Cross-frequency and inter-regional phase synchronization in explicit transitive inference.

Explicit logical reasoning, like transitive inference, is a hallmark of human intelligence. This study investigated cortical oscillations and their interactions in transitive inference with EEG. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, theta (4-7 Hz) and alpha oscillations (8-15 Hz) had distinct functional roles. Frontal theta oscillations distinguished between new and old pairs, reflecting the inference of new information. Parietal alpha oscillations changed with serial position and symbolic distance of the pairs, representing the underlying relational structure. Frontal alpha oscillations distinguished between true and false pairs, linking the new information with the underlying relational structure. Second, theta and alpha oscillations interacted through cross-frequency and inter-regional phase synchronization. Frontal theta-alpha 1:2 phase locking appeared to coordinate spectrally diverse neural activity, enhanced for new versus old pairs and true versus false pairs. Alpha-band frontal-parietal phase coherence appeared to coordinate anatomically distributed neural activity, enhanced for new versus old pairs and false versus true pairs. It suggests that cross-frequency and inter-regional phase synchronization among theta and alpha oscillations supports human transitive inference.

Tracking the habituation of the event-related EEG potential in automatic change detection using an auditory two-tone oddball paradigm.

The mismatch negativity and the P3a of the event-related EEG potential reflect the electrocortical response to a deviant stimulus in a series of stimuli. Although both components have been investigated in various paradigms, these paradigms usually incorporate many repetitions of the same deviant, thus leaving open whether both components vary as a function of the deviant's position in a series of deviant stimuli-i.e. whether they are subject to qualitative/quantitative habituation from one instantiation of a deviant to the next. This is so because the detection of mismatch negativity/P3a in the event-related EEG potential requires an averaging over dozens or hundreds of stimuli, i.e. over many instantiations of the deviant per participant. The present study addresses this research gap. We used a two-tone oddball paradigm implementing only a small number of (deviant) stimuli per participant, but applying it to a large number of participants (n > 230). Our data show that the mismatch negativity amplitude exhibits no decrease as a function of the deviant's position in a series of (standard and) deviant stimuli. Importantly, only after the very first deviant stimulus, a distinct P3a could be detected, indicative of an orienting reaction and an attention shift, and thus documenting a dissociation of mismatch negativity and P3a.

White adipose tissue distribution and amount are associated with increased white matter connectivity.

Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole-body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal-weight, overweight, and obese males. WM connectivity was quantified using microstructure-informed tractography. Connectome-based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.

Basal Ganglia Atrophy as a Marker for Prodromal X-Linked Dystonia-Parkinsonism.

In neurodegenerative diseases, the characterization of the prodromal phase is essential for the future application of disease-modifying therapies. X-linked dystonia-parkinsonism is a hereditary neurodegenerative movement disorder characterized by severe adult-onset dystonia accompanied by parkinsonism. Distinct striatal and pallidal atrophy is present already in early disease stages indicating a long-lasting presymptomatic degenerative process. To gain insight into the prodromal phase of X-linked dystonia-parkinsonism, structural and iron-sensitive magnetic resonance imaging (MRI) was performed in 10 non-manifesting carriers and 24 healthy controls in a double-blind fashion. Seventeen patients with X-linked dystonia-parkinsonism were recruited to replicate previous findings of basal ganglia pathology and iron accumulation. Age at onset was estimated in non-manifesting carriers and patients using the repeat length of the hexanucleotide expansion and 3 single-nucleotide polymorphisms associated with age at onset. Voxel-based morphometry and subcortical volumetry showed striatal and pallidal atrophy in non-manifesting carriers (~10%) and patients (~40%). Substantia nigra volume was similarly reduced in patients (~40%). Caudate volume correlated with time to estimated onset in non-manifesting carriers. Susceptibility-weighted imaging confirmed iron deposition in the anteromedial putamen in patients. Non-manifesting carriers also showed small clusters of iron accumulation in the same area after lowering the statistical threshold. In conclusion, basal ganglia atrophy and iron accumulation precede the clinical onset of X-linked dystonia-parkinsonism and can be detected years before the estimated disease manifestation. It thereby highlights the potential of multimodal imaging to identify clinically unaffected mutation carriers with incipient neurodegeneration and to monitor disease progression independent of clinical measures. Longitudinal studies are needed to further elucidate the onset and progression rate of neurodegeneration in prodromal X-linked dystonia-parkinsonism. ANN NEUROL 2023;93:999-1011.

Threatening an Illusory Limb: An Event-related Potential Study of the Rubber Hand Illusion.

BACKGROUND: The rubber hand illusion (RHI) is a well-established method for studying body ownership: Given adequate concordance of visual, sensory, and proprioceptive stimuli, the individual experiences a rubber hand as his or her own. OBJECTIVE: To study the effects of a threat to the rubber hand. METHODS: We created a typical RHI paradigm but added threatening pain: Both the real hand of an individual and the rubber hand were stroked with a brush, either synchronously (RHI-inducing condition) or asynchronously (control condition), but only the rubber hand was then pricked with a needle to create a threatening pain condition. Event-related potentials (ERPs) were recorded in a group of 23 typically-developed individuals. ERP effects were source-localized using low-resolution electromagnetic tomography. RESULTS: The individuals consistently reported experience of the RHI during the experiment when the brush strokes were applied synchronously to both the real hand and the rubber hand. ERP analysis revealed that synchronous brush stroking gave rise to higher amplitude of frontal ERPs in the 100-200 ms range than asynchronous brush stroking, which was interpreted as reflecting the RHI. In the threatening pain condition, ERPs showed a greater positivity at frontocentral electrodes, source localized in the supplementary motor area (SMA). CONCLUSION: SMA activation could reflect a control mechanism over reflexive motor activity, facilitating a possible threat-related response. Further studies should address ERP effects and the extent of the RHI to standard and threat stimuli in a correlative fashion to further elucidate the functional significance of the neurophysiological findings.

Differences in Implicit Attitudes in West and East Germans as Measured by the Go/NoGo Association Task and Event-related EEG Potentials.

BACKGROUND AND OBJECTIVE: Implicit social cognition refers to attitudes and stereotypes that may reside outside conscious awareness and control but that still affect human behavior. In particular, the implicit favoritism of an ingroup, to which an individual belongs, as opposed to an outgroup, to which the individual does not belong, characterized as ingroup bias, is of interest and is investigated here. METHOD: We used a Go/NoGo association task (GNAT) and behavioral and electroencephalographic (event-related EEG potential [ERP] analysis) measures to investigate the implicit bias toward cities in East Germany, West Germany, and Europe, in 16 individuals each from West and East Germany (mixed gender, M age = 24). The GNAT assesses an individual's Go and NoGo responses for a given association between a target category and either pole (positive or negative) of an evaluative dimension. RESULTS: Behavioral measures revealed slightly faster reaction times to the combination of European city names and negative, as compared with positive, evaluative words in both groups. ERP analysis showed an increased negativity at 400-800 ms poststimulus in the incongruent conditions of East German city/positive word pairings (in West Germans) and West German city/positive word pairings (in East Germans). CONCLUSION: An implicitly moderately negative evaluation of Europe by both groups was exhibited based on the behavioral data, and an increased level of conflict arising from the "incongruent" pairings (ie, as manifestation of an implicitly negative attitude toward East Germany in West Germans, and toward West Germany in East Germans) was exhibited based on the electrophysiological data.

Sweets for my sweet: modulation of the limbic system drives salience for sweet foods after deep brain stimulation in Parkinson's disease.

BACKGROUND: An increase in body weight is observed in the majority of patients with Parkinson's disease (PD) who undergo deep brain stimulation (DBS) of the subthalamic nucleus (STN) although the mechanisms are unclear. OBJECTIVES: To identify the stimulation-dependent effects on reward-associated and attention-associated neural networks and to determine whether these alterations in functional connectivity are associated with the local impact of DBS on different STN parcellations. METHODS: We acquired functional task-related MRI data from 21 patients with PD during active and inactive STN DBS and 19 controls while performing a food viewing paradigm. Electrode placement in the STN was localised using a state-of-the-art approach. Based on the 3D model, the local impact of STN DBS was estimated. RESULTS: STN DBS resulted in a mean improvement of motor function of 22.6%±15.5% (on medication) and an increase of body weight of ~4 kg within 2 years of stimulation. DBS of the limbic proportion of the STN was associated with body weight gain and an increased functional connectivity within the salience network and at the same time with a decreased activity within the reward-related network in the context of sweet food images. CONCLUSIONS: Our findings indicate increased selective attention for high-caloric foods and a sweet food seeking-like behaviour after DBS particularly when the limbic proportion of the STN was stimulated.

Prodromal X-Linked Dystonia-Parkinsonism is Characterized by a Subclinical Motor Phenotype.

BACKGROUND: Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease-modifying therapies at a time point where progressive neurodegeneration can still be modified. OBJECTIVES: The objective of this study was to determine whether motor or non-motor signs of the disease occur as indicators of a prodromal phase of X-linked dystonia-parkinsonism (XDP), a highly-penetrant monogenic movement disorder with striking basal ganglia pathology. METHODS: In addition to a comprehensive clinical assessment, sensor-based balance and gait analyses were performed in non-manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient-boosted trees (GBT) methodology was utilized to classify groups of interest. RESULTS: There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best-performing GBT-based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group. CONCLUSIONS: Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Neural Plasticity in a French Horn Player with Bilateral Amelia.

Precise control of movement and timing play a key role in musical performance. This motor skill requires coordination across multiple joints, muscles, and limbs, which is acquired through extensive musical training from childhood on. Thus, making music can be a strong driver for neuroplasticity. We here present the rare case of a professional french horn player with a congenital bilateral amelia of the upper limbs. We were able to show a unique cerebral and cerebellar somatotopic representation of his toe and feet, that do not follow the characteristic patterns of contralateral cortical and ipsilateral cerebellar layout. Although being a professional horn player who trained his embouchure muscles, including tongue, pharyngeal, and facial muscle usage excessively, there were no obvious signs for an expanded somatosensory representation in this part of the classic homunculus. Compared to the literature and in contrast to control subjects, the musicians' foot movement-related activations occurred in cerebellar areas that are typically more related to hand than to foot activation.

Effects of hunger, satiety and oral glucose on effective connectivity between hypothalamus and insular cortex.

The hypothalamus and insular cortex play an essential role in the integration of endocrine and homeostatic signals and their impact on food intake. Resting-state functional connectivity alterations of the hypothalamus, posterior insula (PINS) and anterior insula (AINS) are modulated by metabolic states and caloric intake. Nevertheless, a deeper understanding of how these factors affect the strength of connectivity between hypothalamus, PINS and AINS is missing. This study investigated whether effective (directed) connectivity within this network varies as a function of prandial states (hunger vs. satiety) and energy availability (glucose levels and/or hormonal modulation). To address this question, we measured twenty healthy male participants of normal weight twice: once after 36 â€‹h of fasting (except water consumption) and once under satiated conditions. During each session, resting-state functional MRI (rs-fMRI) and hormone concentrations were recorded before and after glucose administration. Spectral dynamic causal modeling (spDCM) was used to assess the effective connectivity between the hypothalamus and anterior and posterior insula. Using Bayesian model selection, we observed that the same model was identified as the most likely model for each rs-fMRI recording. Compared to satiety, the hunger condition enhanced the strength of the forward connections from PINS to AINS and reduced the strength of backward connections from AINS to PINS. Furthermore, the strength of connectivity from PINS to AINS was positively related to plasma cortisol levels in the hunger condition, mainly before glucose administration. However, there was no direct relationship between glucose treatment and effective connectivity. Our findings suggest that prandial states modulate connectivity between PINS and AINS and relate to theories of interoception and homeostatic regulation that invoke hierarchical relations between posterior and anterior insula.

Elevation of intracranial pressure affects the relationship between hemoglobin concentration and neuronal activation in human somatosensory cortex.

During neuronal activation, a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) occurs which is the basis of functional brain imaging with blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). Elevated intracranial pressure (eICP) has been shown to impair functional deoxy-Hb changes. This study investigated this effect and its relation to the underlying neuronal activity in the human primary somatosensory cortex (SI). Functional near-infrared spectroscopy (fNIRS) during somatosensory evoked potentials (SEP) monitoring was performed on 75 subjects during conditions of median nerve stimulation (MNS) and resting state, combined with normal breathing (NB) and eICP by escalating breathing maneuvers (breath holding [BH], Valsalva maneuver with 15 mmHg [V15] and 35 mmHg expiratory pressure [V35]). During NB, fNIRS revealed a typical oxygenated hemoglobin concentration (oxy-Hb) increase with deoxy-Hb decrease during MNS enabling SI brain mapping. Breathing maneuvers associated eICP produced a known global change of oxy-Hb and deoxy-Hb with and without MNS. When subtracting measurements during resting state from measurements during MNS, neither functional oxy-Hb nor deoxy-Hb changes could be recovered while SEPs remained unchanged. In conclusion, Valsalva-induced eICP prevents oxy-Hb and deoxy-Hb changes during neuronal activation in SI. This finding raises questions on the validity of oxy-Hb- and deoxy-Hb-based brain imaging (e.g., BOLD-fMRI) during eICP.

Imaging gradual neurodegeneration in a basal ganglia model disease.

OBJECTIVE: X-linked dystonia-parkinsonism (XDP) is a neurodegenerative disease with adult onset dystonia and subsequent parkinsonism. Postmortem and imaging studies revealed remarkable striatal pathology, with a predominant involvement of the striosomal compartment in the early phase. Here, we aimed to disentangle sequential neurodegeneration in the striatum of XDP patients, provide evidence for preferential loss of distinct striatal areas in the early phase, and investigate whether iron accumulation is present. METHODS: We used multimodal structural magnetic resonance imaging (voxel-based morphometry and relaxometry) in 18 male XDP patients carrying a TAF1 mutation and 19 age-matched male controls. RESULTS: Voxel-based relaxometry and morphometry revealed (1) a cluster in the anteromedial putamen showing high iron content and severe atrophy (-55%) and (2) a cluster with reduced relaxation rates as a marker for increased water levels and a lower degree of atrophy (-20%) in the dorsolateral putamen. Iron deposition correlated with the degree of atrophy (ρ = -0.585, p = 0.011) and disease duration (ρ = 0.632, p = 0.005) in the anteromedial putamen. In the dorsolateral putamen, sensorimotor putamen atrophy correlated with disease severity (ρ = -0.649, p = 0.004). INTERPRETATION: This multimodal approach identified a patchy pattern of atrophy within the putamen. Atrophy is advanced and associated with iron accumulation in rostral regions of the striatum, whereas neurodegeneration is moderate and still ongoing in dorsolateral areas. Given the short disease duration and predominant dystonic phenotype, these results are well in line with early and preferential degeneration of striosome-rich striatal areas in XDP. ANN NEUROL 2019;86:517-526.

Structural brain changes in young males addicted to video-gaming.

Excessive video gaming has a number of psychological and social consequences. In this study, we looked at possible changes in gray and white matter and asked whether these changes are correlated to psychological measures. Twentynine players of violent videogames (mean daily playing time 4.7 h) and age matched controls were subjected to a battery of questionnaires assessing aggression, empathy, hostility, internet addiction and psychological well-being. Diffusion tensor and 3D T1-weighted MR images were obtained to examine gray (via voxel-based morphometry) and white (via tract-based spatial statistics) matter changes. Widespread regions of decreased gray matter in the players were found but no region showed increased intensity of gray matter. Density of gray matter showed a negative correlation with the total length of playing in years in the right posterior cingulate gyrus, left pre- and postcentral gyrus, right thalamus, among others. Furthermore, fractional anisotropy, a marker for white matter structure, was decreased in the left and right cingulum in the players. Both, gray and white matter changes correlated with measures of aggression, hostility, self esteem, and the degree of internet addiction. This study thus shows profound changes of brain structure as a function of excessive playing of violent video games.

Effects of a Rhodiola rosea extract on mental resource allocation and attention: An event-related potential dual task study.

Rhodiola rosea extract is widely used to alleviate stress and improve cognition and mental resources. A total of 50 adult participants were treated with 2 × 200 mg R. rosea extract (Rosalin®, WS® 1,375) for 12 weeks and were subjected to a neuropsychological test battery as well as an event-related brain potential measurement in a dual task paradigm prior to administration, after 6 weeks and after 12 weeks. The study followed a single-arm open-label design. Reaction times improved for the attention network task (ANT), the Go/Nogo task, and the divided attention task. Moreover, the orienting effect and the executive effect in the ANT showed an improvement. The P3 component in a dual task paradigm was increased in amplitude. The results of this pilot study show an improvement of mental speed and moreover, suggest improved mental resources. As the current study is single-armed these findings need to be replicated in a double-blind placebo controlled study.

Basal ganglia and cerebellar pathology in X-linked dystonia-parkinsonism.

X-linked dystonia-parkinsonism is a neurodegenerative movement disorder characterized by adult-onset dystonia combined with parkinsonism over the disease course. Previous imaging and pathological findings indicate exclusive striatal atrophy with predominant pathology of the striosomal compartment in the dystonic phase of X-linked dystonia-parkinsonism. The striosome occupies 10-15% of the entire striatal volume and the density of striosomes follows a rostrocaudal gradient with the rostral striatum being considered striosome-rich. Recent quantitative MRI analyses provided evidence for an additional involvement of the white matter and the pallidum. In this study, we aimed to (i) disentangle the degree of atrophy in the different subdivisions of the striatum; (ii) investigate changes of cortical morphology; and (iii) elucidate the role of the cerebellum in X-linked dystonia-parkinsonism. T1-weighted MRI scans were acquired in 17 male X-linked dystonia-parkinsonism patients with predominant dystonia (40.1 ± 7.5 years) and 17 ethnicity-matched male healthy controls (35.2 ± 7.4 years). Voxel-based morphometry used a region of interest-based approach for the basal ganglia and primary motor cortex, whole brain analysis, and a separate analysis of the cerebellum. Cortical thickness and subcortical volume were measured. Volume loss in X-linked dystonia-parkinsonism affected all parts of the striatum (-29% voxel intensity) but was most pronounced in the associative subdivision (-41%; P < 0.001). The volume loss also involved the external and internal pallidum, albeit to a lesser extent than the striatum (-19% and -12%, P<0.001). Cortical thickness was reduced in the frontal (-4.3%) and temporal cortex (-6.1%). In addition, we found grey matter pathology in the associative part of the cerebellum and increased voxel intensities in the anterior sensorimotor part of the cerebellum and the dorsal ponto-mesencephalic brainstem. Taken together, our analysis of subcortical and cortical grey matter in the dystonic phase of X-linked dystonia-parkinsonism showed that (i) the striosome-enriched rostral striatum was most severely affected; and (ii) cortical thickness was only reduced in those regions that predominantly have anatomical connections to striosomes. Moreover, the cerebellum may be implicated in both disease-related and compensatory changes, highlighting the significance of the cerebellum in the pathophysiology of dystonia.

Processing of Local and Global Auditory Deviants in Parkinson Disease: Electrophysiological Evidence for Enhanced Attention Capture.

OBJECTIVE: To investigate automatic auditory-change detection in patients with Parkinson disease (pwPD). BACKGROUND: Previous results regarding changes in preattentive processing in pwPD have been inconclusive. METHODS: We employed a paradigm assessing the preattentive processing of sequences of auditory tones containing deviants at either the local or global level, or at both levels. Twenty pwPD and 20 age-matched healthy controls were exposed to the tone series while they performed a visual task and had their event-related potentials recorded by electroencephalogram. RESULTS: Event-related potentials showed a mismatch negativity, which was largest for the double-deviant stimuli, of intermediate amplitude for the local deviant stimuli, and smallest for the global deviant stimuli. The mismatch negativity was of similar size in the patients and controls, with the exception of the double-deviant condition (larger in controls). By contrast, the subsequent positive component was more pronounced for the Parkinson disease group than controls, particularly for the double-deviant condition. CONCLUSIONS: The larger positivity suggests that pwPD are more prone to distraction than healthy controls, probably because dopaminergic medication shifts the stability-flexibility balance toward cognitive flexibility with increased distractibility.

Vasopressin increases human risky cooperative behavior.

The history of humankind is an epic of cooperation, which is ubiquitous across societies and increasing in scale. Much human cooperation occurs where it is risky to cooperate for mutual benefit because successful cooperation depends on a sufficient level of cooperation by others. Here we show that arginine vasopressin (AVP), a neuropeptide that mediates complex mammalian social behaviors such as pair bonding, social recognition and aggression causally increases humans' willingness to engage in risky, mutually beneficial cooperation. In two double-blind experiments, male participants received either AVP or placebo intranasally and made decisions with financial consequences in the "Stag hunt" cooperation game. AVP increases humans' willingness to cooperate. That increase is not due to an increase in the general willingness to bear risks or to altruistically help others. Using functional brain imaging, we show that, when subjects make the risky Stag choice, AVP down-regulates the BOLD signal in the left dorsolateral prefrontal cortex (dlPFC), a risk-integration region, and increases the left dlPFC functional connectivity with the ventral pallidum, an AVP receptor-rich region previously associated with AVP-mediated social reward processing in mammals. These findings show a previously unidentified causal role for AVP in social approach behavior in humans, as established by animal research.

Neuroimaging abnormalities in individuals exhibiting Parkinson's disease risk markers.

BACKGROUND: The concept of prodromal Parkinson's disease (PD) involves variable combinations of nonmotor features and subtle motor abnormalities as a result of ongoing neurodegeneration in the brain stem including substantia nigra (SN) and abnormal findings upon transcranial sonography and nuclear imaging. Except for nuclear imaging, the predictive value of risk markers for the conversion to overt PD is low. OBJECTIVE: The objective of this study was to determine whether PD risk markers are associated with changes in brain structure and to what extent cognitive changes are risk markers for PD. METHODS: Diffusion-weighted imaging, voxel-based morphometry, and cortical thickness analysis was performed in 29 individuals with hyposmia and/or an increased SN hyperechogenicity (SN+) upon transcranial sonography and 28 controls without these 2 risk markers. Classical parkinsonian signs were an exclusion criterion. All of the participants underwent a neuropsychological test battery addressing executive functions, learning ability, and verbal fluency. RESULTS: In the PD risk group, diffusion-weighted imaging mean diffusivity was increased in 4 left hemisphere clusters (posterior thalamus, inferior longitudinal fasciculus, fornix, corticospinal tract). A negative relationship of mean diffusivity and smell function was present for the posterior thalamus and the corticospinal tract. There was a significant correlation of mean diffusivity values and SN+ in all clusters. Neither voxel-based morphometry nor cortical thickness analysis revealed any group differences. No relevant group differences were observed for cognitive tests included. CONCLUSION: PD-free individuals with PD risk markers show microstructural changes of the white matter, including areas relevant for motor and limbic processes. In addition, our study provides for the first time a neuroanatomical correlate for SN hyperechogenicity. © 2018 International Parkinson and Movement Disorder Society.

Valsalva-induced elevation of intracranial pressure selectively decouples deoxygenated hemoglobin concentration from neuronal activation and functional brain imaging capability.

During neuronal activation, neurovascular coupling leads to a local decrease of deoxygenated hemoglobin concentration (deoxy-Hb) and thus forms the basis of many functional brain mapping methods. In animals, an elevated intracranial pressure (ICP) can attenuate or even reverse this deoxy-Hb signaling. To study the effect of an elevated ICP on functional brain imaging in humans, we used different breathing tasks to modify ICP and analyzed the resulting effect on neurovascular coupling in the motor cortex. Functional near-infrared spectroscopy (fNIRS) was performed on 45 subjects during alternating conditions of finger tapping and resting state combined with four different breathing maneuvers (normal breathing (NB), breath holding without Valsalva maneuver (BH), Valsalva maneuver with 15 mm Hg forced expiratory pressure against resistance (V15) and Valsalva maneuver with 35 mm Hg forced expiratory pressure against resistance (V35)) in randomized order. With escalation of breathing tasks the median amplitude of the functional deoxy-Hb decrease during finger tapping became smaller. In contrast, functional oxygenated hemoglobin concentration (oxy-Hb) and total hemoglobin concentration (total-Hb) responses did not show a significant alteration. The functional oxy-Hb map evoked by finger tapping withstood Valsalva challenges while the functional deoxy-Hb map identified the correct motor cortex in normal breathing conditions only and did not reveal a functional contrast during Valsalva maneuvers. In summary, we conclude that during ICP elevation, deoxy-Hb is not a reliable basis for functional brain imaging. This suggests that the validity of BOLD fMRI during increased ICP might be impaired.

Amyotrophic lateral sclerosis affects cortical and subcortical activity underlying motor inhibition and action monitoring.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by muscular atrophy, spasticity, and bulbar signs caused by loss of upper and lower motor neurons. Evidence suggests that ALS additionally affects other brain areas including premotor cortex and supplementary motor area. Here, we studied movement execution and inhibition in ALS patients using a stop-signal paradigm and functional magnetic resonance imaging. Seventeen ALS patients and 17 age-matched healthy controls performed a stop-signal task that required responding with a button press to a right- or left-pointing black arrow (go-stimuli). In stop-trials, a red arrow (stop-stimulus) was presented shortly after the black arrow indicating to withhold the prepared movement. Patients had by trend higher reaction times in go-trials but did not differ significantly in their inhibition performance. Patients showed stronger inhibition-related activity in inferior, superior, and middle frontal gyri as well as in putamen and pallidum. Error-related activity, conversely, was found to be stronger in healthy controls, particularly in the insula bilaterally. Patients also showed increased activity in the motor cortex during button presses. The results provide evidence for altered prefrontal and subcortical networks underlying motor execution, motor inhibition, and error monitoring in ALS.