Meditation-induced modulation of brain response to transcranial magnetic stimulation

Noninvasive brain stimulation and neuroimaging have revolutionized human neuroscience with a multitude of applications, including diagnostic subtyping, treatment optimization, and relapse prediction. It is therefore particularly relevant to identify robust and clinically valuable brain biomarkers linking symptoms to their underlying neural mechanisms. Brain biomarkers must be reproducible (i.e., have internal reliability) across similar experiments within a laboratory and be generalizable (i.e., have external reliability) across experimental setups, laboratories, brain regions, and disease states. However, reliability (internal and external) is not alone sufficient; biomarkers also must have validity. Validity describes closeness to a true measure of the underlying neural signal or disease state. We propose that these metrics, reliability and validity, should be evaluated and optimized before any biomarker is used to inform treatment decisions. Here, we discuss these metrics with respect to causal brain connectivity biomarkers from coupling transcranial magnetic stimulation (TMS) with electroencephalography (EEG). We discuss controversies around TMS-EEG stemming from the multiple large off-target components (noise) and relatively weak genuine brain responses (signal), as is unfortunately often the case in noninvasive human neuroscience. We review the current state of TMS-EEG recordings, which consist of a mix of reliable noise and unreliable signal. We describe methods for evaluating TMS-EEG biomarkers, including how to assess internal and external reliability across facilities, cognitive states, brain networks, and disorders and how to validate these biomarkers using invasive neural recordings or treatment response. We provide recommendations to increase reliability and validity, discuss lessons learned, and suggest future directions for the field.

Exploring the neurobiology of the profound changes in consciousness induced by classical psychedelic drugs may require novel neuroimaging methods. Serotonergic psychedelic drugs such as psilocybin produce states of increased sensory-emotional awareness and arousal, accompanied by increased spontaneous electroencephalographic (EEG) signal diversity. By directly stimulating cortical tissue, the altered dynamics and propagation of the evoked EEG activity can reveal drug-induced changes in the overall brain state. We combine Transcranial Magnetic Stimulation (TMS) and EEG to reveal that psilocybin produces a state of increased chaotic brain activity which is not a result of altered complexity in the underlying causal interactions between brain regions. We also map the regional effects of psilocybin on TMS-evoked activity and identify changes in frontal brain structures that may be associated with the phenomenology of psychedelic experiences.

As interest grows in near-death experiences (NDEs), it is increasingly important to accurately identify them to facilitate empirical research and reproducibility among assessors. We aimed (1) to reassess the psychometric properties of the NDE scale developed by Greyson (1983) and (2) to validate the Near-Death Experience Content (NDE-C) scale that quantifies NDEs in a more complete way. Internal consistency, construct and concurrent validity analyses were performed on the NDE scale. Based on those results and the most recent empirical evidence, we then developed a new 20-item scale. Internal consistency, explanatory and confirmatory factor, concurrent and discriminant validity analyses were conducted. Results revealed (1) a series of weaknesses in the NDE scale, (2) a 5-factor structure covering relevant dimensions and the very good psychometric properties of the NDE-C scale, including very good internal consistency (Cronbach α = 0.85) and concurrent validity (correlations above 0.76). This new reliable scale should facilitate future research.