Prognostic factors in major depressive disorder: comparing responders and non-responders to Repetitive Transcranial Magnetic Stimulation (rTMS), a naturalistic retrospective chart review.

AIM: Repetitive transcranial magnetic stimulation (rTMS) is widely utilized as an effective treatment for major depressive disorder (MDD) with varying response rates. Factors associated with better treatment outcome remain scarce. This naturalistic retrospective chart review hopes to shed light on easily obtainable and measurable predictive factors for patients referred to rTMS. METHODS: Protocol parameters, medication, rated scales, rTMS protocols, and treatment outcomes were reviewed for 196 patients with MDD who received rTMS at Saint Boniface Hospital between 2013 and 2019. Logistic regression and marginal effects were used to assess the different predictor variables for response (50% reduction or more on the Hamilton Depression Rating Scale (Ham-D)) and remission (Ham-D of ≤7 by the last session). RESULTS: HamD at 10 sessions was predictive of remission, and Sheehan Disability Scale (SDS) at 10 sessions was predictive of response to rTMS. Ham-D, SDS, and Beck Anxiety Inventory were predictive of remission and response by Beck Anxiety Inventory 20 sessions. High frequency rTMS had a similar response and remission rate to low frequency, but higher response rate to intermittent Theta Burst Stimulation with no difference in remission rate. Positive predictive factors of response were lower age and bupropion use. Negative predictive factors were antipsychotics, anticonvulsants, or benzodiazepine use. For remission, antipsychotics or anticonvulsants use were negative predictors; bupropion use and higher resting motor threshold were positive predictors. Severity of depression as measured by baseline HamD was not associated with different probabilities of treatment success.

Improvements in error-monitoring and symptoms following low-frequency rTMS of dorsal anterior cingulate cortex in obsessive compulsive disorder; a randomized, sham-controlled study.

Action monitoring deficit is a core underlying characteristic and endophenotype of Obsessive Compulsive Disorder (OCD). Dorsal anterior cingulate cortex (dACC) is heavily involved in error monitoring and cognitive control, and the hyperactivity in this region is associated with OCD symptom severity. This study aimed to test whether low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) targeting dACC improves both error-monitoring performance and OCD symptoms in a randomized, sham-controlled, double-blind trial design. 20 OCD patients were randomly assigned to receive 20 sessions of Active (n = 10) or Sham (n = 10) rTMS administered twice-daily. Error-monitoring performance and symptom severity were measured pre- and post-treatment using Erikson Flanker tasks and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), with three month symptom follow-up. Following active-but not sham-rTMS, patients showed improved response time for incongruent stimuli, trials following a correct response, and for reporting and correcting errors. Significant OCD symptom improvement was observed at one-month follow-up for patients who received Active (28.0% reduction) but not Sham (11.7% reduction) stimulation. In OCD patients, LF rTMS of the dACC can simultaneously improve on-line adjustment of behaviour-by enhancing the capacity for rapid error monitoring-and clinical symptoms, suggesting a link between error monitoring impairment and OCD pathophysiology.

Oxolipidomics profile in major depressive disorder: Comparing remitters and non-remitters to repetitive transcranial magnetic stimulation treatment.

BACKGROUND: Repetitive Transcranial Magnetic Stimulation [rTMS] is increasingly being used to treat Major Depressive Disorder [MDD]. Given that not all patients respond to rTMS, it would be clinically useful to have reliable biomarkers that predict treatment response. Oxidized phosphatidylcholine [OxPC] and some oxylipins are important plasma biomarkers of oxidative stress and inflammation. Not only is depression associated with oxidative stress, but rTMS has been shown to have anti-oxidative effects. OBJECTIVES: To investigate whether plasma oxolipidomics profiles could predict treatment response in patients with treatment resistant MDD. METHODS: Fourty-eight patients undergoing rTMS treatment for MDD were recruited along with nine healthy control subjects. Plasma OxPCs and oxylipins were extracted and analyzed through high performance liquid chromatography coupled with mass spectrometry. Patients with a Hamilton Depression Rating Scale score [Ham-D] ≤7 post-treatment were defined as having entered remission. RESULTS: Fifty-seven OxPC and 32 oxylipin species were identified in our subjects. MDD patients who entered remission following rTMS had significantly higher pre-rTMS levels of total and fragmented OxPCs compared to non-remitters and controls [one-way ANOVA, p<0.05]. However, no significant changes in OxPC levels were found as a result of rTMS, regardless of treatment response [p>0.05]. No differences in plasma oxylipins were found between remitters and non-remitters at baseline. CONCLUSION: Certain categories of OxPCs may be useful predictive biomarkers for response to rTMS treatment in MDD. Given that elevated oxidized lipids may indicate higher levels of oxidative stress and inflammation in the brain, patients with this phenotype of depression may be more receptive to rTMS treatment.

Accelerated repetitive transcranial magnetic stimulation in the treatment of post-concussion symptoms due to mild traumatic brain injury: a pilot study.

Objective: To investigate the feasibility, tolerability, and efficacy of twice-daily, low frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (DLPFC) in the reduction of chronic post-concussion symptoms (PCS) in patients who have suffered a mild traumatic brain injury (mTBI).Methods: 15 patients with mTBI received 30 sessions of twice-daily LF rTMS (1 Hz) over the right DLPFC. Post-concussion symptoms, pain, disability, fatigue, apathy, agitation, and mood were assessed by a psychiatrist pre- and post-treatment. Cognitive testing was also performed pre-, mid-, and post-rTMS.Results: All participants completed treatment with no serious adverse events. Significant improvements were observed in overall post-concussion symptoms, disability and pain ratings, as well as depression and anxiety symptoms. There was no significant change in overall executive functioning, fatigue severity, apathy, or agitation. Cognitive testing revealed improvements in verbal fluency, working memory, selective attention, and cognitive processing speed.Conclusions: This small-sample pilot study suggests that twice-daily, LF rTMS over the right DLPFC can be safely and tolerably applied and has the potential to improve post-concussion symptoms as well as elements of mood and cognition in patients with mTBI. Larger, sham-controlled studies will be important to confirm these observations.

Attitudes of Psychiatry Residents in Canadian Universities toward Neuroscience and Its Implication in Psychiatric Practice.

OBJECTIVE: Despite recent advances in neuroscience highlighting its potential applications in the assessment and treatment of psychiatric disorders, the training of psychiatrists in neuroscience is lacking. However, it is not clear to what extent Canadian trainees are interested in further learning and using neuroscience in their daily clinical practice. This study explored the attitudes of Canadian psychiatry trainees with regard to neuroscience education and training by asking them to assess their own understanding of neuroscience and the perceived relevance of neuroscience knowledge to effective psychiatric practice. METHODS: An online questionnaire was sent to psychiatry residents at Canadian universities. This questionnaire consisted of self-assessments of neuroscience knowledge, attitudes toward neuroscience education, preferences in learning modalities, and interest in specific neuroscience topics. RESULTS: One hundred and eleven psychiatry residents from psychiatry residency programs at Canadian universities responded to this survey. Participants represented trainees from all 5 years of residency. Almost half of all trainees (49.0%) reported their knowledge of neuroscience to be either "inadequate" or "less than adequate," and only 14.7% of trainees reported that they feel "comfortable" or "very comfortable" discussing neuroscience findings with their patients. 63.7% of Canadian trainees rated the quantity of neuroscience education in their residency program as either less than adequate or inadequate, and 46.1% rated the quality of their neuroscience education as "poor" or "very poor." The vast majority of participants (>70%) felt that additional neuroscience education would be moderately-to-hugely helpful in finding personalized treatments, discovering future treatments, destigmatizing patients with psychiatric illness, and understanding mental illness. CONCLUSIONS: Canadian trainees generally feel that their neuroscience knowledge and the neuroscience education they receive during their psychiatry residencies is inadequate. However, as the first step for any change, the majority of future Canadian psychiatrists are very motivated and have a positive attitude toward neuroscience learning.

Cognitive profiles in major depressive disorder: Comparing remitters and non-remitters to rTMS treatment.

Major Depressive Disorder (MDD) is typically accompanied by cognitive impairment. Repetitive Transcranial Magnetic Stimulation (rTMS) treatment for MDD involves stimulation of the dorsolateral prefrontal cortex which plays an important role in cognition. This study aimed to identify differences in cognitive profiles between remitters and non-remitters to rTMS at baseline and across treatment. 25 patients with MDD performed cognitive tasks at baseline and after 6, 12 and 30 sessions of rTMS. At baseline, there was no difference in simple reaction time (RT) between groups, but remitters (n = 13) showed faster RTs than non-remitters (n = 12) in the Switch and No-Switch conditions of Task Switching. Across sessions, remitters showed a decrease in 3-Back omission errors and RTs to 3-Back, Stroop's Congruent and Incongruent, and Task Switching's Switch and No-Switch conditions, whereas non-remitters only showed improvements in Stroop Congruent and Incongruent RTs. Baseline and final scores on the Hamilton Depression Rating Scale were positively correlated with Switch and No-Switch RTs. This study demonstrates that eventual remitters to rTMS treatment for MDD perform better in cognitive tasks requiring shifting attention, and this difference is observable prior to the start of treatment. Remitters also show improvement in both their mood and cognitive performance.

Efficacy of twice-daily vs once-daily sessions of repetitive transcranial magnetic stimulation in the treatment of major depressive disorder: a retrospective study.

PURPOSE: There is no clinical consensus on the optimal protocol for the treatment of major depressive disorder (MDD) using repetitive transcranial magnetic stimulation (rTMS). Accelerated protocols using more than a single session of treatment per day have been suggested as a means to reduce the overall length of time required for rTMS therapy. The objective of this study is to compare the treatment outcomes of patients with MDD who received two sessions of rTMS per day vs those who received one session per day, keeping the overall number of delivered pulses constant. PATIENTS AND METHODS: In a retrospective study, we compared treatment outcomes of 36 patients with MDD who received 30 sessions of high-frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex. Patients received 3,000 pulses per session (5 s trains, 25 s intertrain interval) at 110% of resting motor threshold using a figure-eight coil. Patients received either two rTMS sessions per day (n=17) or one session per day (n=19). Depression symptoms were assessed by a psychiatrist using the Hamilton Rating Scale for Depression at baseline and after every 10 sessions of rTMS. RESULTS: The majority of patients in both groups responded to treatment, and there was a trend toward greater response rate in the twice-daily (TD) group (82.4%) compared to the once-daily (OD) group (52.6%). TD stimulation was tolerable for patients and produced no adverse side effects. Patients in the TD group experienced an improvement in symptoms faster than the OD group due to the accelerated therapy period. CONCLUSION: Administration of two rTMS treatment sessions per day is tolerable for patients and does not seem to be inferior in efficacy to a OD protocol. TD administration has the benefit of producing symptom improvement over a shorter time span and requires fewer visits to the clinic.

Impaired trial-by-trial adjustment of cognitive control in obsessive compulsive disorder improves after deep repetitive transcranial magnetic stimulation.

BACKGROUND: Adaptive decision making requires the adjustment of behaviour following an error. Some theories suggest that repetitive thoughts and behaviours in obsessive compulsive disorder (OCD) are driven by malfunctioning error monitoring. This malfunction may relate to demonstrated hyperactivity in the medial prefrontal cortex (mPFC), including the dorsal anterior cingulate cortex. In this study, we measured aspects of error monitoring in individuals with OCD and administered deep low frequency repetitive transcranial magnetic stimulation (rTMS) in an attempt to modulate error monitoring capacity. METHODS: For this pilot study, ten OCD patients and 10 aged-matched healthy controls completed modified versions of the Eriksen Flanker task before and after one session of deep 1 Hz rTMS (1200 pulses) over the mPFC (Brodmann areas 24 and 32). OCD patients received nine additional sessions of daily rTMS to assess their clinical response. Flanker tasks were repeated with patients post-treatment. RESULTS: Overall error rates were higher for patients compared to controls. When subjects were asked to report their errors, OCD patients were able to report fewer of their errors than the control group. In contrast to controls, patients did not demonstrate a normal post-error slowing (PES) phenomenon. This abnormal PES was mainly driven by abnormally slow response times (RTs) following correct responses rather than a failure to slow down after errors. Patients' symptoms and slowed RTs following correct responses improved after ten sessions of rTMS. CONCLUSIONS: Certain aspects of error monitoring, namely conscious error report and post error slowing, are impaired in OCD. These impairments can at least be partly corrected by 1 Hz deep rTMS over the mPFC. Simultaneous improvement of OCD symptoms by this method might suggest a correlation between error monitoring impairment and OCD pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov NCT02541812; 09/02/2015.

Non-Invasive Brain Stimulation for the Treatment of Symptoms Following Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a common cause of physical, psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms. OBJECTIVE: This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) have been used to treat symptoms following a TBI. A subsequent discussion attempts to determine the value of these methods in light of their potential risks. METHODS: The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI. RESULTS: Eight case-studies and four multi-subject reports using rTMS and six multi--subject studies using tDCS were found. Two instances of seizure are discussed. CONCLUSION: There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms, such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional investigations.

Posterior cortical atrophy: an investigation of scan paths generated during face matching tasks.

When viewing a face, healthy individuals focus more on the area containing the eyes and upper nose in order to retrieve important featural and configural information. In contrast, individuals with face blindness (prosopagnosia) tend to direct fixations toward individual facial features-particularly the mouth. Presented here is an examination of face perception deficits in individuals with Posterior Cortical Atrophy (PCA). PCA is a rare progressive neurodegenerative disorder that is characterized by atrophy in occipito-parietal and occipito-temporal cortices. PCA primarily affects higher visual processing, while memory, reasoning, and insight remain relatively intact. A common symptom of PCA is a decreased effective field of vision caused by the inability to "see the whole picture." Individuals with PCA and healthy control participants completed a same/different discrimination task in which images of faces were presented as cue-target pairs. Eye-tracking equipment and a novel computer-based perceptual task-the Viewing Window paradigm-were used to investigate scan patterns when faces were presented in open view or through a restricted-view, respectively. In contrast to previous prosopagnosia research, individuals with PCA each produced unique scan paths that focused on non-diagnostically useful locations. This focus on non-diagnostically useful locations was also present when using a restricted viewing aperture, suggesting that individuals with PCA have difficulty processing the face at either the featural or configural level. In fact, it appears that the decreased effective field of view in PCA patients is so severe that it results in an extreme dependence on local processing, such that a feature-based approach is not even possible.

Posterior cortical atrophy: visuomotor deficits in reaching and grasping.

Posterior Cortical Atrophy (PCA) is a rare clinical syndrome characterized by the predominance of higher-order visual disturbances such as optic ataxia, a characteristic of Balint's syndrome. Deficits result from progressive neurodegeneration of occipito-temporal and occipito-parietal cortices. The current study sought to explore the visuomotor functioning of four individuals with PCA by testing their ability to reach out and grasp real objects under various viewing conditions. Experiment 1 had participants reach out and grasp simple, rectangular blocks under visually- and memory-guided conditions. Experiment 2 explored participants' abilities to accurately reach for objects located in their visual periphery. This investigation revealed that PCA patients demonstrate many of the same deficits that have been previously reported in other individuals with optic ataxia, such as "magnetic misreaching"-a pathological reaching bias toward the point of visual fixation when grasping peripheral targets. Unlike many other individuals with optic ataxia, however, the patients in the current study also show symptoms indicative of damage to the more perceptual stream of visual processing, including abolished grip scaling during memory-guided grasping and deficits in face and object identification. These investigations are the first to perform a quantitative analysis of the visuomotor deficits exhibited by patients with PCA. Critically, this study helps characterize common symptoms of PCA, a vital first step for generating effective diagnostic criteria and therapeutic strategies for this understudied neurodegenerative disorder.

A novel integrative method for analyzing eye and hand behaviour during reaching and grasping in an MRI environment.

The development of noninvasive neuroimaging techniques, such as fMRI, has rapidly advanced our understanding of the neural systems underlying the integration of visual and motor information. However, the fMRI experimental design is restricted by several environmental elements, such as the presence of the magnetic field and the restricted view of the participant, making it difficult to monitor and measure behaviour. The present article describes a novel, specialized software package developed in our laboratory called Biometric Integration Recording and Analysis (BIRA). BIRA integrates video with kinematic data derived from the hand and eye, acquired using MRI-compatible equipment. The present article demonstrates the acquisition and analysis of eye and hand data using BIRA in a mock (0 Tesla) scanner. A method for collecting and integrating gaze and kinematic data in fMRI studies on visuomotor behaviour has several advantages: Specifically, it will allow for more sophisticated, behaviourally driven analyses and eliminate potential confounds of gaze or kinematic data.