A Method to Provoke Obsessive Compulsive Symptoms for Basic Research and Clinical Interventions

Obsessive-compulsive disorder (OCD) is a chronic illness in which patients do not achieve remission sufficiently with conventional medication. Deep repetitive transcranial magnetic stimulation (dTMS) for OCD neuromodulates the bilateral anterior cingulate cortex (ACC) and dorsal medial prefrontal cortex (mPFC), which are known to be impaired in OCD. While dTMS treatment for OCD has shown effective results overseas, TMS treatment for OCD has rarely been implemented in Japan, and its effectiveness is unknown. We conducted an FDA-approved dTMS protocol to 26 patients with OCD. In addition, individual exposure stimulation that elicited each patient’s obsessive thoughts was also combined during dTMS treatment. Before and after 30 sessions of TMS treatment, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess changes in the severity of each patient’s obsessive-compulsive disorder. Response to dTMS treatment in patients with OCD was determined by whether the total score on the Y-BOCS after a course of treatment was reduced by 30% or more compared with the score at baseline. The percentage of responders in this case series following the 30 sessions of dTMS treatment was 53.9%. In addition, total Y-BOCS scores and scores on each item were significantly improved. The percent changes in total Y-BOCS scores did not differ between the sexes or between on- and off-medication patients. No obvious adverse events were observed in this case series. In line with the results of TMS studies for OCD patients reported overseas, dTMS treatment for Japanese patients with OCD may have a favorable therapeutic effect.

Personality dimensions and deep repetitive transcranial magnetic stimulation (DTMS) for treatment-resistant depression: A pilot trial on five-factor prediction of antidepressant response

The relationship between Obsessive Compulsive Disorder (OCD) and Obsessive Compulsive Personality Disorder (OCPD) has been the subject of interest for some time due to the historical assumption that OCPD causes OCD. This study systematically examined the association between OCD and OCPD in terms of prevalence and clinical presentation. The specificity of the association between OCD and OCPD was investigated relative to another axis I anxiety disorder (Panic disorder). Data for this study were drawn from measures taken at initial assessment at a specialist treatment centre for anxiety disorders. Of the 359 participants included in this study, 189 had a principal diagnosis of OCD, while 170 had a principal diagnosis of Panic disorder. Measures included SCID I and II interview modules and self-report measures of anxiety, depression, and OCD syptomatology. Significantly elevated rates of OCPD were found in OCD relative to Panic disorder. Regardless of axis I disorder, individuals with comorbid OCPD reported more severe depression relative to those without. Participants with both OCD and OCPD had greater self-reported OCD symptom severity, doubting, ordering, and hoarding symptoms at assessment relative to those without OCPD. Participants with OCD and comorbid OCPD also reported significantly higher levels of alcohol consumption. There appears to be a significant and specific association between OCD and OCPD. Co-occurring OCD and OCPD is associated with greater severity of impairment in terms of certain OCD symptoms. The significant and specific association between OCD and OCPD suggests that OCPD occurs more frequently with OCD than previously suggested. A comorbid OCPD diagnosis is associated with a greater degree of depression, regardless of axis I disorder, either OCD or Panic disorder. This is an important consideration, as depression can interfere with therapeutic progress (Foa, 1979). Participants with OCD and OCPD had greater self-reported OCD severity, along with doubting, ordering, and hoarding symptoms, relative to those without OCPD. In clinical practice, where OCD symptoms are severe, and the primary OCD symptoms include doubting, ordering, and hoarding, this may indicate a need to assess for comorbid OCPD. This may be useful in terms of including relevant information in formulation with the patient, and in addressing these issues in treatment. There may have been a sampling issue, as the study compared patients from a specialist clinic for the treatment of OCD and Panic disorder. Furthermore, OCD referrals were primary, secondary, or tertiary, whereas Panic disorder referrals were primary or secondary from the immediate catchment area only. This suggests the possibility of greater severity of the OCD sample relative to Panic disorder patients. All participants who met criteria for OCD were assessed for OCPD regardless of whether or not this was indicated by the SCID II screener self-report measure, while participants with Panic disorder were interviewed for OCPD only if indicated by the SCID-II screener. Had participants with Panic disorder been assessed for OCPD regardless of whether or not this was indicated by the SCID-II screener, there is a possibility that a higher rate of OCPD in the Panic disorder sample may have been found.

Reversal Learning as a Neuropsychological Indicator for the Neuropathology of Obsessive Compulsive Disorder? A Behavioral Study

The utilization of non-invasive neurostimulation techniques, such as transcranial magnetic stimulation (TMS), is increasingly prevalent in psychiatry due to their efficacy and safety. Although the precise therapeutic mechanisms remain partially unclear, repetitive TMS, particularly high-frequency stimulation, may enhance cognitive functions, contributing to therapeutic benefits. This within-subjects study examined the impact of TMS on cognitive and symptomatic outcomes in patients with obsessive–compulsive disorder (OCD), substance use disorder (SUD), and major depressive disorder (MDD). A total of 44 patients underwent cognitive tests and symptom assessments before and after an intensive four-week TMS treatment phase, followed by a four-week maintenance phase. Cognitive assessments included Raven’s matrices, verbal fluency, and digit span tests, while symptom severity was measured using the Italian version of the SCL-90-R. Decision-making performance was also evaluated by administering a delay discounting (DD) test. Principal component analysis was used to generate a dimensional characterization of subjects along cognitive and symptom-related axes before and after treatment. The results indicated that TMS significantly improved symptom scores, but no significant cognitive enhancement was observed. Statistical analysis based on linear mixed-effects models confirmed these findings, showing a significant fixed effect of TMS treatment on symptoms but not on cognitive performance. DD metrics remained unchanged. These findings suggest that while TMS effectively alleviates clinical symptoms, it does not produce consistent or appreciable enhancement of cognitive functions in these protocols. This study highlights the need for more personalized and combined therapeutic approaches to maximize the benefits of TMS, potentially incorporating cognitive enhancement strategies. Future studies will be useful to explore whether the results we obtained are valid for other pathologies, cognitive tests, and stimulation protocols.

Repetitive Deep Transcranial Magnetic Stimulation Improves Verbal Fluency and Written Language in a Patient with Primary Progressive Aphasia-Logopenic Variant (LPPA)

Freezing of Gait (FOG) is one of the most debilitating gait impairments in Parkinson's disease (PD), leading to increased fall risk and reduced health-related quality of life. The utility of parkinsonian medications is often limited in the case of FOG and it frequently becomes dopamine resistant. Recent studies have suggested that pre-frontal cortex (PFC) dysfunction contributes to FOG; however, most previous findings provide only indirect evidence. To better understand the role of the PFC, we aimed to investigate the impact of high frequency, deep, repetitive transcranial magnetic stimulation (drTMS) of the medial PFC on FOG and its mediators. Nine patients with advanced PD participated in a randomized, cross-over exploratory study. We applied drTMS over the medial PFC for 16weeks, with real and sham conditions; each condition included an intensive (i.e., 3 times a week) phase and a maintenance (once a week) phase. Scores on a FOG-provoking test, the motor part of the Unified Parkinson's Disease Rating Scale, and gait variability significantly improved after real drTMS, but not after the sham condition. Self-report of FOG severity and cognitive scores did not improve. Due to discomfort and pain during treatment, two patients dropped out and the study was halted. These initial findings support the cause-and-effect role of the pre-frontal cortex in FOG among patients with PD. Due to the small sample size, findings should be interpreted cautiously. Further studies are needed to more fully assess the role of the medial PFC in the underlying mechanism of FOG and the possibility of using non-invasive brain stimulation to modify FOG.

Objective: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, safe and efficacious technique for treating various neuropsychiatric disorders, but its underlying mechanisms are poorly understood. A newly developed H-coil allows the stimulation of deeper brain regions. This study is the first to investigate the effects of deep high-frequency rTMS on brain-derived neurotrophic factor (BDNF) serum concentrations in healthy volunteers. We aimed to evaluate the short-term effect of deep rTMS on BDNF serum concentrations. Methods: This was a double-blind, randomized deep high-frequency rTMS study using an H-coil on a cohort of 13 healthy volunteers (NCT01106365). The following stimulation protocols were applied: 18-Hz stimulation of the left dorsolateral prefrontal cortex (PFC), 5-Hz stimulation of the primary motor cortex (MC) and sham stimulation in random order. Blood samples were obtained before, 30 min after and 60 min after each treatment. Results: The BDNF serum concentration decreased significantly after MC and PFC stimulation, but not after sham stimulation. Furthermore, BDNF serum level changes were associated with changes in individual alertness. Conclusion: Although BDNF serum concentrations do not necessarily correlate with BDNF levels in the cerebrospinal fluid or the brain, these results indicate an acute biological effect of deep rTMS on BDNF release, and demonstrate that this change correlates with alertness.

Objective To study the efficacy of repetitive transcranial magneticstimulation(rTMS) of the right prefrontal cortex combined paroxetine for patients with obsessive-compulsive disorder ( OCD) under doubleblind , sham-controlled conditions. Methods Patients were randomly assigned to 2 sessions of real ( n = 32) or sham ( n = 31) rTMS and both group received Paroxetine treatment. rTMS treatments lasted 20 minutes,and the frequency was 10 Hz and the intensity was 100% of motor threshold for real rTMS. Psychopathology was assessed by HAMA.Y-BOCS before the treatment,immediately after the experimental treatment,and 1,2,4,6 weeks after the experimental treatment by an independent reviewer. Results In combined therapy group,9(32. 14% ) recovered, 10(35.71% ) remitted,5( 17. 86% ) improved,4( 14. 29% ) remained unresponsive. In contrast,there were 4(16.36%) recovery,5(21.82%) remission, 10(38.18% ) improvement,6(23.64% ) unresponse in drug therapy group. The outcome of ITT showed all the patients in the two groups significant improvement (the scores of YBOCS( F=56.258, P=0.000) ;the scores of HAMA( F=41.675, P=0.000) after the treatment,but the effectiveness in the combined therapy group was better than that in the drug therapy group (the scores of Y-BOCS, F= 13.652, P=0.028;the scores of HAMA, F= 11.632, P=0.031). Conclusions Repetitive transcranial rTMS of the right prefrontal cortex combined paroxetine is more effective than paroxetine only in treatment of refractory OCD. Key words: Obsessive compulsive disorder ; Refractory ; Repetitive transcranial magnetic stimulation ; Proxetine ;

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study

Depressive symptoms during deep transcranial magnetic stimulation or sham treatment for obsessive-compulsive disorder

Decrease in frequency of ketamine infusions after dTMS in a 19 year old patient with treatment resistant depression: Case report

BackgroundAlcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging. MethodsThis was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures. ResultsBoth craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 ± 0.8% vs. 10.6 ± 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex. ConclusionsWe provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.

Rate of inadvertently induced seizures with deep repetitive transcranial magnetic stimulation

Accelerated rTMS in the treatment of obsessive compulsive disorder: A pilot study on safety and feasibility