna
      • Universitätsklinik für Neurologie
      Vienna, Vienna, Austria
  • 2006–2009
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
  • 2007
    • National Institute on Aging
      • Clinical Immunology Section
      Baltimore, Maryland, United States
  • 1995–2007
    • National Institute of Mental Health (NIMH)
      • • Molecular Imaging Branch
      • • Child Psychiatry Branch
      • • Laboratory of Brain And Cognition
      Maryland, United States
    • University of Barcelona
      • Departament de Medicina
      Barcelona, Catalonia, Spain
    • U.S. Food and Drug Administration
      • Center for Food Safety and Applied Nutrition
      Washington, D. C., DC, United States
  • 2000–2006
    • University of Rostock
      • • Klinik und Poliklinik für Neurologie
      • • Zentrum für Nervenheilkunde
      Rostock, Mecklenburg-Vorpommern, Germany
    • American Academy of Neurology
      Saint Paul, Minnesota, United States
    • Georgetown University
      • Institute for Cognitive and Computational Sciences
      Washington, Washington, D.C., United States
  • 2004
    • University of Minnesota Twin Cities
      Minneapolis, Minnesota, United States
    • Inha University Hospital
      Sinhyeon, South Gyeongsang, South Korea
    • Xuanwu hospital
      Peping, Beijing, China
  • 1993–2004
    • National Eye Institute
      Maryland, United States
  • 2001
    • Goethe-Universität Frankfurt am Main
      Frankfurt, Hesse, Germany
  • 1996–2001
    • Sapienza University of Rome
      • Department of Anatomical, Histological, Forensic Medicine and Orthopedic Science
      Roma, Latium, Italy
    • University of Valencia
      • Department of Physiology
      Valencia, Valencia, Spain
  • 1998
    • Fondazione Salvatore Maugeri IRCCS
      Ticinum, Lombardy, Italy
    • University of Tuebingen
      • Department of Neurology
      Tübingen, Baden-Wuerttemberg, Germany
    • Diabetes Australia, Victoria
      Melbourne, Victoria, Australia
  • 1996–1998
    • Medical University of South Carolina
      • Department of Radiology
      Charleston, South Carolina, United States
  • 1994
    • Hospital Clínic de Barcelona
      • Servicio de Neurología
      Barcino, Catalonia, Spain
  • 1990
    • Howard University
      • Department of Physics & Astronomy
      Washington, WV, United States
  • 1987
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States