[Diagnosis of irreversible loss of brain function ("brain death")-what is new?] / Diagnostik des irreversiblen Hirnfunktionsausfalls ("Hirntod") ­ was ist neu?

The determination of the irreversible cessation of brain function (ICBF) is conducted in Germany according to the guideline of the German Medical Association, which is currently its fourth update issued in July 2015. This article provides an assessment of the current situation including an international comparison. International case reports with allegedly incorrect ICBF diagnosis are reviewed from the point of view of the German guideline. These case reports underpin the validity of the German guideline, especially its following provisions: (1) in patients with known or suspected adaptation to chronic hypercapnia, apnea cannot be diagnosed as usual; therefore in such a case the proof of cerebral circulatory arrest is mandatory; (2) if perfusion scintigraphy is used for proof of cerebral circulatory arrest, only validated lipophilic radiopharmaceuticals are allowed. This is compatible with new research data which indicate that cellular function can be reactivated for several hours after circulatory arrest but not the brain function. The recently updated recommendations of the German Society for Clinical Neurophysiology and Functional Imaging (DGKN) for ancillary testing include editorial adaptations (e.g., the more precise specification of the electrode positions for electroencephalography), standards of display screen with digital electroencephalography and age-related minimum values of mean arterial pressure for Doppler and duplex sonography in children. The novel requirements regarding the institutional organization of ICBF diagnostics in Germany issued in the "Second law on the amendment of transplantation law-improvement of the cooperation and the framework for organ donation" that became effective recently are presented and discussed critically in this review.

Setting things straight: A comparison of measures of saccade trajectory deviation.

In eye movements, saccade trajectory deviation has often been used as a physiological operationalization of visual attention, distraction, or the visual system's prioritization of different sources of information. However, there are many ways to measure saccade trajectories and to quantify their deviation. This may lead to noncomparable results and poses the problem of choosing a method that will maximize statistical power. Using data from existing studies and from our own experiments, we used principal components analysis to carry out a systematic quantification of the relationships among eight different measures of saccade trajectory deviation and their power to detect the effects of experimental manipulations, as measured by standardized effect size. We concluded that (1) the saccade deviation measure is a good default measure of saccade trajectory deviation, because it is somewhat correlated with all other measures and shows relatively high effect sizes for two well-known experimental effects; (2) more generally, measures made relative to the position of the saccade target are more powerful; and (3) measures of deviation based on the early part of the saccade are made more stable when they are based on data from an eyetracker with a high sampling rate. Our recommendations may be of use to future eye movement researchers seeking to optimize the designs of their studies.

Nonphysiological factors in navigated TMS studies; confounding covariates and valid intracortical estimates.

UNLABELLED: Brain stimulation is used to induce transient alterations of neural excitability to probe or modify brain function. For example, single-pulse transcranial magnetic stimulation (TMS) of the motor cortex can probe corticospinal excitability (CSE). Yet, CSE measurements are confounded by a high level of variability. This variability is due to physical and physiological factors. Navigated TMS (nTMS) systems can record physical parameters of the TMS coil (tilt, location, and orientation) and some also estimate intracortical electric fields (EFs) on a trial-by-trial basis. Thus, these parameters can be partitioned with stepwise regression. PURPOSE: The primary objective was to dissociate variance due to physical parameters from variance due to physiological factors for CSE estimates. The secondary objective was to establish the predictive validity of EF estimates from spherical head models. HYPOTHESIS: Variability of physical parameters of TMS predicts CSE variability. METHODS: Event-related measurements of physical parameters were analyzed in stepwise regression. Partitioned parameter variance and predictive validity were compared for a target-controlled and a nontarget-controlled experiment. A control experiment (preinnervation) confirmed the validity of linear data analysis. A bias-free model quantified the effect of divergence from optimum. RESULTS: Partitioning physical parameter variance reduces CSE variability. EF estimates from spherical models were valid. Post hoc analyses showed that even small physical fluctuations can confound the statistical comparison of CSE measurements. CONCLUSIONS: It is necessary to partition physical and physiological variance in TMS studies to make confounded data interpretable. The spatial resolution of nTMS is <5 mm and the EF-estimates are valid.

Brain death determination in patients with veno-arterial extracorporeal membrane oxygenation: A systematic study to address the Harlequin syndrome.

PURPOSE: The Harlequin syndrome may occur in patients treated with venoarterial extracorporal membrane oxygenation (VA-ECMO), in whom blood from the left ventricle and the ECMO system supply different parts of the body with different paCO2-levels. The purpose of this study was to compare two variants of paCO2-analysis to account for the Harlequin syndrome during apnea testing (AT) in brain death (BD) determination. MATERIALS AND METHODS: Twenty-seven patients (median age 48 years, 26-76 years; male n = 19) with VA-ECMO treatment were included who underwent BD determination. In variant 1, simultaneous arterial blood gas (ABG) samples were drawn from the right and the left radial artery. In variant 2, simultaneous ABG samples were drawn from the right radial artery and the postoxygenator ECMO circuit. Differences in paCO2-levels were analysed for both variants. RESULTS: At the start of AT, median paCO2-difference between right and left radial artery (variant 1) was 0.90 mmHg (95%-confidence intervall [CI]: 0.7-1.3 mmHg). Median paCO2-difference between right radial artery and postoxygenator ECMO circuit (variant 2) was 3.3 mmHg (95%-CI: 1.5-6.0 mmHg) and thereby significantly higher compared to variant 1 (p = 0.001). At the end of AT, paCO2-difference according to variant 1 remained unchanged with 1.1 mmHg (95%-CI: 0.9-1.8 mmHg). In contrast, paCO2-difference according to variant 2 increased to 9.9 mmHg (95%-CI: 3.5-19.2 mmHg; p = 0.002). CONCLUSIONS: Simultaneous paCO2-analysis from right and left distal arterial lines is the method of choice to reduce the risk of adverse effects (e.g. severe respiratory acidosis) while performing AT in VA-ECMO patients during BD determination.

The generation of secondary saccades without postsaccadic visual feedback.

Primary saccades are often followed by small secondary saccades, which are generally thought to reduce the distance between the saccade endpoint and target location. Accumulated evidence demonstrates that secondary saccades are subject to various influences, among which retinal feedback during postsaccadic fixation constitutes only one important signal. Recently, we reported that target eccentricity and an orientation bias influence the generation of secondary saccades. In the present study, we examine secondary saccades in the absence of postsaccadic visual feedback. Although extraretinal signals (e.g., efference copy) have received widespread attention in eye-movement studies, it is still unclear whether an extraretinal error signal contributes to the programming of secondary saccades. We have observed that secondary saccade latency and amplitude depend on primary saccade error despite the absence of postsaccadic visual feedback. Strong evidence for an extraretinal error signal influencing secondary saccade programming is given by the observation that secondary saccades are more likely to be oriented in a direction opposite to the primary saccade as primary saccade error shifts from target undershoot to overshoot. We further show how the functional relationship between primary saccade landing position and secondary saccade characteristics varies as a function of target eccentricity. We propose that initial target eccentricity and an extraretinal error signal codetermine the postsaccadic activity distribution in the saccadic motor map when no visual feedback is available.

Intimate Partner Violence and Mental Health Among Transgender and Gender Diverse Young Adults.

Purpose: Research indicates that multiple forms of intimate partner violence (IPV) may be prevalent among transgender and gender diverse (TGD) people, including general forms of IPV (psychological, physical, sexual), as well as identity-specific forms (transgender-related IPV (T-IPV), identity abuse (IA)). Studies also suggest that IPV is associated with negative mental health outcomes in TGD populations, including depression, anxiety, and posttraumatic stress disorder (PTSD). However, little is known about IPV and its association with mental health among TGD young adults. This is noteworthy, as this is a key developmental period for many TGD individuals. Methods: Thus, the present study sought (1) to estimate the lifetime and past-year prevalence of several forms of general and identity-specific IPV among a sample of (N = 200) TGD young adults in New York City and (2) to assess the associations between IPV with recent symptoms of depression, anxiety, and PTSD. To address the study aims, a cross-sectional quantitative survey was conducted between July 2019 and March 2020. Results: Regarding lifetime IPV, IA was most prevalent (57.0%), followed by sexual (40.0%), physical (38.5%), T-IPV (35.5%), and psychological IPV (32.5%). Regarding past-year IPV, psychological IPV was most common (29.0%), followed by IA (27.5%), physical (20.0%), T-IPV (14.0%), and sexual IPV (12.5%). Results of hierarchical regression models indicate that lifetime IA was related to depression, anxiety, and PTSD, while past-year T-IPV was only associated with depression. Conclusions: Taken together, these findings suggest that IPV is highly prevalent among TGD young adults and that IPV - especially identity-specific forms - warrants additional attention from researchers, healthcare professionals, and policymakers, as it may place this population at risk for negative mental health outcomes.

Non-invasive brain stimulation modulates neural correlates of performance monitoring in patients with obsessive-compulsive disorder.

Overactive performance monitoring, as reflected by enhanced neural responses to errors (the error-related negativity, ERN), is considered a biomarker for obsessive-compulsive disorder (OCD) and may be a promising target for novel treatment approaches. Prior research suggests that non-invasive brain stimulation with transcranial direct current stimulation (tDCS) may reduce the ERN in healthy individuals, yet no study has investigated its efficacy in attenuating the ERN in OCD. In this preregistered, randomized, sham-controlled, crossover study, we investigated effects of tDCS on performance monitoring in patients with OCD (n = 28) and healthy individuals (n = 28). Cathodal and sham tDCS was applied over the presupplementary motor area (pre-SMA) in two sessions, each followed by electroencephalogram recording during a flanker task. Cathodal tDCS reduced the ERN amplitude compared to sham tDCS, albeit this effect was only marginally significant (p = .052; mean difference: 0.86 µV). Additionally, cathodal tDCS reduced the correct-response negativity and increased the error positivity. These neural modulations were not accompanied by behavioral changes. Moreover, we found no evidence that the tDCS effect was more pronounced in the patient group. In summary, our findings indicate that tDCS over the pre-SMA modulates neural correlates of performance monitoring across groups. Therefore, this study represents a valuable starting point for future research to determine whether repeated tDCS application induces a more pronounced ERN attenuation and normalizes aberrant performance monitoring in the long term, thereby potentially alleviating obsessive-compulsive symptoms and providing a psychophysiological intervention strategy for individuals who do not benefit sufficiently from existing interventions.

A Qualitative Study of Intimate Partner Violence Among Young Gay and Bisexual Men.

Intimate partner violence (IPV) is prevalent among young gay and bisexual men (YGBM) and is associated with physical and mental health problems, as well as deleterious psychosocial conditions. Most previous studies of IPV among YGBM have been quantitative in nature and have not examined the numerous subtypes of IPV, the chronicity of IPV experiences, and how is IPV manifested in the context of these same-sex relationships. Thus, a qualitative approach may be useful in exploring these multidimensional and understudied experiences. The present qualitative study sought to (a) explore dimensions of IPV victimization, perpetration, and bidirectional IPV among a sample of (n = 26) YGBM living in New York City and (b) explore the chronicity of IPV experiences among these YGBM. Participants were recruited from an ongoing cohort study of YGBM. Participants completed semistructured interviews that included questions about IPV victimization, perpetration, and bidirectional IPV. A modified version of the consensual qualitative research method was used to analyze the data. The YGBM in this study reported numerous forms of physical, psychological, sexual, and financial IPV victimization and perpetration. Bidirectional experiences of IPV were common. The various subtypes of IPV victimization and perpetration are explored in detail in this manuscript. In addition, many participants reported multiple experiences of abuse within the same relationship, and some participants experienced a pattern of abusive relationships over time. This study corroborates findings from quantitative studies, which indicate that IPV is a prevalent and significant health problem among YGBM, and one that warrants additional attention from researchers, practitioners, and policy-makers. Furthermore, this study adds rich qualitative data to the existing literature-data that can be used to help develop and refine future measures of IPV that are tailored for use with YGBM.

Hemifield effects of spatial attention in early human visual cortex.

Early visual areas (V1, V2, V3/VP, V4v) contain representations of the contralateral hemifield within each hemisphere. Little is known about the role of the visual hemifields along the visuo-spatial attention processing hierarchy. It is hypothesized that attentional information processing is more efficient across the hemifields (known as bilateral field advantage) and that the integration of information is greater within one hemifield as compared with across the hemifields. Using functional magnetic resonance imaging we examined the effect of distance and hemifield on parallel attentional processing in the early visual areas (V1-V4v) at individually mapped retinotopic locations aligned adjacently or separately within or across the hemifields. We found that the bilateral field advantage in parallel attentional processing over separated attended locations can be assigned, at least partly, to differences in distractor position integration in early visual areas. These results provide evidence for a greater integration of locations between two attended locations within one hemifield than across both hemifields. This nicely correlates with behavioral findings of a bilateral field advantage in parallel attentional processing (when distractors in between cannot be excluded) and a unilateral field advantage if attention has to be shifted across separated locations (when locations in between were integrated).

Dynamic upper and lower visual field preferences within the human dorsal frontoparietal attention network.

Both in nonhuman primates and in humans, behavioral differences between the upper and lower visual field have been identified in distinct subprocesses of attention. Advantages of the lower field have been explained by its higher spatial resolution; those of the upper field by its higher efficiency in attentional shifting. The physiological basis of visual field asymmetries within in the frontoparietal attention network (FPN) remains unclear. This study investigates the physiological correlates of upper and lower field preferences within the FPN using event-related functional magnetic resonance imaging. The paradigm separated two attentional subprocesses during a visual search task. Whether in the upper or lower field, the attention of subjects was first directed at stationary locations (spatial orienting) and then shifted between locations to search for a target (visual search) in easy or difficult search displays. Depending on the task phase (spatial orienting vs. easy visual search), upper and lower visual field preferences in the FPN changed. The analysis revealed a lower field preference during stationary spatial orienting and an upper field preference during visual search. We conclude that also higher areas represent upper and lower visual field asymmetries depending on distinct subcomponents of visuospatial attentional processing.

Human Premotor Corticospinal Projections Are Engaged in Motor Preparation at Discrete Time Intervals: A TMS-Induced Virtual Lesion Study.

Objectives: The significance of pre-motor (PMC) corticospinal projections in a frontoparietal motor network remains elusive. Temporal activation patterns can provide valuable information about a region's engagement in a hierarchical network. Navigated transcranial magnetic stimulation (nTMS)-induced virtual lesions provide an excellent method to study cortical physiology by disrupting ongoing activity at high temporal resolution and anatomical precision. We use nTMS-induced virtual lesions applied during an established behavioral task demanding pre-motor activation to clarify the temporal activation pattern of pre-motor corticospinal projections. Materials and Methods: Ten healthy volunteers participated in the experiment (4 female, mean age 24 ± 2 years, 1 left-handed). NTMS was used to map Brodmann areae 4 and 6 for primary motor (M1) and PMC corticospinal projections. We then determined the stimulator output intensity required to elicit a 1 mV motor evoked potential (1 mV-MT) through M1 nTMS. TMS pulse were randomly delivered at distinct time intervals (40, 60, 80, 100, 120, and 140 ms) at 1 mV-MT intensity to M1, PMC and the DLPFC (dorsolateral pre-frontal cortex; control condition) before participants had to perform major changes of their trajectory of movement during a tracing task. Each participant performed six trials (20 runs per trial). Task performance and contribution of regions under investigation was quantified through calculating the tracing error induced by the stimulation. Results: A pre-motor stimulation hotspot could be identified in all participants (16.3 ± 1.7 mm medial, 18.6 ± 1.4 mm anterior to the M1 hotspot). NTMS over studied regions significantly affected task performance at discrete time intervals (F(10, 80) = 3.25, p = 0.001). NTMS applied over PMC 120 and 140 ms before changes in movement trajectory impaired task performance significantly more than when applied over M1 (p = 0.021 and p = 0.003) or DLPFC (p = 0.017 and p < 0.001). Stimulation intensity did not account for error size (ß = -0.0074, p = 1). Conclusions: We provide novel evidence that the role of pre-motor corticospinal projections extends beyond that of simple corticospinal motor output. Their activation is crucial for task performance early in the stage of motor preparation suggesting a significant role in shaping voluntary movement. Temporal patterns of human pre-motor activation are similar to that observed in intracortical electrophysiological studies in primates.

Midlevel visual deficits after strokes involving area human V4.

We present the results of 51 stroke patients with free central visual fields of which about half suffer from clear deficits of midlevel vision undetected by standard clinical tests. These patients yield significantly elevated thresholds for detection and/or discrimination between forms defined by motion, colour, or line orientation ('texture'). As demonstrated by voxel-based lesion-symptom mapping (VLSM) the underlying lesions involve mainly area human V4 (hV4) located in the posterior third of the fusiform gyrus and extending into the lingual gyrus. Patient's detection thresholds correlate only very weakly between the submodalities tested, indicating partly separate neural networks on mid-level vision for colour, motion, and texture detection. Correlations are far stronger for form discrimination tasks, indicating partly shared mechanisms for even simple form discrimination of distinct visual submodalities. We conclude that deficits of visual perception are far more common after strokes in visual brain areas than is apparent in clinical practice. Our results further clarify the functional organization of midlevel visual cortical areas.

Transcranial direct current stimulation affects visual perception measured by threshold perimetry.

In this study, we aimed to characterize the effect of anodal and cathodal direct current stimulation (tDCS) on contrast sensitivity inside the central 10 degrees of the visual field in healthy subjects. Distinct eccentricities were investigated separately, since at the cortical level, more central regions of the visual field are represented closer to the occipital pole, i.e. closer to the polarizing electrodes, than are the more peripheral regions. Using a double-blind and sham-controlled within-subject design, we measured the effect of stimulation and potential learning effect separately across testing days. Anodal stimulation of the visual cortex compared to sham stimulation yielded a significant increase in contrast sensitivity within 8° of the visual field. A significant increase in contrast sensitivity between the conditions "pre" and "post" anodal stimulation was only obtained for the central positions at eccentricities smaller than 2°. Cathodal stimulation of the visual cortex did not affect contrast sensitivity at either eccentricity. Perceptual learning across testing days was only observed for threshold perimetry before stimulation. Measuring contrast sensitivity changes after tDCS with a standard clinical tool such as threshold perimetry may provide an interesting perspective in assessing therapeutic effects of tDCS in ophthalmological or neurological defects (e.g. with foveal sparing vs. foveal splitting).

Individualized Template MRI Is a Valid and Reliable Alternative to Individual MRI for Spatial Tracking in Navigated TMS Studies in Healthy Subjects.

Objectives: Navigated transcranial magnetic stimulation (nTMS) provides significant benefits over classic TMS. Yet, the acquisition of individual structural magnetic resonance images (MRIindividual) is a time-consuming, expensive, and not feasible prerequisite in all subjects for spatial tracking and anatomical guidance in nTMS studies. We hypothesize that spatial transformation can be used to adjust MRI templates to individual head shapes (MRIwarped) and that TMS parameters do not differ between nTMS using MRIindividual or MRIwarped. Materials and Methods: Twenty identical TMS sessions, each including four different navigation conditions, were conducted in 10 healthy subjects (one female, 27.4 ± 3.8 years), i.e., twice per subject by two researchers to additionally assess interrater reliabilities. MRIindividual were acquired for all subjects. MRIwarped were obtained through the spatial transformation of a template MRI following a 5-, 9-and 36-point head surface registration (MRIwarped_5, MRIwarped_9, MRIwarped_36). Stimulation hotspot locations, resting motor threshold (RMT), 500 µV motor threshold (500 µV-MT), and mean absolute motor evoked potential difference (MAD) of primary motor cortex (M1) examinations were compared between nTMS using either MRIwarped variants or MRIindividual and non-navigated TMS. Results: M1 hotspots were spatially consistent between MRIindividual and MRIwarped_36 (insignificant deviation by 4.79 ± 2.62 mm). MEP thresholds and variance were also equivalent between MRIindividual and MRIwarped_36 with mean differences of RMT by -0.05 ± 2.28% maximum stimulator output (%MSO; t (19) = -0.09, p = 0.923), 500 µV-MT by -0.15 ± 1.63%MSO (t (19) = -0.41, p = 0.686) and MAD by 70.5 ± 214.38 µV (t (19) = 1.47, p = 0.158). Intraclass correlations (ICC) of motor thresholds were between 0.88 and 0.97. Conclusions: NTMS examinations of M1 yield equivalent topographical and functional results using MRIindividual and MRIwarped if a sufficient number of registration points are used.

Neural mechanisms of concurrent stimulus processing in dual tasks.

Little is known about how the human brain processes multiple relevant information streams competing for behavior. The present study aimed at specifying the interaction of the lateral prefrontal cortex (lPFC) with task-relevant sensory brain regions during concurrent stimulus processing of two relevant stimuli (S1, S2) in a classical dual-task situation. In detail, we tested whether S1 processing is independent of the task relevance of S2 as has been hypothesised in cognitive theories on dual-task processing. Using functional Magnetic Resonance Imaging, we tested two neural mechanisms that might reflect effects of S2 relevance on S1 processing at different temporal overlaps. The results indicate that: (1) activity amplitudes in S1-relevant regions in the inferior temporal cortex were similarly affected by the temporal overlap between the two stimuli when S2 was relevant or irrelevant and (2) only when S2 was relevant in the dual task, significant increases in the functional coupling between S1-relevant regions and dual-task-related regions in the posterior lPFC were present at high temporal overlap. No similar effects were found for S2-relevant regions. These findings suggest that concurrent stimulus processing in dual tasks is realised by transient changes in functional coupling for stimuli with relatively higher priority (S1).

Electrophysiological evidence for cognitive control during conflict processing in visual spatial attention.

Event-related potentials were measured to investigate the role of visual spatial attention mechanisms in conflict processing. We suggested that a more difficult target selection leads to stronger attentional top-down control, thereby reducing the effects of arising conflicts. This hypothesis was tested by varying the selection difficulty in a location negative priming (NP) paradigm. The difficult task resulted in prolonged responses as compared to the easy task. A behavioral NP effect was only evident in the easy task. Psychophysiologically the easy task was associated with reduced parietal N1, enhanced frontocentral N2 and N2pc components and a prolonged P3 latency for the conflict as compared to the control condition. The N2pc effect was also obvious in the difficult task. Additionally frontocentral N2 amplitudes increased and latencies of N2pc and P3 were delayed compared to the easy task. The differences at frontocentral and parietal electrodes are consistent with previous studies ascribing activity in the prefrontal and parietal cortex as the source of top-down attentional control. Thus, we propose that stronger cognitive control is involved in the difficult task, resulting in a reduced behavioral NP conflict.

Delirium is associated with frequency band specific dysconnectivity in intrinsic connectivity networks: preliminary evidence from a large retrospective pilot case-control study.

BACKGROUND: Pathophysiological concepts in delirium are not sufficient to define objective biomarkers suited to improve clinical approaches. Advances in neuroimaging have revalued electroencephalography (EEG) as a tool to assess oscillatory network activity in neuropsychiatric disease. Yet, research in the field is limited to small populations and largely confined to postoperative delirium, which impedes generalizability of findings and planning of prospective studies in other populations. This study aimed to assess effect sizes of connectivity measures in a large mixed population to demonstrate that there are measurable EEG differences between delirium and control patients. METHODS: This retrospective pilot study investigated EEG measures as biomarkers in delirium using a case-control design including patients diagnosed with delirium (DSM-5 criteria) and age-/gender-matched controls drawn from a database of 9980 patients (n = 129 and 414, respectively). Assessors were not blinded for groups. Power spectra and connectivity estimates, using the weighted phase log index, of continuous EEG data were compared between conditions. Alterations of information flow through nodes of intrinsic connectivity networks (ICN; default mode, salience, and executive control network) were evaluated in source space using betweenness centrality. This was done frequency specific and network nodes were defined by the multimodal human cerebral cortex parcellation based on human connectome project data. RESULTS: Delirium and control patients exhibited distinct EEG power, connectivity, and network characteristics (F (72,540) = 70.3, p < .001; F (493,1079) = 2.69, p < .001; and F (718,2159) = 1.14, p = .007, respectively). Connectivity analyses revealed global alpha and regional beta band disconnectivity that was accompanied by theta band hyperconnectivity in delirious patients. Source and network analyses yielded that these changes are not specific to single intrinsic connectivity networks but affect multiple nodes of networks engaged in level of consciousness, attention, working memory, executive control, and salience detection. Effect sizes were medium to strong in this mixed population of delirious patients. CONCLUSIONS: We quantified effect sizes for EEG connectivity and network analyses to be expected in delirium. This study implicates that theta band hyperconnectivity and alpha band disconnectivity may be essential mechanisms in the pathophysiology of delirium. Upcoming prospective studies will build upon these results and evaluate the clinical utility of identified EEG measures as therapeutic and prognostic biomarkers.

Safety Aspects, Tolerability and Modeling of Retinofugal Alternating Current Stimulation.

BACKGROUND: While alternating current stimulation (ACS) is gaining relevance as a tool in research and approaching clinical applications, its mechanisms of action remain unclear. A review by Schutter and colleagues argues for a retinal origin of transcranial ACS' neuromodulatory effects. Interestingly, there is an alternative application form of ACS specifically targeting α-oscillations in the visual cortex via periorbital electrodes (retinofugal alternating current stimulation, rACS). To further compare these two methods and investigate retinal effects of ACS, we first aim to establish the safety and tolerability of rACS. OBJECTIVE: The goal of our research was to evaluate the safety of rACS via finite-element modeling, theoretical safety limits and subjective report. METHODS: 20 healthy subjects were stimulated with rACS as well as photic stimulation and reported adverse events following stimulation. We analyzed stimulation parameters at electrode level as well as distributed metric estimates from an ultra-high spatial resolution magnetic resonance imaging (MRI)-derived finite element human head model and compared them to existing safety limits. RESULTS: Topographical modeling revealed the highest current densities in the anterior visual pathway, particularly retina and optic nerve. Stimulation parameters and finite element modeling estimates of rACS were found to be well below existing safety limits. No serious adverse events occurred. CONCLUSION: Our findings are in line with existing safety guidelines for retinal and neural damage and establish the tolerability and feasibility of rACS. In comparison to tACS, retinofugal stimulation of the visual cortex provides an anatomically circumscribed model to systematically study the mechanisms of action of ACS.

Diagnostic Performance and Utility of Quantitative EEG Analyses in Delirium: Confirmatory Results From a Large Retrospective Case-Control Study.

Background. The lack of objective disease markers is a major cause of misdiagnosis and nonstandardized approaches in delirium. Recent studies conducted in well-selected patients and confined study environments suggest that quantitative electroencephalography (qEEG) can provide such markers. We hypothesize that qEEG helps remedy diagnostic uncertainty not only in well-defined study cohorts but also in a heterogeneous hospital population. Methods. In this retrospective case-control study, EEG power spectra of delirious patients and age-/gender-matched controls (n = 31 and n = 345, respectively) were fitted in a linear model to test their performance as binary classifiers. We subsequently evaluated the diagnostic performance of the best classifiers in control samples with normal EEGs (n = 534) and real-world samples including pathologic findings (n = 4294). Test reliability was estimated through split-half analyses. Results. We found that the combination of spectral power at F3-P4 at 2 Hz (area under the curve [AUC] = .994) and C3-O1 at 19 Hz (AUC = .993) provided a sensitivity of 100% and a specificity of 99% to identify delirious patients among normal controls. These classifiers also yielded a false positive rate as low as 5% and increased the pretest probability of being delirious by 57% in an unselected real-world sample. Split-half reliabilities were .98 and .99, respectively. Conclusion. This retrospective study yielded preliminary evidence that qEEG provides excellent diagnostic performance to identify delirious patients even outside confined study environments. It furthermore revealed reduced beta power as a novel specific finding in delirium and that a normal EEG excludes delirium. Prospective studies including parameters of pretest probability and delirium severity are required to elaborate on these promising findings.

Force Increase in a Repetitive Motor Task Inducing Motor Fatigue.

To evaluate task induced motor fatigue in a well-established finger tapping task, we analyzed tapping parameters and included the time course of measures of force. We hypothesized that a decline in tapping force would reflect task induced motor fatigue, defined by a lengthening of inter-tap intervals (ITI). A secondary aim was to investigate the reliability of tapping data acquisition with the force sensor. Results show that, as expected, tapping speed decreased linearly over time, due to both an increase of ITI and tap duration. In contrast, tapping force increased non-linearly over time and was uncorrelated to changes in tapping speed. Force data could serve as a measure to characterize task induced motor fatigue. Force sensors can assess a decline in tapping speed as well as an independent increase of tapping force. We argue that the increase of force reflects central compensation, i.e. perception of fatigue, due to an increase in task effort and difficulty.