Distinguishing intentional from nonintentional actions through eeg and kinematic markers.

How can an intentional movement be distinguished from the same movement done nonintentionally? How can this distinction be drawn without asking the subject, or in patients who are unable to communicate? Here we address these questions, by focusing on blinking. This is one of the most frequent spontaneous actions in our daily life, but it can also be done intentionally. Furthermore, blinking is often spared in patients with severe brain injuries, and for some, it is the only way to report complex meanings. Using kinematic and EEG-based measures, we found that intentional and spontaneous blinking are preceded by different brain activities, even when they are indistinguishable. Unlike spontaneous ones, intentional blinks are characterized by a slow negative EEG drift, resembling the classic readiness potential. We investigated the theoretical implication of this finding in stochastic decision models as well as the practical significance of using brain-based signals to improve the discrimination between intentional and nonintentional actions. As proof of principle, we considered three brain-injured patients with rare neurological syndromes characterized by motor and communicative impairments. Although further research is needed, our results indicate that brain-based signals can offer a feasible way to infer intentionality even in absence of overt communication.

PerBrain: a multimodal approach to personalized tracking of evolving state-of-consciousness in brain-injured patients: protocol of an international, multicentric, observational study.

BACKGROUND: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project "PerBrain" is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. METHODS: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients' clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients' informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. DISCUSSION: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients' neurological status and their caregivers' mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04798456 . Registered 15 March 2021 - Retrospectively registered.

TAAC - TMS Adaptable Auditory Control: A universal tool to mask TMS clicks.

BACKGROUND: Coupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones. NEW METHOD: Here we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab®-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains. RESULTS: We showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click. COMPARISON WITH EXISTING METHODS: Here, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines) and lower SPLs with respect to standard noises. CONCLUSIONS: At odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.

Sleep-like cortical OFF-periods disrupt causality and complexity in the brain of unresponsive wakefulness syndrome patients.

Unresponsive wakefulness syndrome (UWS) patients may retain intact portions of the thalamocortical system that are spontaneously active and reactive to sensory stimuli but fail to engage in complex causal interactions, resulting in loss of consciousness. Here, we show that loss of brain complexity after severe injuries is due to a pathological tendency of cortical circuits to fall into silence (OFF-period) upon receiving an input, a behavior typically observed during sleep. Spectral and phase domain analysis of EEG responses to transcranial magnetic stimulation reveals the occurrence of OFF-periods in the cortex of UWS patients (N = 16); these events never occur in healthy awake individuals (N = 20) but are similar to those detected in healthy sleeping subjects (N = 8). Crucially, OFF-periods impair local causal interactions, and prevent the build-up of global complexity in UWS. Our findings link potentially reversible local events to global brain dynamics that are relevant for pathological loss and recovery of consciousness.

Abnormal brain oscillations persist after recovery from bipolar depression.

When directly perturbed in healthy subjects, premotor cortical areas generate electrical oscillations in the beta range (20-40Hz). In schizophrenia, major depressive disorder and bipolar disorder (BD), these oscillations are markedly reduced, in terms of amplitude and frequency. However, it still remains unclear whether these abnormalities can be modulated over time, or if they can be still observed after treatment. Here, we employed transcranial magnetic stimulation (TMS) combined with EEG to assess the frontal oscillatory activity in eighteen BD patients before/after antidepressant treatments (sleep deprivation and light therapy), relative to nine healthy controls. In order to detect dominant frequencies, event related spectral perturbations (ERSP) were computed for each TMS/EEG session in all participants, using wavelet decomposition. The natural frequency at which the cortical circuit oscillates was calculated as the frequency value with the largest power across 300ms post-stimulus time interval. Severity of depression markedly decreased after treatment with 12 patients achieving response and nine patients achieving remission. TMS/EEG resulted in a significant activation of the beta/gamma band response (21-50Hz) in healthy controls. In patients, the main frequencies of premotor EEG responses to TMS did not significantly change before/after treatment and were always significantly lower than those of controls (11-27Hz) and comparable in patients achieving remission and in those not responding to treatment. These results suggest that the reduction of natural frequencies is a trait marker of BD, independent from the clinical status of the patients. The present findings shed light on the neurobiological underpinning of severe psychiatric disorders and demonstrate that TMS/EEG represents a unique tool to develop biomarkers in psychiatry.

Cortical reactivity and effective connectivity during REM sleep in humans.

We recorded the electroencephalographic (EEG) responses evoked by transcranial magnetic stimulation (TMS) during the first rapid eye movement (REM) sleep episode of the night and we compared them with the responses obtained during previous wakefulness and NREM sleep. Confirming previous findings, upon falling into NREM sleep, cortical activations became more local and stereotypical, indicating a significant impairment of the intracortical dialogue. During REM sleep, a state in which subjects regain consciousness but are almost paralyzed, TMS triggered more widespread and differentiated patterns of cortical activation, that were similar to the ones observed in wakefulness. Similarly, TMS/hd-EEG may be used to probe the internal dialogue of the thalamocortical system in brain injured patients that are unable to move and communicate.

Automated identification of ERP peaks through Dynamic Time Warping: an application to developmental dyslexia.

OBJECTIVE: This article proposes a method to automatically identify and label event-related potential (ERP) components with high accuracy and precision. METHODS: We present a framework, referred to as peak-picking Dynamic Time Warping (ppDTW), where a priori knowledge about the ERPs under investigation is used to define a reference signal. We developed a combination of peak-picking and Dynamic Time Warping (DTW) that makes the temporal intervals for peak-picking adaptive on the basis of the morphology of the data. We tested the procedure on experimental data recorded from a control group and from children diagnosed with developmental dyslexia. RESULTS: We compared our results with the traditional peak-picking. We demonstrated that our method achieves better performance than peak-picking, with an overall precision, recall and F-score of 93%, 86% and 89%, respectively, versus 93%, 80% and 85% achieved by peak-picking. CONCLUSION: We showed that our hybrid method outperforms peak-picking, when dealing with data involving several peaks of interest. SIGNIFICANCE: The proposed method can reliably identify and label ERP components in challenging event-related recordings, thus assisting the clinician in an objective assessment of amplitudes and latencies of peaks of clinical interest.

Spatiotemporal dynamics of single-letter reading: a combined ERP-FMRI study.

This work investigates the neural correlates of single-letter reading by combining event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), thus exploiting their complementary spatiotemporal resolutions. Three externally-paced reading tasks were administered with an event-related design: passive observation of letters and symbols and active reading aloud of letters. ERP and fMRI data were separately recorded from 8 healthy adults during the same experimental conditions. Due to the presence of artifacts in the EEG signals, two subjects were discarded from further analysis. Independent Component Analysis was applied to ERPs, after dimensionality reduction by Principal Component Analysis: some independent components were clearly related to specific reading functions and the associated current density distributions in the brain were estimated with Low Resolution Electromagnetic Tomography Analysis method (LORETA). The impulse hemodynamic response function was modeled as a linear combination of linear B-spline functions and fMRI statistical analysis was performed by multiple linear regression. fMRI and LORETA maps were superimposed in order to identify the overlapping activations and the activated regions specifically revealed by each modality. The results showed the existence of neuronal networks functionally specific for letter processing and for explicit verbal-motor articulation, including the temporo-parietal and frontal regions. Overlap between fMRI and LORETA results was observed in the inferior temporal-middle occipital gyrus, suggesting that this area has a crucial and multifunctional role for linguistic and reading processes, likely because its spatial location and strong interconnection with the main visual and auditory sensory systems may have favored its specialization in grapheme-phoneme matching.

[Improvement of nursing quality and outcome in intensive care patients with acute kidney failure]. / Die Verbesserung der Pflegequalität und der Ergebnisse bei intensivpflichtigen Patienten mit akutem Nierenversagen.

Collaboration between the Intensive Care Unit (ICU) and nephrology nurses is needed to ensure adequate care of critically ill patients with acute renal failure (ARF). To improve this collaboration a questionnaire was circulated to the 122 ICU nurses in the hospital to appraise their knowledge on ARF. A Refresher Course to update on ARF was then organised. Colleagues' interest in the initiative was elevated: 66% of questionnaires were completed which included 88% of nurses attending the course. The experience showed, through measurable results, that team work is essential to collaborative nursing plans. The initiative allowed improvement in the quality of nurses' communication and was accompanied with a significant reduction in short-term mortality rate of dialyzed ARF patients (45 versus 50%; p = 0.045, chi-square test). Despite the limitations of this short period of observation one year) the results are judged as useful. Collaboration ensures support for colleagues on a daily basis and during critical moments and can encourage appreciation of the nursing profession.

A pilot study of the reading processes combining reading-related potentials (RRPs) and fMRI.

Aim of this work is to describe temporally and spatially the activation of the cerebral areas involved in reading processes by combining fMRI and reading-related potentials (RRPs). RRPs and fMR images were recorded in separate studies during a specifically designed experimental procedure. The protocol consisted of three visual tasks of increasing complexity. In the first two tasks subjects were asked to passively watch at letters and symbols respectively without making any effort in reading or articulating silently them. In the third task subjects were asked to read aloud letters appearing on a screen at a rate of 0.5 Hz. 7 young healthy subjects participated in the experiment. The analysis of RRPs highlighted the following results. During non-alphabetic symbols presentation the amplitude of the potentials was lower in comparison to presentation of letters. Reading aloud generated RRPs of greater amplitude than implicit reading. The analysis of fMRI scans revealed that the visual presentation of both letters and symbols produced similar activation of primary visual areas. Besides these areas, reading aloud activated the motor and pre-motor cortices and the left anterior temporal lobe. The combined analysis of RRPs and fMRI characterizes both temporally and spatially the development of reading processes.