Changes in Cortical Microstructure of the Human Brain Resulting from Long-Term Motor Learning.

The mechanisms subserving motor skill acquisition and learning in the intact human brain are not fully understood. Previous studies in animals have demonstrated a causal relationship between motor learning and structural rearrangements of synaptic connections, raising the question of whether neurite-specific changes are also observable in humans. Here, we use advanced diffusion magnetic resonance imaging (MRI), sensitive to dendritic and axonal processes, to investigate neuroplasticity in response to long-term motor learning. We recruited healthy male and female human participants (age range 19-29) who learned a challenging dynamic balancing task (DBT) over four consecutive weeks. Diffusion MRI signals were fitted using Neurite Orientation Dispersion and Density Imaging (NODDI), a theory-driven biophysical model of diffusion, yielding measures of tissue volume, neurite density and the organizational complexity of neurites. While NODDI indices were unchanged and reliable during the control period, neurite orientation dispersion increased significantly during the learning period mainly in primary sensorimotor, prefrontal, premotor, supplementary, and cingulate motor areas. Importantly, reorganization of cortical microstructure during the learning phase predicted concurrent behavioral changes, whereas there was no relationship between microstructural changes during the control phase and learning. Changes in neurite complexity were independent of alterations in tissue density, cortical thickness, and intracortical myelin. Our results are in line with the notion that structural modulation of neurites is a key mechanism supporting complex motor learning in humans.SIGNIFICANCE STATEMENT The structural correlates of motor learning in the human brain are not fully understood. Results from animal studies suggest that synaptic remodeling (e.g., reorganization of dendritic spines) in sensorimotor-related brain areas is a crucial mechanism for the formation of motor memory. Using state-of-the-art diffusion magnetic resonance imaging (MRI), we found a behaviorally relevant increase in the organizational complexity of neocortical microstructure, mainly in primary sensorimotor, prefrontal, premotor, supplementary, and cingulate motor regions, following training of a challenging dynamic balancing task (DBT). Follow-up analyses suggested structural modulation of synapses as a plausible mechanism driving this increase, while colocalized changes in cortical thickness, tissue density, and intracortical myelin could not be detected. These results advance our knowledge about the neurobiological basis of motor learning in humans.

Implications of quantitative susceptibility mapping at 7 Tesla MRI for microbleeds detection in cerebral small vessel disease.

Background: Cerebral microbleeds (MBs) are a hallmark of cerebral small vessel disease (CSVD) and can be found on T2*-weighted sequences on MRI. Quantitative susceptibility mapping (QSM) is a postprocessing method that also enables MBs identification and furthermore allows to differentiate them from calcifications. Aims: We explored the implications of using QSM at submillimeter resolution for MBs detection in CSVD. Methods: Both 3 and 7 Tesla (T) MRI were performed in elderly participants without MBs and patients with CSVD. MBs were quantified on T2*-weighted imaging and QSM. Differences in the number of MBs were assessed, and subjects were classified in CSVD subgroups or controls both on 3T T2*-weighted imaging and 7T QSM. Results: 48 participants [mean age (SD) 70.9 (8.8) years, 48% females] were included: 31 were healthy controls, 6 probable cerebral amyloid angiopathy (CAA), 9 mixed CSVD, and 2 were hypertensive arteriopathy [HA] patients. After accounting for the higher number of MBs detected at 7T QSM (Median = Mdn; Mdn7T-QSM = 2.5; Mdn3T-T2 = 0; z = 4.90; p < 0.001) and false positive MBs (6.1% calcifications), most healthy controls (80.6%) demonstrated at least one MB and more MBs were discovered in the CSVD group. Conclusions: Our observations suggest that QSM at submillimeter resolution improves the detection of MBs in the elderly human brain. A higher prevalence of MBs than so far known in healthy elderly was revealed.

Distinct interacting cortical networks for stimulus-response and repetition-suppression.

Non-invasive studies consider the initial neural stimulus response (SR) and repetition suppression (RS) - the decreased response to repeated sensory stimuli - as engaging the same neurons. That is, RS is a suppression of the SR. We challenge this conjecture using electrocorticographic (ECoG) recordings with high spatial resolution in ten patients listening to task-irrelevant trains of auditory stimuli. SR and RS were indexed by high-frequency activity (HFA) across temporal, parietal, and frontal cortices. HFASR and HFARS were temporally and spatially distinct, with HFARS emerging later than HFASR and showing only a limited spatial intersection with HFASR: most HFASR sites did not demonstrate HFARS, and HFARS was found where no HFASR could be recorded. ß activity was enhanced in HFARS compared to HFASR cortical sites. θ activity was enhanced in HFASR compared to HFARS sites. Furthermore, HFASR sites propagated information to HFARS sites via transient θ:ß phase-phase coupling. In contrast to predictive coding (PC) accounts our results indicate that HFASR and HFARS are functionally linked but have minimal spatial overlap. HFASR might enable stable and rapid perception of environmental stimuli across extended temporal intervals. In contrast HFARS might support efficient generation of an internal model based on stimulus history.

Test-retest reliability of multi-parametric maps (MPM) of brain microstructure.

Multiparameter mapping (MPM) is a quantitative MRI protocol that is promising for studying microstructural brain changes in vivo with high specificity. Reliability values are an important prior knowledge for efficient study design and facilitating replicable findings in development, aging and neuroplasticity research. To explore longitudinal reliability of MPM we acquired the protocol in 31 healthy young subjects twice over a rescan interval of 4 weeks. We assessed the within-subject coefficient of variation (WCV), the between-subject coefficient of variation (BCV), and the intraclass correlation coefficient (ICC). Using these metrics, we investigated the reliability of (semi-) quantitative magnetization transfer saturation (MTsat), proton density (PD), transversal relaxation (R2*) and longitudinal relaxation (R1). To increase relevance for explorative studies in development and training-induced plasticity, we assess reliability both on local voxel- as well as ROI-level. Finally, we disentangle contributions and interplay of within- and between-subject variability to ICC and assess the optimal degree of spatial smoothing applied to the data. We reveal evidence that voxelwise ICC reliability of MPMs is moderate to good with median values in cortex (subcortical GM): MT: 0.789 (0.447) PD: 0.553 (0.264) R1: 0.555 (0.369) R2*: 0.624 (0.477). The Gaussian smoothing kernel of 2 to 4 mm FWHM resulted in optimal reproducibility. We discuss these findings in the context of longitudinal intervention studies and the application to research designs in neuroimaging field.

Editor's Choice - Relevance of Infarct Size, Timing of Surgery, and Peri-operative Management for Non-ischaemic Cerebral Complications After Carotid Endarterectomy.

OBJECTIVE: To assess the incidence of post-operative non-ischaemic cerebral complications as a pivotal outcome parameter with respect to size of cerebral infarction, timing of surgery, and peri-operative management in patients with symptomatic carotid stenosis who underwent carotid endarterectomy (CEA). METHODS: Retrospective analysis of prospectively collected single centre CEA registry data. Consecutive patients with symptomatic carotid stenosis were subjected to standard patch endarterectomy. Brain infarct size was measured from the axial slice of pre-operative computed tomography/magnetic resonance imaging demonstrating the largest infarct dimension and was categorised as large (> 4 cm2), small (≤ 4 cm2), or absent. CEA was performed early (within 14 days) or delayed (15 - 180 days) after the ischaemic event. Peri-operative antiplatelet regimen (none, single, dual) and mean arterial blood pressure during surgery and at post-operative stroke unit monitoring were registered. Non-ischaemic post-operative cerebral complications were recorded comprising haemorrhagic stroke and encephalopathy, i.e., prolonged unconsciousness, delirium, epileptic seizure, or headache. RESULTS: 646 symptomatic patients were enrolled of whom 340 (52.6%) underwent early CEA; 367 patients (56.8%) demonstrated brain infarction corresponding to stenosis induced symptoms which was small in 266 (41.2%) and large in 101 (15.6%). Post-operative non-ischaemic cerebral complications occurred in 12 patients (1.9%; 10 encephalopathies, two haemorrhagic strokes) and were independently associated with large infarcts (adjusted odds ratio [OR] 6.839; 95% confidence interval [CI] 1.699 - 27.534) and median intra-operative mean arterial blood pressure in the upper quartile, i.e., above 120 mmHg (adjusted OR 13.318; 95% CI 2.749 - 64.519). Timing of CEA after the ischaemic event, pre-operative antiplatelet regimen, and post-operative blood pressure were not associated with non-ischaemic cerebral complications. CONCLUSION: Infarct size and unintended high peri-operative blood pressure may increase the risk of non-ischaemic complications at CEA independently of whether performed early or delayed.

Multiscale criticality measures as general-purpose gauges of proper brain function.

The brain is universally regarded as a system for processing information. If so, any behavioral or cognitive dysfunction should lend itself to depiction in terms of information processing deficiencies. Information is characterized by recursive, hierarchical complexity. The brain accommodates this complexity by a hierarchy of large/slow and small/fast spatiotemporal loops of activity. Thus, successful information processing hinges upon tightly regulating the spatiotemporal makeup of activity, to optimally match the underlying multiscale delay structure of such hierarchical networks. Reduced capacity for information processing will then be expressed as deviance from this requisite multiscale character of spatiotemporal activity. This deviance is captured by a general family of multiscale criticality measures (MsCr). MsCr measures reflect the behavior of conventional criticality measures (such as the branching parameter) across temporal scale. We applied MsCr to MEG and EEG data in several telling degraded information processing scenarios. Consistently with our previous modeling work, MsCr measures systematically varied with information processing capacity: MsCr fingerprints showed deviance in the four states of compromised information processing examined in this study, disorders of consciousness, mild cognitive impairment, schizophrenia and even during pre-ictal activity. MsCr measures might thus be able to serve as general gauges of information processing capacity and, therefore, as normative measures of brain health.

Mind-wandering Is Accompanied by Both Local Sleep and Enhanced Processes of Spatial Attention Allocation.

Mind-wandering (MW) is a subjective, cognitive phenomenon, in which thoughts move away from the task toward an internal train of thoughts, possibly during phases of neuronal sleep-like activity (local sleep, LS). MW decreases cortical processing of external stimuli and is assumed to decouple attention from the external world. Here, we directly tested how indicators of LS, cortical processing, and attentional selection change in a pop-out visual search task during phases of MW. Participants' brain activity was recorded using magnetoencephalography, MW was assessed via self-report using randomly interspersed probes. As expected, the performance decreased under MW. Consistent with the occurrence of LS, MW was accompanied by a decrease in high-frequency activity (HFA, 80-150 Hz) and an increase in slow wave activity (SWA, 1-6 Hz). In contrast, visual attentional selection as indexed by the N2pc component was enhanced during MW with the N2pc amplitude being directly linked to participants' performance. This observation clearly contradicts accounts of attentional decoupling that would predict a decrease in attention-related responses to external stimuli during MW. Together, our results suggest that MW occurs during phases of LS with processes of attentional target selection being upregulated, potentially to compensate for the mental distraction during MW.

Detection of Cerebral Microbleeds With Venous Connection at 7-Tesla MRI.

OBJECTIVE: Cerebral microbleeds (MBs) are a common finding in patients with cerebral small vessel disease (CSVD) and Alzheimer disease as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein. METHODS: 7-Tesla (7T) MRI was conducted and MBs were counted on quantitative susceptibility mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein. RESULTS: A total of 51 people (mean age [SD] 70.5 [8.6] years, 37% female) participated in the study: 20 had CSVD (cerebral amyloid angiopathy [CAA] with strictly lobar MBs [n = 8], hypertensive arteriopathy [HA] with strictly deep MBs [n = 5], or mixed lobar and deep MBs [n = 7], 72.4 [6.1] years, 30% female) and 31 were healthy controls (69.4 [9.9] years, 42% female). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. Patients with CAA showed the highest ratio of venous to total MBs (19%) (HA = 9%, mixed = 18%, controls = 5%). CONCLUSION: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathologic studies are needed to confirm our observations.

The role of the anterior nuclei of the thalamus in human memory processing.

Extensive neuroanatomical connectivity between the anterior thalamic nuclei (ATN) and hippocampus and neocortex renders them well-placed for a role in memory processing, and animal, lesion, and neuroimaging studies support such a notion. The deep location and small size of the ATN have precluded their real-time electrophysiological investigation during human memory processing. However, ATN electrophysiological recordings from patients receiving electrodes implanted for deep brain stimulation for pharmacoresistant focal epilepsy have enabled high temporal resolution study of ATN activity. Theta frequency synchronization of ATN and neocortical oscillations during successful memory encoding, enhanced phase alignment, and coupling between ATN local gamma frequency activity and frontal neocortical and ATN theta oscillations provide evidence of an active role for the ATN in memory encoding, potentially integrating information from widespread neocortical sources. Greater coupling of a broader gamma frequency range with theta oscillations at rest than during memory encoding provides additional support for the hypothesis that the ATN play a role in selecting local, task-relevant high frequency activity associated with particular features of a memory trace.

Deep Brain Stimulation for Refractory Focal Epilepsy: Unraveling the Insertional Effect up to Five Months Without Stimulation.

INTRODUCTION: Following electrode implantation, a subgroup of patients treated with deep brain stimulation (DBS) for focal epilepsy exhibits a reduction of seizure frequency before stimulation is initiated. Microlesioning of the target structure has been postulated to be the cause of this "insertional" effect (IE). We examined the occurrence and duration of this IE in a group of patients with focal epilepsy following electrode implantation in the anterior nuclei of the thalamus (ANT) and/or nucleus accumbens (NAC) for DBS treatment. MATERIALS AND METHODS: Changes in monthly seizure frequency compared to preoperative baseline were assessed one month (14 patients) and five months (four patients) after electrode implantation. A group analysis between patients with implantation of bilateral ANT-electrodes (four patients), NAC-electrodes (one patient) as well as ANT and NAC-electrodes (nine patients) was performed. RESULTS: In this cohort, seizure frequency decreased one month after electrode implantation by 57.1 ± 30.1%, p ≤ 0.001 (compared to baseline). No significant difference within stimulation target subcohorts was found (p > 0.05). Out of the four patients without stimulation for five months following electrode insertion, three patients showed seizure frequency reduction lasting two to three months, while blinded to their stimulation status. CONCLUSION: An IE might explain seizure frequency reduction in our cohort. This effect seems to be independent of the number of implanted electrodes and of the target itself. The time course of the blinded subgroup of epilepsy patients suggests a peak of the lesional effect at two to three months after electrode insertion.

Longitudinal Reproducibility of Neurite Orientation Dispersion and Density Imaging (NODDI) Derived Metrics in the White Matter.

Diffusion-weighted magnetic resonance imaging (DWI) is undergoing constant evolution with the ambitious goal of developing in-vivo histology of the brain. A recent methodological advancement is Neurite Orientation Dispersion and Density Imaging (NODDI), a histologically validated multi-compartment model to yield microstructural features of brain tissue such as geometric complexity and neurite packing density, which are especially useful in imaging the white matter. Since NODDI is increasingly popular in clinical research and fields such as developmental neuroscience and neuroplasticity, it is of vast importance to characterize its reproducibility (or reliability). We acquired multi-shell DWI data in 29 healthy young subjects twice over a rescan interval of 4 weeks to assess the within-subject coefficient of variation (CVWS), between-subject coefficient of variation (CVBS) and the intraclass correlation coefficient (ICC), respectively. Using these metrics, we compared regional and voxel-by-voxel reproducibility of the most common image analysis approaches (tract-based spatial statistics [TBSS], voxel-based analysis with different extents of smoothing ["VBM-style"], ROI-based analysis). We observed high test-retest reproducibility for the orientation dispersion index (ODI) and slightly worse results for the neurite density index (NDI). Our findings also suggest that the choice of analysis approach might have significant consequences for the results of a study. Collectively, the voxel-based approach with Gaussian smoothing kernels of ≥4 mm FWHM and ROI-averaging yielded the highest reproducibility across NDI and ODI maps (CVWS mostly ≤3%, ICC mostly ≥0.8), respectively, whilst smaller kernels and TBSS performed consistently worse. Furthermore, we demonstrate that image quality (signal-to-noise ratio [SNR]) is an important determinant of NODDI metric reproducibility. We discuss the implications of these results for longitudinal and cross-sectional research designs commonly employed in the neuroimaging field.

Frontotemporal Regulation of Subjective Value to Suppress Impulsivity in Intertemporal Choices.

Impulsive decisions arise from preferring smaller but sooner rewards compared with larger but later rewards. How neural activity and attention to choice alternatives contribute to reward decisions during temporal discounting is not clear. Here we probed (1) attention to and (2) neural representation of delay and reward information in humans (both sexes) engaged in choices. We studied behavioral and frequency-specific dynamics supporting impulsive decisions on a fine-grained temporal scale using eye tracking and MEG recordings. In one condition, participants had to decide for themselves but pretended to decide for their best friend in a second prosocial condition, which required perspective taking. Hence, conditions varied in the value for themselves versus that pretending to choose for another person. Stronger impulsivity was reliably found across three independent groups for prosocial decisions. Eye tracking revealed a systematic shift of attention from the delay to the reward information and differences in eye tracking between conditions predicted differences in discounting. High-frequency activity (175-250 Hz) distributed over right frontotemporal sensors correlated with delay and reward information in consecutive temporal intervals for high value decisions for oneself but not the friend. Collectively, the results imply that the high-frequency activity recorded over frontotemporal MEG sensors plays a critical role in choice option integration.SIGNIFICANCE STATEMENT Humans face decisions between sooner smaller rewards and larger later rewards daily. An objective benefit of losing weight over a longer time might be devalued in face of ice cream because they prefer currently available options because of insufficiently considering long-term alternatives. The degree of contribution of neural representation and attention to choice alternatives is not clear. We investigated correlates of such decisions in participants deciding for themselves or pretending to choose for a friend. Behaviorally participants discounted less in self-choices compared with the prosocial condition. Eye movement and MEG recordings revealed how participants represent choice options most evident for options with high subjective value. These results advance our understanding of neural mechanisms underlying decision-making in humans.

Impact of Stimulus Features on the Performance of a Gaze-Independent Brain-Computer Interface Based on Covert Spatial Attention Shifts.

Regaining communication abilities in patients who are unable to speak or move is one of the main goals in decoding brain waves for brain-computer interface (BCI) control. Many BCI approaches designed for communication rely on attention to visual stimuli, commonly applying an oddball paradigm, and require both eye movements and adequate visual acuity. These abilities may, however, be absent in patients who depend on BCI communication. We have therefore developed a response-based communication BCI, which is independent of gaze shifts but utilizes covert shifts of attention to the left or right visual field. We recorded the electroencephalogram (EEG) from 29 channels and coregistered the vertical and horizontal electrooculogram. Data-driven decoding of small attention-based differences between the hemispheres, also known as N2pc, was performed using 14 posterior channels, which are expected to reflect correlates of visual spatial attention. Eighteen healthy participants responded to 120 statements by covertly directing attention to one of two colored symbols (green and red crosses for "yes" and "no," respectively), presented in the user's left and right visual field, respectively, while maintaining central gaze fixation. On average across participants, 88.5% (std: 7.8%) of responses were correctly decoded online. In order to investigate the potential influence of stimulus features on accuracy, we presented the symbols with different visual angles, by altering symbol size and eccentricity. The offline analysis revealed that stimulus features have a minimal impact on the controllability of the BCI. Hence, we show with our novel approach that spatial attention to a colored symbol is a robust method with which to control a BCI, which has the potential to support severely paralyzed people with impaired eye movements and low visual acuity in communicating with their environment.

MRI phenotyping of underlying cerebral small vessel disease in mixed hemorrhage patients.

OBJECTIVE: To investigate underlying cerebral small vessel disease (CSVD) in patients with mixed cerebral hemorrhages patterns and phenotype them according to the contribution of the two most common sporadic CSVD subtypes: cerebral amyloid angiopathy (CAA) vs. hypertensive arteriopathy (HA). METHODS: Brain MRIs of patients with intracerebral hemorrhages (ICHs) and/or cerebral microbleeds (CMBs) were assessed for the full spectrum of CSVD markers using validated scales: ICHs, CMBs, cortical superficial siderosis (cSS), white matter hyperintensities, MRI-visible perivascular spaces (PVS). PVS predominance pattern was grouped as centrum-semiovale (CSO)-PVS predominance, basal-ganglia (BG)-PVS predominance, CSO-PVS and BG-PVS equality. Patients with mixed cerebral hemorrhages were classified into mixed CAA-pattern or mixed HA-pattern according to the existence of cSS and/or a CSO-PVS predominance pattern and comparisons were performed. RESULTS: We included 110 patients with CAA (strictly lobar ICHs/CMBs), 33 with HA (strictly deep ICHs/CMBs) and 97 with mixed lobar/deep ICHs/CMBs. Mixed patients were more similar to HA with respect to their MRI-CSVD markers, vascular risk profile and cerebrospinal fluid (CSF) measures. In the mixed patients, 33 (34%) had cSS, a CSO-PVS predominance pattern, or both, and were defined as mixed CAA-pattern cases. The mixed CAA-pattern patients were more alike CAA patients regarding their MRI-CSVD markers, CSF and genetic profile. CONCLUSION: Our findings suggest that the heterogeneous group of patients with mixed cerebral hemorrhages distribution can be further phenotyped according to the predominant underlying CSVD. cSS presence and a CSO-PVS predominance pattern could serve as strongly suggestive markers of a contribution from CAA among patients with mixed hemorrhages.

Early Shift of Attention Is Not Regulated by Mind Wandering in Visual Search.

Unique to humans is the ability to report subjective awareness of a broad repertoire of external and internal events. Even when asked to focus on external information, the human's mind repeatedly wanders to task-unrelated thoughts, which limits reading comprehension or the ability to withhold automated manual responses. This led to the attentional decoupling account of mind wandering (MW). However, manual responses are not an ideal parameter to study attentional decoupling, given that during MW, the online adjustment of manual motor responses is impaired. Hence, whether early attentional mechanisms are indeed downregulated during MW or only motor responses being slowed is not clear. In contrast to manual motor responses, eye movements are considered a sensitive proxy of attentional shifts. Using a simple target detection task, we asked subjects to indicate whether a target was presented within a visual search display by pressing a button while we recorded eye movements and unpredictably asked the subjects to rate their actual level of MW. Generally, manual reaction times increased with MW, both in target absent and present trials. But importantly, even in trials with MW, subjects detected earlier a presented than an absent target. The decoupling account would predict more fixations of the target before pressing the button during MW. However, our results did not corroborate this assumption. Most importantly, subject's time to direct gaze at the target was equally fast in trials with and without MW. Our results corroborate our hypothesis that during MW early, bottom-up driven attentional processes are not decoupled but selectively manual motor responses are slowed.

Decoding the covert shift of spatial attention from electroencephalographic signals permits reliable control of a brain-computer interface.

OBJECTIVE: One of the main goals of brain-computer interfaces (BCI) is to restore communication abilities in patients. BCIs often use event-related potentials (ERPs) like the P300 which signals the presence of a target in a stream of stimuli. The P300 and related approaches, however, are inherently limited, as they require many stimulus presentations to obtain a usable control signal. Many approaches depend on gaze direction to focus the target, which is also not a viable approach in many cases, because eye movements might be impaired in potential users. Here we report on a BCI that avoids both shortcomings by decoding spatial target information, independent of gaze shifts. APPROACH: We present a new method to decode from the electroencephalogram (EEG) covert shifts of attention to one out of four targets simultaneously presented in the left and right visual field. The task is designed to evoke the N2pc component-a hemisphere lateralized response, elicited over the occipital scalp contralateral to the attended target. The decoding approach involves decoding of the N2pc based on data-driven estimation of spatial filters and a correlation measure. MAIN RESULTS: Despite variability of decoding performance across subjects, 22 out of 24 subjects performed well above chance level. Six subjects even exceeded 80% (cross-validated: 89%) correct predictions in a four-class discrimination task. Hence, the single-trial N2pc proves to be a component that allows for reliable BCI control. An offline analysis of the EEG data with respect to their dependence on stimulation time and number of classes demonstrates that the present method is also a workable approach for two-class tasks. SIGNIFICANCE: Our method extends the range of strategies for gaze-independent BCI control. The proposed decoding approach has the potential to be efficient in similar applications intended to decode ERPs.

Textural markers of ultrasonographic nerve alterations in amyotrophic lateral sclerosis.

Ultrasound has revealed cross-sectional nerve area (CSA) reduction in amyotrophic lateral sclerosis (ALS), but little is known about the sonographic nerve texture beyond CSA alterations. In a large cohort of 177 ALS patients and 57 control subjects, we investigated the covariance and disease-specific signature of several sonographic texture features of the median and ulnar nerves and their relationship to the patients' clinical characteristics. ALS patients showed atrophic nerves, a loss of the intranerve structures' echoic contrast, elevated coarseness, and a trend toward lower cluster shading compared with controls. A reduction in intranerve echoic contrast was related to longer disease duration and poorer functional status in ALS. Sonographic texture markers point toward a significant reorganization of the deep nerve microstructure in ALS. Future studies will be needed to further substantiate the markers' potential to assess peripheral nerve alterations in ALS.

Modification of In-Hospital Recommendation and Prescription of Anticoagulants for Secondary Prevention of Stroke after Launch of Direct Oral Anticoagulants and Change of National Guidelines.

INTRODUCTION: Approximately 1 out of 4 stroke patients suffers ischemic stroke secondary to atrial fibrillation (AF). Although indicated, withholding of anticoagulants for secondary prevention is a widespread phenomenon. OBJECTIVE: We examined the longitudinal change of recommendation and prescription of secondary preventive anticoagulation in AF patients in an acute stroke center setting focusing on the impact of the introduction of direct oral anticoagulants (DOACs) and the change of national stroke prevention guidelines. METHODS: Consecutive patients admitted with an acute cerebrovascular ischemic event underwent regular diagnostic work-up. Pseudonymized clinical data were entered into the institution's stroke registry. In those patients with AF, discharge letters were collected and evaluated for temporal trends and affecting factors of recommended and prescribed antithrombotic secondary medication at the time of discharge from hospital. RESULTS: Of 7,175 patients admitted between January 2009 and December 2018, 1,812 (25.3%) suffered stroke caused by AF. Frequency of patients with recommended anticoagulation increased within the observation period from 66.7 to 95.8% (per year; adjusted odds ratio [OR], 1.309; confidence interval [CI], 1.153-1.486). Independently from this time trend, DOAC approval (adjusted OR, 4.026; CI 1.962-8.265) and guideline change (adjusted OR, 2.184; CI, 1.006-4.743) were associated with an increasing frequency of recommendation for anticoagulation. The rate of patients already receiving recommended anticoagulation for secondary prevention at discharge increased from 42.1 to 62.5%. Introduction of DOACs was not associated with this trend, and guideline change was even associated with decreasing frequency of anticoagulated patients at hospital discharge (adjusted OR, 0.641; CI, 0.414-0.991). Fear of early intracerebral bleeding was the most common reason for withholding anticoagulation (37%) at hospital discharge and stayed stable during the observation period. CONCLUSIONS: Changing national guidelines with discard of contraindications for anticoagulation and the introduction of DOACs led to a broader recommendation of oral anticoagulation. However, both, new guidelines and DOACs, were not found to be associated with an increasing percentage of patients discharged from our hospital already on recommended anticoagulant prevention. This might be explained by the decreasing length of hospital stay during the study period and a missing evidence of early bleeding risk of DOACs in patients with acute brain infarction. Evidence-based data to close this therapeutic gap are needed.

Peripheral Nerve Imaging Aids in the Diagnosis of Immune-Mediated Neuropathies-A Case Series.

BACKGROUND: Diagnosis of immune-mediated neuropathies and their differentiation from amyotrophic lateral sclerosis (ALS) can be challenging, especially at early disease stages. Accurate diagnosis is, however, important due to the different prognosis and available treatment options. We present one patient with a left-sided dorsal flexor paresis and initial suspicion of ALS and another with multifocal sensory deficits. In both, peripheral nerve imaging was the key for diagnosis. METHODS: We performed high-resolution nerve ultrasound (HRUS) and 7T or 3T magnetic resonance neurography (MRN). RESULTS: In both patients, HRUS revealed mild to severe, segmental or inhomogeneous, nerve enlargement at multiple sites, as well as an area increase of isolated fascicles. MRN depicted T2 hyperintense nerves with additional contrast-enhancement. DISCUSSION: Peripheral nerve imaging was compatible with the respective diagnosis of an immune-mediated neuropathy, i.e., multifocal motor neuropathy (MMN) in patient 1 and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) in patient 2. Peripheral nerve imaging, especially HRUS, should play an important role in the diagnostic work-up for immune-mediated neuropathies and their differentiation from ALS.