[Show abstract][Hide abstract] ABSTRACT: Evidence shows that repetitive transcranial magnetic stimulation (rTMS) changes cortical inhibition (CI) and excitability and that these changes may relate to its therapeutic effects. This study aimed to investigate the effects of differing durations or 'doses' of rTMS on cortical inhibition and excitability in healthy subjects.
Four different experiments were conducted: 1 session of 1200pulses of 1 or 20Hz active or sham rTMS; 10 sessions of 1 or 20Hz active or sham rTMS, 1200pulses/session; 1 session of 3600pulses of 1 or 20Hz active or sham rTMS; 1 session of 6000pulses of 20Hz active or sham rTMS. Measures of cortical inhibition and excitability included short-interval intracortical inhibition, long interval cortical inhibition, cortical silent period (CSP), motor evoked potential amplitude, resting motor threshold and intracortical facilitation.
Only 6000pulses of 20Hz rTMS lead to a significant lengthening of the CSP and therefore potentiation of CI. There were no changes to excitability measures.
Only high frequency rTMS potentiated CI. Longer treatment durations are required to produce such changes.
Studies investigating the therapeutic effects of rTMS may benefit from extended dosing with increased number of pulses per session. CSP lengthening may be used to guide treatment response.
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 10/2013; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brain derived neurotrophic factor (BDNF) has been associated with the pathophysiology of schizophrenia (SCZ). However, it remains unclear whether alterations in BDNF observed in patients with SCZ are a core part of disease neurobiology or a consequence of treatment. In this manuscript we review existing knowledge relating the function of BDNF to synaptic transmission and neural plasticity and the relationship between BDNF and both pharmacological and non-pharmacological treatments for SCZ. With regards to synaptic transmission, exposure to BDNF or lack of this neurotrophin results in alteration to both excitatory and inhibitory synapses. Many authors have also evaluated the effects of both pharmacological and non-pharmacological treatments for SCZ in BDNF and despite some controversial results, it seems that medicated and non-medicated patients present with lower levels of BDNF when compared to controls. Further data suggests that typical antipsychotics may decrease BDNF expression whereas mixed results have been obtained with atypical antipsychotics. The authors found few studies reporting changes in BDNF after non-pharmacological treatments for SCZ, so the existing evidence in this area is limited. Although the study of BDNF provides some new insights into understanding of the pathophysiology and treatment of SCZ, additional work in this area is needed.
Journal of Psychiatric Research 01/2012; 46(1):1-11. · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a complex and heterogeneous psychiatric disorder. Auditory verbal hallucinations occur in 50-70% of patients with schizophrenia and are associated with significant distress, decreased quality of life and impaired social functioning. This study aimed to investigate the effects of active compared with sham 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to the left temporal-parietal cortex in patients with schizophrenia treated with clozapine. Symptom dimensions that were evaluated included general psychopathology, severity of auditory hallucinations, quality of life and functionality. Seventeen right-handed patients with refractory schizophrenia experiencing auditory verbal hallucinations and treated with clozapine were randomly allocated to receive either active rTMS or sham stimulation. A total of 384 min of rTMS was administered over 20 days using a double-masked, sham-controlled, parallel design. There was a significant reduction in Brief Psychiatric Rating Scale (BPRS) scores in the active group compared with the sham group. There was no significant difference between active and sham rTMS on Quality of Life Scale (QLS), Auditory Hallucinations Rating Scale (AHRS), Clinical Global Impressions (CGI) and functional assessment staging (FAST) scores. Compared with sham stimulation, active rTMS of the left temporoparietal cortex in clozapine-treated patients showed a positive effect on general psychopathology. However, there was no effect on refractory auditory hallucinations. Further studies with larger sample sizes are needed to confirm these findings.
Psychiatry Research 12/2010; 188(2):203-7. · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several lines of evidence suggest that major depressive disorder is associated with deficits in gamma-aminobutyric acid (GABA) inhibitory neurotransmission. Transcranial magnetic stimulation represents a noninvasive technique to measure cortical inhibition. In this study, we endeavored to measure cortical inhibition in medicated patients with treatment resistant major depressive disorder (TRD), unmedicated patients with major depressive disorder, and medicated euthymic patients with a history of major depressive disorder and compare them with healthy subjects.
Twenty-five patients with TRD, 16 unmedicated patients with major depressive disorder, 19 medicated euthymic patients with previous major depressive disorder (i.e., 17-item Hamilton Rating Scale for Depression < 8), and 25 healthy subjects were enrolled. Cortical inhibition was measured with transcranial magnetic stimulation paradigms known as short-interval cortical inhibition and the cortical silent period, which index GABA(A) and GABA(B) receptor-mediated inhibitory neurotransmission, respectively.
All major depressive disorder patient groups demonstrated significant cortical silent period deficits compared with healthy subjects. By contrast, only TRD patients demonstrated significant deficits in short-interval cortical inhibition compared with healthy subjects, medicated euthymic major depressive disorder patients, and unmedicated major depressive disorder patients. The TRD patients also demonstrated a significantly greater resting motor threshold compared with all other clinical subgroups and healthy subjects, suggesting that TRD was also associated with hypoexcitability of the frontal cortex.
Our findings suggest that GABA(B) neurophysiological deficits are closely related to pathophysiology of major depressive disorder. Our findings also suggest that more severe illness is selectively associated with GABA(A) receptor-mediated inhibitory deficits.
[Show abstract][Hide abstract] ABSTRACT: Recent reports have demonstrated that long interval cortical inhibition (LICI) can be indexed in the dorsolateral prefrontal cortex (DLPFC) in healthy controls. LICI is a neurophysiologic process indexed using transcranial magnetic stimulation and is closely associated with cortical GABA(B) receptor mediated inhibitory neurotransmission. Several previous studies have also reported that gamma band activity represents a neurophysiological process that is mediated, in part, through GABAergic inhibitory neurotransmission and may subserve several cognitive operations including working memory (WM) in the DLPFC. The intension of the current study, therefore, was to directly evaluate the relationship between these neurophysiological processes in healthy subjects. Eleven right-handed healthy subjects participated in this experiment in which gamma band activity was measured through simultaneous recording of electroencephalography (EEG) during the N-back task, a cognitive task designed to index WM. LICI was recorded through EEG from the left DLFPC, left motor cortex and through EMG of peripheral hand muscles in a separate session according to previously published methods. There was no evidence for a relationship in the DLPFC between LICI and gamma band activity elicited during the N-back task, though there was a significant relationship between LICI and performance on the 3-back condition, the N-back condition of greatest difficulty. In conclusion these data provide evidence to suggest that in the DLPFC, there is no direct relationship between GABA(B) receptor mediated inhibitory neurotransmission and gamma band activity. However, our data does suggest that LICI was related to 3-back performance providing evidence implicating DLPFC GABAergic inhibitory neurotransmission in WM performance.
Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS) 08/2008; 39(3):150-5. · 3.16 Impact Factor