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.

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.

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.

Cytosolic, but not matrix, calcium is essential for adjustment of mitochondrial pyruvate supply.

Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca2+). Current models assume that cytosolic Ca2+ regulates workload and that mitochondrial Ca2+ uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS. This implies that adaptive activation of mitochondrial dehydrogenases by intramitochondrial Ca2+ cannot be the exclusive mechanism for OXPHOS control. We hypothesized that cytosolic Ca2+, but not mitochondrial matrix Ca2+, may adapt OXPHOS to workload by adjusting the rate of pyruvate supply from the cytosol to the mitochondria. Here, we studied the role of malate-aspartate shuttle (MAS)-dependent substrate supply in OXPHOS responses to changing Ca2+ concentrations in isolated brain and heart mitochondria, synaptosomes, fibroblasts, and thymocytes from WT and MCU KO mice and the isolated working rat heart. Our results indicate that extramitochondrial Ca2+ controls up to 85% of maximal pyruvate-driven OXPHOS rates, mediated by the activity of the complete MAS, and that intramitochondrial Ca2+ accounts for the remaining 15%. Of note, the complete MAS, as applied here, included besides its classical NADH oxidation reaction the generation of cytosolic pyruvate. Part of this largely neglected mechanism has previously been described as the "mitochondrial gas pedal." Its implementation into OXPHOS control models integrates seemingly contradictory results and warrants a critical reappraisal of metabolic control mechanisms in health and disease.

The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3.

A well-accepted model of episodic memory involves the processing of spatial and non-spatial information by segregated pathways and their association within the hippocampus. However, these pathways project to distinct proximodistal levels of the hippocampus. Moreover, spatial and non-spatial subnetworks segregated along this axis have been recently described using memory tasks with either a spatial or a non-spatial salient dimension. Here, we tested whether the concept of segregated subnetworks and the traditional model are reconcilable by studying whether activity within CA1 and CA3 remains segregated when both dimensions are salient, as is the case for episodes. Simultaneously, we investigated whether temporal or spatial information bound to objects recruits similar subnetworks as items or locations per se, respectively. To do so, we studied the correlations between brain activity and spatial and/or temporal discrimination ratios in proximal and distal CA1 and CA3 by detecting Arc RNA in mice. We report a robust proximodistal segregation in CA1 for temporal information processing and in both CA1 and CA3 for spatial information processing. Our results suggest that the traditional model of episodic memory and the concept of segregated networks are reconcilable, to a large extent and put forward distal CA1 as a possible "home" location for time cells.

Hippocampal vascular reserve associated with cognitive performance and hippocampal volume.

Medial temporal lobe dependent cognitive functions are highly vulnerable to hypoxia in the hippocampal region, yet little is known about the relationship between the richness of hippocampal vascular supply and cognition. Hippocampal vascularization patterns have been categorized into a mixed supply from both the posterior cerebral artery and the anterior choroidal artery or a single supply by the posterior cerebral artery only. Hippocampal arteries are small and affected by pathological changes when cerebral small vessel disease is present. We hypothesized, that hippocampal vascularization patterns may be important trait markers for vascular reserve and modulate (i) cognitive performance; (ii) structural hippocampal integrity; and (iii) the effect of cerebral small vessel disease on cognition. Using high-resolution 7 T time-of-flight angiography we manually classified hippocampal vascularization patterns in older adults with and without cerebral small vessel disease in vivo. The presence of a mixed supplied hippocampus was an advantage in several cognitive domains, including verbal list learning and global cognition. A mixed supplied hippocampus also was an advantage for verbal memory performance in cerebral small vessel disease. Voxel-based morphometry showed higher anterior hippocampal grey matter volume in mixed, compared to single supply. We discuss that a mixed hippocampal supply, as opposed to a single one, may increase the reliability of hippocampal blood supply and thereby provide a hippocampal vascular reserve that protects against cognitive impairment.

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.

The spatio-temporal profile of multisensory integration.

Task-irrelevant visual stimuli can enhance auditory perception. However, while there is some neurophysiological evidence for mechanisms that underlie the phenomenon, the neural basis of visually induced effects on auditory perception remains unknown. Combining fMRI and EEG with psychophysical measurements in two independent studies, we identified the neural underpinnings and temporal dynamics of visually induced auditory enhancement. Lower- and higher-intensity sounds were paired with a non-informative visual stimulus, while participants performed an auditory detection task. Behaviourally, visual co-stimulation enhanced auditory sensitivity. Using fMRI, enhanced BOLD signals were observed in primary auditory cortex for low-intensity audiovisual stimuli which scaled with subject-specific enhancement in perceptual sensitivity. Concordantly, a modulation of event-related potentials could already be observed over frontal electrodes at an early latency (30-80 ms), which again scaled with subject-specific behavioural benefits. Later modulations starting around 280 ms, that is in the time range of the P3, did not fit this pattern of brain-behaviour correspondence. Hence, the latency of the corresponding fMRI-EEG brain-behaviour modulation points at an early interplay of visual and auditory signals in low-level auditory cortex, potentially mediated by crosstalk at the level of the thalamus. However, fMRI signals in primary auditory cortex, auditory thalamus and the P50 for higher-intensity auditory stimuli were also elevated by visual co-stimulation (in the absence of any behavioural effect) suggesting a general, intensity-independent integration mechanism. We propose that this automatic interaction occurs at the level of the thalamus and might signify a first step of audiovisual interplay necessary for visually induced perceptual enhancement of auditory perception.

Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease - a two-case study.

Alzheimer's disease (AD) is associated with deterioration of memory and cognitive function and a degeneration of neurons of the nucleus basalis of Meynert (NBM). The NBM is the major input source of acetylcholine (ACh) to the cortex. The decreasing cholinergic innervation of the cortex due to degeneration of the NBM might be the cause of loss of memory function. NBM-Deep brain stimulation (NBM-DBS) is considered to serve as a potential therapeutic option for patients with AD by supporting residual cholinergic transmission to stabilize oscillatory activity in memory-relevant circuits. However, whether DBS could improve sensory memory functions in patients with AD is not clear. Here, in a passive auditory oddball paradigm, patients with AD (N = 2) listened to repetitive background tones (standard tones) randomly interrupted by frequency deviants in two blocks with NBM-DBS OFF and then NBM-DBS ON, while age-matched healthy controls (N = 6) repeated the experiment twice. The mismatch negativity in NBM-DBS OFF significantly differed from controls in both blocks, but not under NBM-DBS, which was likely due to a pronounced P50 increase overlapping with the N1 in NBM-DBS OFF. This early complex of EEG components recovered under stimulation to a normal level as defined by responses in controls. In this temporal interval, we found in patients with NBM-DBS ON (but not with NBM-DBS OFF) and in controls a strong repetition suppression effect to standard tones - with more attenuated responses to frequently repeated standard tones. This highlights the role of NBM-DBS for sensory gating of familiar auditory information into sensory memory.

Electroencephalography reveals a selective disruption of cognitive control processes in craving cigarette smokers.

Addiction to nicotine is extremely challenging to overcome, and the intense craving for the next cigarette often leads to relapse in smokers who wish to quit. To dampen the urges of craving and inhibit unwanted behaviour, smokers must harness cognitive control, which is itself impaired in addiction. It is likely that craving may interact with cognitive control, and the present study sought to test the specificity of such interactions. To this end, data from 24 smokers were gathered using EEG and behavioural measures in a craving session (following a three-hour nicotine abstention period) and a non-craving session (having just smoked). In both sessions, participants performed a task probing various facets of cognitive control (response inhibition, task switching and conflict processing). Results showed that craving smokers were less flexible with the implementation of cognitive control, with demands of task switching and incongruency yielding greater deficits under conditions of craving. Importantly, inhibitory control was not affected by craving, suggesting that the interactions of craving and cognitive control are selective. Together, these results provide evidence that smokers already exhibit specific control-related deficits after brief nicotine deprivation. This disruption of cognitive control while craving may help to explain why abstinence is so difficult to maintain.

Laryngeal Movement Disorders in Multiple System Atrophy: A Diagnostic Biomarker?

BACKGROUND: Multiple system atrophy (MSA) is a rare neurodegenerative disorder, and its parkinsonian variant can be difficult to delineate from Parkinson's disease (PD). Despite laryngeal dysfunction being associated with decreased life expectancy and quality of life, systematic assessments of laryngeal dysfunction in large cohorts are missing. OBJECTIVES: The objective of this study was to systematically assess laryngeal dysfunction in MSA and PD and identify laryngeal symptoms that allow for differentiating MSA from PD. METHODS: Patients with probable or possible MSA underwent flexible endoscopic evaluation of swallowing performing a systematic task protocol. Findings were compared with an age-matched PD cohort. RESULTS: A total of 57 patients with MSA (64 [59-71] years; 35 women) were included, and task assessments during endoscopic examination compared with 57 patients with PD (67 [60-73]; 28 women). Patients with MSA had a shorter disease duration (4 [3-5] years vs 7 [5-10]; P < 0.0001) and higher disease severity (Hoehn & Yahr stage 4 [3-4] vs 3 [2-4]; P < 0.0001). Of the patients with MSA, 43.9% showed clinically overt laryngeal dysfunction with inspiratory stridor. During endoscopic task assessment, however, 93% of patients with MSA demonstrated laryngeal dysfunction in contrast with only 1.8% of patients with PD (P < 0.0001). Irregular arytenoid cartilages movements were present in 91.2% of patients with MSA, but in no patients with PD (P < 0.0001). Further findings included vocal fold motion impairment (75.4%), paradoxical vocal fold motion (33.3%), and vocal fold fixation (19.3%). One patient with PD showed vocal fold motion impairment. CONCLUSION: Laryngeal movement disorders are highly prevalent in patients with MSA when assessed by a specific task protocol despite the lack of overt clinical symptoms. Our data suggest that irregular arytenoid cartilage movements could be used as a clinical marker to delineate MSA from PD with a specificity of 1.0 and sensitivity 0.9. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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.

7T MR neurography-ultrasound fusion for peripheral nerve imaging.

BACKGROUND: We present one patient with an initial diagnosis of Guillain-Barré syndrome (GBS) and one with Charcot-Marie-Tooth disease (CMT) type 1A. METHODS: Both patients underwent ankle tibial nerve fusion-imaging of high-resolution ultrasound (HRUS) with 7T MR neurography (MRN). RESULTS: In GBS, the nerve was enlarged, T2-hyperintense, and showed increased vascularization 21 months after symptom onset. In CMT1A, the enlarged nerve was T2-isointense with normal endoneurial blood flow. CONCLUSIONS: We demonstrate the utility of 7T-MRN-HRUS-fusion-imaging. In GBS, there was evidence of ongoing inflammation resulting in a changed diagnosis to acute-onset chronic demyelinating polyradiculoneuropathy and maintenance of immunotherapy. By MRN-HRUS-fusion, patients with presumed peripheral axonal degeneration could be shown to display imaging markers associated with peripheral nervous system inflammation. Thus, more accurate identification of a treatable inflammatory component may become possible.

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.

Default mode network connectivity change corresponds to ketamine's delayed glutamatergic effects.

Ketamine exerts rapid antidepressant effects peaking 24 h after a single infusion, which have been suggested to be reflected by both reduced functional connectivity (FC) within default mode network (DMN) and altered glutamatergic levels in the perigenual anterior cingulate cortex (pgACC) at 24 h. Understanding the interrelation and time point specificity of ketamine-induced changes of brain circuitry and metabolism is thus key to future therapeutic developments. We investigated the correlation of late glutamatergic changes with FC changes seeded from the posterior cingulate cortex (PCC) and tested the prediction of the latter by acute fractional amplitude of low-frequency fluctuations (fALFF). In a double-blind, randomized, placebo-controlled study of 61 healthy subjects, we compared effects of subanesthetic ketamine infusion (0.5 mg/kg over 40 min) on resting-state fMRI and MR-Spectroscopy at 7 T 1 h and 24 h post-infusion. FC decrease between PCC and dorsomedial prefrontal cortex (dmPFC) was found at 24 h post-infusion (but not 1 h) and this FC decrease correlated with glutamatergic changes at 24 h in pgACC. Acute increase in fALFF was found in ventral PCC at 1 h which was not observed at 24 h and inversely correlated with the reduced dPCC FC towards the dmPFC at 24 h. The correlation of metabolic and functional markers of delayed ketamine effects and their temporal specificity suggest a potential mechanistic relationship between glutamatergic modulation and reconfiguration of brain regions belonging to the DMN.

Direct Evidence for Prediction Signals in Frontal Cortex Independent of Prediction Error.

Predictive coding (PC) has been suggested as one of the main mechanisms used by brains to interact with complex environments. PC theories posit top-down prediction signals, which are compared with actual outcomes, yielding in turn prediction error (PE) signals, which are used, bottom-up, to modify the ensuing predictions. However, disentangling prediction from PE signals has been challenging. Critically, while many studies found indirect evidence for PC in the form of PE signals, direct evidence for the prediction signal is mostly lacking. Here, we provide clear evidence, obtained from intracranial cortical recordings in human surgical patients, that the human lateral prefrontal cortex evinces prediction signals while anticipating an event. Patients listened to task-irrelevant sequences of repetitive tones including infrequent predictable or unpredictable pitch deviants. The broadband high-frequency amplitude (HFA) was decreased prior to the onset of expected relative to unexpected deviants in the frontal cortex only, and its amplitude was sensitive to the increasing likelihood of deviants following longer trains of standards in the unpredictable condition. Single-trial HFA predicted deviations and correlated with poststimulus response to deviations. These results provide direct evidence for frontal cortex prediction signals independent of PE signals.

Acute symptomatic extracranial internal carotid occlusion - natural course and clinical impact.

Background: To assess the vascular and clinical course of acute symptomatic extracranial internal carotid artery (ICA) occlusion. Patients and methods: Patients with an acute ischemic event in the anterior circulation and corresponding extracranial ICA occlusion at CT angiography and/or color-coded duplex sonography underwent recurrent duplex follow-up for detection of spontaneous recanalization. Stroke recurrence and functional outcome 4.5 months after the ischemic index event assessed by modified Rankin scale served as secondary outcome parameters. Results: 133 patients (91 men, mean age 62.3 years, SD 10.8) demonstrated symptomatic occlusion of the extracranial ICA with open intracranial ICA and open middle cerebral artery and were followed-up for spontaneous recanalization. Twenty-eight recanalized spontaneously, 25 to high-grade focal stenosis within 12 days, revealing an early cumulative recanalization rate of 23 %. Detection of recanalization was independently associated with de novo dual anti-platelet therapy (adjusted odds ratio [OR], 3.24; 95 % confidence interval [CI], 1.34 to 7.80). Ischemic recurrence occurred in 16 patients, of which 10 deemed to be embolic and 5 hemodynamic. Spontaneous ICA recanalization and an exhausted cerebrovascular reserve in the hemisphere distal to the occluded ICA were both independently associated with the occurrence of a recurrent ischemic event at Cox regression. An increasing NIHSS score at admission, a decreasing middle cerebral artery flow velocity and an ischemic recurrence independently predicted poor outcome (modified Rankin scale 3 to 6) in multivariate analysis. Conclusions: Acute symptomatic extracranial ICA occlusion is an unstable condition with frequent spontaneous recanalization to severe stenosis and early embolic stroke recurrence, demanding appropriate prevention especially in those patients with only mild deficit.

Transcranial Static Magnetic Field Stimulation Over the Temporal Cortex Modulating the Right Ear Advantage in Dichotic Listening.

OBJECTIVE: Transcranial static magnetic field stimulation (tSMS) has proposed a new, promising, and simple non-invasive brain stimulation method. While several studies gained certain evidence about tSMS effects in the motor, somatosensory, and visual domains, there is still a controversial debate about its general effectiveness. In the present study, we investigated potential tSMS effects on auditory speech processing as measured by a dichotic listening (DL) task. MATERIALS AND METHODS: Fifteen healthy participants received in randomized order on three different days one session of either sham, tSMS over the left, or tSMS over the right auditory cortex (AC). Under stimulation, participants performed a standard DL task with consonant-vowel syllables. Simultaneously, we recorded electroencephalogram from central sites (Fz, Cz, Pz). RESULTS: TSMS over the left AC changed the behavioral performance and modulated auditory evoked potentials. Stimulation of the left AC significantly reduced the right ear advantage during the DL task and the N1 component of auditory evoked potentials in response to these syllables. CONCLUSIONS: The preliminary results of the present exploratory study demonstrate the ability of tSMS to modulate human brain activity on a behavioral as well as physiologic level. Furthermore, tSMS effects on acoustic processing may have clinical implications by fostering potential approaches for a treatment of speech-related pathologies associated with hyperexcitability in the AC.

Cortical Mechanisms of Prioritizing Selection for Rejection in Visual Search.

In visual search, the more one knows about a target, the faster one can find it. Surprisingly, target identification is also faster with knowledge about distractor-features. The latter is paradoxical, as it implies that to avoid the selection of an item, the item must somehow be selected to some degree. This conundrum has been termed the "ignoring paradox", and, to date, little is known about how the brain resolves it. Here, in data from four experiments using neuromagnetic brain recordings in male and female humans, we provide evidence that this paradox is resolved by giving distracting information priority in cortical processing. This attentional priority to distractors manifests as an enhanced early neuromagnetic index, which occurs before target-related processing, and regardless of distractor predictability. It is most pronounced on trials for which a response rapidly occurred, and is followed by a suppression of the distracting information. These observations together suggest that in visual search items cannot be ignored without first being selected.SIGNIFICANCE STATEMENT How can we ignore distracting stimuli in our environment? To do this successfully, a logical hypothesis is that as few neural resources as possible should be devoted to distractor processing. Yet, to avoid devoting resources to a distractor, the brain must somehow mark what to avoid; this is a philosophical problem, which has been termed the "ignoring paradox" or "white bear phenomenon". Here, we use MEG recordings to determine how the human brain resolves this paradox. Our data show that distractors are not only processed, they are given temporal priority, with the brain building a robust representation of the to-be-ignored items. Thus, successful suppression of distractors can only be achieved if distractors are first strongly neurally represented.