Aims. Schizophrenia is a neuropsychiatric disorder associated with mental and motor disturbances. We aimed to investigate motor control, especially central silent period (CSP) in subjects with schizophrenia ( ) on long-term antipsychotic treatment compared to healthy controls ( ). Methods. Latency and duration of motor evoked potentials (MEPs) and CSPs were measured with the help of single pulse transcranial magnetic stimulation (TMS) and intramuscular electrodes. After stimulation of the dominant and nondominant motor cortex of abductor digiti minimi (ADM) and tibialis anterior (TA) muscle areas, respective responses were measured on the contralateral side. Results. MEPs did not differ significantly between the groups. Multiple CSPs were found predominantly in subjects with schizophrenia, which showed a higher number of CSPs in the dominant ADM and the longest summarized duration of CSPs in the nondominant ADM ( ) compared to controls. Conclusions. There were multiple CSPs predominantly in the upper extremities and in the dominant body side in subjects with schizophrenia. Behind multiple CSPs may lie an impaired regulation of excitatory or inhibitory neurotransmitter systems in central motor pathways. Further research is needed to clarify the role of the intramuscular recording methods and the effect of antipsychotics on the results. 1. Introduction Transcranial magnetic stimulation (TMS) of the motor cortex is a useful non-invasive method that enables investigation of motor cortex excitability and central inhibitory mechanisms in the central nervous system. The commonly measured parameters of the motor responses include motor conduction time (MCT), transient suppression of ongoing motor activity (central silent period = CSP), and latency and duration of CSP and motor evoked potential (MEP) amplitude. The lowest stimulus intensity that induces an appropriate response in the target muscle is considered to be motor threshold of the motor cortex [1]. The induction mechanism of the central silent period (CSP) is not completely understood. It has been suggested to consist of an initial part of spinal origin and of a later part of cortical origin [2–4] or to be of cortical, supraspinal origin, being generated in the primary motor cortex [5]. The CSP is probably controlled by complex subcortical extrapyramidal systems with numerous interneuronal synapses associated with (GABAergic) inhibitory circuits [6]. There are several TMS studies dealing with motor control in schizophrenia [7, 8], which is considered to be a neuropsychiatric disorder associated with
References
[1]
R. Cantello, M. Gianelli, C. Civardi, and R. Mutani, “Magnetic brain stimulation: the silent period after the motor evoked potential,” Neurology, vol. 42, no. 10, pp. 1951–1959, 1992.
[2]
R. Chen, A. M. Lozano, and P. Ashby, “Mechanism of the silent period following transcranial magnetic stimulation. Evidence from epidural recordings,” Experimental Brain Research, vol. 128, no. 4, pp. 539–542, 1999.
[3]
L. S？is？nen, E. Pirinen, S. Teitti et al., “Factors influencing cortical silent period: optimized stimulus location, intensity and muscle contraction,” Journal of Neuroscience Methods, vol. 169, no. 1, pp. 231–238, 2008.
[4]
H. Roick, H. J. von Giesen, and R. Benecke, “On the origin of the postexcitatory inhibition seen after transcranial magnetic brain stimulation in awake human subjects,” Experimental Brain Research, vol. 94, no. 3, pp. 489–498, 1993.
[5]
A. Schnitzler and R. Benecke, “The silent period after transcranial magnetic stimulation is of exclusive cortical origin: evidence from isolated cortical ischemic lesions in man,” Neuroscience Letters, vol. 180, no. 1, pp. 41–45, 1994.
[6]
C. Trompetto, A. Buccolieri, and G. Abbruzzese, “Intracortical inhibitory circuits and sensory input: a study with transcranial magnetic stimulation in humans,” Neuroscience Letters, vol. 297, no. 1, pp. 17–20, 2001.
[7]
H. M. Haraldsson, F. Ferrarelli, N. H. Kalin, and G. Tononi, “Transcranial magnetic stimulation in the investigation and treatment of schizophrenia: a review,” Schizophrenia Research, vol. 71, no. 1, pp. 1–16, 2004.
[8]
E. Soubasi, E. Chroni, P. Gourzis, A. Zisis, S. Beratis, and P. Papathanasopoulos, “Cortical motor neurophysiology of patients with schizophrenia: a study using transcranial magnetic stimulation,” Psychiatry Research, vol. 176, no. 2-3, pp. 132–136, 2010.
[9]
P. Dazzan and R. M. Murray, “Neurological soft signs in first-episode psychosis: a systematic review,” British Journal of Psychiatry. Supplement, vol. 181, no. 43, pp. s50–s57, 2002.
[10]
B. K. Puri, N. J. Davey, P. H. Ellaway, and S. W. Lewis, “An investigation of motor function in schizophrenia using transcranial magnetic stimulation of the motor cortex,” British Journal of Psychiatry, vol. 169, no. 6, pp. 690–695, 1996.
[11]
P. B. Fitzgerald, T. L. Brown, Z. J. Daskalakis, and J. Kulkarni, “A transcranial magnetic stimulation study of inhibitory deficits in the motor cortex in patients with schizophrenia,” Psychiatry Research, vol. 114, no. 1, pp. 11–22, 2002.
[12]
B. Boroojerdi, R. T？pper, H. Foltys, and U. Meincke, “Transcallosal inhibition and motor conduction studies in patients with schizophrenia using transcranial magnetic stimulation,” British Journal of Psychiatry, vol. 175, pp. 375–379, 1999.
[13]
N. J. Davey, B. K. Puri, H. S. Lewis, S. W. Lewis, and P. H. Ellaway, “Effects of antipsychotic medication on electromyographic responses to transcranial magnetic stimulation of the motor cortex in schizophrenia,” Journal of Neurology Neurosurgery and Psychiatry, vol. 63, no. 4, pp. 468–473, 1997.
[14]
Z. J. Daskalakis, B. K. Christensen, R. Chen, P. B. Fitzgerald, R. B. Zipursky, and S. Kapur, “Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation,” Archives of General Psychiatry, vol. 59, no. 4, pp. 347–354, 2002.
[15]
T. Wobrock, M. Schneider, D. Kadovic et al., “Reduced cortical inhibition in first-episode schizophrenia,” Schizophrenia Research, vol. 105, no. 1–3, pp. 252–261, 2008.
[16]
A. Pascual-Leone, D. S. Manoach, R. Birnbaum, and D. C. Goff, “Motor cortical excitability in schizophrenia,” Biological Psychiatry, vol. 52, no. 1, pp. 24–31, 2002.
[17]
P. B. Fitzgerald, T. L. Brown, J. Z. Daskalakis, and J. Kulkarni, “A transcranial magnetic stimulation study of the effects of olanzapine and risperidone on motor cortical excitability in patients with schizophrenia,” Psychopharmacology, vol. 162, no. 1, pp. 74–81, 2002.
[18]
P. B. Fitzgerald, T. L. Brown, N. A. U. Marston et al., “Reduced plastic brain responses in schizophrenia: a transcranial magnetic stimulation study,” Schizophrenia Research, vol. 71, no. 1, pp. 17–26, 2004.
[19]
U. Ziemann, F. Tergau, D. Bruns, J. Baudewig, and W. Paulus, “Changes in human motor cortex excitability induced by dopaminergic and anti-dopaminergic drugs,” Electroencephalography and Clinical Neurophysiology, vol. 105, no. 6, pp. 430–437, 1997.
[20]
S. M. Stahl and L. Mignon, Antipsychotics. Treating Psychosis, Mania and Depression, Cambridge University Press, 2010.
[21]
S. K. Liu, P. B. Fitzgerald, M. Daigle, R. Chen, and Z. J. Daskalakis, “The relationship between cortical inhibition, antipsychotic treatment, and the symptoms of schizophrenia,” Biological Psychiatry, vol. 65, no. 6, pp. 503–509, 2009.
[22]
Z. J. Daskalakis, B. K. Christensen, P. B. Fitzgerald, B. Moller, S. I. Fountain, and R. Chen, “Increased cortical inhibition in persons with schizophrenia treated with clozapine,” Journal of Psychopharmacology, vol. 22, no. 2, pp. 203–209, 2008.
[23]
T. Wobrock, T. Schneider-Axmann, W. Retz et al., “Motor circuit abnormalities in first-episode schizophrenia assessed with transcranial magnetic stimulation,” Pharmacopsychiatry, vol. 42, no. 5, pp. 194–201, 2009.
[24]
A. Currà, N. Modugno, M. Inghilleri, M. Manfredi, M. Hallett, and A. Berardelli, “Transcranial magnetic stimulation techniques in clinical investigation,” Neurology, vol. 59, no. 12, pp. 1851–1859, 2002.
[25]
M. Bajbouj, S. H. Lisanby, U. E. Lang, H. Danker-Hopfe, I. Heuser, and P. Neu, “Evidence for impaired cortical inhibition in patients with unipolar major depression,” Biological Psychiatry, vol. 59, no. 5, pp. 395–400, 2006.
[26]
M. M. Richter, A. C. Ehlis, C. P. Jacob, and A. J. Fallgatter, “Cortical excitability in adult patients with attention-deficit/hyperactivity disorder (ADHD),” Neuroscience Letters, vol. 419, no. 2, pp. 137–141, 2007.
[27]
B. D. Greenberg, U. Ziemann, G. Corá-Locatelli et al., “Altered cortical excitability in obsessive-compulsive disorder,” Neurology, vol. 54, no. 1, pp. 142–147, 2000.
[28]
S. R. Kay, A. Fiszbein, and L. A. Opler, “The positive and negative syndrome scale (PANSS) for schizophrenia,” Schizophrenia Bulletin, vol. 13, no. 2, pp. 261–276, 1987.
[29]
M. R. Munetz and S. Benjamin, “How to examine patients using the abnormal involuntary movement scale,” Hospital and Community Psychiatry, vol. 39, no. 11, pp. 1172–1177, 1988.
[30]
G. M. Simpson and J. W. Angus, “A rating scale for extrapyramidal side effects,” Acta Psychiatrica Scandinavica, Supplement, vol. 212, pp. 11–19, 1970.
[31]
T. R. E. Barnes, “A rating scale for drug-induced akathisia,” British Journal of Psychiatry, vol. 154, pp. 672–676, 1989.
[32]
J. Addington and D. Addington, “Neurocognitive and social functioning in schizophrenia,” Schizophrenia Bulletin, vol. 25, no. 1, pp. 173–182, 1999.
[33]
A. F. Lehman, J. Kreyenbuhl, R. W. Buchanan et al., “The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2003,” Schizophrenia Bulletin, vol. 30, no. 2, pp. 193–217, 2004.
[34]
K. Sim, H. C. Su, S. Fujii et al., “High-dose antipsychotic use in schizophrenia: a comparison between the 2001 and 2004 Research on East Asia Psychotropic Prescription (REAP) studies,” British Journal of Clinical Pharmacology, vol. 67, no. 1, pp. 110–117, 2009.
[35]
U. Ziemann, “TMS and drugs,” Clinical Neurophysiology, vol. 115, no. 8, pp. 1717–1729, 2004.
[36]
V. Di Lazzaro, F. Pilato, M. Dileone, P. A. Tonali, and U. Ziemann, “Dissociated effects of diazepam and lorazepam on short-latency afferent inhibition,” Journal of Physiology, vol. 569, part 1, pp. 315–323, 2005.
[37]
R. C. Oldfield, “The assessment and analysis of handedness: the Edinburgh inventory,” Neuropsychologia, vol. 9, no. 1, pp. 97–113, 1971.
[38]
S. D. Nandedkar and D. B. Sanders, “Recording characteristics of monopolar EMG electrodes,” Muscle and Nerve, vol. 14, no. 2, pp. 108–112, 1991.
[39]
P. E. Barkhaus and S. D. Nandedkar, “Recording characteristics of the surface EMG electrodes,” Muscle and Nerve, vol. 17, no. 11, pp. 1317–1323, 1994.
[40]
P. E. Barkhaus, M. I. Periquet, and S. D. Nandedkar, “Influence of the surface EMG electrode on the compound muscle action potential,” Electromyography and Clinical Neurophysiology, vol. 46, no. 4, pp. 235–239, 2006.
[41]
C. W. Hess, K. R. Mills, and N. M. F. Murray, “Responses in small hand muscles from magnetic stimulation of the human brain,” Journal of Physiology, vol. 388, pp. 397–419, 1987.
[42]
J. C. Rothwell, P. D. Thompson, B. L. Day et al., “Motor cortex stimulation in intact man. I. General characteristics of EMG responses in different muscles,” Brain, vol. 110, no. 5, pp. 1173–1190, 1987.
[43]
A. Priori, A. Berardelli, M. Inghilleri, N. Accornero, and M. Manfredi, “Motor cortical inhibition and the dopaminergic system: pharmacological changes in the silent period after transcranial brain stimulation in normal subjects, patients with Parkinson's disease and drug-induced parkinsonism,” Brain, vol. 117, part 2, pp. 317–323, 1994.
[44]
M. C. Ridding, R. Inzelberg, and J. C. Rothwell, “Changes in excitability of motor cortical circuitry patients with Parkinson's disease,” Annals of Neurology, vol. 37, no. 2, pp. 181–188, 1995.
[45]
M. Entezari-Taher, J. R. Singleton, C. R. Jones, G. Meekins, J. H. Petajan, and A. G. Smith, “Changes in excitability of motor cortical circuitry in primary restless legs syndrome,” Neurology, vol. 53, no. 6, pp. 1201–1205, 1999.
[46]
W. G. Ondo, K. D. Vuong, and J. Jankovic, “Exploring the relationship between Parkinson disease and restless legs syndrome,” Archives of Neurology, vol. 59, no. 3, pp. 421–424, 2002.
[47]
J. M. Jarcho, E. A. Mayer, Z. K. Jiang, N. A. Feier, and E. D. London, “Pain, affective symptoms, and cognitive deficits in patients with cerebral dopamine dysfunction,” Pain, vol. 153, no. 4, pp. 744–754, 2012.
[48]
A. Ahlgrén-Rimpil？inen, H. Lauerma, S. K？hk？nen, J. Markkula, and I. Rimpil？inen, “Recurrent csps after transcranial magnetic stimulation of motor cortex in restless legs syndrome,” Neurology Research International, vol. 2012, Article ID 628949, 7 pages, 2012.
[49]
M. P. Caligiuri, J. B. Lohr, and D. V. Jeste, “Parkinsonism in neuroleptic-naive schizophrenic patients,” American Journal of Psychiatry, vol. 150, no. 9, pp. 1343–1348, 1993.
