Structural Connectivity Remote From Lesions Correlates With Somatosensory Outcome Poststroke.

Background and Purpose: Changes in connectivity of white matter fibers remote to a stroke lesion, suggestive of structural connectional diaschisis, may impact on clinical impairment and recovery after stroke. However, until recently, we have not had tract-specific techniques to map changes in white matter tracts in vivo in humans to enable investigation of potential mechanisms and clinical impact of such remote changes. Our aim was to identify and quantify white matter tracts that are affected remote from a stroke lesion and to investigate the associations between reductions in tract-specific connectivity and impaired touch discrimination function after stroke. Methods: We applied fixel-based analysis to diffusion magnetic resonance imaging data from 37 patients with stroke (right lesion =16; left lesion =21) and 26 age-matched healthy adults. Three quantitative metrics were compared between groups: fiber density; fiber-bundle cross-section; and a combined measure of both (fiber-bundle cross-section) that reflects axonal structural connectivity. Results: Compared with healthy adults, patients with stroke showed significant common fiber-bundle cross-section and fiber density reductions in 4 regions remote from focal lesions that play roles in somatosensory and spatial information processing. Structural connectivity along the somatosensory fibers of the lesioned hemisphere was correlated with contralesional hand touch function. Touch function of the ipsilesional hand was associated with connectivity of the superior longitudinal fasciculus, and, for the right-lesion group, the corpus callosum. Conclusions: Remote tract-specific reductions in axonal connectivity indicated by diffusion imaging measures are observed in the somatosensory network after stroke. These remote white matter connectivity reductions, indicative of structural connectional diaschisis, are associated with touch impairment in patients with stroke.

Normal Pressure Hydrocephalus Associated with Alzheimer's Disease.

OBJECTIVE: The aim was to investigate whether neurodegenerative biomarkers in cerebrospinal fluid (CSF) differentiate patients with suspected normal pressure hydrocephalus (NPH) who respond to CSF drainage from patients who do not respond. METHODS: Data from 62 consecutive patients who presented with magnetic resonance imaging changes indicative of NPH were studied with regard to cognitive and gait functions before and after drainage of 40-50ml of CSF. Additionally, S100 protein, neuron-specific enolase, ß-amyloid protein, tau protein and phospho-tau were determined in CSF. Statistical analyses were carried out with ANOVA and multiple linear regression. RESULTS: Patients with CSF constellations typical for Alzheimer's disease (n = 28) improved significantly in cognitive and gait-related functions after CSF drainage. In contrast, those patients without a CSF constellation typical for Alzheimer's disease (n = 34) did not improve in cognitive and gait-related functions after CSF drainage. In addition, positive CSF biomarkers for Alzheimer's disease predicted these improvements. INTERPRETATION: Our data suggest an association between Alzheimer's disease and NPH changes, supporting the recently suggested dichotomy of a neurodegenerative NPH and a true idiopathic NPH, with the latter appearing to be rare. ANN NEUROL 2020;88:703-711.

Belief formation - A driving force for brain evolution.

The topic of belief has been neglected in the natural sciences for a long period of time. Recent neuroscience research in non-human primates and humans, however, has shown that beliefs are the neuropsychic product of fundamental brain processes that attribute affective meaning to concrete objects and events, enabling individual goal setting, decision making and maneuvering in the environment. With regard to the involved neural processes they can be categorized as empirical, relational, and conceptual beliefs. Empirical beliefs are about objects and relational beliefs are about events as in tool use and in interactions between subjects that develop below the level of awareness and are up-dated dynamically. Conceptual beliefs are more complex being based on narratives and participation in ritual acts. As neural processes are known to require computational space in the brain, the formation of inceasingly complex beliefs demands extra neural resources. Here, we argue that the evolution of human beliefs is related to the phylogenetic enlargement of the brain including the parietal and medial frontal cortex in humans.

Reduced gray matter volume in the left prefrontal, occipital, and temporal regions as predictors for posttraumatic stress disorder: a voxel-based morphometric study.

The concept of acute stress disorder (ASD) was introduced as a diagnostic entity to improve the identification of traumatized people who are likely to develop posttraumatic stress disorder (PTSD). Neuroanatomical models suggest that changes in the prefrontal cortex, amygdala, and hippocampus play a role in the development of PTSD. Using voxel-based morphometry, this study aimed to investigate the predictive power of gray matter volume (GMV) alterations for developing PTSD. The GMVs of ASD patients (n = 21) were compared to those of PTSD patients (n = 17) and healthy controls (n = 18) in whole-brain and region-of-interest analyses. The GMV alterations seen in ASD patients shortly after the traumatic event (T1) were also correlated with PTSD symptom severity and symptom clusters 4 weeks later (T2). Compared with healthy controls, the ASD patients had significantly reduced GMV in the left visual cortex shortly after the traumatic event (T1) and in the left occipital and prefrontal regions 4 weeks later (T2); no significant differences in GMV were seen between the ASD and PTSD patients. Furthermore, a significant negative association was found between the GMV reduction in the left lateral temporal regions seen after the traumatic event (T1) and PTSD hyperarousal symptoms 4 weeks later (T2). Neither amygdala nor hippocampus alterations were predictive for the development of PTSD. These data suggest that gray matter deficiencies in the left hemispheric occipital and temporal regions in ASD patients may predict a liability for developing PTSD.

From Believing to Belief: A General Theoretical Model.

Cognitive neuroscience research has begun to explore the mental processes underlying what a belief and what believing are. Recent evidence suggests that believing involves fundamental brain functions that result in meaningful probabilistic representations, called beliefs. When relatively stable, these beliefs allow for guidance of behavior in individuals and social groups. However, they are also fluid and can be modified by new relevant information, interpersonal contact, social pressure, and situational demands. We present a theoretical model of believing that can account for the formation of both empirically grounded and metaphysical beliefs.

Spontaneous Arm Movement Activity during Sleep in Epileptic and Non-Epileptic Patients.

PURPOSE: Epilepsy has a complex interaction with sleep. The purpose of this study was to explore the relation between spontaneous arm movements and sleep architecture in patients with epilepsy. METHODS: This prospective study included 53 patients with suspected epilepsy (44 ± 18 years; 30 females, 23 males) and 55 age-matched patients with non-epileptic seizures (42 ± 15: 27 females, 28 males). Twenty-four-hour-video-electroencephalography recordings were combined with accelerometry of movement activity of both arms using actiwatches. RESULTS: Patients with suspected epilepsy showed a higher occurrence of epileptic discharges (p = 0.0001) and abnormal focal slowing (p = 0.027) in the electroencephalogram (EEG) than the patients with non-epileptic seizures. Also, the epilepsy patients showed a shorter rapid eye movement-sleep duration compared to controls (0.0001). Accelerometry revealed that the patients with epilepsy moved their dominant right arm more frequently during the night (p = 0.014) than the controls, although there was no difference in arm movement activity during day time. CONCLUSION: The patients with reported epilepsy exhibited higher spontaneous arm movement activity during sleep. This may be related to abnormal sleep architecture or abnormal EEG activity but was not related to epileptic seizures.

An fMRI study of training voluntary smooth circular eye movements.

Despite a large number of recent studies, the promise of fMRI methods to produce valuable insights into motor skill learning has been restricted to sequence learning paradigms, or manual training paradigms where a relatively advanced capacity for sensory-motor integration and effector coordination already exists. We therefore obtained fMRIs from 16 healthy adults trained in a new paradigm that demanded voluntary smooth circular eye movements without a moving target. This aimed to monitor neural activation during two possible motor learning processes: (a) the smooth pursuit control system develops a new perceptual-motor relationship and successfully becomes involved in voluntary action in which it is not normally involved or (b) the saccadic system normally used for voluntary eye movement and which only exhibits linear action skill develops new dynamic coordinative control capable of smooth circular movement. Participants were able to improve within half an hour, typically demonstrating saccadic movement with progressively reduced amplitudes, which better approximated smooth circular movement. Activity in the inferior premotor cortex was significantly modulated and decreased during the progress of learning. In contrast, activations in dorsal premotor and parietal cortex along the intraparietal sulcus, the supplementary eye field and the anterior cerebellum did not change during training. Thus, the decrease of activity in inferior premotor cortex was critically related to the learning progress in visuospatial eye movement control.

Posterior and prefrontal contributions to the development posttraumatic stress disorder symptom severity: an fMRI study of symptom provocation in acute stress disorder.

Acute stress disorder (ASD) is predictive of the development of posttraumatic stress disorder (PTSD). In response to symptom provocation, the exposure to trauma-related pictures, ASD patients showed increased activation of the medial posterior areas of precuneus and posterior cingulate cortex as well as of superior prefrontal cortex in a previous study. The current study aimed at investigating which activated areas are predictive of the development of PTSD. Nineteen ASD patients took part in an fMRI study in which they were shown personalized trauma-related and neutral pictures within 4 weeks of the traumatic event. They were assessed for severity of PTSD 4 weeks later. Activation contrasts between trauma-related and neutral pictures were correlated with subsequent PTSD symptom severity. Greater activation in, among others, right medial precuneus, left retrosplenial cortex, precentral and right superior temporal gyrus as well as less activation in lateral, superior prefrontal and left fusiform gyrus was related to subsequently increased PTSD severity. The results are broadly in line with neural areas related to etiological models of PTSD, namely multisensory associative learning recruiting posterior regions on the one hand and failure to reappraise maladaptive cognitions, thought to involve prefrontal areas, on the other.

Between- and within-site variability of fMRI localizations.

This study provides first data about the spatial variability of fMRI sensorimotor localizations when investigating the same subjects at different fMRI sites. Results are comparable to a previous patient study. We found a median between-site variability of about 6 mm independent of task (motor or sensory) and experimental standardization (high or low). An intraclass correlation coefficient analysis using data quality measures indicated a major influence of the fMRI site on variability. In accordance with this, within-site localization variability was considerably lower (about 3 mm). We conclude that the fMRI site is a considerable confound for localization of brain activity. However, when performed by experienced clinical fMRI experts, brain pathology does not seem to have a relevant impact on the reliability of fMRI localizations. Hum Brain Mapp 37:2151-2160, 2016. © 2016 Wiley Periodicals, Inc.

Manifestations, social impact, and decay of conceptual beliefs: A cultural perspective.

INTRODUCTION: Believing comprises multifaceted processes that integrate information from the outside world through meaning-making processes with personal relevance. METHODS: Qualitative Review of the current literature in social cognitive neuroscience. RESULTS: Although believing develops rapidly outside an individual's conscious awareness, it results in the formation of beliefs that are stored in memory and play an important role in determining an individual's behavior. Primal beliefs reflect an individual's experience of objects and events, whereas conceptual beliefs are based on narratives that are held in social groups. Conceptual beliefs can be about autobiographical, political, religious, and other aspects of life and may be encouraged by participation in group rituals. We hypothesize that assertions of future gains and rewards that transcend but are inherent in these codices provide incentives to follow the norms and rules of social groups. CONCLUSION: The power of conceptual beliefs to provide cultural orientation is likely to fade when circumstances and evidence make it clear that what was asserted no longer applies.

Activation of thalamus in motor imagery results from gating by hypnosis.

The ability to mentally imagine the performance of automatic movements has been well-established being employed in sports and physiotherapy as a tool for motor learning and rehabilitation. This is probably mediated by engagement of the same brain areas as during real motor performance. Here we investigated the effect of hypnotic trance on the cerebral activation pattern engaged in motor imagery in 16 healthy, right-handed subjects using fMRI. Motor imagery as compared with rest was related to activations in the left medial frontal areas (preSMA/SMA), prefrontal- and frontal areas, putamen and inferior parietal areas. When compared with performance of the same movements motor imagery resulted in activation of the left middle frontal cortex, precuneus, and posterior cingulate. Under hypnotic trance there was one extra-activation in the left thalamus which occurred specifically in the motor imagery condition. The regional beta indices were highly correlated among the areas of the cortical-subcortical motor network. Our data accord with the notion that hypnotic trance enhances the motor control circuit engaged in motor imagery by modulating the gating function of the thalamus.

Variability of clinical functional MR imaging results: a multicenter study.

PURPOSE: To investigate intersite variability of clinical functional magnetic resonance (MR) imaging, including influence of task standardization on variability and use of various parameters to inform the clinician whether the reliability of a given functional localization is high or low. MATERIALS AND METHODS: Local ethics committees approved the study; all participants gave written informed consent. Eight women and seven men (mean age, 40 years) were prospectively investigated at three experienced functional MR sites with 1.5- (two sites) or 3-T (one site) MR. Nonstandardized motor and highly standardized somatosensory versions of a frequently requested clinical task (localization of the primary sensorimotor cortex) were used. Perirolandic functional MR variability was assessed (peak activation variability, center of mass [COM] variability, intraclass correlation values, overlap ratio [OR], activation size ratio). Data quality measures for functional MR images included percentage signal change (PSC), contrast-to-noise ratio (CNR), and head motion parameters. Data were analyzed with analysis of variance and a correlation analysis. RESULTS: Localization of perirolandic functional MR activity differed by 8 mm (peak activity) and 6 mm (COM activity) among sites. Peak activation varied up to 16.5 mm (COM range, 0.4-16.5 mm) and 45.5 mm (peak activity range, 1.8-45.5 mm). Signal strength (PSC, CNR) was significantly lower for the somatosensory task (mean PSC, 1.0% ± 0.5 [standard deviation]; mean CNR, 1.2 ± 0.4) than for the motor task (mean PSC, 2.4% ± 0.8; mean CNR, 2.9 ± 0.9) (P < .001, both). Intersite variability was larger with low signal strength (negative correlations between signal strength and peak activation variability) even if the task was highly standardized (mean OR, 22.0% ± 18.9 [somatosensory task] and 50.1% ± 18.8 [motor task]). CONCLUSION: Clinical practice and clinical functional MR biomarker studies should consider that the center of task-specific brain activation may vary up to 16.5 mm, with the investigating site, and should maximize functional MR signal strength and evaluate reliability of local results with PSC and CNR.

In vitro neuronal network activity in NMDA receptor encephalitis.

BACKGROUND: Anti-NMDA-encephalitis is caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR) and characterized by a severe encephalopathy with psychosis, epileptic seizures and autonomic disturbances. It predominantly occurs in young women and is associated in 59% with an ovarian teratoma. RESULTS: We describe effects of cerebrospinal fluid (CSF) from an anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis patient on in vitro neuronal network activity (ivNNA). In vitro NNA of dissociated primary rat cortical populations was recorded by the microelectrode array (MEA) system.The 23-year old patient was severely affected but showed an excellent recovery following multimodal immunomodulatory therapy and removal of an ovarian teratoma. Patient CSF (pCSF) taken during the initial weeks after disease onset suppressed global spike- and burst rates of ivNNA in contrast to pCSF sampled after clinical recovery and decrease of NMDAR antibody titers. The synchrony of pCSF-affected ivNNA remained unaltered during the course of the disease. CONCLUSION: Patient CSF directly suppresses global activity of neuronal networks recorded by the MEA system. In contrast, pCSF did not regulate the synchrony of ivNNA suggesting that NMDAR antibodies selectively regulate distinct parameters of ivNNA while sparing their functional connectivity. Thus, assessing ivNNA could represent a new technique to evaluate functional consequences of autoimmune encephalitis-related CSF changes.

Bridging the Gap Between Believing and Memory Functions.

Believing has recently been recognized as a fundamental brain function linking a person's experience with his or her attitude, actions and predictions. In general, believing results from the integration of ambient information with emotions and can be reinforced or modulated in a probabilistic fashion by new experiences. Although these processes occur in the subliminal realm, humans can become aware of what they believe and express it verbally. We explain how believing is interwoven with memory functions in a multifaceted fashion. Linking the typically rapid and adequate reactions of a subject to what he/she believes is enabled by working memory. Perceptions are stored in episodic memory as beneficial or aversive events, while the corresponding verbal descriptions of what somebody believes are stored in semantic memory. After recall from memory of what someone believes, personally relevant information can be communicated to other people. Thus, memory is essential for maintaining what people believe.

Evolution of neurodegeneration in patients with normal pressure hydrocephalus: a monocentric follow up study.

BACKGROUND: The aim of this study was to examine in patients with idiopathic and neurodegenerative normal pressure hydrocephalus (NPH) if motor and cognitive performance as well as changes in biomarkers in cerebrospinal fluid (CSF) evolve differently. METHODS: 41 patients with a typical clinical and MR-/CT-morphological presentation of NPH divided into an Alzheimer-negative (AD-, n = 25) and an Alzheimer-positive (AD+, n = 16) group according to neurodegenerative biomarkers (S100 protein, neuron-specific enolase, ß-amyloid 1-42, Tau protein, phospho-Tau, protein-level and CSF pressure) in CSF. Follow-up of cognitive and gait functions before and after a spinal tap of 40-50 ml CSF of up to 49 months. Clinical, motor, neuropsychological and CSF biomarkers were analyzed using a repeated multifactorial analysis of variance (ANOVA) with post-hoc testing. RESULTS: Gait and neuropsychological performance and CSF biomarkers evolved differently between the AD- and AD+ patients. In particular, the AD+ patients benefited from the spinal tap regarding short-term memory. In contrast, gait parameters worsened over time in the AD+ patients, although they showed a relevant improvement after the first tap. CONCLUSIONS: The results substantiate the recently reported association between a tap-responsive NPH and CSF changes of Alzheimer disease. Furthermore, they suggest that the AD changes in CSF manifest in an age-related fashion in AD- patients presenting with NPH.

Processes of believing - a review and conceptual account.

Processes of believing are thought to have an important impact on the control of human behavior. Recently, neuroimaging and neurophysiological studies have shown that believe processes involve brain areas known to be involved in emotion-related and cognitive processing. But there is a discrepancy between the increasing interest in empirical research and the lack of coherent terminology and conceptualization. We will show that in processes of believing, the medial frontal cortex plays a critical role within a widespread cortico-subcortical network owing to its role in valuation of internal and external events and in subjective control of action. Also, we will describe a model of processes of believing that integrates the divergent neurophysiological and conceptual aspects as a starting point for further interdisciplinary research questions.

Congenitally altered motor experience alters somatotopic organization of human primary motor cortex.

Human motor development is thought to result from a complex interaction between genes and experience. The well-known somatotopic organization of the primate primary motor cortex (M1) emerges postnatally. Although adaptive changes in response to learning and use occur throughout life, somatotopy is maintained as reorganization is restricted to modifications within major body part representations. We report of a unique opportunity to evaluate the influence of experience on the genetically determined somatotopic organization of motor cortex in humans. We examined the motor "foot" representation in subjects with congenitally compromised hand function and compensatory skillful foot use. Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) of M1 revealed that the foot was represented in the classical medial foot area of M1 and was several centimetres away in nonadjacent cortex in the vicinity of the lateral "hand" area. Both areas had direct output to the spinal motor neurons innervating foot muscles and were behaviorally relevant because experimental disruption of either area by TMS altered reaction times. We demonstrate a unique, nonsomatotopically organized M1 in humans, which emerged as a function of grossly altered motor behavior from the earliest stages of development. Our results imply that during early motor development experience may play a more critical role in the shaping of genetically determined neural networks than previously assumed.

Beliefs: A challenge in neuropsychological disorders.

INTRODUCTION: Beliefs have recently been defined as the neural product of perception of objects and events in the external world and of an affirmative internal affective state reflecting personal meaning. It is, however, undetermined in which way diseases of the brain affect these integrative processes. METHODS: Here, the formation and updating of abnormal beliefs in cerebral disorders are described. RESULTS: It will be shown that well-defined neuropsychological syndromes resulting from brain lesions also interfere with the neural processes that enable the formation, up-dating and communication of beliefs. Similarly, in neuropsychiatric disorders abnormal and delusional beliefs appear to be caused by altered perception and/or misattribution of aversive meaning. CONCLUSION: Given the importance of beliefs for ordinary social behaviour, abnormal beliefs are a challenge in neuropsychological disorders.