|
1
|
Jodoin M, Herrero Babiloni A, Provost C, Blais H, Bellemare A, Desjardins M, Rouleau DM, De Beaumont L. 10-Day Theta Burst Stimulation Intervention Facilitates the Clinical Rehabilitation of Patients After an Isolated Limb Fracture: A Longitudinal SHAM-Controlled Pilot Study. Am J Phys Med Rehabil 2024; 103:e152-e161. [PMID: 38709663 DOI: 10.1097/phm.0000000000002543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/08/2024]
Abstract
OBJECTIVE We investigated if theta burst stimulation could enhance recovery by reducing key symptoms when implemented acutely postfracture in participants with an isolated upper limb fracture. METHODS/DESIGN This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous theta burst stimulation protocol. Two main groups were included: I) participants with isolated upper limb fracture receiving active theta burst stimulation and II) patients with isolated upper limb fracture receiving SHAM/placebo. Another group (III) of healthy individuals was the reference group. Disability and pain intensity were collected through questionnaires (disabilities of the Arm, Shoulder, and Hand as well as numerical rating scale (NRA)) at three time points (baseline; 72 hrs after intervention, 3 mos after injury). Group III completed the baseline assessment. RESULTS Seventy-nine participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between intervention and time approached significance (F = 2.33; P = 0.11), whereas it was significant for pain (F = 3.42; P = 0.04). At 3 mos after injury, the ACTIVE group reported reduced disability (F = 4.71; P = 0.04) and pain (F = 5.84; P = 0.02) at 3 mos after injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. CONCLUSIONS In isolated upper limb fracture patients, a 10-day theta burst stimulation intervention implemented acutely posttrauma had beneficial effects on symptoms of functional recovery and pain at 3 mos after trauma.
Collapse
Affiliation(s)
- Marianne Jodoin
- From the Sacre-Coeur Hospital, University of Montreal, Montreal, Quebec, Canada (MJ, AHB, CP, HB, AB, MD, DMR, LDB); Department of Psychology, University of Montreal, Montreal, Quebec, Canada (MJ, MD); Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada (AHB); and Department of Surgery, University of Montreal, Montreal, Quebec, Canada (DMR, LDB)
| | | | | | | | | | | | | | | |
Collapse
|
|
2
|
Shamli Oghli Y, Grippe T, Arora T, Hoque T, Darmani G, Chen R. Mechanisms of theta burst transcranial ultrasound induced plasticity in the human motor cortex. Brain Stimul 2023; 16:1135-1143. [PMID: 37524296 DOI: 10.1016/j.brs.2023.07.056] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 07/27/2023] [Accepted: 07/28/2023] [Indexed: 08/02/2023] Open
Abstract
BACKGROUND Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique with high depth penetrance and spatial resolution. Theta-burst TUS (tbTUS) is a plasticity-inducing protocol which increases motor cortical excitability for up to 30 min following 80s of sonication. While this protocol may have therapeutic potential for the treatment of psychiatric and neurological disorders, the mechanisms of action of TUS remain unclear. OBJECTIVE We conducted the first pharmacological study to examine the mechanisms of TUS in human primary motor cortex. By administering brain-active drugs with known mechanisms of action, we aimed to elucidate the mechanisms of tbTUS. METHODS Fourteen healthy subjects participated in a within-subjects randomized, double-blind, cross-over study with five visits. At each visit, one of four study drugs (carbamazepine - Na+ channel blocker, nimodipine - L-type Ca2+ channel blocker, lorazepam - positive allosteric modulator of gamma-aminobutyric acid (GABA) type A receptor, dextromethorphan - N-methyl-d-aspartate receptor antagonist) or placebo was administered in random order, followed by tbTUS. RESULTS The plasticity effects of tbTUS on motor cortex excitability measured by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation were reduced by all study drugs compared to placebo. CONCLUSION tbTUS may induce NMDA-dependent synaptic plasticity since the effects are blocked by increased GABAA receptor activities and voltage-gated Na+ and Ca2+ channels blockers. These results are consistent with the hypotheses that tbTUS induced long-term potentiation-like mechanisms and that TUS involves activation of mechanosensitive Na+ and Ca2+ channels. Alternatively, non-specific pharmacologically induced changes in excitatory/inhibitory balance might have interfered with the effects of tbTUS.
Collapse
Affiliation(s)
- Yazan Shamli Oghli
- Institute of Medical Science, University of Toronto, Toronto, Canada; Krembil Research Institute, University Health Network, Toronto, Canada; Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, United States
| | - Talyta Grippe
- Krembil Research Institute, University Health Network, Toronto, Canada
| | - Tarun Arora
- Krembil Research Institute, University Health Network, Toronto, Canada; Division of Clinical Neuroscience, Department of Neurology, Section for Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway
| | - Tasnuva Hoque
- Krembil Research Institute, University Health Network, Toronto, Canada
| | - Ghazaleh Darmani
- Krembil Research Institute, University Health Network, Toronto, Canada
| | - Robert Chen
- Institute of Medical Science, University of Toronto, Toronto, Canada; Krembil Research Institute, University Health Network, Toronto, Canada.
| |
Collapse
|
|
3
|
Lee J, Lee CW, Jang Y, You JS, Park YS, Ji E, Yu H, Oh S, Ryoo HA, Cho N, Park JY, Yoon J, Baek JH, Park HY, Ha TH, Myung W. Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial. Front Psychiatry 2022; 13:969199. [PMID: 36203828 PMCID: PMC9530445 DOI: 10.3389/fpsyt.2022.969199] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 08/26/2022] [Indexed: 11/13/2022] Open
Abstract
Background Although transcranial direct current stimulation (tDCS) is known to be a promising therapeutic modality for unipolar depression, the efficacy and safety of tDCS for bipolar depressive episodes (BD) are still unknown and clinical trials of home-based tDCS treatment are scarce. As a result, we set out to investigate the efficacy and safety of home-based tDCS for the treatment BD. Methods Participants (n = 64), diagnosed as bipolar disorder as per the diagnostic and statistical manual of mental disorders (DSM-5), were randomly assigned to receive tDCS. Hamilton Depression Rating Scale (HDRS-17) scores were measured at the baseline, week 2, 4, and 6, and home-based tDCS (for 30 min with 2 mA) was self-administered daily. Results Of the 64 patients (15.6% bipolar disorder I, 84.4% bipolar disorder II), 41 patients completed the entire assessment. In the intention-to-treat analysis, time-group interaction for the HDRS-17 [F (3, 146.36) = 2.060; p = 0.108] and adverse effect differences between two groups were not statistically significant, except the pain score, which was higher in the active group than the sham group (week 0-2: p < 0.01, week 2-4: p < 0.05, and week 4-6: p < 0.01). Conclusion Even though we found no evidence for the efficacy of home-based tDCS for patients with BD, this tool was found to be a safe and tolerable treatment modality for BD. Clinical trial registration [https://clinicaltrials.gov/show/NCT03974815], identifier [NCT03974815].
Collapse
Affiliation(s)
- Jangwon Lee
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Chan Woo Lee
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Yoonjeong Jang
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Ji Seon You
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Yun Seong Park
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Eunjeong Ji
- Medical Research Collaborating Centre, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Hyeona Yu
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Sunghee Oh
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Hyun A. Ryoo
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Nayoung Cho
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Ji Yoon Park
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Joohyun Yoon
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Ji Hyun Baek
- Department of Psychiatry, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Hye Youn Park
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Tae Hyon Ha
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
| | - Woojae Myung
- Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seoul, South Korea
- Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea
| |
Collapse
|
|
4
|
The effects of non-invasive brain stimulation on sleep disturbances among different neurological and neuropsychiatric conditions: A systematic review. Sleep Med Rev 2021; 55:101381. [PMID: 32992227 DOI: 10.1016/j.smrv.2020.101381] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 04/17/2020] [Accepted: 06/09/2020] [Indexed: 12/11/2022]
|
|
5
|
Minzenberg MJ, Leuchter AF. The effect of psychotropic drugs on cortical excitability and plasticity measured with transcranial magnetic stimulation: Implications for psychiatric treatment. J Affect Disord 2019; 253:126-140. [PMID: 31035213 DOI: 10.1016/j.jad.2019.04.067] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 03/03/2019] [Accepted: 04/08/2019] [Indexed: 01/08/2023]
Abstract
OBJECTIVE Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for neuropsychiatric disorders. Patients in rTMS treatment typically receive concomitant psychotropic medications, which affect neuronal excitability and plasticity and may interact to affect rTMS treatment outcomes. A greater understanding of these drug effects may have considerable implications for optimizing multi-modal treatment of psychiatric patients, and elucidating the mechanism(s) of action (MOA) of rTMS. METHOD We summarized the empirical literature that tests how psychotropic drugs affect cortical excitability and plasticity, using varied experimental TMS paradigms. RESULTS Glutamate antagonists robustly attenuate plasticity, largely without changes in excitability per se; antiepileptic drugs show the opposite pattern of effects, while calcium channel blockers attenuate plasticity. Benzodiazepines have moderate and variable effects on plasticity, and negligible effects on excitability. Antidepressants with potent 5HT transporter inhibition reduce both excitability and alter plasticity, while antidepressants with other MOAs generally lack either effect. Catecholaminergic drugs, cholinergic agents and lithium have minimal effects on excitability but exhibit robust and complex, non-linear effects in TMS plasticity paradigms. LIMITATIONS These effects remain largely untested in sustained treatment protocols, nor in clinical populations. In addition, how these medications impact clinical response to rTMS remains largely unknown. CONCLUSIONS Psychotropic medications exert robust and varied effects on cortical excitability and plasticity. We encourage the field to more directly and fully investigate clinical pharmaco-TMS studies to improve outcomes.
Collapse
Affiliation(s)
- M J Minzenberg
- Neuromodulation Division, Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, Los Angeles, CA 90024, United States.
| | - A F Leuchter
- Neuromodulation Division, Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, 760 Westwood Plaza, Los Angeles, CA 90024, United States
| |
Collapse
|
|
6
|
Herrero Babiloni A, Guay S, Nixdorf DR, de Beaumont L, Lavigne G. Non-invasive brain stimulation in chronic orofacial pain: a systematic review. J Pain Res 2018; 11:1445-1457. [PMID: 30122975 PMCID: PMC6078189 DOI: 10.2147/jpr.s168705] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that are being explored as therapeutic alternatives for the management of various chronic pain conditions. Objective The primary objective of this systematic review is to assess the efficacy of TMS and tDCS in reducing clinical pain intensity in chronic orofacial pain (OFP) disorders. The secondary objectives are to describe adverse effects, duration of relief, and TMS/tDCS methodologies used in chronic OFP disorders. Methods A search was performed in MEDLINE, Embase, Web of Science, Scopus, and Google Scholar. Inclusion criteria were 1) population: adults diagnosed with chronic OFP including neuropathic and non-neuropathic disorders; 2) intervention: active TMS or tDCS stimulation regardless of the used protocol; 3) comparison: sham TMS or tDCS stimulation; and 4) outcome: primary outcome was patient reported pain intensity. Secondary outcomes were duration of pain relief, adverse effects, and methodological parameters. Risk of bias and quality of study reporting were also assessed. Results A total of 556 individual citations were identified by the search strategy, with 14 articles meeting selection criteria (TMS=11; tDCS=3). Data were obtained for a total of 228 patients. Included OFP disorders were trigeminal neuralgia, trigeminal neuropathy, burning mouth syndrome, atypical facial pain, and temporomandibular disorders. Significant pain reductions were obtained in both techniques. More number of sessions yielded to more durable effects. Overall, high risk of bias and poor study quality were found. Conclusion TMS and tDCS appear to be safe and promising alternatives to reduce pain intensity in different chronic OFP disorders. Additional research effort is needed to reduce bias, improve quality, and characterize optimal brain stimulation parameters to promote their efficacy.
Collapse
Affiliation(s)
- Alberto Herrero Babiloni
- Research Center, Hôpital du Sacré-Coeur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Université De Montreal, Montreal, QC, Canada,
| | - Samuel Guay
- Research Center, Hôpital du Sacré-Coeur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Université De Montreal, Montreal, QC, Canada,
| | - Donald R Nixdorf
- Division of TMD & Orofacial Pain, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.,Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN, USA
| | - Louis de Beaumont
- Research Center, Hôpital du Sacré-Coeur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Université De Montreal, Montreal, QC, Canada,
| | - Gilles Lavigne
- Research Center, Hôpital du Sacré-Coeur de Montréal, CIUSSS du Nord-de-l'Île-de-Montréal, Université De Montreal, Montreal, QC, Canada,
| |
Collapse
|
|
7
|
Ceccanti M, Onesti E, Rubino A, Cambieri C, Tartaglia G, Miscioscia A, Frasca V, Inghilleri M. Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole. Brain Stimul 2018; 11:775-781. [DOI: 10.1016/j.brs.2018.02.007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Revised: 02/03/2018] [Accepted: 02/05/2018] [Indexed: 12/13/2022] Open
|
|
8
|
Cambieri C, Iacovelli E, Gori MC, Onesti E, Ceccanti M, Frasca V, Inghilleri M. Effects of visual deprivation on primary motor cortex excitability: a study on healthy subjects based on repetitive transcranial magnetic stimulation. Exp Brain Res 2017; 235:2059-2067. [DOI: 10.1007/s00221-017-4945-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Accepted: 03/15/2017] [Indexed: 10/19/2022]
|
|
9
|
Onesti E, Gori MC, Frasca V, Inghilleri M. Transcranial magnetic stimulation as a new tool to control pain perception. World J Anesthesiol 2016; 5:15-27. [DOI: 10.5313/wja.v5.i1.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Revised: 10/07/2015] [Accepted: 12/15/2015] [Indexed: 02/06/2023] Open
Abstract
Treatment for chronic pain is frequently unsuccessful or characterized by side-effects. The high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been suggested in the management of refractory chronic pain. Various studies have shown that HF-rTMS sessions of long-duration applied at primary motor cortex induce pain relief through mechanisms of plastic changes. Efficacy of rTMS mostly depends on stimulation parameters, but this aspect requires better characterization. A rationale to target other cortical areas exists. Current data are promising, but a careful analysis of stimulation settings and maintenance treatment design are need.
Collapse
|
|
10
|
Trebbastoni A, Pichiorri F, D’Antonio F, Campanelli A, Onesti E, Ceccanti M, de Lena C, Inghilleri M. Altered Cortical Synaptic Plasticity in Response to 5-Hz Repetitive Transcranial Magnetic Stimulation as a New Electrophysiological Finding in Amnestic Mild Cognitive Impairment Converting to Alzheimer's Disease: Results from a 4-year Prospective Cohort Study. Front Aging Neurosci 2016; 7:253. [PMID: 26793103 PMCID: PMC4709411 DOI: 10.3389/fnagi.2015.00253] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 12/21/2015] [Indexed: 01/26/2023] Open
Abstract
INTRODUCTION To investigate cortical excitability and synaptic plasticity in amnestic mild cognitive impairment (aMCI) using 5 Hz repetitive transcranial magnetic stimulation (5 Hz-rTMS) and to assess whether specific TMS parameters predict conversion time to Alzheimer's disease (AD). MATERIALS AND METHODS Forty aMCI patients (single- and multi-domain) and 20 healthy controls underwent, at baseline, a neuropsychological examination and 5 Hz-rTMS delivered in trains of 10 stimuli and 120% of resting motor threshold (rMT) intensity over the dominant motor area. The rMT and the ratio between amplitude of the 1st and the 10th motor-evoked potential elicited by the train (X/I-MEP ratio) were calculated as measures of cortical excitability and synaptic plasticity, respectively. Patients were followed up annually over a period of 48 months. Analysis of variance for repeated measures was used to compare TMS parameters in patients with those in controls. Spearman's correlation was performed by considering demographic variables, aMCI subtype, neuropsychological test scores, TMS parameters, and conversion time. RESULTS Thirty-five aMCI subjects completed the study; 60% of these converted to AD. The baseline rMT and X/I-MEP ratio were significantly lower in patients than in controls (p = 0.04 and p = 0.01). Spearman's analysis showed that conversion time correlated with the rMT (0.40) and X/I-MEP ratio (0.51). DISCUSSION aMCI patients displayed cortical hyperexcitability and altered synaptic plasticity to 5 Hz-rTMS when compared with healthy subjects. The extent of these changes correlated with conversion time. These alterations, which have previously been observed in AD, are thus present in the early stages of disease and may be considered as potential neurophysiological markers of conversion from aMCI to AD.
Collapse
Affiliation(s)
| | - Floriana Pichiorri
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
- Neuroelectrical Imaging and Brain Computer Interface Laboratory, Fondazione Santa Lucia – Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Fabrizia D’Antonio
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | | | - Emanuela Onesti
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | - Marco Ceccanti
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | - Carlo de Lena
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | - Maurizio Inghilleri
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
11
|
Golaszewski S, Schwenker K, Bergmann J, Brigo F, Christova M, Trinka E, Nardone R. Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study. Neurosci Lett 2016; 610:218-22. [PMID: 26562314 DOI: 10.1016/j.neulet.2015.11.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 11/03/2015] [Accepted: 11/05/2015] [Indexed: 11/28/2022]
Abstract
We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies.
Collapse
Affiliation(s)
- Stefan Golaszewski
- Department of Neurology and Neuroscience Institute, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria; TMS & fMRI Lab, Department of Neurology, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria.
| | - Kerstin Schwenker
- Department of Neurology and Neuroscience Institute, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria; TMS & fMRI Lab, Department of Neurology, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Jürgen Bergmann
- Department of Neurology and Neuroscience Institute, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Francesco Brigo
- Department of Neurology, Franz Tappeiner Hospital, Merano, Italy; Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Italy
| | - Monica Christova
- Department of Physiology, Medical University of Graz, Graz, Austria
| | - Eugen Trinka
- Department of Neurology and Neuroscience Institute, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria
| | - Raffaele Nardone
- Department of Neurology and Neuroscience Institute, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria; Department of Neurology, Franz Tappeiner Hospital, Merano, Italy
| |
Collapse
|
|
12
|
Conte A, Li Voti P, Pontecorvo S, Quartuccio ME, Baione V, Rocchi L, Cortese A, Bologna M, Francia A, Berardelli A. Attention-related changes in short-term cortical plasticity help to explain fatigue in multiple sclerosis. Mult Scler 2015; 22:1359-66. [PMID: 26672995 DOI: 10.1177/1352458515619780] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 10/26/2015] [Indexed: 12/25/2022]
Abstract
BACKGROUND In multiple sclerosis (MS), pathophysiology of fatigue is only partially known. OBJECTIVE The aim of this study was to investigate whether the attention-induced modulation on short- and long-term cortical plasticity mechanisms in primary motor area (M1) is abnormal in patients with MS-related fatigue. METHODS All participants underwent 5-Hz repetitive transcranial magnetic stimulation (rTMS), reflecting short-term plasticity, and paired associative stimulation (PAS), reflecting long-term plasticity, and were asked to focus their attention on the hand contralateral to the M1 stimulated. A group of age-matched healthy subjects acted as control. RESULTS In patients with MS, 5-Hz rTMS and PAS failed to induce the normal increase in motor-evoked potential (MEP). During the attention-demanding condition, 5-Hz rTMS- and PAS-induced responses differed in patients with MS with and without fatigue. Whereas in patients with fatigue neither technique induced the attention-induced MEP increase, in patients without fatigue they both increased the MEP response, although they did so less efficiently than in healthy subjects. Attention-induced changes in short-term cortical plasticity inversely correlated with fatigue severity. CONCLUSION Short-term and long-term plasticity mechanisms are abnormal in MS possibly owing to widespread changes in ion-channel expression. Fatigue in MS reflects disrupted cortical attentional networks related to movement control.
Collapse
Affiliation(s)
- Antonella Conte
- IRCCS Neuromed Institute, Pozzilli, ItalyDepartment of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | | | | | | | - Viola Baione
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Rocchi
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | - Antonio Cortese
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | | | - Ada Francia
- Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| | - Alfredo Berardelli
- IRCCS Neuromed Institute, Pozzilli, ItalyDepartment of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy
| |
Collapse
|
|
13
|
Cipriani C, Romagnoli E, Cilli M, Piemonte S, Pepe J, Minisola S. Quality of life in patients with primary hyperparathyroidism. Expert Rev Pharmacoecon Outcomes Res 2014; 14:113-21. [PMID: 24397607 DOI: 10.1586/14737167.2014.873702] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The clinical picture of primary hyperparathyroidism (PHPT) has changed over the last three decades and many asymptomatic patients are now diagnosed through the unexpected finding of high serum calcium levels. However, though not yet considered as typical features of the disease and therefore not included in the guidelines for surgery, many data are available on neuropsycological manifestations and their impact on quality of life in asymptomatic patients. PHPT patients indeed show early experience nonspecific symptoms, such as weakness, depression, sleep disturbance, memory loss and anxiety. Although the underlining mechanisms have not been still identified, the prevalence of psychiatric and cognitive deficits has been investigated in many studies, as well as the possible association with quality of life and well-being improvement after surgery. This article aims to review the current knowledge on quality of life in PHPT patients before and after surgery and the possible clinical implications of these findings.
Collapse
Affiliation(s)
- Cristiana Cipriani
- Department of Internal Medicine and Medical Disciplines, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy
| | | | | | | | | | | |
Collapse
|
|
14
|
Nedolya NA, Trofimov BA. [1,7]-Electrocyclization reactions in the synthesis of azepine derivatives. Chem Heterocycl Compd (N Y) 2013. [DOI: 10.1007/s10593-013-1236-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
|
|
15
|
Sommer M, Rummel M, Norden C, Rothkegel H, Lang N, Paulus W. Mechanisms of human motor cortex facilitation induced by subthreshold 5-Hz repetitive transcranial magnetic stimulation. J Neurophysiol 2013; 109:3060-6. [PMID: 23536708 DOI: 10.1152/jn.01089.2012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Our knowledge about the mechanisms of human motor cortex facilitation induced by repetitive transcranial magnetic stimulation (rTMS) is still incomplete. Here we used pharmacological conditioning with carbamazepine, dextrometorphan, lorazepam, and placebo to elucidate the type of plasticity underlying this facilitation, and to probe if mechanisms reminiscent of long-term potentiation are involved. Over the primary motor cortex of 10 healthy subjects, we applied biphasic rTMS pulses of effective posterior current direction in the brain. We used six blocks of 200 pulses at 5-Hz frequency and 90% active motor threshold intensity and controlled for corticospinal excitability changes using motor-evoked potential (MEP) amplitudes and latencies elicited by suprathreshold pulses before, in between, and after rTMS. Target muscle was the dominant abductor digiti minimi muscle; we coregistered the dominant extensor carpi radialis muscle. We found a lasting facilitation induced by this type of rTMS. The GABAergic medication lorazepam and to a lesser extent the ion channel blocker carbamazepine reduced the MEP facilitation after biphasic effective posteriorly oriented rTMS, whereas the N-methyl-d-aspartate receptor-antagonist dextrometorphan had no effect. Our main conclusion is that the mechanism of the facilitation induced by biphasic effective posterior rTMS is more likely posttetanic potentiation than long-term potentiation. Additional findings were prolonged MEP latency under carbamazepine, consistent with sodium channel blockade, and larger MEP amplitudes from extensor carpi radialis under lorazepam, suggesting GABAergic involvement in the center-surround balance of excitability.
Collapse
Affiliation(s)
- Martin Sommer
- Dept. of Clinical Neurophysiology, Univ. of Goettingen, Goettingen, Germany.
| | | | | | | | | | | |
Collapse
|
|
16
|
Non-invasive brain stimulation in the functional evaluation of alcohol effects and in the treatment of alcohol craving: A review. Neurosci Res 2012; 74:169-76. [DOI: 10.1016/j.neures.2012.08.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Revised: 07/21/2012] [Accepted: 08/09/2012] [Indexed: 01/18/2023]
|
|
17
|
I-wave origin and modulation. Brain Stimul 2012; 5:512-25. [DOI: 10.1016/j.brs.2011.07.008] [Citation(s) in RCA: 219] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2011] [Revised: 07/15/2011] [Accepted: 07/21/2011] [Indexed: 12/16/2022] Open
|
|
18
|
Nitsche MA, Müller-Dahlhaus F, Paulus W, Ziemann U. The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs. J Physiol 2012; 590:4641-62. [PMID: 22869014 DOI: 10.1113/jphysiol.2012.232975] [Citation(s) in RCA: 130] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.
Collapse
Affiliation(s)
- Michael A Nitsche
- M. A. Nitsche: Georg-August-University, University Medical Centre, Dept Clinical Neurophysiology, Robert-Koch-Str. 40, 37099 Göttingen, Germany.
| | | | | | | |
Collapse
|
|
19
|
Chronic treatment with rivastigmine in patients with Alzheimer’s disease: A study on primary motor cortex excitability tested by 5Hz-repetitive transcranial magnetic stimulation. Clin Neurophysiol 2012; 123:902-9. [DOI: 10.1016/j.clinph.2011.09.010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Revised: 09/01/2011] [Accepted: 09/05/2011] [Indexed: 12/27/2022]
|
|
20
|
Sommer M, Gileles E, Knappmeyer K, Rothkegel H, Polania R, Paulus W. Carbamazepine reduces short-interval interhemispheric inhibition in healthy humans. Clin Neurophysiol 2012; 123:351-7. [DOI: 10.1016/j.clinph.2011.07.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Revised: 06/29/2011] [Accepted: 07/15/2011] [Indexed: 11/16/2022]
|
|
21
|
Nedolya NA, Tarasova OA, Volostnykh OG, Albanov AI, Trofimov BA. Simultaneous synthesis of 4,5-dihydro-3H-azepines and 3H-azepines, bearing alkoxy and alkylsulfanyl substituents, through metallation of 2-aza-1,3,5-trienes by t-BuOK. J Organomet Chem 2011. [DOI: 10.1016/j.jorganchem.2011.07.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
22
|
Iacovelli E, Gilio F, Mascia ML, Scillitani A, Romagnoli E, Pichiorri F, Fucile S, Minisola S, Inghilleri M. Acute and chronic effects of hypercalcaemia on cortical excitability as studied by 5 Hz repetitive transcranial magnetic stimulation. J Physiol 2011; 589:1619-26. [PMID: 21300754 DOI: 10.1113/jphysiol.2010.201111] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
We designed the present study to disclose changes in cortical excitability in humans with hypercalcaemia, by delivering repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1). In 22 patients with chronic hypercalcaemia related to primary hyperparathyroidism and 22 age-matched healthy subjects 5 Hz-rTMS was delivered at rest and during a sustained voluntary contraction of the target muscle. Changes in the resting motor threshold (RMT), motor evoked potential (MEP) amplitudes and cortical silent period (CSP) duration were measured and compared in patients and healthy controls. Two of the 22 patients were re-tested after parathyroidectomy when serum calcium had normalized. In a subgroup of healthy subjects, changes in the rTMS parameters were tested before and after acute hypercalcaemia. No significant difference between healthy normocalcaemic subjects and chronic hypercalcaemic patients was found in the RMT values and MEP amplitude and CSP duration evoked by the first stimulus of the trains. During the course of 5 Hz-rTMS trains, MEP size increased significantly less in patients with chronic hypercalcaemia than in healthy subjects, whereas the CSP duration lengthened to a similar extent in both groups. In the two patients studied after parathyroidectomy, rTMS elicited a normal MEP amplitude facilitation. Our findings indicate that acute hypercalcaemia significantly decreased the MEP amplitude facilitation. Given that 5 Hz-rTMS modulates cortical excitability through mechanisms resembling short-term synaptic enhancement, the reduction of MEP amplitude facilitation by hypercalcaemia may be related to Ca2+-dependent changes in synaptic plasticity.
Collapse
Affiliation(s)
- Elisa Iacovelli
- Department of Neurological Sciences, 'Sapienza' University of Rome, Viale dell'Università 30, 00185 Rome, Italy
| | | | | | | | | | | | | | | | | |
Collapse
|
|
23
|
Transcranial Magnetic Stimulation as a Tool for Brain Cortex Excitability Analysis in Migraine Pathophysiology. Biocybern Biomed Eng 2011. [DOI: 10.1016/s0208-5216(11)70015-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
|
|
24
|
Pell GS, Roth Y, Zangen A. Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: Influence of timing and geometrical parameters and underlying mechanisms. Prog Neurobiol 2011; 93:59-98. [DOI: 10.1016/j.pneurobio.2010.10.003] [Citation(s) in RCA: 223] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2010] [Revised: 10/14/2010] [Accepted: 10/20/2010] [Indexed: 01/10/2023]
|
|
25
|
Joo EY, Kim HJ, Lim YH, Ji KH, Hong SB. Zonisamide changes unilateral cortical excitability in focal epilepsy patients. J Clin Neurol 2010; 6:189-95. [PMID: 21264199 PMCID: PMC3024523 DOI: 10.3988/jcn.2010.6.4.189] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2010] [Revised: 06/25/2010] [Accepted: 06/25/2010] [Indexed: 11/17/2022] Open
Abstract
Background and Purpose To evaluate changes in cortical excitability induced by zonisamide (ZNS) in focal epilepsy patients. Methods Twenty-four drug-naїve focal epilepsy patients (15 males; overall mean age 29.8 years) were enrolled. The transcranial magnetic stimulation parameters obtained using two Magstim 200 stimulators were the resting motor threshold, amplitude of the motor-evoked potential (MEP), cortical silent period, short intracortical inhibition, and intracortical facilitation. These five transcranial magnetic stimulation parameters were measured before and after ZNS, and the findings were compared. Results All 24 patients were treated with ZNS monotherapy (200-300 mg/day) for 8-12 weeks. After ZNS, MEP amplitudes decreased (-36.9%) significantly in epileptic hemispheres (paired t-test with Bonferroni's correction for multiple comparisons, p<0.05), whereas the mean resting motor threshold, cortical silent period, short intracortical inhibition, and intracortical facilitation were unchanged (p>0.05). ZNS did not affect cortical excitability in nonepileptic hemispheres. Conclusions These findings suggest that ZNS decreases cortical excitability only in the epileptic hemispheres of focal epilepsy patients. MEP amplitudes may be useful for evaluating ZNS-induced changes in cortical excitability.
Collapse
Affiliation(s)
- Eun Yeon Joo
- Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | | | | | | | | |
Collapse
|
|
26
|
Changes in interhemispheric inhibition following successful epilepsy surgery: a TMS study. J Neurol 2010; 258:68-73. [DOI: 10.1007/s00415-010-5683-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2010] [Revised: 07/19/2010] [Accepted: 07/19/2010] [Indexed: 10/19/2022]
|
|
27
|
Suppa A, Iezzi E, Conte A, Belvisi D, Marsili L, Modugno N, Fabbrini G, Berardelli A. Dopamine influences primary motor cortex plasticity and dorsal premotor-to-motor connectivity in Parkinson's disease. Cereb Cortex 2010; 20:2224-33. [PMID: 20051362 DOI: 10.1093/cercor/bhp288] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
We investigated abnormal premotor to motor (PMd-to-M1) connectivity in Parkinson's disease (PD) with repetitive transcranial magnetic stimulation (rTMS). We studied 28 patients off and on dopaminergic therapy and 28 healthy subjects. We delivered 5 Hz rTMS over M1 before and after conditioning PMd with 5 Hz rTMS. In healthy subjects, motor-evoked potentials (MEPs) elicited by M1-rTMS were facilitated and PMd-rTMS left MEPs unchanged. In patients, before PMd-rTMS, M1-rTMS induced no MEP facilitation, whereas after PMd-rTMS, it significantly facilitated MEPs only when patients were on therapy. In the second experiment, we delivered M1-rTMS under 3 different attention-demanding tasks: eyes closed, attention directed to the stimulated hand, and attention directed to the nonstimulated hand. In healthy subjects, a more pronounced MEP facilitation was present when subjects directed attention to the stimulated hand. In patients, the MEP facilitation was present when attention was directed to the stimulated hand only when patients were on therapy. Finally, we delivered M1-rTMS in patients on therapy while they were looking at the stimulated hand, before and after 1 Hz PMd-rTMS. PMd-rTMS reduced the attention-induced MEP facilitation. We conclude that in addition to abnormal M1 plasticity, the reduced MEP facilitation in PD also reflects altered PMd-to-M1 connectivity.
Collapse
Affiliation(s)
- A Suppa
- Department of Neurological Sciences, Sapienza University of Rome, Rome, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Conte A, Barbanti P, Frasca V, Iacovelli E, Gabriele M, Giacomelli E, Aurilia C, Pichiorri F, Gilio F, Inghilleri M. Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura. Pain 2010; 148:43-48. [DOI: 10.1016/j.pain.2009.09.031] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2009] [Revised: 07/18/2009] [Accepted: 09/29/2009] [Indexed: 11/28/2022]
|
|
29
|
Vollono C, Ferraro D, Miliucci R, Vigevano F, Valeriani M. The Abnormal Recovery Cycle of Somatosensory Evoked Potential Components in Children with Migraine can be Reversed by Topiramate. Cephalalgia 2009; 30:17-26. [DOI: 10.1111/j.1468-2982.2009.01892.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
The aim of this study was to compare the recovery cycle of somatosensory evoked potentials (SEPs) in children with migraine without aura before and after treatment with topiramate. Eleven migraine children were studied before and after a 3-month treatment with topiramate at the average dose of 1.3 mg/kg/day. We calculated the SEP latency and amplitude modifications after paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals, comparing them with a single stimulus condition assumed as baseline. In nine patients, who had a significant reduction in headache frequency after treatment, the recovery cycles of the P24 ( P = 0.03) and N30 ( P < 0.005) potentials were longer after than before topiramate treatment. In two migraineurs who did not show any improvement, the recovery cycles of the cortical SEP components were even shorter after treatment. Our results suggest that topiramate efficacy in paediatric migraine prophylaxis is probably related to restored cortical excitability.
Collapse
Affiliation(s)
- C Vollono
- Headache Centre, Neurology
Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Catholic
University, Rome, Italy
| | - D Ferraro
- Institute of Neurology,
Department of Neurosciences, Catholic University, Rome, Italy
| | - R Miliucci
- Headache Centre, Neurology
Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Catholic
University, Rome, Italy
| | - F Vigevano
- Headache Centre, Neurology
Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Catholic
University, Rome, Italy
| | - M Valeriani
- Headache Centre, Neurology
Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Catholic
University, Rome, Italy
| |
Collapse
|
|
30
|
rTMS for suppressing neuropathic pain: a meta-analysis. THE JOURNAL OF PAIN 2009; 10:1205-16. [PMID: 19464959 DOI: 10.1016/j.jpain.2009.03.010] [Citation(s) in RCA: 149] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2008] [Revised: 01/21/2009] [Indexed: 12/31/2022]
Abstract
UNLABELLED This pooled individual data (PID)-based meta-analysis collectively assessed the analgesic effect of repetitive transcranial magnetic stimulation (rTMS) on various neuropathic pain states based on their neuroanatomical hierarchy. Available randomized controlled trials (RCTs) were screened. PID was coded for age, gender, pain neuroanatomical origins, pain duration, and treatment parameters analyses. Coded pain neuroanatomical origins consist of peripheral nerve (PN); nerve root (NR); spinal cord (SC); trigeminal nerve or ganglion (TGN); and post-stroke supraspinal related pain (PSP). Raw data of 149 patients were extracted from 5 (1 parallel, 4 cross-over) selected (from 235 articles) RCTs. A significant (P < .001) overall analgesic effect (mean percent difference in pain visual analog scale (VAS) score reduction with 95% confidence interval) was detected with greater reduction in VAS with rTMS in comparison to sham. Including the parallel study (Khedr et al), the TGN subgroup was found to have the greatest analgesic effect (28.8%), followed by PSP (16.7%), SC (14.7%), NR (10.0%), and PN (1.5%). The results were similar when we excluded the parallel study with the greatest analgesic effect observed in TGN (33.0%), followed by SC (14.7%), PSP (10.5%), NR (10.0%), and PN (1.5%). In addition, multiple (vs single, P = .003) sessions and lower (>1 and < or =10 Hz) treatment frequency range (vs >10 Hz) appears to generate better analgesic outcome. In short, rTMS appears to be more effective in suppressing centrally than peripherally originated neuropathic pain states. PERSPECTIVE This is the first PID-based meta-analysis to assess the differential analgesic effect of rTMS on neuropathic pain based on the neuroanatomical origins of the pain pathophysiology and treatment parameters. The derived information serves as a useful resource in regards to treatment parameters and patient population selection for future rTMS-pain studies.
Collapse
|
|
31
|
Möller C, Arai N, Lücke J, Ziemann U. Hysteresis effects on the input–output curve of motor evoked potentials. Clin Neurophysiol 2009; 120:1003-8. [DOI: 10.1016/j.clinph.2009.03.001] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2008] [Revised: 02/27/2009] [Accepted: 03/03/2009] [Indexed: 11/28/2022]
|
|
32
|
Gilio F, Iacovelli E, Frasca V, Gabriele M, Giacomelli E, De Lena C, Cipriani AM, Inghilleri M. Electrical and magnetic repetitive transcranial stimulation of the primary motor cortex in healthy subjects. Neurosci Lett 2009; 455:1-3. [DOI: 10.1016/j.neulet.2009.03.035] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2008] [Revised: 01/18/2009] [Accepted: 03/09/2009] [Indexed: 11/17/2022]
|
|
33
|
Nitsche MA, Paulus W. Noninvasive brain stimulation protocols in the treatment of epilepsy: current state and perspectives. Neurotherapeutics 2009; 6:244-50. [PMID: 19332316 PMCID: PMC5084200 DOI: 10.1016/j.nurt.2009.01.003] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2008] [Revised: 01/12/2009] [Accepted: 01/13/2009] [Indexed: 11/17/2022] Open
Abstract
In epileptic seizures, there is an enhanced probability of neuronal networks to fire synchronously at high frequency, initiated by a paroxysmal depolarisation shift. Reducing neuronal excitability is a common target of antiepileptic therapies. Beyond or in addition to pharmacological interventions, excitability-reducing brain stimulation is pursued as an alternative therapeutic approach. Hereby, noninvasive brain stimulation tools, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have gained increased interest as efficient tools to modulate cortical excitability and activity. In animal models, stimulation-induced cortical excitability diminution has been shown to be suited to reduce seizures. Clinical studies conducted to date, however, have shown mixed results. Reasons for this, as well as possible optimization strategies that might lead to more efficient future stimulation protocols, will be discussed.
Collapse
Affiliation(s)
- Michael A Nitsche
- Department of Clinical Neurophysiology, Georg-August-University, 37099 Goettingen, Germany.
| | | |
Collapse
|
|
34
|
Ziemann U, Paulus W, Nitsche MA, Pascual-Leone A, Byblow WD, Berardelli A, Siebner HR, Classen J, Cohen LG, Rothwell JC. Consensus: Motor cortex plasticity protocols. Brain Stimul 2008; 1:164-82. [PMID: 20633383 DOI: 10.1016/j.brs.2008.06.006] [Citation(s) in RCA: 465] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2008] [Accepted: 06/09/2008] [Indexed: 12/11/2022] Open
Abstract
Noninvasive transcranial stimulation is being increasingly used by clinicians and neuroscientists to alter deliberately the status of the human brain. Important applications are the induction of virtual lesions (for example, transient dysfunction) to identify the importance of the stimulated brain network for a certain sensorimotor or cognitive task, and the induction of changes in neuronal excitability, synaptic plasticity or behavioral function outlasting the stimulation, for example, for therapeutic purposes. The aim of this article is to review critically the properties of the different currently used stimulation protocols, including a focus on their particular strengths and weaknesses, to facilitate their appropriate and conscientious application.
Collapse
Affiliation(s)
- Ulf Ziemann
- Department Neurology, Goethe-University Frankfurt, Germany.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Acute and chronic effects of ethanol on cortical excitability. Clin Neurophysiol 2008; 119:667-674. [PMID: 18083628 DOI: 10.1016/j.clinph.2007.10.021] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2007] [Revised: 10/22/2007] [Accepted: 10/30/2007] [Indexed: 01/20/2023]
Abstract
OBJECTIVE We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.
Collapse
|
|
36
|
Joo EY, Kim SH, Seo DW, Hong SB. Zonisamide decreases cortical excitability in patients with idiopathic generalized epilepsy. Clin Neurophysiol 2008; 119:1385-92. [DOI: 10.1016/j.clinph.2008.02.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2007] [Revised: 01/22/2008] [Accepted: 02/12/2008] [Indexed: 11/24/2022]
|
|
37
|
Nedolya NA, Tarasova OA, Albanov AI, Volostnykh OG, Brandsma L, Trofimov BA. A new approach to densely functionalised azepines and dihydroazepines. MENDELEEV COMMUNICATIONS 2008. [DOI: 10.1016/j.mencom.2008.05.018] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
|
|
38
|
Gilio F, Iacovelli E, Conte A, Frasca V, Gabriele M, Giacomelli E, Bettolo CM, Scaldaferri N, Trebbastoni A, Prencipe M, Inghilleri M. Asymmetric responses to repetitive transcranial magnetic stimulation (rTMS) over the left and right primary motor cortex in a patient with lateralized progressive limb-kinetic apraxia. Neurosci Lett 2008; 437:125-9. [DOI: 10.1016/j.neulet.2008.03.072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2008] [Revised: 03/01/2008] [Accepted: 03/19/2008] [Indexed: 01/23/2023]
|
|
39
|
Changes in intracortical excitability after successful epilepsy surgery. Epilepsy Res 2008; 79:55-62. [DOI: 10.1016/j.eplepsyres.2007.12.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2007] [Revised: 10/31/2007] [Accepted: 12/29/2007] [Indexed: 11/17/2022]
|
|
40
|
Artemenko AR, Kurenkov AL, Filatova EG, Nikitin SS, Kaube H, Katsarava Z. Effects of Topiramate on Migraine Frequency and Cortical Excitability in Patients with Frequent Migraine. Cephalalgia 2008; 28:203-8. [DOI: 10.1111/j.1468-2982.2007.01491.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
We studied the excitability of the visual and motor cortex in 36 patients with frequent migraine without aura (30 women, mean age 38.6 ± 10.0 years) before and after treatment with topiramate (100 mg/day) using transcranial magnetic stimulation. Treatment with topiramate resulted in reduction of both headache frequency (12.0 ± 1.3 to 5.8 ± 3.2 migraine days per month; P = 0.004) and cortical excitability: motor cortex thresholds increased on the right side from 43.8 ± 7.5% to 47.7 ± 9.2% ( P = 0.049) and on the left side from 43.4 ± 7.0% to 47.2 ± 9.6% ( P = 0.047), and phosphene thresholds increased from 58.9 ± 11.1% to 71.2 ± 11.2% ( P = 0.0001). Reduction of headache frequency correlated inversely with an increase of visual thresholds and did not correlate with motor thresholds. The effect of topiramate in migraine prevention is complex and can not be explained simply by inhibition of cortical excitability.
Collapse
Affiliation(s)
- AR Artemenko
- Division of Autonomic Nervous System Pathology
- Alexander Vein Headache Clinic, Moscow, Russia
| | - AL Kurenkov
- Division of Cerebral Palsy, Scientific Centre of Children Health
- Alexander Vein Headache Clinic, Moscow, Russia
| | - EG Filatova
- Department of Neurology, Moscow Medical Academy
- Alexander Vein Headache Clinic, Moscow, Russia
| | - SS Nikitin
- Division of Pathology Motor Neurone, Institute of General Pathology and Pathophysiology
| | - H Kaube
- Department of Neurology and Neurophysiology, University of Freiburg, Freiburg
- Division of Clinical Neurosciences, University of Southampton, Southampton, UK
| | - Z Katsarava
- Department of Neurology, University of Essen, Essen, Germany
| |
Collapse
|
|
41
|
Suppa A, Bologna M, Gilio F, Lorenzano C, Rothwell JC, Berardelli A. Preconditioning Repetitive Transcranial Magnetic Stimulation of Premotor Cortex Can Reduce But Not Enhance Short-Term Facilitation of Primary Motor Cortex. J Neurophysiol 2008; 99:564-70. [DOI: 10.1152/jn.00753.2007] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Short trains of suprathreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) evoke motor potentials (MEPs) in hand muscles that progressively increase in amplitude via a mechanism that is thought to be similar to short-term potentiation described in animal preparations. Long trains of subthreshold rTMS over dorsal premotor cortex (PMd) are known to affect the amplitude of single-pulse MEPs evoked from M1. We tested whether PMd-rTMS affects short-term facilitation in M1. We also explored the effect of PMd-rTMS on M1 responses evoked by single-pulse TMS of different polarities. We tested in 15 healthy subjects short-term facilitation in left M1 (10 suprathreshold TMS pulses at 5 Hz) after applying rTMS to left PMd (1,500 subthreshold pulses at 1 and 5 Hz). In a sample of subjects we delivered single-pulse TMS with different polarities and paired-pulse TMS at short intervals (SICI) after PMd-rTMS. Short-term facilitation in M1 was reduced after applying 1 Hz to PMd, but was unaffected after 5-Hz PMd-rTMS. PMd-rTMS with 1 Hz reduced the amplitude of MEPs evoked by monophasic posteroanterior (PA) or biphasic anteroposterior (AP)–PA but had little effect on MEPs by monophasic AP or biphasic PA–AP single-pulse TMS. PMd-rTMS left SICI unchanged. PMd-rTMS (1 Hz) reduces short-term facilitation in M1 induced by short 5-Hz trains. This effect is likely to be caused by reduced facilitation of I-wave inputs to corticospinal neurons.
Collapse
|
|
42
|
Loo CK, McFarquhar TF, Mitchell PB. A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Int J Neuropsychopharmacol 2008; 11:131-47. [PMID: 17880752 DOI: 10.1017/s1461145707007717] [Citation(s) in RCA: 131] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
There is growing interest worldwide in rTMS as a clinical treatment for depression. Apart from efficacy, its safety as a clinical treatment must be considered before its widespread use can be advocated. All published, sham-controlled rTMS depression trials were reviewed for reported side-effects and outcomes of formal neuropsychological testing. In addition, all reports of seizures occurring with rTMS were reviewed. Other safety concerns (effects on hearing; headache, pain, induced currents in electrical circuits, histotoxicity, electromagnetic field exposure, psychiatric complications, safety in pregnancy) are discussed. Common side-effects were of a minor nature, e.g. headache. There was a low incidence of accidental seizures and induced hypomania, both of which were associated with identified risk factors for which subjects should be screened. Long-term effects of repeated rTMS sessions are as yet unknown. When given within recommended guidelines, the overall safety profile of rTMS is good, and supports its further development as a clinical treatment.
Collapse
Affiliation(s)
- Colleen K Loo
- School of Psychiatry, University of New South Wales, Sydney, Australia.
| | | | | |
Collapse
|
|
43
|
Conte A, Gilio F, Iezzi E, Frasca V, Inghilleri M, Berardelli A. Attention influences the excitability of cortical motor areas in healthy humans. Exp Brain Res 2007; 182:109-17. [PMID: 17516055 DOI: 10.1007/s00221-007-0975-3] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2007] [Accepted: 04/23/2007] [Indexed: 01/23/2023]
Abstract
We investigated whether human attentional processes influence the size of the motor evoked potentials (MEP) facilitation and the duration of the cortical silent period (CSP) elicited by high-frequency repetitive transcranial magnetic stimulation (rTMS). In healthy subjects we assessed the effects of 5 Hz-rTMS, delivered in trains of 10 stimuli at suprathreshold intensity over the hand motor area, on the MEP size and CSP duration in different attention-demanding conditions: "relaxed," "target hand," and "non-target hand" condition. We also investigated the inhibitory effects of 1 Hz-rTMS conditioning to the premotor cortex on the 5 Hz-rTMS induced MEP facilitation. F-waves evoked by ulnar nerve stimulation were also recorded. rTMS trains elicited a larger MEP size facilitation when the subjects looked at the target hand whereas the increase in CSP duration during rTMS remained unchanged during the three attention-demanding conditions. The conditioning inhibitory stimulation delivered to the premotor cortex decreased the MEP facilitation during the "target hand" condition, leaving the MEP facilitation during the other conditions unchanged. None of the attentional conditions elicited changes in the F wave. In healthy subjects attentional processes influence the size of the MEP facilitation elicited by high-frequency rTMS and do so through premotor-to-motor connections.
Collapse
Affiliation(s)
- Antonella Conte
- Department of Neurological Sciences, University of Rome La Sapienza, Viale dell'Università, 30, 00185 Rome, Italy
| | | | | | | | | | | |
Collapse
|
|
44
|
Gilio F, Suppa A, Bologna M, Lorenzano C, Fabbrini G, Berardelli A. Short‐term cortical plasticity in patients with dystonia: A study with repetitive transcranial magnetic stimulation. Mov Disord 2007; 22:1436-1443. [PMID: 17516450 DOI: 10.1002/mds.21465] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold (RMT) intensity produces a progressive facilitation of motor-evoked potential (MEP) amplitude that outlasts the end of stimulation. This phenomenon is related to a short-term enhancement of cortical excitatory interneurones. In this study, we investigated whether 5 Hz-rTMS elicits similar MEP facilitation during stimulation and similar facilitatory after-effects in patients with upper limb dystonia and healthy subjects. Trains of 5, 10, and 20 stimuli were delivered at 120% RMT over the primary motor cortex with the subjects at rest. rTMS-trains were followed by single test stimuli delivered at various interstimulus intervals (0.5-10 s) at 120% RMT using a conditioning-test paradigm. Single conditioning stimuli were also delivered. The effects of suprathreshold 1 Hz-rTMS were also tested. The MEP amplitude during the course of the trains and of the test stimuli was measured. In control experiments, we investigated the role of the afferent inputs elicited by muscle twitches after ulnar nerve stimulation on the MEP amplitude. In patients and healthy subjects, MEP amplitude increased significantly during the course of 5 Hz-trains. In both groups the MEP facilitation outlasted the end of 5 Hz-rTMS, however the facilitatory after-effects were more pronounced and lasted longer in patients than in healthy subjects. MEP amplitudes during and after 1 Hz-rTMS remained unchanged. Ulnar nerve stimulation did not change the test MEP amplitude. We conclude that in patients with upper limb dystonia there is an abnormal recovery from MEP facilitation after suprathreshold 5 Hz-rTMS suggesting an abnormal pattern of short-term cortical plasticity.
Collapse
Affiliation(s)
- Francesca Gilio
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Rome, Italy
| | - Antonio Suppa
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Rome, Italy
| | - Matteo Bologna
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Rome, Italy
| | - Cinzia Lorenzano
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Rome, Italy
| | - Giovanni Fabbrini
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Rome, Italy
| | - Alfredo Berardelli
- Department of Neurological Sciences and Neuromed Institute (IRCCS), University of Rome "La Sapienza", Rome, Italy
| |
Collapse
|
|
45
|
Abstract
Damage to a nerve should only lead to sensory loss. While this is common, the incidence of spontaneous pain, allodynia and hyperalgesia indicate marked changes in the nervous system that are possible compensations for the loss of normal function that arises from the sensory loss. Neuropathic pain arises from changes in the damaged nerve which then alter function in the spinal cord and the brain and lead to plasticity in areas adjacent to those directly influenced by the neuropathy. The peripheral changes drive central compensations so that the mechanisms involved are multiple and located at a number of sites. Nerve damage increases the excitability of both the damaged and undamaged nerve fibres, neuromas and the cell bodies in the dorsal root ganglion. These peripheral changes are substrates for the ongoing pain and the efficacy of excitability blockers such as carbamazepine, lamotrigine and mexiletine, all anti-convulsants. A better understanding of ion channels at the sites of injury has shown important roles of particular sodium, potassium and calcium channels in the genesis of neuropathic pain. Within the spinal cord, increases in the activity of calcium channels and the receptors for glutamate, especially the N-methyl-D-aspartate (NMDA) receptor, trigger wind-up and central hyperexcitability. Increases in transmitter release, neuronal excitability and receptive field size result from the damage to the peripheral nerves. Ketamine and gabapentin/pregabalin, again with anti-convulsant activity, may interact with these mechanisms. Ketamine acts on central spinal mechanisms of excitability whereas gabapentin acts on a subunit of calcium channels that is responsible for the release of pain transmitters into the spinal cord. In addition to these spinal mechanisms of hyperexcitability, spinal cells participate in a spinal-supraspinal loop that involves parts of the brain involved in affective responses to pain but also engages descending excitatory and inhibitory systems that use the monoamines. These pathways become more active after nerve injury and are the site of action of anti-depressants. This chapter reviews the evidence and mechanisms of drugs, both anti-depressants and anti-convulsants, that are believed to be effective in pain control, with a major emphasis on the neuropathic state.
Collapse
Affiliation(s)
- A H Dickenson
- Dept. Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
| | | |
Collapse
|
|
46
|
Conte A, Gilio F, Iacovelli E, Bettolo CM, Di Bonaventura C, Frasca V, Carbone A, Prencipe M, Berardelli A, Inghilleri M. Effects of repetitive transcranial magnetic stimulation on spike-and-wave discharges. Neurosci Res 2007; 57:140-2. [PMID: 17088005 DOI: 10.1016/j.neures.2006.09.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2006] [Revised: 09/25/2006] [Accepted: 09/26/2006] [Indexed: 11/16/2022]
Abstract
Aim of this study was to evaluate the effect of 5Hz-suprathreshold repetitive transcranial magnetic stimulation (rTMS) on the duration of the spike-and-wave discharges (SWDs) in a patient presenting idiopathic absence seizures. At the moment of the study the patient presented a mild blunting of consciousness due to the high frequency of absences and EEG recordings showed sub-continuous, generalized, symmetrical and synchronous 3c/s SWDs, petit mal status. Trains of 10 stimuli (120% resting motor threshold) were delivered at 5Hz frequency at the beginning of the SWDs. 5Hz-rTMS trains significantly changed the EEG activity by reducing the duration of SWDs without changing the intervals between two consecutive discharges. rTMS had not significant after-effects on the epileptic activity and patient's clinical status. Despite the limitations of a single case report, our neurophysiological findings suggest that 5Hz-suprathreshold rTMS delivered in short trains induces a transitory interference of the ongoing epileptic activity.
Collapse
Affiliation(s)
- Antonella Conte
- Department of Neurological Sciences, University of Rome La Sapienza, Rome, Italy
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Segerdahl M. Multiple dose gabapentin attenuates cutaneous pain and central sensitisation but not muscle pain in healthy volunteers. Pain 2006; 125:158-64. [PMID: 16781073 DOI: 10.1016/j.pain.2006.05.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Revised: 04/25/2006] [Accepted: 05/03/2006] [Indexed: 11/22/2022]
Abstract
Various muscle pains constitute a large clinical problem, both for patients and clinicians. Gabapentin is an established therapy in neuropathic pain and reduces cutaneous pain in healthy volunteers. Gabapentin in combination with other analgesics reduces post-operative pain. No data exist on the effect of gabapentin on muscle pain. This study investigates the effect of gabapentin on muscle and cutaneous pain in healthy volunteers. Sixteen healthy volunteers, 8 male/8 female, were included in this double-blind three-session crossover study comparing the effects of 0, 1200, 1800 and 2600 mg (pre-treatment, titrated over 4 doses) gabapentin and placebo. Muscle pain was induced by infusing 0.5 ml of hypertonic saline into the anterior tibial muscle. Simultaneously, subjects graded pain on a computerized visual analog scale (VAS, 0-10). Total (AUC, VAS*duration in s) and maximal pain (VAS(max)) were assessed. Areas of local and referred pain were measured. Further, continuous intracutaneous electrical stimulation was applied to the forearm. Current was increased until pain intensity 5/10 or until subjects reached a cut-off of 70 mA. Spontaneous pain (VAS 0-10), areas of secondary hyperalgesia to pinprick (cm2) and mechanical pain threshold (g) within this area were assessed. Gabapentin pre-treatment reduced sensitivity to electrical induction of skin pain by 14%, p=0.016. Secondary hyperalgesia was induced, but areas were reduced after pre-treatment, p<0.05. Mechanical pain thresholds were unaffected. Pain induced by intramuscular infusion of hypertonic saline was not affected by gabapentin. In conclusion, single or repeated dosing of gabapentin reduced cutaneous but not muscle pain in healthy volunteers.
Collapse
Affiliation(s)
- M Segerdahl
- Department for Clinical Science, Intervention and Technology, Division for Anesthesiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden.
| |
Collapse
|
|
48
|
Gilio F, Conte A, Vanacore N, Frasca V, Inghilleri M, Berardelli A. Excitatory and inhibitory after-effects after repetitive magnetic transcranial stimulation (rTMS) in normal subjects. Exp Brain Res 2006; 176:588-93. [PMID: 16900360 DOI: 10.1007/s00221-006-0638-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2006] [Accepted: 07/14/2006] [Indexed: 12/31/2022]
Abstract
We investigated the post-train effects of repetitive transcranial magnetic stimulation (rTMS) on motor evoked potential (MEP) size and cortical silent period (SP) duration. rTMS was delivered over the primary motor cortex in trains of 5, 10, 20, 40 and 60 stimuli in normal subjects at rest and in trains of 5, 10 and 20 stimuli during voluntary muscle contraction. The intensity of stimulation was 120% of resting motor threshold. Test MEPs were delivered at different interstimulus intervals after rTMS ended. At rest, 5 Hz trains produced an increase in the MEP size that persisted after the end of the trains. Trains of 5 stimuli produced after-effects that persisted for 0.5 s, whereas trains of 40 and 60 stimuli produced a facilitation that lasted for several seconds. 5 Hz-rTMS delivered during muscle contraction increased the SP duration during stimulation but the increase persisted for only 1 s after the train ended. The present experiments show that the after-effects of rTMS on MEP amplitude and SP duration have different time-courses. rTMS probably elicits its after-effects on excitatory and inhibitory cortical elements through different physiological mechanisms.
Collapse
Affiliation(s)
- F Gilio
- Dipartimento Scienze Neurologiche, Università di Roma La Sapienza, Viale dell'Università, 30, 00185, Rome, Italy
| | | | | | | | | | | |
Collapse
|
|
49
|
Inghilleri M, Gilio F, Conte A, Frasca V, Marini Bettolo C, Iacovelli E, Gregori B, Prencipe M, Berardelli A. Topiramate and cortical excitability in humans: a study with repetitive transcranial magnetic stimulation. Exp Brain Res 2006; 174:667-72. [PMID: 16896986 DOI: 10.1007/s00221-006-0506-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2006] [Accepted: 04/11/2006] [Indexed: 10/24/2022]
Abstract
Repetitive transcranial magnetic stimulation (rTMS) delivered at 5 Hz frequency and suprathreshold intensity progressively increases the size of muscle evoked potentials (MEPs) and the duration of the cortical silent period (CSP) in normal subjects. The aim of this study was to evaluate the effects of topiramate (TPM) at different doses on cortical excitability variables tested with rTMS. We tested the facilitation of the MEP size and CSP duration evoked by focal rTMS in eight patients before and after treatment with TPM at different doses for chronic neuropathic pain. In each patient, rTMS (5 Hz frequency-120% resting motor threshold) was applied at baseline and during the TPM induction phase (drug intake schedule: week I 25 mg/day, week II 50 mg/day, week III 75 mg/day, week IV 100 mg/day) and total TPM plasma concentrations were measured. The effects on the MEP size of 5 Hz-rTMS delivered over repeated sessions were tested in eight control subjects. TPM had no effect on the resting motor threshold. Antiepileptic treatment at increasing doses abolished the normal rTMS-induced MEP facilitation. ANOVA showed that this was a dose-related effect. Accordingly, in patients receiving TPM at higher doses (75 and 100 mg) rTMS failed to elicit the MEP facilitation. TPM left the progressive lengthening of the CSP during the rTMS train unchanged. In control subjects, rTMS applied over repeated sessions elicited a constant increase in MEP size. Our results suggest that TPM modulates the excitatory intracortical interneurons probably by altering rTMS-induced synaptic potentiation. These drug-induced effects are related to TPM doses and plasma concentrations. In conclusion, rTMS may be useful for quantifying the effectiveness of antiepileptic drugs and for assessing individual responses to different drugs but acting through similar mechanisms, thus combining functional neurophysiological information and laboratory data.
Collapse
Affiliation(s)
- M Inghilleri
- Dipartimento Scienze Neurologiche, Università di Roma La Sapienza, Rome, Italy.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Mohammadi B, Krampfl K, Petri S, Bogdanova D, Kossev A, Bufler J, Dengler R. Selective and nonselective benzodiazepine agonists have different effects on motor cortex excitability. Muscle Nerve 2006; 33:778-84. [PMID: 16598788 DOI: 10.1002/mus.20531] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Transcranial magnetic stimulation (TMS) is a useful method to study pharmacological effects on motor cortex excitability. Zolpidem is a selective agonist of the benzodiazepine receptor subtype BZ1 and has a distinct pharmacological profile compared to diazepam. To study the different effects of these two drugs on the cortical inhibitory system, TMS was performed before and after administration of a single oral dose of zolpidem (10 mg) and diazepam (5 mg) in six healthy volunteers. TMS tests included the determination of resting and active motor threshold (MT) and measurements of the amplitudes of motor evoked potentials, intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), and long-latency intracortical inhibition (LICI), and determination of the cortical silent period (CSP). Both drugs were without effect on the active or resting MT and decreased the ICF. Prolongation of the CSP and enhancement of LICI only in the presence of zolpidem point to a specific BZ1-related mechanism underlying the long-lasting component of cortical inhibition. This selective modulation of the CSP and the LICI points to a specific role of BZ1 receptors in the control of inhibitory neuronal loops within the primary motor cortex.
Collapse
Affiliation(s)
- Bahram Mohammadi
- Department of Neurology and Clinical Neurophysiology, Medical School of Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
| | | | | | | | | | | | | |
Collapse
|