Saba Shahab

rTMS of the Dorsomedial Prefrontal Cortex for Major Depression: Safety, Tolerability, Effectiveness, and Outcome Predictors for 10 Hz Versus Intermittent Theta-burst Stimulation

BACKGROUND Conventional rTMS protocols for major depression commonly employ stimulation sessions lasting >30 min. However, recent studies have sought to improve costs, capacities, and outcomes by employing briefer protocols such as theta burst stimulation (iTBS). OBJECTIVE To compare safety, effectiveness, and outcome predictors for DMPFC-rTMS with 10 Hz (30 min) versus iTBS (6 min) protocols, in a large, naturalistic, retrospective case series. METHODS A chart review identified 185 patients with a medication-resistant major depressive episode who underwent 20-30 sessions of DMPFC-rTMS (10 Hz, n = 98; iTBS, n = 87) at a single Canadian clinic from 2011 to 2014. RESULTS Clinical characteristics of 10 Hz and iTBS patients did not differ prior to treatment, aside from significantly higher age in iTBS patients. A total 7912 runs of DMPFC-rTMS (10 Hz, 4274; iTBS, 3638) were administered, without any seizures or other serious adverse events, and no significant differences in rates of premature discontinuation between groups. Dichotomous outcomes did not differ significantly between groups (Response/remission rates: Beck Depression Inventory-II: 10 Hz, 40.6%/29.2%; iTBS, 43.0%/31.0%. 17-item Hamilton Rating Scale for Depression: 10 Hz, 50.6%/38.5%; iTBS, 48.5%/27.9%). On continuous outcomes, there was no significant difference between groups in pre-treatment or post-treatment scores, or percent improvement on either measure. Mixed-effects modeling revealed no significant group-by-time interaction on either measure. CONCLUSIONS Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears comparable. Randomized trials comparing 10 Hz to iTBS may be warranted.

Gray Matter Neuritic Microstructure Deficits in Schizophrenia and Bipolar Disorder

BACKGROUND Postmortem studies have demonstrated considerable dendritic pathologies among persons with schizophrenia and to some extent among those with bipolar I disorder. Modeling gray matter (GM) microstructural properties is now possible with a recently proposed diffusion-weighted magnetic resonance imaging modeling technique: neurite orientation dispersion and density imaging. This technique may bridge the gap between neuroimaging and histopathological findings. METHODS We performed an extended series of multishell diffusion-weighted imaging and other structural imaging series using 3T magnetic resonance imaging. Participants scanned included individuals with schizophrenia (n = 36), bipolar I disorder (n = 29), and healthy controls (n = 35). GM-based spatial statistics was used to compare neurite orientation dispersion and density imaging-driven microstructural measures (orientation dispersion index and neurite density index [NDI]) among groups and to assess their relationship with neurocognitive performance. We also investigated the accuracy of these measures in the prediction of group membership, and whether combining them with cortical thickness and white matter fractional anisotropy further improved accuracy. RESULTS The GM-NDI was significantly lower in temporal pole, anterior parahippocampal gyrus, and hippocampus of the schizophrenia patients than the healthy controls. The GM-NDI of patients with bipolar I disorder did not differ significantly from either schizophrenia patients or healthy controls, and it was intermediate between the two groups in the post hoc analysis. Regardless of diagnosis, higher performance in spatial working memory was significantly associated with higher GM-NDI mainly in the frontotemporal areas. The addition of GM-NDI to cortical thickness resulted in higher accuracy to predict group membership. CONCLUSIONS GM-NDI captures brain differences in the major psychoses that are not accessible with other structural magnetic resonance imaging methods. Given the strong association of GM-NDI with disease state and neurocognitive performance, its potential utility for biological subtyping should be further explored.

Age Differences in Visual-Auditory Self-Motion Perception during a Simulated Driving Task.

Recent evidence suggests that visual-auditory cue integration may change as a function of age such that integration is heightened among older adults. Our goal was to determine whether these changes in multisensory integration are also observed in the context of self-motion perception under realistic task constraints. Thus, we developed a simulated driving paradigm in which we provided older and younger adults with visual motion cues (i.e., optic flow) and systematically manipulated the presence or absence of congruent auditory cues to self-motion (i.e., engine, tire, and wind sounds). Results demonstrated that the presence or absence of congruent auditory input had different effects on older and younger adults. Both age groups demonstrated a reduction in speed variability when auditory cues were present compared to when they were absent, but older adults demonstrated a proportionally greater reduction in speed variability under combined sensory conditions. These results are consistent with evidence indicating that multisensory integration is heightened in older adults. Importantly, this study is the first to provide evidence to suggest that age differences in multisensory integration may generalize from simple stimulus detection tasks to the integration of the more complex and dynamic visual and auditory cues that are experienced during self-motion.

Examining the Effect of Age on Visual-Vestibular Self-Motion Perception Using a Driving Paradigm.

Previous psychophysical research has examined how younger adults and non-human primates integrate visual and vestibular cues to perceive self-motion. However, there is much to be learned about how multisensory self-motion perception changes with age, and how these changes affect performance on everyday tasks involving self-motion. Evidence suggests that older adults display heightened multisensory integration compared with younger adults; however, few previous studies have examined this for visual–vestibular integration. To explore age differences in the way that visual and vestibular cues contribute to self-motion perception, we had younger and older participants complete a basic driving task containing visual and vestibular cues. We compared their performance against a previously established control group that experienced visual cues alone. Performance measures included speed, speed variability, and lateral position. Vestibular inputs resulted in more precise speed control among older adults, but not younger adults, when traversing curves. Older adults demonstrated more variability in lateral position when vestibular inputs were available versus when they were absent. These observations align with previous evidence of age-related differences in multisensory integration and demonstrate that they may extend to visual–vestibular integration. These findings may have implications for vehicle and simulator design when considering older users.

Sex and Diffusion Tensor Imaging of White Matter in Schizophrenia: A Systematic Review Plus Meta-analysis of the Corpus Callosum

Sex is considered an understudied variable in health research. Schizophrenia is a brain disorder with known sex differences in epidemiology and clinical presentation. We systematically reviewed the literature for sex-based differences of diffusion properties of white matter tracts in schizophrenia. We then conducted a meta-analysis examining sex-based differences in the genu and splenium of the corpus callosum in schizophrenia. Medline and Embase were searched to identify relevant papers. Studies fulfilling the following criteria were included: (1) included individuals with a diagnosis of schizophrenia, (2) included a control group of healthy individuals, (3) included both sexes in the patient and the control groups, (4) used diffusion tensor imaging, and (5) involved analyzing metrics of white matter microstructural integrity. Fractional anisotropy (FA) was used as the measure of interest in the meta-analysis. Of 730 studies reviewed, 75 met the inclusion criteria. Most showed no effect of sex, however, those that did found either that females have lower FA than males, or that the effect of disease in females is larger than that in males. The findings of the meta-analysis in the corpus callosum supported this result. There is a recognized need for studies on schizophrenia with a sufficient sample of female patients. Lack of power undermines the ability to detect sex-based differences. Understanding the sex-specific impact of illness on neural circuits may help inform development of new treatments, and improvement of existing interventions.

Depression Predicts Functional Outcome in Geriatric Inpatient Rehabilitation.

OBJECTIVE To evaluate the effect of depression on functional recovery in geriatric patients who have completed an inpatient rehabilitation program. DESIGN Prospective cohort study. SETTING Inpatient rehabilitation unit of a university-affiliated geriatric hospital. PARTICIPANTS Convenience sample of patients (N=65; mean age, 81.6y; 25 men) admitted to rehabilitation over a 10-month period. Patients >60 years of age who were proficient in English and capable of providing informed consent were eligible to participate in the study. INTERVENTIONS Depression was assessed using both the Geriatric Depression Scale-short form (GDS-15) and the Patient Health Questionnaire (9-item screen for depression) (PHQ-9). Measures of well-established predictors of rehabilitation outcome, which may interact with depression, were also obtained, and multiple regression linear modeling was used to evaluate the relation between depression and functional outcome over and above the contribution of these other factors. MAIN OUTCOME MEASURE FIM (Functional Independence Measure) at discharge from the rehabilitation program. RESULTS Depression, as assessed by the GDS-15, but not the PHQ-9, was predictive of functional outcome (standardized beta=-.151, P=.030) after controlling for other significant predictors, which included baseline disability, pain, cognition, and educational level. Participation in recreational, but not physio- or occupational, therapy additionally contributed to a small amount of variance in the functional outcome. CONCLUSIONS Our findings suggest that self-report of depression is an independent predictor of functional outcome in high-tolerance, short-duration geriatric rehabilitation. Routine assessment of depressive symptoms in older adults using an instrument (eg, GDS-15) may help identify those at risk for poorer outcomes in rehabilitation.