rTMS Responders Research Articles

Multimodal workflows optimally predict response to repetitive transcranial magnetic stimulation in patients with schizophrenia: a multisite machine learning analysis

The response variability to repetitive transcranial magnetic stimulation (rTMS) challenges the effective use of this treatment option in patients with schizophrenia. This variability may be deciphered by leveraging predictive information in structural MRI, clinical, sociodemographic, and genetic data using artificial intelligence. We developed and cross-validated rTMS response prediction models in patients with schizophrenia drawn from the multisite RESIS trial. The models incorporated pre-treatment sMRI, clinical, sociodemographic, and polygenic risk score (PRS) data. Patients were randomly assigned to receive active (N = 45) or sham (N = 47) rTMS treatment. The prediction target was individual response, defined as ≥20% reduction in pre-treatment negative symptom sum scores of the Positive and Negative Syndrome Scale. Our multimodal sequential prediction workflow achieved a balanced accuracy (BAC) of 94% (non-responders: 92%, responders: 95%) in the active-treated group and 50% in the sham-treated group. The clinical, clinical + PRS, and sMRI-based classifiers yielded BACs of 65%, 76%, and 80%, respectively. Apparent sadness, inability to feel, educational attainment PRS, and unemployment were most predictive of non-response in the clinical + PRS model, while grey matter density reductions in the default mode, limbic networks, and the cerebellum were most predictive in the sMRI model. Our sequential modelling approach provided superior predictive performance while minimising the diagnostic burden in the clinical setting. Predictive patterns suggest that rTMS responders may have higher levels of brain grey matter in the default mode and salience networks which increases their likelihood of profiting from plasticity-inducing brain stimulation methods, such as rTMS. The future clinical implementation of our models requires findings to be replicated at the international scale using stratified clinical trial designs.

Psychomotor retardation: What about the partial responders to magnetic transcranial stimulation in treatment resistant depression ?

ObjectivePsychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25–50%) and non-reponders (no clinically relevant improvement). Our secondary aim was to investigate baseline psychomotor performances associated with non-response and response even partial. MethodsFifty-four patients with treatment-resistant unipolar depression and treated by either high frequency 10 Hz rTMS or iTBS for 4 weeks (20 sessions) underwent assessment including French Retardation Rating Scale for Depression (ERD), Verbal Fluency test, and Trail Making Test A. before, just after treatment and one month later. Results20 patients were responders (R, 21 partial responders (PR) and 13 non-responders (NR). rTMS treatment improved psychomotor performances in the R and PR groups unlike NR patients whose psychomotor performance was not enhanced by treatment. At baseline, participants, later identified as partial responders, showed significantly higher performances than non-responders. ConclusionHigher cognitivo-motor performances at baseline may be associated with clinical improvement after rTMS treatment. This work highlights the value of objective psychomotor testing for the identification of rTMS responders and partial responders, and thus may be useful for patient selection and protocol individualization such as treatment continuation for early partial responders.

Predictive values of pre-treatment brain age models to rTMS effects in neurocognitive disorder with depression: Secondary analysis of a randomised sham-controlled clinical trial.

One major challenge in developing personalised repetitive transcranial magnetic stimulation (rTMS) is that the treatment responses exhibited high inter-individual variations. Brain morphometry might contribute to these variations. This study sought to determine whether individual's brain morphometry could predict the rTMS responders and remitters. This was a secondary analysis of data from a randomised clinical trial that included fifty-five patients over the age of 60 with both comorbid depression and neurocognitive disorder. Based on magnetic resonance imaging scans, estimated brain age was calculated with morphometric features using a support vector machine. Brain-predicted age difference (brain-PAD) was computed as the difference between brain age and chronological age. The rTMS responders and remitters had younger brain age. Every additional year of brain-PAD decreased the odds of relieving depressive symptoms by ∼25.7% in responders (Odd ratio [OR] = 0.743, p = .045) and by ∼39.5% in remitters (OR = 0.605, p = .022) in active rTMS group. Using brain-PAD score as a feature, responder-nonresponder classification accuracies of 85% (3rd week) and 84% (12th week), respectively were achieved. In elderly patients, younger brain age appears to be associated with better treatment responses to active rTMS. Pre-treatment brain age models informed by morphometry might be used as an indicator to stratify suitable patients for rTMS treatment. ClinicalTrials.gov Identifier: ChiCTR-IOR-16008191.

Identifying predictive biomarkers for repetitive transcranial magnetic stimulation response in depression patients with explainability

Repetitive Transcranial Magnetic Stimulation (rTMS) is an evidence-based treatment for depression. However, the patterns of response to this treatment modality are inconsistent. Whilst many people see a significant reduction in the severity of their depression following rTMS treatment, some patients do not. To support and improve patient outcomes, recent work is exploring the possibility of using Machine Learning to predict rTMS treatment outcomes. Our proposed model is the first to combine functional magnetic resonance imaging (fMRI) connectivity with deep learning techniques to predict treatment outcomes before treatment starts. Furthermore, with the use of Explainable AI (XAI) techniques, we identify potential biomarkers that may discriminate between rTMS responders and non-responders. Our experiments utilize 200 runs of repeated bootstrap sampling on two rTMS datasets. We compare performances between our proposed feedforward deep neural network against existing methods, and compare the average accuracy, balanced accuracy and F1-score on a held-out test set. The results of these experiments show that our model outperforms existing methods with an average accuracy of 0.9423, balanced accuracy of 0.9423, and F1-score of 0.9461 in a sample of 61 patients. We found that functional connectivity measures between the Subgenual Anterior Cingulate Cortex and Centeral Opercular Cortex are a key determinant of rTMS treatment response. This knowledge provides psychiatrists with further information to explore the potential mechanisms of responses to rTMS treatment. Our developed prototype is ready to be deployed across large datasets in multiple centres and different countries.

Functional connectivity analysis of the depression connectome provides potential markers and targets for transcranial magnetic stimulation

BackgroundDespite efforts to improve targeting accuracy of the dorsolateral prefrontal cortex (DLPFC) as a repetitive transcranial magnetic stimulation (rTMS) target for Major Depressive Disorder (MDD), the heterogeneity in clinical response remains unexplained. ObjectiveWe sought to compare the patterns of functional connectivity from the DLPFC treatment site in patients with MDD who were TMS responders to those who were TMS non-responders. MethodsBaseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI, and diffusion weighted imaging scans were obtained from 37 participants before they underwent a course of rTMS to left Brodmann area 46. A novel machine learning method was utilized to identify brain regions associated with each item of the Beck's Depression Inventory II (BDI-II), and for 26 participants who underwent rTMS treatment over the left Brodmann area 46, identify regions differentiating rTMS responders and non-responders. ResultsNine parcels of the Human Connectome Project Multimodal Parcellation Atlas matched to at least three items of the Beck's Depression Inventory II (BDI-II) as predictors of response to rTMS, with many in the temporal, parietal and cingulate cortices. Additionally, pre-treatment mapping for 17 items of the BDI-II demonstrated significant variability in symptom to parcel mapping. When parcels associated with symptom presence and symptom resolution were compared, 15 parcels were uniquely associated with resolution (potential targets), and 12 parcels were associated with both symptom presence and resolution (blockers or biomarkers). ConclusionsMachine learning approaches show promise for the development of pathoanatomical diagnosis and treatment algorithms for MDD. Prospective studies are required to facilitate clinical translation.

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study.

Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied. We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention. rTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study. This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects. www.ClinicalTrials.gov, identifier: NCT05187000.

Grey Matter Covariance Predicts Response to rTMS in Depression

Clinical response to repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD) is variable. Structural covariance networks have been shown to recapitulate functional network architecture and are disrupted in neuropsychiatric disorders. Whether structural covariance networks can be used to predict response to rTMS in depression is unclear. Using multivariate cortical mapping, we assessed whether pre-treatment structural covariance could differentiate rTMS responders compared to non-responders and healthy controls (HC).

Effect of repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD) on cognitive control

BackgroundMajor Depressive Disorder (MDD) is commonly accompanied by cognitive control dysfunction that may persist after remission of clinical symptoms with antidepressant medication treatment. Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment alternative for medication-resistant MDD. In this study, we investigated whether rTMS treatment had a beneficial effect not only on depressive symptoms, but on also cognitive control dysfunction. Methods77 subjects with MDD received a 30-session treatment course of 10 Hz rTMS administered at the left dorsolateral prefrontal cortex (DLPFC). Treatment efficacy was assessed using the Inventory of Depressive Symptomatology Self-Rated (IDS-SR) before and after treatment, with clinical response defined as 50% or greater decrease in the IDS-SR score at treatment 30. Cognitive control function was assessed before and after treatment using the Stroop word-color interference task. We examined changes in Stroop accuracy and reaction time for congruent and incongruent trials, as well as in relation to changes in depressive symptoms. ResultsPerformance accuracy improved particularly for the rTMS responders in the incongruent condition, with older subjects benefitting most from the rTMS treatment. Improvement in reaction times was positively associated with clinical improvement, especially in the incongruent condition. LimitationsWe used a single cognitive task in a naturalistic setting without control for individual rTMS treatment parameters or concomitant medication. ConclusionsOverall, these results indicate that rTMS treatment for MDD has beneficial effects on psychomotor speed and cognitive control. Future studies should extend these findings to larger patient populations and other cognitive domains.

Dorsolateral prefrontal γ-aminobutyric acid in patients with treatment-resistant depression after transcranial magnetic stimulation measured with magnetic resonance spectroscopy

The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPFC). In 26 adults with TRD, we used Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) spectral-editing MRS to measure GABA in the left DLPFC before and after standard clinical treatment with rTMS. All participants but 1 were medicated, including 12 patients on GABA agonist agents. Mean GABA in the DLPFC increased 10.0% (p = 0.017) post-rTMS in the overall sample. As well, GABA increased significantly in rTMS responders (n = 12; 23.6%, p = 0.015) but not in nonresponders (n = 14; 4.1%, p = not significant). Changes in GABA were not significantly affected by GABAergic agonists, but clinical response was less frequent (p = 0.005) and weaker (p = 0.035) in the 12 participants who were receiving GABA agonists concomitant with rTMS treatment. This study had an open-label design in a population receiving naturalistic treatment. Treatment using rTMS was associated with increases in GABA levels at the stimulation site in the left DLPFC, and the degree of GABA change was related to clinical improvement. Participants receiving concomitant treatment with a GABA agonist were less likely to respond to rTMS. These findings were consistent with earlier studies showing the effects of rTMS on GABA levels and support a GABAergic model of depression.

New insights into precision medicine and target engagement in neuromodulation depression treatments

In depression treatment there is a clear need for novel treatments, biomarkers and personalized treatment approaches. This symposium addresses rTMS in the treatment of depression and specifically focusses on target engagement principles of these treatments and the ability to individualise treatments. Topics covered include: – a new method to quantify the DLPFC-sgACC-vagal nerve pathway as a measure of target engagement of rTMS in the treatment of depression that can also be used to individualise rTMS stimulation locations by specifically looking at heart rate decelaration (Neuro-Cardiac-Guided TMS); – baseline clinical and EEG measures that dissociate rTMS responders and non-responders, using a strict discovery-replication approach; – Accelerated Theta Burst Stimulation and effects on depressive symptoms and suicide ideation with insights from brain perfusion and functional connectivity.

Added value of multiple versus single sessions of repetitive transcranial magnetic stimulation in predicting motor cortex stimulation efficacy for refractory neuropathic pain.

Selection criteria for offering patients motor cortex stimulation (MCS) for refractory neuropathic pain are a critical topic of research. A single session of repetitive transcranial magnetic stimulation (rTMS) has been advocated for selecting MCS candidates, but it has a low negative predictive value. Here the authors investigated whether multiple rTMS sessions would more accurately predict MCS efficacy. Patients included in this longitudinal study could access MCS after at least four rTMS sessions performed 3-4 weeks apart. The positive (PPV) and negative (NPV) predictive values of the four rTMS sessions and the correlation between the analgesic effects of the two treatments were assessed. Twelve MCS patients underwent an average of 15.9 rTMS sessions prior to surgery; nine of the patients were rTMS responders. Postoperative follow-up was 57.8 ± 15.6 months (mean ± standard deviation). Mean percentage of pain relief (%R) was 21% and 40% after the first and fourth rTMS sessions, respectively. The corresponding mean durations of pain relief were respectively 2.4 and 12.9 days. A cumulative effect of the rTMS sessions was observed on both %R and duration of pain relief (p < 0.01). The %R value obtained with MCS was 35% after 6 months and 43% at the last follow-up. Both the PPV and NPV of rTMS were 100% after the fourth rTMS session (p = 0.0045). A significant correlation was found between %R or duration of pain relief after the fourth rTMS session and %R at the last MCS follow-up (R2 = 0.83, p = 0.0003). Four rTMS sessions predicted MCS efficacy better than a single session in neuropathic pain patients. Taking into account the cumulative effects of rTMS, the authors found a high-level correlation between the analgesic effects of rTMS and MCS.

Changes in brain connectivity during a sham-controlled, transcranial magnetic stimulation trial for depression

BackgroundThe subgenual anterior cingulate cortex (sgACC) has been implicated in major depressive disorder (MDD), and this study evaluated sgACC connectivity before and after repetitive transcranial magnetic stimulation (rTMS) treatment. MethodsThirty-two MDD patients entered a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex (dlFPC). Subjects underwent resting state functional magnetic resonance imaging before and after 20 sessions of high frequency rTMS. Seed voxels identified the affective network (AN; sgACC, amygdala), default mode network (DMN; posterior cingulate cortex [PCC]), and fronto-parietal network (FPN; dlPFC stimulation site). ResultsThere was no significant effect of active rTMS over sham on the primary outcome measure (Montgomery-Asberg Depression Scale rating), with both groups improving over time, and no specific effect of rTMS (sham vs active) on connectivity. However, among patients who showed significant improvement, sgACC connectivity decreased for sham (to AN, trend to DMN) and active rTMS responders (to AN, DMN, FPN), but not in non-responders, who tended to maintain connectivity. Including subjects who started with sham but then received open-label active treatment, baseline connectivity from the PCC to the anterior insula was greater in non-responders compared to responders (n = 27, excluding 5 sham responders). LimitationsThe sample size was small; the stimulation target was non-standard, and the lack of a significant clinical effect of rTMS limits conclusions about negative findings. ConclusionssgACC connectivity reduces along with depressive symptoms, not specific to rTMS therapy. Altered connectivity of DMN with anterior insula may reflect a type of patient less likely to respond to an intervention.

Sleep disturbances in obsessive-compulsive disorder: Association with non-response to repetitive transcranial magnetic stimulation (rTMS)

Background Repetitive transcranial magnetic stimulation (rTMS) is a promising augmentation strategy for treatment-refractory OCD. However, a substantial group still fails to respond. Sleep disorders, e.g. circadian rhythm sleep disorders (CRSD), are highly prevalent in OCD and might mediate treatment response. The aims of the current study were to compare sleep disturbances between OCD patients and healthy subjects as well as between rTMS responders and non-responders, and most importantly to determine sleep-related predictors of rTMS non-response.Methods 22 OCD patients received at least 10 sessions rTMS combined with psychotherapy. Sleep disturbances were measured using questionnaires and actigraphy. Sleep in patients was compared to healthy subjects. Treatment response was defined as >35% reduction on YBOCS. Treatment response prediction models were based on measures of CRSD and insomnia.Results Sleep disturbances were more prevalent in OCD patients than healthy subjects. The OCD group consisted of 12 responders and 10 non-responders. The CRSD model could accurately predict non-response with 83% sensitivity and 63% specificity, whereas the insomnia model could not.Conclusions CRSD is more prevalent in OCD patients than healthy subjects, specifically in rTMS non-responders. Therefore, CRSD may serve as a biomarker for different subtypes of OCD corresponding with response to specific treatment approaches.

Sleep disturbances in obsessive-compulsive disorder: association with non-response to repetitive transcranial magnetic stimulation (rTMS)

Background Repetitive transcranial magnetic stimulation (rTMS) is a promising augmentation strategy for treatment-refractory OCD. However, a substantial group still fails to respond. Sleep disorders, e.g. circadian rhythm sleep disorders (CRSD), are highly prevalent in OCD and might mediate treatment response. The aims of the current study were to compare sleep disturbances between OCD patients and healthy subjects as well as between rTMS responders and non-responders, and most importantly to determine sleep-related predictors of rTMS non-response. Methods 22 OCD patients received at least 10 sessions rTMS combined with psychotherapy. Sleep disturbances were measured using questionnaires and actigraphy. Sleep in patients was compared to healthy subjects. Treatment response was defined as >35% reduction on YBOCS. Treatment response prediction models were based on measures of CRSD and insomnia. Results Sleep disturbances were more prevalent in OCD patients than healthy subjects. The OCD group consisted of 12 responders and 10 non-responders. The CRSD model could accurately predict non-response with 83% sensitivity and 63% specificity, whereas the insomnia model could not. Conclusions CRSD is more prevalent in OCD patients than healthy subjects, specifically in rTMS non-responders. Therefore, CRSD may serve as a biomarker for different subtypes of OCD corresponding with response to specific treatment approaches.

Identification of rTMS responders vs. non-responders for MDD via a network theory approach on fMRIs

Identification of rTMS responders vs. non-responders for MDD via a network theory approach on fMRIs

1829 – Effects of repetitive transcranial magnetic stimulation (rTMS) on specific symptom clusters in depersonalization disorder (DPD)

DPD is a highly disabling condition for which no efficacious treatment exists. Imaging and neurophysiology findings suggest that the right temporo-parietal junction (RTPJ) plays a crucial role in the conscious experience of the normal embodied self, mediating spatial unity of mind and body, a process impaired in DPD. We tested the potential therapeutic value of RTPJ rTMS and found that after 3 weeks 6/12 DPD patients responded with 51% reduction on the Cambridge Depersonalization Scale (CDS). After 3 more weeks of RTPJ rTMS responders showed 68% improvement. Here we present results of 3 and 6 weeks of RTPJ rTMS on each of four cardinal symptom domains of depersonalization, i.e. emotional numbing, anomalous subjective recall, alienation from surroundings, and anomalous body experiences. In responders we performed a retrospective analysis and applied repeated measures ANOVA on the average scores of each of the four symptom domains derived by the CDS. Responders to 3 weeks of RTPJ rTMS showed a significant improvement (71% reduction; P= 0.01) in anomalous body experiences. However, after receiving 3 more weeks of RTPJ rTMS they reported further reduction in anomalous body experiences (76% reduction; P= 0.00) and a clinically significant improvement in alienation from surroundings (54% reduction; P= 0.02), emotional numbing (52% reduction; P= 0.05), and anomalous subjective recall (57% reduction; P= 0.11). This is the first study suggesting that RTPJ rTMS may show therapeutic promise in DPD, and that anomalous body experiences scores might represent an early predictor of response for the remaining symptoms.

Neural Correlates of the Antinociceptive Effects of Repetitive Transcranial Magnetic Stimulation on Central Pain After Stroke

Background. Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. Objective. The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. Methods. Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. Results. Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. Conclusion. Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression

The aim of this study was to determine the predictive value of whole-brain voxel-based regional cerebral blood flow (rCBF) for repetitive transcranial magnetic stimulation (rTMS) response in patients with pharmacoresistant depression. Thirty-three right-handed patients who met DSM-IV criteria for major depressive disorder (unipolar or bipolar depression) were included before rTMS. rTMS response was defined as at least 50% reduction in the baseline Beck Depression Inventory scores. The predictive value of (99m)Tc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) for rTMS response was studied before treatment by comparing rTMS responders to non-responders at voxel level using Statistical Parametric Mapping (SPM) (p < 0.001, uncorrected). Of the patients, 18 (54.5%) were responders to rTMS and 15 were non-responders (45.5%). There were no statistically significant differences in demographic and clinical characteristics (p > 0.10). In comparison to responders, non-responders showed significant hypoperfusions (p < 0.001, uncorrected) in the left medial and bilateral superior frontal cortices (BA10), the left uncus/parahippocampal cortex (BA20/BA35) and the right thalamus. The area under the curve for the combination of SPECT clusters to predict rTMS response was 0.89 (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value for the combination of clusters were: 94, 73, 81 and 92%, respectively. This study shows that, in pharmacoresistant depression, pretreatment rCBF of specific brain regions is a strong predictor for response to rTMS in patients with homogeneous demographic/clinical features.

FC26-05 - Differences in depression symptoms between RTMS responders and rTMS non-responders in a sample of tinnitus affected people

IntroductionThe clinic of psychiatry and psychotherapy and the clinic of otolaryngology of the clinic of Nuremberg offer an interdisciplinary consultation for patients suffering from tinnitus aurium and comorbid major depression and/or insomnia.ObjectivesPrediction variables are needed regarding the treatment of subjective ear noises by low frequency rTMS.The aim of the present study was to examinea)if rTMS responders and non-responders differ in significant parameters prior to the rTMS treatmentb)and if improvement of tinnitus complaints is associated with mood change.MethodsFrom June 2008 to July 2010 109 outpatients with chronic tinnitus were treated with rTMS (1 Hz, 2000 impulses, intensity 110% motor-treshold, 10 proceedings, stimulation of left auditory cortex). Prior to and afterwards the proceedings clinical assessment regarding the severity of tinnitus (TQ) and depressive symptoms (BDI II, MADRS) took place.ResultsResponse to rTMS was defined as reduction in the TQ score of ≥ 5 points (54 responder, 18 female, 36 male; 55 non-responder, 16 female, 39 male). The samples did not differ in age (MR = 56,4, SDR = 13,3; MNR = 57,3, SDNR = 12,2). The subsamples differed significantly regarding depression symptoms before rTMS, as non-responder being more depressive than rTMS-responder (table 1; MADRS: p = 0.008 **; BDI II: p = 0.01**).Furthermore there is a significant interaction between BDI and the response/non-response criterion indicating a higher decrease of depression symptoms in rTMS responders.

Transcranial magnetic stimulation for the treatment of tinnitus: 4-year follow-up in treatment responders—a retrospective analysis

Repetitive transcranial magnetic stimulation (rTMS) over the temporal cortex has been proposed as a new approach for the treatment of tinnitus. Even if most studies have shown beneficial effects, there is only limited knowledge about clinical predictors for treatment response and about the duration of treatment effects. In this study, we compared clinical characteristics of rTMS responders and nonresponders and assessed long-term outcome in the responder group. Results from 235 patients, who were treated with rTMS because of chronic tinnitus were analysed. Patients received either a standard protocol of low-frequency rTMS (n = 188; 110% motor threshold, 1 Hz, 2000 stimuli/day) over the left temporal cortex or combined frontal and temporal rTMS (n = 47; 110% motor threshold, 1000 stimuli at 20 Hz, left dorsolateral prefrontal cortex plus 1000 stimuli at 1 Hz left temporal cortex). Response criterion was defined as an improvement of at least 10 points in the tinnitus questionnaire (TQ) score between baseline and the follow-up assessment 90 days after treatment. For the entire study group there was a highly significant effect of treatment on the TQ score. Fifty patients (21.3%) were responders according to the above mentioned definition. The response criterion was fulfilled by 19.7% of the patients receiving left temporal rTMS and by 26% of the patients receiving combined rTMS. The only significant difference between responders and nonresponders was a higher baseline score of the TQ in the responder group. There were no significant differences in all other assessed patient parameters (gender, age, tinnitus duration, tinnitus laterality, motor threshold, handedness). Ninety days after treatment the average TQ reduction in the responder group was 18.2 points as compared with baseline. At the two long-term follow-up assessments (2.12 ± 1.17 years and 3.9 ± 1.17 years after treatment) the improvement in the responder group was still 14.2, respective 14.4 points. These data underscore the clinical relevance of rTMS in the treatment of tinnitus. A potential explanation for the observed long-lasting clinical effects is that rTMS interferes with tinnitus related neuronal activity and thus facilitates the intrinsic ability of the brain to restore normal function.