Chronometric TMS-fMRI of personalized left dorsolateral prefrontal target reveals state-dependency of subgenual anterior cingulate cortex effects.

Transcranial magnetic stimulation (TMS) applied to a left dorsolateral prefrontal cortex (DLPFC) area with a specific connectivity profile to the subgenual anterior cingulate cortex (sgACC) has emerged as a highly effective non-invasive treatment option for depression. However, antidepressant outcomes demonstrate significant variability among therapy plans and individuals. One overlooked contributing factor is the individual brain state at the time of treatment. In this study we used interleaved TMS-fMRI to investigate the influence of brain state on acute TMS effects, both locally and remotely. TMS was performed during rest and during different phases of cognitive task processing. Twenty healthy participants were included in this study. In the first session, imaging data for TMS targeting were acquired, allowing for identification of individualized targets in the left DLPFC based on highest anti-correlation with the sgACC. The second session involved chronometric interleaved TMS-fMRI measurements, with 10 Hz triplets of TMS administered during rest and at distinct timings during an N-back task. Consistent with prior findings, interleaved TMS-fMRI revealed significant BOLD activation changes in the targeted network. The precise timing of TMS relative to the cognitive states during the task demonstrated distinct BOLD response in clinically relevant brain regions, including the sgACC. Employing a standardized timing approach for TMS using a task revealed more consistent modulation of the sgACC at the group level compared to stimulation during rest. In conclusion, our findings strongly suggest that acute local and remote effects of TMS are influenced by brain state during stimulation. This study establishes a basis for considering brain state as a significant factor in designing treatment protocols, possibly improving TMS treatment outcomes.

Theta burst stimulation for depression: a systematic review and network and pairwise meta-analysis.

In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression.

Neural response during prefrontal theta burst stimulation: Interleaved TMS-fMRI of full iTBS protocols.

BACKGROUND: Left prefrontal intermittent theta-burst stimulation (iTBS) has emerged as a safe and effective transcranial magnetic stimulation (TMS) treatment protocol in depression. Though network effects after iTBS have been widely studied, the deeper mechanistic understanding of target engagement is still at its beginning. Here, we investigate the feasibility of a novel integrated TMS-fMRI setup and accelerated echo planar imaging protocol to directly observe the immediate effects of full iTBS treatment sessions. OBJECTIVE/HYPOTHESIS: In our effort to explore interleaved iTBS-fMRI feasibility, we hypothesize that TMS will induce acute BOLD signal changes in both the stimulated area and interconnected neural regions. METHODS: Concurrent TMS-fMRI with full sessions of neuronavigated iTBS (i.e. 600 pulses) of the left dorsolateral prefrontal cortex (DLPFC) was investigated in 18 healthy participants. In addition, we conducted four TMS-fMRI sessions in a single patient on long-term maintenance iTBS for bipolar depression to test the transfer to clinical cases. RESULTS: Concurrent TMS-fMRI was feasible for iTBS sequences with 600 pulses. During interleaved iTBS-fMRI, an increase of the BOLD signal was observed in a network including bilateral DLPFC regions. In the clinical case, a reduced BOLD response was found in the left DLPFC and the subgenual anterior cingulate cortex, with high variability across individual sessions. CONCLUSIONS: Full iTBS sessions as applied for the treatment of depressive disorders can be established in the interleaved iTBS-fMRI paradigm. In the future, this experimental approach could be valuable in clinical samples, for demonstrating target engagement by iTBS protocols and investigating their mechanisms of therapeutic action.

Improved brain stimulation targeting by optimising image acquisition parameters.

Functional connectivity analysis from rs-fMRI data has been used for determining cortical targets in therapeutic applications of non-invasive brain stimulation using transcranial magnetic stimulation (TMS). Reliable connectivity measures are therefore essential for every rs-fMRI-based TMS targeting approach. Here, we examine the effect of echo time (TE) on the reproducibility and spatial variability of resting-state connectivity measures. We acquired multiple runs of single-echo fMRI data with either short (TE = 30 ms) or long (TE = 38 ms) echo time to investigate inter-run spatial reproducibility of a clinically relevant functional connectivity map, i.e., originating from the sgACC. We find that connectivity maps obtained from TE = 38 ms rs-fMRI data are significantly more reliable than those obtained from TE = 30 ms data sets. Our results clearly show that optimizing sequence parameters can be beneficial for ensuring high-reliability resting-state acquisition protocols to be used for TMS targeting. The differences between reliability in connectivity measures for different TEs could inform future clinical research in optimising MR sequences.

Concurrent TMS/fMRI reveals individual DLPFC dose-response pattern.

BACKGROUND: TMS is a valuable tool in both research and clinical settings, playing a crucial role in understanding brain-behavior relationships and providing treatment for various neurological and psychiatric conditions. Importantly, TMS over left DLPFC is an FDA approved treatment for MDD. Despite its potential, response variability to TMS remains a challenge, with stimulation parameters, particularly the stimulation intensity, being a primary contributor to these differences. OBJECTIVE: The objective of this study was to establish dose-response relationships of TMS stimulation in DLPFC by means of concurrent TMS/fMRI. METHODS: Here, we stimulated 15 subjects at different stimulation intensities of 80, 90, 100 and 110 % relative to the motor threshold during concurrent TMS/fMRI. The experiment comprised two sessions: one session to collect anatomical data in order to perform neuronavigation and one session dedicated to dose-response mapping. We calculated GLMs for each intensity level and each subject, as well as at a group-level per intensity. RESULTS: On a group level, we show that the strongest BOLD-response was at 100 % stimulation. However, investigating individual dose response-relationships showed differences in response patterns across the group: subjects that responded to subthreshold stimulation, subjects that required above threshold stimulation in order to show a significant BOLD-response and atypical responders. CONCLUSIONS: We observed qualitative inter-subject variability in terms of dose-response relationship to TMS over left DLPFC, which hints towards the motor threshold not being directly transferable to the excitability of the DLPFC. Concurrent TMS/fMRI might have the potential to improve response rates to rTMS applications. As such, it may be valuable in the future to consider implementing this approach prior to clinical TMS or validating more cost-effective methods to determine dose and target with respect to changes in clinical symptoms.

Combining stimulus types for improved coverage in population receptive field mapping.

Retinotopy experiments using population receptive field (pRF) mapping are ideal for assigning regions in the visual field to cortical brain areas. While various designs for visual stimulation were suggested in the literature, all have specific shortcomings regarding visual field coverage. Here we acquired high-resolution 7 Tesla fMRI data to compare pRF-based coverage maps obtained with the two most commonly used stimulus variants: moving bars; rotating wedges and expanding rings. We find that stimulus selection biases the spatial distribution of pRF centres. In addition, eccentricity values and pRF sizes obtained from wedge/ring or bar stimulation runs show systematic differences. Wedge/ring stimulation results show lower eccentricity values and strongly reduced pRF sizes compared to bar stimulation runs. Statistical comparison shows significantly higher pRF centre numbers in the foveal 2° region of the visual field for wedge/ring compared to bar stimuli. We suggest and evaluate approaches for combining pRF data from different visual stimulus patterns to obtain improved mapping results.

Reproducibility of amygdala activation in facial emotion processing at 7T.

Despite its importance as the prime method for non-invasive assessment of human brain function, functional MRI (fMRI) was repeatedly challenged with regards to the validity of the fMRI-derived brain activation maps. Amygdala fMRI was particularly targeted, as the amygdala's anatomical position in the ventral brain combined with strong magnetic field inhomogeneities and proximity to large vessels pose considerable obstacles for robust activation mapping. In this high-resolution study performed at ultra-high field (7T) fMRI, we aimed at (1) investigating systematic replicability of amygdala group-level activation in response to an established emotion processing task by varying task instruction and acquisition parameters and (2) testing for intra- and intersession reliability. At group-level, our results show statistically significant activation in bilateral amygdala and fusiform gyrus for each of the runs acquired. In addition, while fusiform gyrus activations are consistent across runs and sessions, amygdala activation levels show habituation effects across runs. This amygdala habituation effect is replicated in a session repeated two weeks later. Varying task instruction between matching emotions and matching persons does not change amygdala activation strength. Also, comparing two acquisition protocols with repetition times of either 700 â€‹ms or 1400 â€‹ms did not result in statistically significant differences of activation levels. Regarding within-subject reliability of amygdala activation, despite considerable variance in individual habituation patterns, we report fair to good inter-session reliability for the first run and excellent reliability for averages over runs. We conclude that high-resolution fMRI at 7T allows for robust mapping of amygdala activation in a broad range of variations. Our results of amygdala 7T fMRI are suitable to inform methodology and may encourage future studies to continue using emotion discrimination paradigms in clinical and non-clinical applications.

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI.

Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p < 0.001, FWE-corrected). Temporoparietal junction (TPJ) baseline activity significantly predicted non-remission after 2 antidepressant trials (p = 0.005, FWE-corrected). The results underline the importance of the medial thalamus, attention networks in MD and antidepressant treatment. Moreover, by using a sigmoid model, this study provides a novel method to analyze the dynamic nature of response and remission for future trials.

Correction to: The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI.

The author list was presented as last name, first name. The names should have been listed as:Christoph Kraus, Manfred Klöbl, Martin Tik, Bastian Auer, Thomas Vanicek, Nicole Geissberger, Daniela M. Pfabigan, Andreas Hahn, Michael Woletz, Katharina Paul, Arkadiusz Komorowski, Siegfried Kasper, Christian Windischberger, Claus Lamm, Rupert Lanzenberger.

Modulations in resting state networks of subcortical structures linked to creativity.

Creativity is a sine qua non ability for almost all aspects of everyday life. Although very profound behavioural models were provided by 21st century psychologists, the neural correlates of these personality features associated with creativity are largely unknown. Recent models suggest strong relationships between dopamine release and various creative skills. Herein, we employed functional connectivity analyses of resting-state functional magnetic imaging data in order to shed light on these neural underpinnings of creative aspects. For improved sensitivity, we performed the study at ultra-high magnetic field (7 T). Seed regions were defined based on subcortical (ventral tegmental area/substantia nigra, nucleus caudatus) activation foci of a remote associates task (RAT). In addition, bilateral PCC was used as seed region to examine the default-mode network. Network strength across subjects was regressed against a battery of psychological variables related to creativity. Dopaminergic network variations turned out to be indicative for individual differences in creative traits. In this regard, the caudate network showed stronger connectivity in individuals with higher extraversion measures, while connectivity with the midbrain network was found increased with higher ideational behaviour and emotional stability.

Beware detrending: Optimal preprocessing pipeline for low-frequency fluctuation analysis.

Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility to assess brain function independent of explicit tasks and individual performance. This absence of explicit stimuli in rs-fMRI makes analyses more susceptible to nonneural signal fluctuations than task-based fMRI. Data preprocessing is a critical procedure to minimise contamination by artefacts related to motion and physiology. We herein investigate the effects of different preprocessing strategies on the amplitude of low-frequency fluctuations (ALFFs) and its fractional counterpart, fractional ALFF (fALFF). Sixteen artefact reduction schemes based on nuisance regression are applied to data from 82 subjects acquired at 1.5 T, 30 subjects at 3 T, and 23 subjects at 7 T, respectively. In addition, we examine test-retest variance and effects of bias correction. In total, 569 data sets are included in this study. Our results show that full artefact reduction reduced test-retest variance by up to 50%. Polynomial detrending of rs-fMRI data has a positive effect on group-level t-values for ALFF but, importantly, a negative effect for fALFF. We show that the normalisation process intrinsic to fALFF calculation causes the observed reduction and introduce a novel measure for low-frequency fluctuations denoted as high-frequency ALFF (hfALFF). We demonstrate that hfALFF values are not affected by the negative detrending effects seen in fALFF data. Still, highest grey matter (GM) group-level t-values were obtained for fALFF data without detrending, even when compared to an exploratory detrending approach based on autocorrelation measures. From our results, we recommend the use of full nuisance regression including polynomial detrending in ALFF data, but to refrain from using polynomial detrending in fALFF data. Such optimised preprocessing increases GM group-level t-values by up to 60%.

Hippocampal Subfields in Acute and Remitted Depression-an Ultra-High Field Magnetic Resonance Imaging Study.

BACKGROUND: Studies investigating hippocampal volume changes after treatment with serotonergic antidepressants in patients with major depressive disorder yielded inconsistent results, and effects on hippocampal subfields are unclear. METHODS: To detail treatment effects on total hippocampal and subfield volumes, we conducted an open-label study with escitalopram followed by venlafaxine upon nonresponse in 20 unmedicated patients with major depressive disorder. Before and after 12 weeks treatment, we measured total hippocampal formation volumes and subfield volumes with ultra-high field (7 Tesla), T1-weighted, structural magnetic resonance imaging, and FreeSurfer. Twenty-eight remitted patients and 22 healthy subjects were included as controls. We hypothesized to detect increased volumes after treatment in major depressive disorder. RESULTS: We did not detect treatment-related changes of total hippocampal or subfield volumes in patients with major depressive disorder. Secondary results indicated that the control group of untreated, stable remitted patients, compared with healthy controls, had larger volumes of the right hippocampal-amygdaloid transition area and right fissure at both measurement time points. Depressed patients exhibited larger volumes of the right subiculum compared with healthy controls at MRI-2. Exploratory data analyses indicated lower baseline volumes in the subgroup of remitting (n = 10) vs nonremitting (n = 10) acute patients. CONCLUSIONS: The results demonstrate that monoaminergic antidepressant treatment in major depressive disorder patients was not associated with volume changes in hippocampal subfields. Studies with larger sample sizes to detect smaller effects as well as other imaging modalities are needed to further assess the impact of antidepressant treatment on hippocampal subfields.

Unsmoothed functional MRI of the human amygdala and bed nucleus of the stria terminalis during processing of emotional faces.

Functional neuroimaging of the human amygdala has been of great interest to uncover the neural underpinnings of emotions, mood, motivation, social cognition, and decision making, as well as their dysfunction in psychiatric disorders. Yet, several factors limit in vivo imaging of amygdalar function, most importantly its location deep within the temporal lobe adjacent to air-filled cavities that cause magnetic field inhomogeneities entailing signal dropouts. Additionally, the amygdala and the extended amygdalar region consist of several substructures, which have been assigned different functions and have important implications for functional and effective connectivity studies. Here we show that high-resolution ultra-high field fMRI at 7T can be used to overcome these fundamental challenges for acquisition and can meet some of the demands posed by the complex neuroanatomy and -physiology in this region. Utilizing the inherently high SNR, we use an optimized preprocessing and data analysis strategy to demonstrate that imaging of the (extended) amygdala is highly reliable and robust. Using unsmoothed single-subject data allowed us to differentiate brain activation during processing of emotional faces in the central and basolateral amygdala and, for the first time, in the bed nucleus of the stria terminalis (BNST), which is critically involved in the neural mechanisms of anxiety and threat monitoring. We also provide a quantitative assessment of single subject sensitivity, which is relevant for connectivity studies that rely on time course extraction of functionally-defined volumes of interest.

Ultra-high-field fMRI insights on insight: Neural correlates of the Aha!-moment.

Finding creative solutions to difficult problems is a fundamental aspect of human culture and a skill highly needed. However, the exact neural processes underlying creative problem solving remain unclear. Insightful problem solving tasks were shown to be a valid method for investigating one subcomponent of creativity: the Aha!-moment. Finding insightful solutions during a remote associates task (RAT) was found to elicit specific cortical activity changes. Considering the strong affective components of Aha!-moments, as manifested in the subjectively experienced feeling of relief following the sudden emergence of the solution of the problem without any conscious forewarning, we hypothesized the subcortical dopaminergic reward network to be critically engaged during Aha. To investigate those subcortical contributions to insight, we employed ultra-high-field 7 T fMRI during a German Version of the RAT. During this task, subjects were exposed to word triplets and instructed to find a solution word being associated with all the three given words. They were supposed to press a button as soon as they felt confident about their solution without further revision, allowing us to capture the exact event of Aha!-moment. Besides the finding on cortical involvement of the left anterior middle temporal gyrus (aMTG), here we showed for the first time robust subcortical activity changes related to insightful problem solving in the bilateral thalamus, hippocampus, and the dopaminergic midbrain comprising ventral tegmental area (VTA), nucleus accumbens (NAcc), and caudate nucleus. These results shed new light on the affective neural mechanisms underlying insightful problem solving.

High-sensitivity TMS/fMRI of the Human Motor Cortex Using a Dedicated Multichannel MR Coil.

PURPOSE: To validate a novel setup for concurrent TMS/fMRI in the human motor cortex based on a dedicated, ultra-thin, multichannel receive MR coil positioned between scalp and TMS system providing greatly enhanced sensitivity compared to the standard birdcage coil setting. METHODS: A combined TMS/fMRI design was applied over the primary motor cortex based on 1Hz stimulation with stimulation levels of 80%, 90%, 100%, and 110% of the individual active motor threshold, respectively. Due to the use of a multichannel receive coil we were able to use multiband-accelerated (MB=2) EPI sequences for the acquisition of functional images. Data were analysed with SPM12 and BOLD-weighted signal intensity time courses were extracted in each subject from two local maxima (individual functional finger tapping localiser, fixed MNI coordinate of the hand knob) next to the hand area of the primary motor cortex (M1) and from the global maximum. RESULTS: We report excellent image quality without noticeable signal dropouts or image distortions. Parameter estimates in the three peak voxels showed monotonically ascending activation levels over increasing stimulation intensities. Across all subjects, mean BOLD signal changes for 80%, 90%, 100%, 110% of the individual active motor threshold were 0.43%, 0.63%, 1.01%, 2.01% next to the individual functional finger tapping maximum, 0.73%, 0.91%, 1.34%, 2.21% next to the MNI-defined hand knob and 0.88%, 1.09%, 1.65%, 2.77% for the global maximum, respectively. CONCLUSION: Our results show that the new setup for concurrent TMS/fMRI experiments using a dedicated MR coil array allows for high-sensitivity fMRI particularly at the site of stimulation. Contrary to the standard birdcage approach, the results also demonstrate that the new coil can be successfully used for multiband-accelerated EPI acquisition. The gain in flexibility due to the new coil can be easily combined with neuronavigation within the MR scanner to allow for accurate targeting in TMS/fMRI experiments.

Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity.

Transcranial magnetic stimulation (TMS) is a powerful non-invasive technique for the modulation of brain activity. While the precise mechanism of action is still unknown, TMS is applied in cognitive neuroscience to establish causal relationships between stimulation and subsequent changes in cerebral function and behavioral outcome. In addition, TMS is an FDA-approved therapeutic agent in psychiatric disorders, especially major depression. Successful repetitive TMS in such disorders is usually applied over the left dorso-lateral prefrontal cortex (DLPFC) and treatment response mechanism was therefore supposed to be based on modulations in functional networks, particularly the meso-cortico-limbic reward circuit. However, mechanistic evidence for the direct effects of rTMS over DLPFC is sparse. Here we show the specificity and temporal evolution of rTMS effects by comparing connectivity changes within 20 common independent components in a sham-controlled study. Using an unbiased whole-brain resting-state network (RSN) approach, we successfully demonstrate that stimulation of left DLPFC modulates anterior cingulate cortex (ACC) connectivity in one specific meso-cortico-limbic network, while all other networks are neither influenced by rTMS nor by sham treatment. The results of this study show that the neural correlates of TMS treatment response are also traceable in DLPFC stimulation of healthy brains and therefore represent direct effects of the stimulation procedure.

Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria.

Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are - at least in part - responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males.

Effectiveness of rTMS and tDCS treatment for chronic TBI symptoms: A systematic review and meta-analysis.

INTRODUCTION: Traumatic brain injury (TBI) is a major cause of long-term disability with conventional treatments frequently falling short to restore a good quality-of-life. Non-invasive brain stimulation (NIBS) techniques have shown potential as therapeutic options for neuropsychiatric conditions, including TBI sequelae. This study aims at providing a systematic review and meta-analysis on the effectiveness of repetitive transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) on post-TBI symptoms. METHODS: Fifteen randomized controlled trials (RCTs) on adult TBI patients that examined the effects of multiple treatment sessions of NIBS techniques were selected from five databases. Symptoms were clustered into four categories: depression, anxiety, headache and cognitive dysfunctions. Meta-analysis was performed using correlated and hierarchical effects models. RESULTS: There were only few and heterogeneous studies with generally small sample sizes. Most studies targeted the dorsolateral prefrontal cortex (dlPFC). Overall, the effects of NIBS were small. However, there was a significant effect for overall symptoms (0.404, p = 0.031). Moreover, subgroup analyses revealed significant overall effects for anxiety (0.195, p = 0.020) and headache (0.354, p = 0.040). CONCLUSIONS: To date, there is limited evidence supporting the effectiveness of NIBS concerning treatment for TBI sequelae. The observed effect sizes were modest, suggesting subtle improvements rather than drastic changes. While NIBS techniques remain promising for treating neuropsychiatric conditions, larger RCT studies with longer follow-ups, optimized stimulation parameters and standardized methodology are required to establish their efficacy in addressing TBI sequelae.

Accelerated Theta Burst Stimulation: Safety, Efficacy, and Future Advancements.

Theta burst stimulation (TBS) is a noninvasive brain stimulation technique that can be used to modulate neural networks underlying psychiatric and neurological disorders. TBS can be delivered intermittently or continuously. The conventional intermittent TBS protocol is approved by the U.S. Food and Drug Administration to treat otherwise treatment-resistant depression, but the 6-week duration limits the applicability of this therapy. Accelerated TBS protocols present an opportunity to deliver higher pulse doses in shorter periods of time, thus resulting in faster and potentially more clinically effective treatment. However, the acceleration of TBS delivery raises questions regarding the relative safety, efficacy, and durability compared with conventional TBS protocols. In this review paper, we present the data from accelerated TBS trials to date that support the safety and effectiveness of accelerated protocols while acknowledging the need for more durability data. We discuss the stimulation parameters that seem to be important for the efficacy of accelerated TBS protocols and possible avenues for further optimization.

Citizen science approach to assessing patient perception of MRI with flexible radiofrequency coils.

Magnetic Resonance Imaging (MRI) is a major medical imaging modality, which is non-invasive and provides unique soft tissue contrast without ionizing radiation. The successful completion of MRI exams critically depends on patient compliance, and, thus patient comfort. The design, appearance and usability of local MRI radiofrequency (RF) coils potentially influences the patients' perception of the exam. However, systematic investigations and empirical evidence for these aspects are missing. A questionnaire specifically evaluating the impact of RF coils on patient comfort in MRI would be a valuable addition to clinical studies comparing the performance of novel flexible RF coils with standard rigid coils. This paper describes the development of such a questionnaire in the scope of a citizen science (CS) initiative conducted with a group of students at the upper secondary school level. In this work, the CS initiative is presented in the format of a case report and its impact on scientific projects and the students' education is outlined. The resulting questionnaire is made available in German and English so as to be directly applicable by researchers working on the clinical evaluation of novel RF coils or the comfort evaluation of specific hardware setups in general.