Adding a Second iTBS Block in 15 or 60 Min Time Interval Does Not Increase iTBS Effects on Motor Cortex Excitability and the Responder Rates.

The use of metaplasticity-based intermittent theta-burst stimulation (iTBS) protocols including several stimulation blocks could be a possible approach to increasing stimulation effectiveness. Our aim was to investigate the neurophysiological effects of two protocols with a short and a long interval between blocks. Seventeen healthy volunteers received four protocols in a pseudorandomized order: iTBS 0-15 (two blocks of active iTBS of primary motor cortex (M1) separated by 15 min and a control stimulation block of the vertex in 60 min from the first block); iTBS 0-60 (active iTBS, a control block in 15 min, and an active block in 60 min); iTBS 0 (active iTBS and two control blocks with the same intervals); and Control (three control blocks). The motor evoked potentials (MEPs) were measured before the first and after the second and third blocks. We have shown no significant differences between the effects of the protocols on both the motor cortex excitability and the responder rates. No significant changes of MEPs were observed after all the protocols. The reliability for the responsiveness to a single block between two sessions was insignificant. Our data confirm low reproducibility of the response to iTBS and suggest that the use of repeated protocols does not increase the responder rates or neurophysiological effects of iTBS.

Combining HF rTMS over the Left DLPFC with Concurrent Cognitive Activity for the Offline Modulation of Working Memory in Healthy Volunteers: A Proof-of-Concept Study.

It has been proposed that the effectiveness of non-invasive brain stimulation (NIBS) as a cognitive enhancement technique may be enhanced by combining the stimulation with concurrent cognitive activity. However, the benefits of such a combination in comparison to protocols without ongoing cognitive activity have not yet been studied. In the present study, we investigate the effects of fMRI-guided high-frequency repetitive transcranial magnetic stimulation (HF rTMS) over the left dorsolateral prefrontal cortex (DLPFC) on working memory (WM) in healthy volunteers, using an n-back task with spatial and verbal stimuli and a spatial span task. In two combined protocols (TMS + WM + (maintenance) and TMS + WM + (rest)) trains of stimuli were applied in the maintenance and rest periods of the modified Sternberg task, respectively. We compared them to HF rTMS without a cognitive load (TMS + WM-) and control stimulation (TMS - WM + (maintenance)). No serious adverse effects appeared in this study. Among all protocols, significant effects on WM were shown only for the TMS + WM- with oppositely directed influences of this protocol on storage and manipulation in spatial WM. Moreover, there was a significant difference between the effects of TMS + WM- and TMS + WM + (maintenance), suggesting that simultaneous cognitive activity does not necessarily lead to an increase in TMS effects.

Brain Activations and Functional Connectivity Patterns Associated with Insight-Based and Analytical Anagram Solving.

Insight is one of the most mysterious problem-solving phenomena involving the sudden emergence of a solution, often preceded by long unproductive attempts to find it. This seemingly unexplainable generation of the answer, together with the role attributed to insight in the advancement of science, technology and culture, stimulate active research interest in discovering its neuronal underpinnings. The present study employs functional Magnetic resonance imaging (fMRI) to probe and compare the brain activations occurring in the course of solving anagrams by insight or analytically, as judged by the subjects. A number of regions were activated in both strategies, including the left premotor cortex, left claustrum, and bilateral clusters in the precuneus and middle temporal gyrus. The activated areas span the majority of the clusters reported in a recent meta-analysis of insight-related fMRI studies. At the same time, the activation patterns were very similar between the insight and analytical solutions, with the only difference in the right sensorimotor region probably explainable by subject motion related to the study design. Additionally, we applied resting-state fMRI to study functional connectivity patterns correlated with the individual frequency of insight anagram solutions. Significant correlations were found for the seed-based connectivity of areas in the left premotor cortex, left claustrum, and left frontal eye field. The results stress the need for optimizing insight paradigms with respect to the accuracy and reliability of the subjective insight/analytical solution classification. Furthermore, the short-lived nature of the insight phenomenon makes it difficult to capture the associated neural events with the current experimental techniques and motivates complementing such studies by the investigation of the structural and functional brain features related to the individual differences in the frequency of insight-based decisions.

Detecting the Potential for Consciousness in Unresponsive Patients Using the Perturbational Complexity Index.

The difficulties of behavioral evaluation of prolonged disorders of consciousness (DOC) motivate the development of brain-based diagnostic approaches. The perturbational complexity index (PCI), which measures the complexity of electroencephalographic (EEG) responses to transcranial magnetic stimulation (TMS), showed a remarkable sensitivity in detecting minimal signs of consciousness in previous studies. Here, we tested the reliability of PCI in an independently collected sample of 24 severely brain-injured patients, including 11 unresponsive wakefulness syndrome (UWS), 12 minimally conscious state (MCS) patients, and 1 emergence from MCS patient. We found that the individual maximum PCI value across stimulation sites fell within the consciousness range (i.e., was higher than PCI*, which is an empirical cutoff previously validated on a benchmark population) in 11 MCS patients, yielding a sensitivity of 92% that surpassed qualitative evaluation of resting EEG. Most UWS patients (n = 7, 64%) showed a slow and stereotypical TMS-EEG response, associated with low-complexity PCI values (i.e., ≤PCI*). Four UWS patients (36%) provided high-complexity PCI values, which might suggest a covert capacity for consciousness. In conclusion, this study successfully replicated the performance of PCI in discriminating between UWS and MCS patients, further motivating the application of TMS-EEG in the workflow of DOC evaluation.

Stimulation of the Angular Gyrus Improves the Level of Consciousness.

BACKGROUND: Navigated repetitive transcranial magnetic stimulation (rTMS) is a promising tool for neuromodulation. In previous studies it has been shown that the activity of the default mode network (DMN) areas, particularly of its key region-the angular gyrus-is positively correlated with the level of consciousness. Our study aimed to explore the effect of rTMS of the angular gyrus as a new approach for disorders of consciousness (DOC) treatment; Methods: A 10-session 2-week high-frequency rTMS protocol was delivered over the left angular gyrus in 38 DOC patients with repeated neurobehavioral assessments obtained at baseline and in 2 days after the stimulation course was complete; Results: 20 Hz-rTMS over left angular gyrus improved the coma recovery scale revised (CRS-R) total score in minimally conscious state (MCS) patients. We observed no effects in vegetative state (VS) patients; and Conclusions: The left angular gyrus is likely to be effective target for rTMS in patients with present signs of consciousness.