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  • 1
    Language: English
    In: Psychopharmacology, Feb, 2010, Vol.208(2), p.353(11)
    Description: Byline: Thomas Wobrock (1), Alkomiet Hasan (1), Berend Malchow (1), Claus Wolff-Menzler (1), Birgit Guse (1), Nicolas Lang (2), Thomas Schneider-Axmann (1), Ullrich K. H. Ecker (3), Peter Falkai (1) Keywords: Schizophrenia; Substance abuse; Cortical inhibition; Transcranial magnetic stimulation (TMS); Cannabinoids; Electrophysiology Abstract: Rationale/objectives There is a high prevalence of substance use disorder (SUD) in first-episode schizophrenia (SZ), but its contribution to the underlying SZ pathophysiology remains unclear. Several studies using transcranial magnetic stimulation (TMS) have observed abnormalities in human motor cortex (M1) excitability in SZ. Studies on cortical excitability comparing SZ patients with and without comorbid substance abuse are lacking. Methods A total of 29 first-episode SZ patients participated in this study 12 had a history of comorbid cannabis abuse (SZ-SUD) and 17 did not (SZ-NSUD). We applied TMS to right and left M1 areas to assess the resting motor threshold (RMT), short-interval cortical inhibition (SICI), intracortical facilitation (ICF), and the contralateral cortical silent period (CSP). Results In SICI and ICF conditions, right M1 stimulation led to significantly higher motor evoked potential ratios in SZ-SUD compared to SZ-NSUD. This suggests lower cortical inhibition and increased ICF in first-episode SZ with previous cannabis abuse. There were no group differences in RMT and CSP duration. Neither were there any significant correlations between psychopathology (as indexed by Positive and Negative Syndrome Scale), disease characteristics, the extent of cannabis abuse, and TMS parameters (SICI, ICF, and CSP). Conclusions Comorbid cannabis abuse may potentiate the reduced intracortical inhibition and enhanced ICF observed in first-episode SZ patients in some previous studies. This finding suggests an increased alteration of GABA.sub.A and NMDA receptor activity in cannabis-abusing first-episode patients as compared to schizophrenia patients with no history of substance abuse. This may constitute a distinct vulnerability factor in this special population. Author Affiliation: (1) Department of Psychiatry and Psychotherapy, Georg-August-University Gottingen, Von-Siebold-Strasse 5, 37075, Gottingen, Germany (2) Department of Neurology, Christian-Albrechts-University Kiel, 24195, Kiel, Germany (3) School of Psychology, University of Western Australia, Crawley, WA, 6009, Australia Article History: Registration Date: 18/11/2009 Received Date: 09/07/2009 Accepted Date: 16/11/2009 Online Date: 09/12/2009 Article note: T. Wobrock and A. Hasan contributed equally.
    Keywords: Marijuana ; Cannabinoids ; Substance Abuse ; Gaba ; N-methyl-d-aspartate ; Schizophrenia ; Comorbidity ; Psychotherapy
    ISSN: 0033-3158
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  • 2
    In: Schizophrenia Bulletin, 2016, Vol. 42(suppl1), pp.S95-S109
    Description: Despite many years of research, there is still an urgent need for new therapeutic options for the treatment of cognitive deficits in schizophrenia. Noninvasive brain stimulation (NIBS) has been proposed to be such a novel add-on treatment option. The main objective of this review was to systematically evaluate the cognitive effects of repetitive NIBS in schizophrenia. As most studies have not been specifically designed to investigate cognition as primary outcome, we have focused on both, primary and secondary outcomes. The PubMed/MEDLINE database (1985–2015) was systematically searched for interventional studies investigating the effects of repetitive NIBS on schizophrenia symptoms. All interventional clinical trials using repetitive transcranial stimulation, transcranial theta burst stimulation, and transcranial direct current stimulation for the treatment of schizophrenia were extracted and analyzed with regard to cognitive measures as primary or secondary outcomes. Seventy-six full-text articles were assessed for eligibility of which 33 studies were included in the qualitative synthesis. Of these 33 studies, only 4 studies included cognition as primary outcome, whereas 29 studies included cognitive measures as secondary outcomes. A beneficial effect of frontal NIBS could not be clearly established. No evidence for a cognitive disruptive effect of NIBS (temporal lobe) in schizophrenia could be detected. Finally, a large heterogeneity between studies in terms of inclusion criteria, stimulation parameters, applied cognitive measures, and follow-up intervals was observed. This review provides the first systematic overview regarding cognitive effects of repetitive NIBS in schizophrenia.
    Keywords: Schizophrenia ; Cognition ; Noninvasive Brain Stimulation ; Rtms ; Tdcs ; Neuroplasticity
    ISSN: 0586-7614
    E-ISSN: 1745-1701
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  • 3
    Language: English
    In: Psychiatry Research: Neuroimaging, 2011, Vol.193(1), pp.56-59
    Description: In schizophrenia patients reduced cerebral asymmetry is an important finding and this may reflect a disturbance in cortical development. We investigated planum temporale (PT) volume and asymmetry in 23 first-episode schizophrenia patients compared to healthy controls and found for the first time an in vivo volume asymmetry of PT to the right hemisphere.
    Keywords: Magnetic Resonance Imaging ; Cortical Asymmetry ; Cortical Development ; Medicine
    ISSN: 0925-4927
    E-ISSN: 1872-7506
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  • 4
    Language: English
    In: Behavioural Brain Research, 10 October 2011, Vol.224(1), pp.15-22
    Description: ► Disturbed plasticity is considered to underlie the pathophysiology of schizophrenia. ► Transcranial magnetic stimulation and transcranial direct current stimulation allow the investigation of cortical plasticity to awake humans. ► Schizophrenia patients showed an impaired LTP-like plasticity, which is related to the disease course compared to healthy controls. ► Schizophrenia patients displayed a cortical disinhibition compared to healthy controls. ► Dysfunctional NMDA-receptors and GABA-receptors may account for the plasticity deficits in schizophrenia. Neural and cortical plasticity represent the ability of the brain to reorganize its function in response to a challenge. Plasticity involves changing synaptic activity and connectivity. Long-term-potentiation is one important mechanism underlying these synaptic changes. Disturbed neuronal plasticity is considered to be part of the pathophysiology of schizophrenia and has been linked to the different clinical features of this severe illness. The aim of the present study was to investigate nonfocal cortical plasticity and cortical excitability in recent-onset and multi-episode schizophrenia compared with healthy subjects. Nonfocal cortical plasticity can be induced in the motor cortex of healthy subjects with anodal transcranial direct current stimulation. Animal and human research indicates that this long-term-potentiation-like plasticity is glutamate-dependent and that these plasticity shifts can last for several hours. Transcranial direct current stimulation-induced plasticity was monitored by transcranial magnetic stimulation-generated motor evoked potentials. Well-characterized transcranial magnetic stimulation protocols were applied to determine the physiological basis of plasticity changes. Multi-episode schizophrenia patients showed significantly reduced long-term-potentiation-like plasticity compared to recent-onset schizophrenia patients and healthy controls. All schizophrenia patients demonstrated reduced cortical inhibition. Our results indicate that the long-term-potentiation-like plasticity deficit in schizophrenia patients is related to the disease course. Disturbances of N-methyl- -aspartate, gamma-aminobutyric acid and dopamine receptors may account for this plasticity deficit. LTP-like plasticity deficits might be related to disturbed information processing in schizophrenia patients.
    Keywords: Schizophrenia ; Nmda ; Cortical Plasticity ; Gaba ; Transcranial Direct Current Stimulation ; Transcranial Magnetic Stimulation ; Anatomy & Physiology
    ISSN: 0166-4328
    E-ISSN: 0166-4328
    E-ISSN: 18727549
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  • 5
    Language: English
    In: Behavioural Brain Research, 01 May 2014, Vol.264, pp.17-25
    Description: Transcranial magnetic stimulation is an established method to probe inhibitory and facilitatory networks within the human motor cortex. Reduced motor-cortical inhibition is a common finding in schizophrenia patients. Based on neuropathological findings, the reduced cortical inhibition in schizophrenia has been linked mainly to alterations in GABAergic neurotransmission. The aim of this study was to investigate the impact of disease state on intracortical inhibitory and facilitatory networks measured by TMS in schizophrenia. Cortical excitability was investigated in a pooled cross-sectional sample of recent-onset-schizophrenia (RO–SZ), chronically-ill schizophrenia patients (CH–SZ) and healthy controls (HC) using single- and paired-pulse TMS applied to the left primary motor cortex. The sample included 41 RO–SZ, 42 CH–SZ and 59 HC. Analyses were focused on resting motor threshold (RMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). There was a significant difference regarding the mean CSP durations across our three study groups ( = 0.002). Subgroup comparisons revealed a shorter CSP in HC compared to RO–SZ ( 〈 0.001). Three group comparisons of SICI ( = 0.098) and RMT ( = 0.075) showed differences at a trend-level. An overall comparison between HC and all patients showed a significantly reduced SICI ( = 0.031) and prolonged CSP ( = 0.003) in schizophrenia patients. This is the largest and first cross-sectional investigation of various excitability parameters in schizophrenia patients. These findings indicate general alterations of cortical inhibition, with differences between recent-onset and chronically-ill schizophrenia patients.
    Keywords: Transcranial Magnetic Stimulation ; Gabaa ; Cortical Silent Period ; Short-Interval Intracortical Inhibition ; Intracortical Facilitation ; Anatomy & Physiology
    ISSN: 0166-4328
    E-ISSN: 0166-4328
    E-ISSN: 18727549
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  • 6
    In: Neuropsychopharmacology, 2014
    Description: Impaired neuroplastic responses following noninvasive brain stimulation have been reported repeatedly in schizophrenia patients. These findings have been associated with deficits in GABAergic, glutamatergic, and cholinergic neurotransmission. Although various neurophysiological studies have indicated a relationship between nicotine and neuroplasticity in healthy individuals, the present study is the first investigation into the impact of nicotine on LTD-like plasticity in patients with schizophrenia. Cortical excitability and cortical plasticity were explored in 30 schizophrenia patients (17 smoker, 13 nonsmoker) and 45 healthy controls (13 smoker, 32 nonsmoker) by using single-pulse transcranial magnetic stimulation (TMS) before and following cathodal transcranial direct current stimulation (tDCS) applied to the left primary motor cortex. Our analysis revealed abolished LTD-like plasticity in nonsmoking schizophrenia patients. However, these plasticity deficits were not present in smoking schizophrenia patients. In healthy controls, significant MEP reductions following cathodal tDCS were observed in nonsmoking individuals, but only trend-level reductions in smokers. In smoking schizophrenia patients, the severity of negative symptoms correlated positively with reduced neuroplasticity, whereas nonsmoking patients displayed the opposite effect. Taken together, the data of our study support the notion of an association between chronic smoking and the restitution of impaired LTD-like plasticity in schizophrenia patients. Although replication and further research are needed to better understand this relationship, our findings indicate that nicotine intake might stabilize the impaired inhibition-facilitation balance in the schizophrenic brain through a complex interaction between cortical plasticity, and GABAergic and cholinergic neurotransmission, and might explain the reduced prevalence of negative symptoms in this population.
    Keywords: Medicine ; Pharmacy, Therapeutics, & Pharmacology ; Anatomy & Physiology;
    ISSN: 0893-133X
    E-ISSN: 1740634X
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  • 7
    Language: English
    In: Journal of Psychiatric Research, September 2016, Vol.80, pp.1-2
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jpsychires.2016.05.005 Byline: Alkomiet Hasan, Caroline Brinkmann, Wolfgang Strube, Ulrich Palm, Berend Malchow, John C. Rothwell, Peter Falkai, Thomas Wobrock Author Affiliation: (a) Department of Psychiatry and Psychotherapy, Ludwig-Maximilians University, Munich, Germany (b) Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany (c) Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, UK (d) Centre of Mental Health, Darmstadt-Dieburg Clinics, Darmstadt, Germany
    Keywords: Medicine
    ISSN: 0022-3956
    E-ISSN: 1879-1379
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  • 8
    Language: English
    In: Journal of Psychiatric Research, February 2015, Vol.61, pp.196-204
    Description: Impaired neural plasticity has been proposed as an important pathophysiological feature underlying the neurobiology and symptomatology of schizophrenia. In this proof-of-concept study, we aimed to explore cortical plasticity in schizophrenia patients with two different transcranial theta-burst (TBS) paradigms. TBS induces Ca -dependent long-term-potentiation (LTP)-like and long-term-depression (LTP)-like plasticity in the human motor cortex. A total of 10 schizophrenia patients and 10 healthy controls were included in this study. Cortical excitability was investigated using transcranial magnetic stimulation in each study participant before and after TBS applied to the left primary motor-cortex on two different days. cTBS600 was used to induce LTD-like and cTBS300 was used to induce LTP-like plasticity in the absence of any prior motor-cortex activation. Repeated measures ANOVAs showed a significant interaction between the timecourse, the study group and the stimulation paradigm (cTBS600 vs. cTBS300) for the left, but not for the right hemisphere. Healthy controls showed an MEP amplitude decrease at a trend level following cTBS600 and a numeric, but not significant, increase in MEP amplitudes following cTBS300. Schizophrenia patients did not show an MEP amplitude decrease following cTBS600, but surprisingly a significant MEP decrease following cTBS300. The proportion of subjects showing the expected changes in motor-cortex excitability following both cTBS paradigms was higher in healthy controls. These preliminary results indicate differences in cortical plasticity following two different cTBS protocols in schizophrenia patients compared to healthy controls. However, the incomplete plasticity response in the healthy controls and the proof-of-concept nature of this study need to be considered as important limitations.
    Keywords: Schizophrenia ; Neural Plasticity ; Calcium Signaling ; Theta-Burst Stimulation ; Cortical Excitability ; Medicine
    ISSN: 0022-3956
    E-ISSN: 1879-1379
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  • 9
    Language: German
    In: DNP - Der Neurologe und Psychiater, 6/2012, Vol.13(6), pp.81-91
    ISSN: 1616-2455
    Source: Springer (via CrossRef)
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  • 10
    Language: English
    In: Experimental Brain Research, 2012, Vol.217(1), pp.15-23
    Description: Animal studies using polarising currents have shown that induction of synaptic long-term potentiation (LTP) and long-term depression (LTD) by bursts of patterned stimulation is affected by the membrane potential of the postsynaptic neurone. The aim of the present experiments was to test whether it is possible to observe similar phenomena in humans with the aim of improving present protocols of inducing synaptic plasticity for therapeutic purposes. We tested whether the LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human motor cortex, an analogue of patterned electrical stimulation in animals, were affected by simultaneous transcranial direct-current stimulation (tDCS), a non-invasive method of polarising cortical neurones in humans. Nine healthy volunteers were investigated in a single-blind, balanced cross-over study; continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with concurrent application of tDCS (〈200 s, anodal, cathodal, sham). Cathodal tDCS increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS changed the effects of cTBS towards facilitation, but had no impact on iTBS. Cortical motor thresholds and intracortical inhibitory/facilitatory networks were not altered by any of the stimulation protocols. We conclude that the after effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS changes the membrane potential of the apical dendrites of cortical pyramidal neurones and that this changes the response to patterned synaptic input evoked by TBS. The data show that it may be possible to enhance LTP-like plasticity after TBS in the human cortex.
    Keywords: Motor cortex plasticity ; Long-term potentiation ; Long-term depression ; Plasticity regulation
    ISSN: 0014-4819
    E-ISSN: 1432-1106
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