Concurrent TMS-fMRI for causal network perturbation and proof of target engagement.

The experimental manipulation of neural activity by neurostimulation techniques overcomes the inherent limitations of correlative recordings, enabling the researcher to investigate causal brain-behavior relationships. But only when stimulation and recordings are combined, the direct impact of the stimulation on neural activity can be evaluated. In humans, this can be achieved non-invasively through the concurrent combination of transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI). Concurrent TMS-fMRI allows the assessment of the neurovascular responses evoked by TMS with excellent spatial resolution and full-brain coverage. This enables the functional mapping of both local and remote network effects of TMS in cortical as well as deep subcortical structures, offering unique opportunities for basic research and clinical applications. The purpose of this review is to introduce the reader to this powerful tool. We will introduce the technical challenges and state-of-the art solutions and provide a comprehensive overview of the existing literature and the available experimental approaches. We will highlight the unique insights that can be gained from concurrent TMS-fMRI, including the state-dependent assessment of neural responsiveness and inter-regional effective connectivity, the demonstration of functional target engagement, and the systematic evaluation of stimulation parameters. We will also discuss how concurrent TMS-fMRI during a behavioral task can help to link behavioral TMS effects to changes in neural network activity and to identify peripheral co-stimulation confounds. Finally, we will review the use of concurrent TMS-fMRI for developing TMS treatments of psychiatric and neurological disorders and suggest future improvements for further advancing the application of concurrent TMS-fMRI.

Transcranial Magnetic Stimulation of the Medial Prefrontal Cortex Decreases Emotional Memory Schemas.

Mood-congruent memory bias is a critical characteristic of depression, but the underlying neural mechanism is largely unknown. Negative memory schemas might enhance encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to perturb medial prefrontal cortex (mPFC) processing, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data were recorded continuously during the night before and after encoding. We observed a significantly lower false recognition of negative critical lures following mPFC inhibition, but no differences in veridical memory. These findings were supported by reaction time data, showing a relative slower response to negative compared with positive critical lures. The current findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.

Sleep fragmentation and lucid dreaming.

Lucid dreaming-the phenomenon of experiencing waking levels of self-reflection within one's dreams-is associated with more wake-like levels of neural activation in prefrontal brain regions. In addition, alternating periods of wakefulness and sleep might increase the likelihood of experiencing a lucid dream. Here we investigate the association between sleep fragmentation and lucid dreaming, with a multi-centre study encompassing four different investigations into subjective and objective measures of sleep fragmentation, nocturnal awakenings, sleep quality and polyphasic sleep schedules. Results across these four studies provide a more nuanced picture into the purported connection between sleep fragmentation and lucid dreaming: While self-assessed numbers of awakenings, polyphasic sleep and physiologically validated wake-REM sleep transitions were associated with lucid dreaming, neither self-assessed sleep quality, nor physiologically validated numbers of awakenings were. We discuss these results, and their underlying neural mechanisms, within the general question of whether sleep fragmentation and lucid dreaming share a causal link.

Virtual reality training of lucid dreaming.

Metacognitive reflections on one's current state of mind are largely absent during dreaming. Lucid dreaming as the exception to this rule is a rare phenomenon; however, its occurrence can be facilitated through cognitive training. A central idea of respective training strategies is to regularly question one's phenomenal experience: is the currently experienced world real, or just a dream? Here, we tested if such lucid dreaming training can be enhanced with dream-like virtual reality (VR): over the course of four weeks, volunteers underwent lucid dreaming training in VR scenarios comprising dream-like elements, classical lucid dreaming training or no training. We found that VR-assisted training led to significantly stronger increases in lucid dreaming compared to the no-training condition. Eye signal-verified lucid dreams during polysomnography supported behavioural results. We discuss the potential mechanisms underlying these findings, in particular the role of synthetic dream-like experiences, incorporation of VR content in dream imagery serving as memory cues, and extended dissociative effects of VR session on subsequent experiences that might amplify lucid dreaming training during wakefulness. This article is part of the theme issue 'Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation'.