Stephanie Njau

Effect of Electroconvulsive Therapy on Striatal Morphometry in Major Depressive Disorder

Patients with major depression show reductions in striatal and paleostriatal volumes. The functional integrity and connectivity of these regions are also shown to change with antidepressant response. Electroconvulsive therapy (ECT) is a robust and rapidly acting treatment for severe depression. However, whether morphological changes in the dorsal and ventral striatum/pallidum relate to or predict therapeutic response to ECT is unknown. Using structural MRI, we assessed cross-sectional effects of diagnosis and longitudinal effects of ECT for volume and surface-based shape metrics of the caudate, putamen, pallidum, and nucleus accumbens in 53 depressed patients (mean age: 44.1 years, 13.8 SD; 52% female) and 33 healthy controls (mean age: 39.3 years, 12.4 SD; 57% female). Patients were assessed before ECT, after their second ECT, and after completing an ECT treatment index. Controls were evaluated at two time points. Support vector machines determined whether morphometric measures at baseline predicted ECT-related clinical response. Patients showed smaller baseline accumbens and pallidal volumes than controls (P<0.05). Increases in left putamen volume (P<0.03) occurred with ECT. Global increases in accumbens volume and local changes in pallidum and caudate volume occurred in patients defined as treatment responders. Morphometric changes were absent across time in controls. Baseline volume and shape metrics predicted overall response to ECT with up to 89% accuracy. Results support that ECT elicits structural plasticity in the dorsal and ventral striatum/pallidum. The morphometry of these structures, forming key components of limbic-cortical-striatal-pallidal-thalamic circuitry involved in mood and emotional regulation, may determine patients likely to benefit from treatment.

Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression

Background Electroconvulsive therapy (ECT) is a highly effective brain stimulation treatment for severe depression. Identifying neurochemical changes linked with ECT may point to biomarkers and predictors of successful treatment response. Methods We used proton magnetic resonance spectroscopy (1H-MRS) to measure longitudinal changes in glutamate/glutamine (Glx), creatine (Cre), choline (Cho) and N-acetylaspartate (NAA) in the dorsal (dACC) and subgenual anterior cingulate cortex (sgACC) and bilateral hippocampus in patients receiving ECT scanned at baseline, after the second ECT session and after the ECT treatment series. Patients were compared with demographically similar controls at baseline. Controls were assessed twice to establish normative values and variance. Results We included 50 patients (mean age 43.78 ± 14 yr) and 33 controls (mean age 39.33 ± 12 yr) in our study. Patients underwent a mean of 9 ± 4.1 sessions of ECT. At baseline, patients showed reduced Glx in the sgACC, reduced NAA in the left hippocampus and increased Glx in the left hippocampus relative to controls. ECT was associated with significant increases in Cre in the dACC and sgACC and decreases in NAA in the dACC and right hippocampus. Lower NAA levels in the dACC at baseline predicted reductions in depressive symptoms. Both ECT and symptom improvement were associated with decreased Glx in the left hippocampus and increased Glx in the sgACC. Limitations Attrition and clinical heterogeneity may have masked more subtle findings. Conclusion ECT elicits robust effects on brain chemistry, impacting Cre, NAA and Glx, which suggests restorative and neurotrophic processes. Differential effects of Glx in the sgACC and hippocampus, which approach control values with treatment, may reflect previously implicated underactive cortical and overactive subcortical limbic circuitry in patients with major depression. NAA levels at baseline are predictive of therapeutic outcome and could inform future treatment strategies.

Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex

Electroconvulsive therapy (ECT) is a highly effective and rapidly acting treatment for severe depression. To understand the biological bases of therapeutic response, we examined variations in cortical thickness from magnetic resonance imaging (MRI) data in 29 patients scanned at three time points during an ECT treatment index series and in 29 controls at two time points. Changes in thickness across time and with symptom improvement were evaluated at high spatial resolution across the cortex and within discrete cortical regions of interest. Patients showed increased thickness over the course of ECT in the bilateral anterior cingulate cortex (ACC), inferior and superior temporal, parahippocampal, entorhinal and fusiform cortex and in distributed prefrontal areas. No changes across time occurred in controls. In temporal and fusiform regions showing significant ECT effects, thickness differed between patients and controls at baseline and change in thickness related to therapeutic response in patients. In the ACC, these relationships occurred in treatment responders only, and thickness measured soon after treatment initiation predicted the overall ECT response. ECT leads to widespread neuroplasticity in neocortical, limbic and paralimbic regions and changes relate to the extent of antidepressant response. Variations in ACC thickness, which discriminate treatment responders and predict response early in the course of ECT, may represent a biomarker of overall clinical outcome. Because post-mortem studies show focal reductions in glial density and neuronal size in patients with severe depression, ECT-related increases in thickness may be attributable to neuroplastic processes affecting the size and/or density of neurons and glia and their connections.

Structural connectivity and response to ketamine therapy in major depression: A preliminary study

BACKGROUND Ketamine elicits an acute antidepressant effect in patients with major depressive disorder (MDD). Here, we used diffusion imaging to explore whether regional differences in white matter microstructure prior to treatment may predict clinical response 24h following ketamine infusion in 10 MDD patients. METHODS FSLs Tract-Based Spatial Statistics (TBSS) established voxel-level differences in fractional anisotropy (FA) between responders (patients showing >50% improvement in symptoms 24h post-infusion) and non-responders in major white matter pathways. Follow-up regions-of-interest (ROI) analyses examined differences in FA and radial (RD), axial (AD) and mean diffusivity (MD) between responders and non-responders and 15 age- and sex-matched controls, with groups compared pairwise. RESULTS Whole brain TBSS (p<0.05, corrected) and confirmatory tract-based regions-of-interest analyses showed larger FA values in the cingulum and forceps minor in responders compared to non-responders; complementary decreases in RD occurred in the cingulum (p<0.05). Only non-responders differed from controls showing decreased FA in the forceps minor, increased RD in the cingulum and forceps minor, and increased MD in the forceps minor (p<0.05). LIMITATIONS Non-responders showed an earlier age of onset and longer current depressive episode than responders. Though these factors did not interact with diffusion metrics, results may be impacted by the limited sample size. CONCLUSIONS Though findings are considered preliminary, significant differences in FA, RD and MD shown in non-responders compared to responders and controls in fronto-limbic and ventral striatal pathways suggest that the structural architecture of specific functional networks mediating emotion may predict ketamine response in MDD.

Short- and Long-term Cognitive Outcomes in Patients with Major Depression Treated with Electroconvulsive Therapy

Objectives The risk of cognitive impairment is a concern for patients with major depressive disorder receiving electroconvulsive therapy (ECT). Here, we evaluate the acute, short-term and long-term effects of ECT on tests of processing speed, executive function, memory, and attention. Methods Forty-four patients with major depressive disorder receiving ECT (61% right unilateral, 39% mixed right unilateral–bitemporal, left unilateral, and/or bitemporal lead placement) underwent a cognitive battery prior to ECT (T1), after 2 sessions (T2), and at the end of the index (T3). Thirty-two patients returned for a 6-month follow-up (T4). Thirty-three control subjects were assessed at 2 times approximately 4 weeks apart (C1 and C2). Results At baseline, patients showed deficits in processing speed, executive function, and memory compared with control subjects. Including depression severity and lead placement covariates, linear mixed-model analysis showed significant improvement in only processing speed between T1 and T3 and between T1 and T4 in patients. An acute decline in attention and verbal memory was observed at T2, but performance returned to baseline levels at T3. Longitudinal cognitive outcomes did not differ in patients defined as ECT responders/nonresponders. Limitations Episodic memory was not measured, and medications were not controlled between T3 and T4. Control subjects also showed improvements in processing speed, suggesting practice effects for some measures. Conclusions In this naturalistic ECT treatment study, results show that the initiation of ECT may transiently affect memory and executive function, but cognition is largely unaffected during and after ECT. Whereas some functions might improve, others will at least remain stable up to 6 months following the ECT index.

Linking optic radiation volume to visual perception in schizophrenia and bipolar disorder

People with schizophrenia typically show visual processing deficits on masking tasks and other performance-based measures, while people with bipolar disorder may have related deficits. The etiology of these deficits is not well understood. Most neuroscientific studies of perception in schizophrenia and bipolar disorder have focused on visual processing areas in the cerebral cortex, but perception also depends on earlier components of the visual system that few studies have examined in these disorders. Using diffusion weighted imaging (DWI), we investigated the structure of the primary sensory input pathway to the cortical visual system: the optic radiations. We used probabilistic tractography to identify the optic radiations in 32 patients with schizophrenia, 31 patients with bipolar disorder, and 30 healthy controls. The same participants also performed a visual masking task outside the scanner. We characterized the optic radiations with three structural measures: fractional anisotropy, mean diffusivity, and tract volume. We did not find significant differences in those structural measures across groups. However, we did find a significant correlation between the volume of the optic radiations and visual masking thresholds that was unique to the schizophrenia group and explained variance in masking performance above and beyond that previously accounted for by differences in visual cortex. Thus, individual differences in the volume of the optic radiations explained more variance in visual masking performance in the schizophrenia group than the bipolar or control groups. This suggests that individual differences in the structure of the subcortical visual system have an important influence on visual processing in schizophrenia.

Data-driven cluster selection for subcortical shape and cortical thickness predicts recovery from depressive symptoms

Patients with major depressive disorder (MDD) who do not achieve full symptomatic recovery after antidepressant treatment have a higher risk of relapse. Compared to pharmacotherapies, electroconvulsive therapy (ECT) more rapidly produces a greater extent of response in severely depressed patients. However, prediction of which candidates are most likely to improve after ECT remains challenging. Using structural MRI data from 42 ECT patients scanned prior to ECT treatment, we developed a random forest classifier based on data-driven shape cluster selection and cortical thickness features to predict remission. Right hemisphere hippocampal shape and right inferior temporal cortical thickness was most predictive of remission, with the predicted probability of recovery decreasing when these regions were thicker prior to treatment. Remission was predicted with an average 73% balanced accuracy. Classification of MRI data may help identify treatment-responsive patients and aid in clinical decision-making. Our results show promise for the development of personalized treatment strategies.

Denoising of MR spectroscopy signals using total variation and iterative Gauss-Seidel gradient updates

We present a fast variational approach for denoising signals from magnetic resonance spectroscopy (MRS). Differently from the TV approaches applied to denoising of images, this is the first time to our knowledge that it has been used for the processing of free induction decay signals from single-voxel spectroscopy (SVS) acquisitions. Another novelty in this study is the direct use of the Euler Lagrange formulation coupled with Gauss Seidel gradient updates to improve the speed of iteration and reduce ringing. Results from brain MRS signals show improvement in signal to noise ratio as well as reduction in estimation error in the quantification of metabolites.