Flexible Adaptive Paradigms for fMRI Using a Novel Software Package ‘Brain Analysis in Real-Time’ (BART)

In this work we present a new open source software package offering a unified framework for the real-time adaptation of fMRI stimulation procedures. The software provides a straightforward setup and highly flexible approach to adapt fMRI paradigms while the experiment is running. The general framework comprises the inclusion of parameters from subject’s compliance, such as directing gaze to visually presented stimuli and physiological fluctuations, like blood pressure or pulse. Additionally, this approach yields possibilities to investigate complex scientific questions, for example the influence of EEG rhythms or fMRI signals results themselves. To prove the concept of this approach, we used our software in a usability example for an fMRI experiment where the presentation of emotional pictures was dependent on the subject’s gaze position. This can have a significant impact on the results. So far, if this is taken into account during fMRI data analysis, it is commonly done by the post-hoc removal of erroneous trials. Here, we propose an a priori adaptation of the paradigm during the experiment’s runtime. Our fMRI findings clearly show the benefits of an adapted paradigm in terms of statistical power and higher effect sizes in emotion-related brain regions. This can be of special interest for all experiments with low statistical power due to a limited number of subjects, a limited amount of time, costs or available data to analyze, as is the case with real-time fMRI

Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron‑sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes

Main effect of emotion.

<p>All subjects’ t-map results for the second level analysis of ‘negative > neutral’ contrast.</p

Behavioral results.

<p>The post-hoc analysis of eye tracking data shows the correct functionality of the software by 100% fixations for all subjects in the adapted condition. In addition, it shows difference in fixation compliance and gaze distance from the center of the screen for the non-adapted picture presentation. Due to the bimodal distribution of this parameter, subjects were divided into subgroups.</p

Exemplarily results for the increase of effect sizes due to adaption.

<p>In the ROI analysis for non-adapted vs. adapted picture presentations based on regions involved in emotional processing (main effect of emotion, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118890#pone.0118890.g006" target="_blank">Fig. 6</a>) we found enhanced brain responses for adapted trials in Low-Compliant which, due to the adaptation, met the activation levels in High-Compliant. This picture shows this exemplarily for the right pulvinar and insula, the results are summarized in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118890#pone.0118890.t002" target="_blank">Table 2</a>.</p

Experimental paradigm.

<p>The experiment’s paradigm consisted of 60 negative and 60 neutral IAPS pictures, each presented in adapted and non-adapted manner over the course of the experiment. Each picture was presented for 500 ms with a fixation cross in between. In the adapted condition the picture presentation was shifted in time until subjects directed their gaze position toward the center of the screen and hence fixated the center of the subsequently presented picture. The main purpose of the study was to investigate the benefits of this trial adaptation.</p