A protocol for a multicenter randomized and personalized controlled trial using rTMS in patients with disorders of consciousness.

Background: Improving the functional recovery of patients with DoC remains one of the greatest challenges of the field. Different theories exist about the role of the anterior (prefrontal areas) versus posterior (parietal areas) parts of the brain as hotspots for the recovery of consciousness. Repetitive transcranial magnetic stimulation (rTMS) is a powerful non-invasive brain stimulation technique for the treatment of DoC. However, a direct comparison of the effect of TMS treatment on the front versus the back of the brain has yet to be performed. In this study, we aim to assess the short- and long-term effects of frontal and parietal rTMS on DoC recovery and characterize responders phenotypically. Methods/design: Ninety patients with subacute and prolonged DoC will be included in a two-part multicenter prospective study. In the first phase (randomized controlled trial, RCT), patients will undergo four rTMS sessions in a crossover design over 10 days, targeting (i) the left dorsolateral prefrontal cortex (DLPFC) and (ii) the left angular gyrus (AG), as well as (iii & iv) their sham alternatives. In the second phase (longitudinal personalized trial), patients will receive personalized stimulations for 20 working days targeting the brain area that showed the best results in the RCT and will be randomly assigned to either active or sham intervention. The effects of rTMS on neurobehavioral and neurophysiological functioning in patients with DoC will be evaluated using clinical biomarkers of responsiveness (i.e., the Coma Recovery Scale-Revised; CRS-R), and electrophysiological biomarkers (e.g., power spectra, functional and effective connectivity, perturbational complexity index before and after intervention). Functional long-term outcomes will be assessed at 3 and 6 months post-intervention. Adverse events will be recorded during the treatment phase. Discussion: This study seeks to identify which brain region (front or back) is best to stimulate for the treatment of patients with DoC using rTMS, and to characterize the neural correlates of its action regarding recovery of consciousness and functional outcome. In addition, we will define the responders' profile based on patients' characteristics and functional impairments; and develop biomarkers of responsiveness using EEG analysis according to the clinical responsiveness to the treatment. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04401319, Clinicaltrials.gov, n° NCT04401319.

Optimizing home-based long-term intensive care for neurological patients with neurorehabilitation outreach teams - protocol of a multicenter, parallel-group randomized controlled trial (OptiNIV-Study).

BACKGROUND: Even with high standards of acute care and neurological early rehabilitation (NER) a substantial number of patients with neurological conditions still need mechanical ventilation and/or airway protection by tracheal cannulas when discharged and hence home-based specialised intensive care nursing (HSICN). It may be possible to improve the home care situation with structured specialized long-term neurorehabilitation support and following up patients with neurorehabilitation teams. Consequently, more people might recover over an extended period to a degree that they were no longer dependent on HSICN. METHODS: This healthcare project and clinical trial implements a new specialised neurorehabilitation outreach service for people being discharged from NER with the need for HSICN. The multicentre, open, parallel-group RCT compares the effects of one year post-discharge specialized outpatient follow-up to usual care in people receiving HSICN. Participants will randomly be assigned to receive the new form of healthcare (intervention) or the standard healthcare (control) on a 2:1 basis. Primary outcome is the rate of weaning from mechanical ventilation and/or decannulation (primary outcome) after one year, secondary outcomes include both clinical and economic measures. 173 participants are required to corroborate a difference of 30 vs. 10% weaning success rate statistically with 80% power at a 5% significance level allowing for 15% attrition. DISCUSSION: The OptiNIV-Study will implement a new specialised neurorehabilitation outreach service and will determine its weaning success rates, other clinical outcomes, and cost-effectiveness compared to usual care for people in need for mechanical ventilation and/or tracheal cannula and hence HSICN after discharge from NER. TRIAL REGISTRATION: The trial OptiNIV has been registered in the German Clinical Trials Register (DRKS) since 18.01.2022 with the ID DRKS00027326 .

Informal Caregivers of Patients with Disorders of Consciousness: a Qualitative Study of Communication Experiences and Information Needs with Physicians.

Due to improvements in medicine, the figures of patients with disorders of consciousness (DoC) are increasing. Diagnostics of DoC and prognostication of rehabilitation outcome is challenging but necessary to evaluate recovery potential and to decide on treatment options. Such decisions should be made by doctors and patients' surrogates based on medico-ethical principles. Meeting information needs and communicating effectively with caregivers as the patients´ most common surrogate-decision makers is crucial, and challenging when novel tech-nologies are introduced. This qualitative study aims to explore information needs of informal DoC caregivers, how they manage the obtained information and their perceptions and experiences with caregiver-physician communication in facilities that implemented innovative neurodiagnostics studies. In 2021, we conducted semi-structured interviews with nine caregivers of clinically stable DoC patients in two rehabilitation centers in Italy and Germany. Participants were selected based on consecutive purposeful sampling. Caregivers were recruited at the facilities after written informed consent. All interviews were recorded, transcribed verbatim and translated. For analysis, we used reflexive thematic analysis according to Braun & Clarke (2006). Caregivers experienced the conversations emotionally, generally based on the value of the information provided. They reported to seek positive information, comfort and empathy with-in the communication of results of examinations. They needed detailed information to gain a deep understanding and a clear picture of their loved-one's condition. The results suggest a mismatch between the perspectives of caregivers and the perspectives of medical profession-als, and stress the need for more elaborate approaches to the communication of results of neu-rodiagnostics studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12152-022-09503-0.

Reducing variability of perceptual decision making with offline theta-burst TMS of dorsal medial frontal cortex.

BACKGROUND: Recent evidence suggests that the dorsal medial frontal cortex (dMFC) may make an important contribution to perceptual decision-making, and not only to motor control. OBJECTIVE/HYPOTHESIS: By fitting psychometric functions to behavioural data after TMS we tested whether the dMFC is critical specifically for the precision and/or bias of perceptual judgements. Additionally we aimed to disentangle potential roles of the dMFC in dealing with perceptual versus response switching. METHODS: A subjective visual vertical task (SVV) was used in which participants weight visual (and other, e.g., vestibular) information to establish whether a line is oriented vertically. To ensure a high perceptual demand (putatively necessary to demonstrate a dMFC involvement) SVV lines were presented inside pop-out targets within a visual search array. Distinct features of perceptual performance were analysed before as compared to following theta-burst TMS stimulation of the dMFC, a control site, or no stimulation, in three groups, each of 20 healthy participants. RESULTS: dMFC stimulation improved the precision of verticality judgments. Moreover, dMFC stimulation improved accuracy, selectively when response switches occurred with perceptual repeats. CONCLUSION: These findings point to a causal role of the dMFC in establishing the precision of perceptual decision making, demonstrably dissociable from an additional role in motor control in attentionally demanding contexts.

Egocentric processing in the roll plane and dorsal parietal cortex: A TMS-ERP study of the subjective visual vertical.

The intraparietal sulcus within the dorsal right posterior parietal cortex is associated with spatial orientation and attention in relation to egocentric reference frames, such as left or right hemifield. It remains unclear whether it plays a causal role in the human in the roll plane (i.e. when visual stimuli are tilted clockwise or anticlockwise) which this is an important aspect of egocentric visual processing with clinical relevance in vestibular disorders. The subjective visual vertical (SVV) task measures the deviation between an individual's subjective vertical perception and the veridical vertical, involves the integration of visual, and vestibular information, and relies on a distributed network of multisensory regions that shows right lateralization and inter-areal inhibition. This study used combined TMS-EEG to investigate the role of the human dorsal parietal cortex in verticality perception using the SVV task in darkness. Participants were sorted according to their baseline bias at this task i.e. those with either a slight counterclockwise versus clockwise bias when judging a line to be truly vertical. Right parietal TMS facilitated verticality perception, reducing the difference between groups. ERPs suggested that the behavioral TMS effect occurred through normalizing individual SVV biases, evident frontally and late in the trial, and which was abolished after right parietal TMS. Effects were site and task specific, shown with a homologous left hemisphere control, and a landmark task performed on the same stimuli. These results support a right lateralization of visual-vestibular cognition and a distinct representation of the roll plane for egocentric processing in dorsal parietal cortex.

Single-session transcranial direct current stimulation induces enduring enhancement of visual processing speed in patients with major depression.

Attentional deficits are considered key cognitive symptoms in major depressive disorder (MDD) arising from abnormal activation patterns within dorsolateral prefrontal cortex (dlPFC) alertness networks. Altering these activity patterns with transcranial direct current stimulation (tDCS) might thus ameliorate alertness-dependent cognitive deficits in MDD patients. In a double-blind, randomized, sham-controlled study, we investigated the effect of a single session of anodal tDCS (2 mA) applied to the left dlPFC on different parameters of visual attention based on Bundesen's theory of visual attention (Psychol Rev 97(4):523-547, 1990) in a group of 20 patients with MDD and a control group of 20 healthy participants. The parametric attention assessment took place before, immediately after and 24 h after tDCS intervention. It revealed a selective impairment in visual processing speed as a primary functional deficit in MDD at baseline assessment. Furthermore, a significant stimulation condition × time point interaction showed that verum tDCS over the left dlPFC resulted in a processing speed enhancement 24 h post-stimulation in MDD patients. In healthy control participants, we did not find similar tDCS-induced effects. Our results suggest that even a single session of tDCS over the dlPFC can induce enduring neurocognitive benefits that indicate an amelioration of cortical under-arousal in MDD patients in a time frame beyond that of immediate, excitability increases that are directly induced by the current.

Influence of person- and situation-specific characteristics on collision avoidance behavior in human locomotion.

In everyday situations, pedestrians deploy successful strategies to avoid collisions with other persons crossing their paths. In this study, 2 experiments were conducted to investigate to what extent personal or situational characteristics affect role attribution and contribution to successful collision avoidance in human locomotion. Pairs of subjects walked at their natural speed from a start to a goal point. Walking paths were defined in such a way that subjects would collide halfway on their trajectory, if they did not actively avoid colliding by speed or path adjustments. In the first experiment, we investigated whether crossing order, path, and speed adjustments correlate with subject-specific parameters, such as gender, height, and personality traits. It is interesting that individuals' collision avoidance behavior was not correlated with any of these factors. In the second experiment, initial walking speed and heading were used to predict the crossing order. It was found that these 2 parameters are sufficient to estimate future role attribution with 95% confidence already 2.5 m before the crossing; that is, even before any collision avoidance behavior is initiated. In sum, this suggests that collision avoidance strategies in human locomotion are based on situational rather than on personal characteristics. These situational characteristics result in role attributions, which are highly predictable within and across pairs of pedestrians, whereby the role-dependent contribution of the pedestrian giving way is of greater relevance for successful collision avoidance. (PsycINFO Database Record

Vision of the active limb impairs bimanual motor tracking in young and older adults.

Despite the intensive investigation of bimanual coordination, it remains unclear how directing vision toward either limb influences performance, and whether this influence is affected by age. To examine these questions, we assessed the performance of young and older adults on a bimanual tracking task in which they matched motor-driven movements of their right hand (passive limb) with their left hand (active limb) according to in-phase and anti-phase patterns. Performance in six visual conditions involving central vision, and/or peripheral vision of the active and/or passive limb was compared to performance in a no vision condition. Results indicated that directing central vision to the active limb consistently impaired performance, with higher impairment in older than young adults. Conversely, directing central vision to the passive limb improved performance in young adults, but less consistently in older adults. In conditions involving central vision of one limb and peripheral vision of the other limb, similar effects were found to those for conditions involving central vision of one limb only. Peripheral vision alone resulted in similar or impaired performance compared to the no vision (NV) condition. These results indicate that the locus of visual attention is critical for bimanual motor control in young and older adults, with older adults being either more impaired or less able to benefit from a given visual condition.