Acute TMS/fMRI response explains offline TMS network effects - An interleaved TMS-fMRI study.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an FDA-approved therapeutic option for treatment resistant depression. However, exact mechanisms-of-action are not fully understood and individual responses are variable. Moreover, although previously suggested, the exact network effects underlying TMS' efficacy are poorly understood as of today. Although, it is supposed that DLPFC stimulation indirectly modulates the sgACC, recent evidence is sparse. METHODS: Here, we used concurrent interleaved TMS/fMRI and state-of-the-science purpose-designed MRI head coils to delineate networks and downstream regions activated by DLPFC-TMS. RESULTS: We show that regions of increased acute BOLD signal activation during TMS resemble a resting-state brain network previously shown to be modulated by offline TMS. There was a topographical overlap in wide spread cortical and sub-cortical areas within this specific RSN#17 derived from the 1000 functional connectomes project. CONCLUSION: These data imply a causal relation between DLPFC-TMS and activation of the ACC and a broader network that has been implicated in MDD. In the broader context of our recent work, these data imply a direct relation between initial changes in BOLD activity mediated by connectivity to the DLPFC target site, and later consolidation of connectivity between these regions. These insights advance our understanding of the mechanistic targets of DLPFC-TMS and may provide novel opportunities to characterize and optimize TMS therapy in other neurological and psychiatric disorders.

Artificial scotoma estimation based on population receptive field mapping.

Population receptive field (pRF) mapping based on functional magnetic resonance imaging (fMRI) is an ideal method for obtaining detailed retinotopic information. One particularly promising application of pRF mapping is the estimation and quantification of visual field effects, for example scotomata in patients suffering from macular dysfunction or degeneration (MD) or hemianopic defects in patients with intracranial dysfunction. However, pRF mapping performance is influenced by a number of factors including spatial and temporal resolution, distribution of dural venous sinuses and patient performance. This study addresses the ability of current pRF methodology to assess the size of simulated scotomata in healthy individuals. The data demonstrate that central scotomata down to a radius of 2.35° (4.7° diameter) visual angle can be reliably estimated in single subjects using high spatial resolution protocols and multi-channel receive array coils.

Imaging the neuroplastic effects of ketamine with VBM and the necessity of placebo control.

In the last years a plethora of studies have investigated morphological changes induced by behavioural or pharmacological interventions using structural T1-weighted MRI and voxel-based morphometry (VBM). Ketamine is thought to exert its antidepressant action by restoring neuroplasticity. In order to test for acute impact of a single ketamine infusion on grey matter volume we performed a placebo-controlled, double-blind investigation in healthy volunteers using VBM. 28 healthy individuals underwent two MRI sessions within a timeframe of 2 weeks, each consisting of two structural T1-weighted MRIs within a single session, one before and one 45min after infusion of S-ketamine (bolus of 0.11mg/kg, followed by an maintenance infusion of 0.12mg/kg) or placebo (0.9% NaCl infusion) using a crossover design. In the repeated-measures ANOVA with time (post-infusion/pre-infusion) and medication (placebo/ketamine) as factors, no significant effect of interaction and no effect of medication was found (FWE-corrected). Importantly, further post-hoc t-tests revealed a strong "decrease" of grey matter both in the placebo and the ketamine condition over time. This effect was evident mainly in frontal and temporal regions bilaterally with t-values ranging from 4.95 to 5.31 (FWE-corrected at p<0.05 voxel level). The vulnerabilities of VBM have been repeatedly demonstrated, with reports of influence of blood flow, tissue water and direct effects of pharmacological compounds on the MRI signal. Here again, we highlight that the relationship between intervention and VBM results is apparently subject to a number of physiological influences, which are partly unknown. Future studies focusing on the effects of ketamine on grey matter should try to integrate known influential factors such as blood flow into analysis. Furthermore, the results of this study highlight the importance of a carefully performed placebo condition in pharmacological fMRI studies.

Eyetracker-based gaze correction for robust mapping of population receptive fields.

Functional MRI enables the acquisition of a retinotopic map that relates regions of the visual field to neural populations in the visual cortex. During such a "population receptive field" (PRF) experiment, stable gaze fixation is of utmost importance in order to correctly link the presented stimulus patterns to stimulated retinal regions and the resulting Blood Oxygen Level Dependent (BOLD) response of the appropriate region within the visual cortex. A method is described that compensates for unstable gaze fixation by recording gaze position via an eyetracker and subsequently modifies the input stimulus underlying the PRF analysis according to the eyetracking measures. Here we show that PRF maps greatly improve when the method is applied to data acquired with either saccadic or smooth eye movements. We conclude that the technique presented herein is useful for studies involving subjects with unstable gaze fixation, particularly elderly patient populations.

When differences matter: rTMS/fMRI reveals how differences in dispositional empathy translate to distinct neural underpinnings of self-other distinction in empathy.

Self-other distinction is crucial for empathy, since it prevents the confusion of self-experienced emotions with those of others. We aimed to extend our understanding of the neurocognitive mechanisms of self-other distinction. Thirty-one female participants underwent continuous theta burst transcranial magnetic stimulation (cTBS) targeting the right supramarginal gyrus (rSMG), a sub-region of the temporoparietal junction previously shown to be involved in self-other distinction, and the vertex, a cortical control site. Right after stimulation they completed a visuo-tactile empathy task in an MRI scanner. Self-other distinction was assessed by differences in emotion judgments, and brain activity between conditions differing in the requirement for self-other distinction. Effects of brain stimulation on self-other distinction depended on individual differences in dispositional empathic understanding: cTBS of rSMG, compared to vertex, enhanced self-other distinction in participants with lower dispositional empathic understanding, but diminished it in participants with higher empathic understanding. On the neural level, this inverse relationship between empathic disposition and self-other distinction performance was linked to a reduction of cTBS-induced rSMG activity in persons with lower dispositional empathy, and an increase in those with higher dispositional empathy. These two opposite impacts of cTBS were associated with two anatomically and functionally distinct networks. These findings open up novel perspectives on the causal role of rSMG in self-other distinction and empathy. They also suggest that considering individual differences may yield novel insights into how brain stimulation affects higher-level affect and cognition, and its neural correlates.

Default mode network deactivation during emotion processing predicts early antidepressant response.

Several previous functional magnetic resonance imaging (fMRI) studies have demonstrated the predictive value of brain activity during emotion processing for antidepressant response, with a focus on clinical outcome after 6-8 weeks. However, longitudinal studies emphasize the paramount importance of early symptom improvement for the course of disease in major depressive disorder (MDD). We therefore aimed to assess whether neural activity during the emotion discrimination task (EDT) predicts early antidepressant effects, and how these predictive measures relate to more sustained response. Twenty-three MDD patients were investigated once with ultrahigh-field 7T fMRI and the EDT. Following fMRI, patients received Escitalopram in a flexible dose schema and were assessed with the Hamilton Depression Rating Scale (HAMD) before, and after 2 and 4 weeks of treatment. Deactivation of the precuneus and posterior cingulate cortex (PCC) during the EDT predicted change in HAMD scores after 2 weeks of treatment. Baseline EDT activity was not predictive of HAMD change after 4 weeks of treatment. The precuneus and PCC are integral components of the default mode network (DMN). We show that patients who exhibit stronger DMN suppression during emotion processing are more likely to show antidepressant response after 2 weeks. This is, to our knowledge, the first study to show that DMN activity predicts early antidepressant effects. However, DMN deactivation did not predict response at 4 weeks, suggesting that our finding is representative of early, likely treatment-related, yet unspecific symptom improvement. Regardless, early effects may be harnessed for optimization of treatment regimens and patient care.