Hippocampal subfield plasticity is associated with improved spatial memory.

Physical exercise studies are generally underrepresented in young adulthood. Seventeen subjects were randomized into an intervention group (24.2 ± 3.9 years; 3 trainings/week) and 10 subjects into a passive control group (23.7 ± 4.2 years), over a duration of 6 months. Every two months, performance diagnostics, computerized spatial memory tests, and 3 Tesla magnetic resonance imaging were conducted. Here we find that the intervention group, compared to controls, showed increased cardiorespiratory fitness, spatial memory performance and subregional hippocampal volumes over time. Time-by-condition interactions occurred in right cornu ammonis 4 body and (trend only) dentate gyrus, left hippocampal tail and left subiculum. Increases in spatial memory performance correlated with hippocampal body volume changes and, subregionally, with left subicular volume changes. In conclusion, findings support earlier reports of exercise-induced subregional hippocampal volume changes. Such exercise-related plasticity may not only be of interest for young adults with clinical disorders of hippocampal function, but also for sedentary normal cohorts.

MRgFUS of the nucleus ventralis intermedius in essential tremor modulates functional connectivity within the classical tremor network and beyond.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus is an incisionless lesional treatment for essential tremor. OBJECTIVE: To examine relationships between tremor severity and functional connectivity in patients with essential tremor and to assess long-term changes in the tremor network after sonication of the ventral intermediate nucleus. METHODS: Twenty-one patients with essential tremor (70.33 ± 11.32 years) were included in the final analysis and underwent resting state functional magnetic resonance imaging at 3 T before and 6 months after treatment. Tremor severity (Fahn-Tolosa-Marin Clinical Rating Scale) was evaluated and functional connectivity was investigated using independent component analysis. RESULTS: MRgFUS of the thalamic ventral intermediate nucleus reduced contralateral tremor effectively. Multiple regression analysis revealed exclusively negative correlations between FC and tremor severity, notably in the right cerebellar lobe VI and the left cerebellar lobe VIIIa (cerebellar network), in the left occipital fusiform gyrus (lateral visual network), the anterior division of the left superior temporal gyrus (fronto-parieto-temporal network), and in the posterior division of the left parahippocampal gyrus and the bilateral lingual gyri (default mode network). Six months after treatment, increased functional connectivity was observed in almost all tremor-associated clusters, except the cluster localized in the left cerebellum. CONCLUSIONS: Our findings suggest that tremor-related activity in essential tremor extends beyond the classical cerebellar network, additionally involving areas related to visual processing. Functional restoration of network activity after sonication of the ventral intermediate nucleus is observed within the classical tremor network (cerebellum) and notably also in visual processing areas.

Cortical Amyloid Burden Relates to Basal Forebrain Volume in Subjective Cognitive Decline.

BACKGROUND: Atrophy of cholinergic basal forebrain (BF) nuclei is a frequent finding in magnetic resonance imaging (MRI) volumetry studies that examined patients with prodromal or clinical Alzheimer's disease (AD), but less clear for individuals in earlier stages of the clinical AD continuum. OBJECTIVE: To examine BF volume reductions in subjective cognitive decline (SCD) participants with AD pathologic changes. METHODS: The present study compared MRI-based BF volume measurements in age- and sex-matched samples of N = 24 amyloid-positive and N = 24 amyloid-negative SCD individuals, based on binary visual ratings of Florbetaben positron emission tomography (PET) measurements. Additionally, we assessed associations of BF volume with cortical amyloid burden, based on semiquantitative Centiloid (CL) analyses. RESULTS: Group differences approached significance for BF total volume (p = 0.061) and the Ch4 subregion (p = 0.059) only, showing the expected relative volume reductions for the amyloid-positive subgroup. There were also significant inverse correlations between BF volumes and CL values, which again were most robust for BF total volume and the Ch4 subregion. CONCLUSIONS: The results are consistent with the hypothesis that amyloid-positive SCD individuals, which are considered to represent a transitional stage on the clinical AD continuum, already show incipient alterations of BF integrity. The negative association with a continuous measure of cortical amyloid burden also suggests that this may reflect an incremental process. Yet, further research is needed to evaluate whether BF changes already emerge at "grey zone" levels of amyloid accumulation, before amyloidosis is reliably detected by PET visual readings.

Physical Activity Alters Functional Connectivity of Orbitofrontal Cortex Subdivisions in Healthy Young Adults: A Longitudinal fMRI Study.

Physical activity (PA) plays an important role in affect processing. Studies describe the orbitofrontal cortex (OFC) as a major hub for emotion processing and the pathophysiology of affective disorders. Subregions of the OFC show diverse functional connectivity (FC) topographies, but the effect of chronic PA on subregional OFC FC still lacks scientific understanding. Therefore, we aimed at investigating the effects of regular PA on the FC topographies of OFC subregions in healthy individuals within a longitudinal randomized controlled exercise study. Participants (age: 18-35 years) were randomly assigned to either an intervention group (IG; N = 18) or a control group (CG; N = 10). Fitness assessments, mood questionnaires, and resting state functional magnetic resonance imaging (rsfMRI) were performed four times over the duration of 6 months. Using a detailed parcellation of the OFC, we created subregional FC topography maps at each time point and applied a linear mixed model to assess the effects of regular PA. The posterior-lateral right OFC showed a group and time interaction, revealing decreased FC with the left dorsolateral prefrontal cortex in the IG, while FC in the CG increased. Group and time interaction in the anterior-lateral right OFC with the right middle frontal gyrus was driven by increased FC in the IG. The posterior-lateral left OFC showed a group and time interaction based on differential change in FC to the left postcentral gyrus and the right occipital gyrus. This study emphasized regionally distinctive FC changes induced by PA within the lateral OFC territory, while providing aspects for further research.

Regional cortical perfusion increases induced by a 6-month endurance training in young sedentary adults.

Physical inactivity is documented as a health risk factor for chronic diseases, accelerated aging, and cognitive impairment. Physical exercise, on the other hand, plays an important role in healthy aging by promoting positive muscular, cardiovascular, and central nervous system adaptions. Prior studies on the effects of exercise training on cerebral perfusion have focused largely on elderly cohorts or patient cohorts, while perfusion effects of exercise training in young sedentary adults have not yet been fully assessed. Therefore, the present study examined the physiological consequence of a 6-month endurance exercise training on brain perfusion in 28 young sedentary adults randomly assigned to an intervention group (IG; regular physical exercise) or a control group (CG; without physical exercise). The IG performed an extensive running interval training three times per week over 6 months. Performance diagnostics and MRI were performed every 2 months, and training intensity was adapted individually. Brain perfusion measurements with pseudo-continuous arterial spin labeling were analyzed using the standard Oxford ASL pipeline. A significant interaction effect between group and time was found for right superior temporal gyrus (STG) perfusion, driven by an increase in the IG and a decrease in the CG. Furthermore, a significant time effect was observed in the right middle occipital region in the IG only. Perfusion increases in the right STG, in the ventral striatum, and in primary motor areas were significantly associated with increases in maximum oxygen uptake (VO2max). Overall, this study identified region-specific increases in local perfusion in a cohort of young adults that partly correlated with individual performance increases, hence, suggesting exercise dose dependency. Respective adaptations in brain perfusion are discussed in the context of physical exercise-induced vascular plasticity.

Coherent Structural and Functional Network Changes after Thalamic Lesions in Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus is a novel incisionless ablative treatment for essential tremor (ET). OBJECTIVE: The aim was to study the structural and functional network changes induced by unilateral sonication of the ventral intermediate nucleus in ET. METHODS: Fifteen essential tremor patients (66.2 ± 15.4 years) underwent probabilistic tractography and functional magnetic resonance imaging (MRI) during unilateral postural tremor-eliciting tasks using 3-T MRI before, 1 month (N = 15), and 6 months (N = 10) post unilateral sonication. RESULTS: Tractography identified tract-specific alterations within the dentato-thalamo-cortical tract (DTCT) affected by the unilateral lesion after sonication. Relative to the treated hand, task-evoked activation was significantly reduced in contralateral primary sensorimotor cortex and ipsilateral cerebellar lobules IV/V and VI, and vermis. Dynamic causal modeling revealed a significant decrease in excitatory drive from the cerebellum to the contralateral sensorimotor cortex. CONCLUSIONS: Thalamic lesions induced by sonication induce specific functional network changes within the DTCT, notably reducing excitatory input to ipsilateral sensorimotor cortex in ET. ©[2022] International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effects of a 6-Month Aerobic Exercise Intervention on Mood and Amygdala Functional Plasticity in Young Untrained Subjects.

Acute exercise has beneficial effects on mood and is known to induce modulations in functional connectivity (FC) within the emotional network. However, the long-term effects of exercise on affective brain circuits remain largely unknown. Here, we investigated the effects of 6 months of regular exercise on mood, amygdala structure, and functional connectivity. This study comprised N = 18 healthy sedentary subjects assigned to an intervention group (IG; 23.9 ± 3.9 years; 3 trainings/week) and N = 10 subjects assigned to a passive control group (CG; 23.7 ± 4.2 years). At baseline and every two months, performance diagnostics, mood questionnaires, and structural and resting-state-fMRI were conducted. Amygdala-nuclei segmentation and amygdala-to-whole-brain FC analysis were performed. Linear mixed effects models and correlation analyses were conducted between FC, relVO2max, and mood scores. Data showed increases in relVO2max exclusively in the IG. Stronger anticorrelation in amygdala-precuneus FC was found, along with a stronger positive correlation in the amygdala-temporal pole FC in the IG after 4 and 6 months, while mood and amygdala volume did not reveal significant interactions. The relVO2max/amygdala-temporal pole FC correlated positively, and the amygdala-precuneus/amygdala-temporal pole FC correlated negatively. Findings suggest that exercise induced long-term modulations of the amygdala FC with the precuneus and temporal pole, shedding light on potential mechanisms by which exercise has positive influences on mood-related networks, typically altered in affective disorders.

Cortical representation of experimental periodontal pain: a functional magnetic resonance imaging study.

The aim of this study was to investigate central pain representations during loading of the periodontium induced by orthodontic and occlusal stress. Nineteen healthy male volunteers (25.7 ± 2.8 years) were tested on two consecutive days: after phenotyping (questionnaires) and determination of warmth (WPT) and heat (HPT) pain thresholds, functional magnetic resonance imaging was performed as event-related paradigm including 36 tooth clenchings of 3 s duration, alternating with rest periods varying between 20-30 s. The task was performed in absence (T1) and 24 h after placement of an elastic separator between the second bicuspid and the first molar on the right side of the lower jaw (T2). No significant changes in WPT and HPT were observed but pain ratings were significantly elevated at T2. Significantly elevated activation at T2, as compared to T1, was found in bilateral sensorimotor cortex, bilateral secondary sensory cortex, supplementary motor area, right rolandic operculum, and bilateral insula. Our data show for the first time in humans that periodontal stimulation, as tested by tooth clenching in the presence of an elastic separator, goes along with specific expressions of pain at behavioral and neuronal network levels. Findings supplement the existing neuroimaging literature on odontogenic pain.

Sequelae of Premature Birth in Young Adults : Incidental Findings on Routine Brain MRI.

BACKGROUND AND PURPOSE: Qualitative studies about the abnormalities appreciated on routine magnetic resonance imaging (MRI) sequences in prematurely born adults are lacking. This article aimed at filling this knowledge gap by (1) qualitatively describing routine imaging findings in prematurely born adults, (2) evaluating measures for routine image interpretation and (3) investigating the impact of perinatal variables related to premature birth. METHODS: In this study two board-certified radiologists assessed T1-weighted and FLAIR-weighted images of 100 prematurely born adults born very preterm (VP <32 weeks) and/or at very low birth weight (VLBW <1500 g) and 106 controls born at full term (FT) (mean age 26.8 ± 0.7 years). The number of white matter lesions (WML) was counted according to localization. Lateral ventricle volume (LVV) was evaluated subjectively and by measurements of Evans' index (EI) and frontal-occipital-horn ratio (FOHR). Freesurfer-based volumetry served as reference standard. Miscellaneous incidental findings were noted as free text. RESULTS: The LVV was increased in 24.7% of VP/VLBW individuals and significantly larger than in FT controls. This was best identified by measurement of FOHR (AUC = 0.928). Ventricular enlargement was predicted by low gestational age (odds ratio: 0.71, 95% CI 0.51-0.98) and presence of neonatal intracranial hemorrhage (odds ratio: 0.26, 95% CI 0.07-0.92). The numbers of deep and periventricular WML were increased while subcortical WMLs were not. CONCLUSION: Enlargement of the LVV and deep and periventricular WMLs are typical sequelae of premature birth that can be appreciated on routine brain MRI. To increase sensitivity of abnormal LVV detection, measurement of FOHR seems feasible in clinical practice.

Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status.

BACKGROUND: Amyloid-ß accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework. OBJECTIVE: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus. METHODS: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAß+) and amyloidnegative SCD (SCDß-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB). RESULTS: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAß+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAß+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAß+) and precuneus SUVRFBB (both groups). CONCLUSION: While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAß+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-ß load, highlighting incipient pathology in stage 2 of the AD continuum.

Hippocampal subfield volumes are nonspecifically reduced in premature-born adults.

Reduced global hippocampus volumes have been demonstrated in premature-born individuals, from newborns to adults; however, it is unknown whether hippocampus subfield (HCSF) volumes are differentially affected by premature birth and how relevant they are for cognitive performance. To address these questions, we investigated magnetic resonance imaging (MRI)-derived HCSF volumes in very premature-born adults, and related them with general cognitive performance in adulthood. We assessed 103 very premature-born (gestational age [GA] <32 weeks and/or birth weight <1,500 g) and 109 term-born individuals with cognitive testing and structural MRI at 26 years of age. HCSFs were automatically segmented based on three-dimensional T1- and T2-weighted sequences and studied both individually and grouped into three functional units, namely hippocampus proper (HP), subicular complex (SC), and dentate gyrus (DG). Cognitive performance was measured using the Wechsler-Adult-Intelligence-Scale (full-scale intelligence quotient [FS-IQ]) at 26 years. We observed bilateral volume reductions for almost all HCSF volumes in premature-born adults and associations with GA and neonatal treatment intensity but not birth weight. Left-sided HP, SC, and DG volumes were associated with adult FS-IQ. Furthermore, left DG volume was a mediator of the association between GA and adult FS-IQ in premature-born individuals. Results demonstrate nonspecifically reduced HCSF volumes in premature-born adults; but specific associations with cognitive outcome highlight the importance of the left DG. Data suggest that specific interventions toward hippocampus function might be promising to lower adverse cognitive effects of prematurity.

Decreased cortical thickness mediates the relationship between premature birth and cognitive performance in adulthood.

Cortical thickness (CTh) reflects cortical properties such as dendritic complexity and synaptic density, which are not only vulnerable to developmental disturbances caused by premature birth but also highly relevant for cognitive performance. We tested the hypotheses whether CTh in young adults is altered after premature birth and whether these aberrations are relevant for general cognitive abilities. We investigated CTh based on brain structural magnetic resonance imaging and surface-based morphometry in a large and prospectively collected cohort of 101 very premature-born adults (<32 weeks of gestation and/or birth weight [BW] below 1,500 g) and 111 full-term controls at 26 years of age. Cognitive performance was assessed by full-scale intelligence quotient (IQ) using the Wechsler Adult Intelligence Scale. CTh was reduced in frontal, parietal, and temporal associative cortices predominantly in the left hemisphere in premature-born adults compared to controls. We found a significant positive association of CTh with both gestational age and BW, particularly in the left hemisphere, and a significant negative association between CTh and intensity of neonatal treatment within limited regions bilaterally. Full-scale IQ and CTh in the left hemisphere were positively correlated. Furthermore, CTh in the left hemisphere acted as a mediator on the association between premature birth and full-scale IQ. Results provide evidence that premature born adults have widespread reduced CTh that is relevant for their general cognitive performance. Data suggest lasting reductions in cortical microstructure subserving CTh after premature birth.

MRI follow-up after magnetic resonance-guided focused ultrasound for non-invasive thalamotomy: the neuroradiologist's perspective.

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) systems are increasingly used to non-invasively treat tremor; consensus on imaging follow-up is poor in these patients. This study aims to elucidate how MRgFUS lesions evolve for a radiological readership with regard to clinical outcome. METHODS: MRgFUS-induced lesions and oedema were retrospectively evaluated based on DWI, SWI, T2-weighted and T1-weighted 3-T MRI data acquired 30 min and 3, 30 and 180 days after MRgFUS (n = 9 essential tremor, n = 1 Parkinson's patients). Lesions were assessed volumetrically, visually and by ADC measurements and compared with clinical effects using non-parametric testing. RESULTS: Thirty minutes after treatment, all lesions could be identified on T2-weighted images. Immediate oedema was rare (n = 1). Lesion volume as well as oedema reached a maximum on day 3 with a mean lesion size of 0.4 ± 0.2 cm3 and an oedema volume 3.7 ± 1.2 times the lesion volume. On day 3, a distinct diffusion-restricted rim was noted that corresponded well with SWI. Lesion shrinkage after day 3 was observed in all sequences. Lesions were no longer detectable on DWI in n = 7/10, on T2-weighted images in n = 4/10 and on T1-weighted images in n = 4/10 on day 180. No infarcts or haemorrhage were observed. There was no correlation between lesion size and initial motor skill improvement (p = 0.99). Tremor reduction dynamics correlated strongly with lesion shrinkage between days 3 and 180 (p = 0.01, R = 0.76). CONCLUSION: In conclusion, cerebral MRgFUS lesions variably shrink over months. SWI is the sequence of choice to identify lesions after 6 months. Lesion volume is arguably associated with intermediate-term outcome.

Prominent White Matter Involvement in Multiple System Atrophy of Cerebellar Type.

BACKGROUND: Sporadic degenerative ataxia patients fall into 2 major groups: multiple system atrophy with predominant cerebellar ataxia (MSA-C) and sporadic adult-onset ataxia (SAOA). Both groups have cerebellar volume loss, but little is known about the differential involvement of gray and white matter in MSA-C when compared with SAOA. OBJECTIVES: The objective of this study was to identify structural differences of brain gray and white matter between both patient groups. METHODS: We used magnetic resonance imaging to acquire T1-weighted images and diffusion tensor images from 12 MSA-C patients, 31 SAOA patients, and 55 healthy controls. Magnetic resonance imaging data were analyzed with voxel-based-morphometry, tract-based spatial statistics, and tractography-based regional diffusion tensor images analysis. RESULTS: Whole-brain and cerebellar-focused voxel-based-morphometry analysis showed gray matter volume loss in both patient groups when compared with healthy controls, specifically in the cerebellar areas subserving sensorimotor functions. When compared with controls, the SAOA and MSA-C patients showed white matter loss in the cerebellum, whereas brainstem white matter was reduced only in the MSA-C patients. The tract-based spatial statistics revealed reduced fractional anisotropy within the pons and cerebellum in the MSA-C patients both in comparison with the SAOA patients and healthy controls. In addition, tractography-based regional analysis showed reduced fractional anisotropy along the corticospinal tracts in MSA-C, but not SAOA. CONCLUSION: Although in our cohort extent and distribution of gray and white matter loss were similar between the MSA-C and SAOA patients, magnetic resonance imaging data showed prominent microstructural white matter involvement in the MSA-C patients that was not present in the SAOA patients. Our findings highlight the significance of microstructural white matter changes in the differentiation between both conditions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

An analysis of MRI derived cortical complexity in premature-born adults: Regional patterns, risk factors, and potential significance.

Premature birth bears an increased risk for aberrant brain development concerning its structure and function. Cortical complexity (CC) expresses the fractal dimension of the brain surface and changes during neurodevelopment. We hypothesized that CC is altered after premature birth and associated with long-term cognitive development. One-hundred-and-one very premature-born adults (gestational age <32 weeks and/or birth weight <1500 â€‹g) and 111 term-born adults were assessed by structural MRI and cognitive testing at 26 years of age. CC was measured based on MRI by vertex-wise estimation of fractal dimension. Cognitive performance was measured based on Griffiths-Mental-Development-Scale (at 20 months) and Wechsler-Adult-Intelligence-Scales (at 26 years). In premature-born adults, CC was decreased bilaterally in large lateral temporal and medial parietal clusters. Decreased CC was associated with lower gestational age and birth weight. Furthermore, decreased CC in the medial parietal cortices was linked with reduced full-scale IQ of premature-born adults and mediated the association between cognitive development at 20 months and IQ in adulthood. Results demonstrate that CC is reduced in very premature-born adults in temporoparietal cortices, mediating the impact of prematurity on impaired cognitive development. These data indicate functionally relevant long-term alterations in the brain's basic geometry of cortical organization in prematurity.

Effects of low- and high-intensity exercise on emotional face processing: an fMRI face-matching study.

Physical exercise has positive effects on mood and it reduces clinical depression and states of anxiety. While previous work mostly used subjective measures to study the effect of exercise upon emotions, this study for the first time employed blood oxygen level dependent functional magnetic resonance imaging (fMRI) to unravel associated neuronal changes of the emotional face-processing network in response to acute exercise. A total of 25 male athletes underwent fitness assessments to define two standardized 30 min exercise interventions (low and high intensity). The Positive and Negative Affect Schedule (PANAS) was completed pre- and post-exercise and neuronal responses to neutral, happy and fearful facial expressions were determined using an fMRI-based face-matching paradigm. Complete data sets were acquired in 21 participants (mean age, 27.2 ± 4.2 years). Both exercise interventions induced significant increases of the PANAS positive affect scale. Modulations of brain activation patterns following acute exercise were found only for fearful facial stimuli vs forms: reduced brain activation in posterior cingulate cortex/precuneus for the low condition and reduced activity in caudate nucleus and ventral anterior putamen for the high condition. In conclusion, this study provides first in vivo evidence that acute strenuous exercise interferes with emotional face-processing brain regions in an emotion type-specific manner.

Aberrant gyrification contributes to the link between gestational age and adult IQ after premature birth.

Gyrification is a hallmark of human brain development, starting in the second half of gestation in primary cortices, followed by unimodal and then transmodal associative cortices. Alterations in gyrification have been noted in premature-born newborns and children, suggesting abnormal cortical folding to be a permanent feature of prematurity. Furthermore, both gyrification and prematurity are tightly linked with cognitive performance, indicating a link between prematurity, gyrification, and cognitive performance. To investigate this triangular relation, we tested the following two hypotheses: (i) gyrification is aberrant in premature-born adults; and (ii) aberrant gyrification contributes to the impact of prematurity on adult cognitive performance. One hundred and one very premature-born adults (i.e. adults born before 32 weeks of gestation, and/or with birth weight <1500 g) and 111 mature-born adults were assessed by structural MRI and cognitive testing at 27 years of age. Gyrification was measured by local cortical absolute mean curvature (AMC), evaluated through structural MRI. Cognitive performance was assessed by the Wechsler Adult Intelligence Scale, full-scale IQ test. Two-sample t-tests, regression and mediation analyses were used to assess AMC group differences and the relation between AMC, birth-related variables, and full-scale IQ. Three key findings were identified. First, local AMC was widely increased in fronto-temporo-parietal primary and associative cortices of very premature-born adults. Increase of AMC was inversely associated with gestational age and birth weight and positively associated with medical complications at birth, respectively. Second, increased AMC of temporal associative cortices specifically contributed to the association between prematurity and reduced adult IQ (two-path mediation), indicating that aberrant gyrification of temporal associative cortices is critical for impaired cognitive performance after premature birth. Finally, further investigation of the relationship of gyrification between the early folding postcentral cortices and associative temporal cortices, folding later during neurodevelopment, revealed that the effect of gyrification abnormalities in associative temporal cortices on adult IQ is influenced itself by gyrification abnormalities occurring in the early folding postcentral cortices (three-path mediation). These results indicate that gyrification development across cortical areas in the brain conveys prematurity effects on adult IQ. Overall, these results provide evidence that premature birth leads to permanently aberrant gyrification patterns suggesting an altered neurodevelopmental trajectory. Statistical mediation modelling suggests that both aberrant gyrification itself as well as its propagation across the cortex express aspects of impaired neurodevelopment after premature birth and lead to reduced cognitive performance in adulthood. Thus, markers of gyrification appear as potential candidates for prognosis and treatment of prematurity effects.

Disentangling motor planning and motor execution in unmedicated de novo Parkinson's disease patients: An fMRI study.

Many studies have used functional magnetic resonance imaging to unravel the neuronal underpinnings of motor system abnormalities in Parkinson's disease, indicating functional inhibition at the level of basal ganglia-thalamo-cortical motor networks. The study aim was to extend the characterization of functional motor changes in Parkinson's Disease by dissociating between two phases of action (i.e. motor planning and motor execution) during an automated unilateral finger movement sequence with the left and right hand, separately. In essence, we wished to identify neuronal dysfunction and potential neuronal compensation before (planning) and during (execution) automated sequential motor behavior in unmedicated early stage Parkinson's Disease patients. Twenty-two Parkinson's Disease patients (14 males; 53 ±â€¯11 years; Hoehn and Yahr score 1.4 ±â€¯0.6; UPDRS (part 3) motor score 16 ±â€¯6) and 22 healthy controls (14 males; 49 ±â€¯12 years) performed a pre-learnt four finger sequence (index, ring, middle and little finger, in order), either self-initiated (FREE) or externally triggered (REACT), within an 8-second time window. Findings were most pronounced during FREE with the clinically most affected side, where motor execution revealed significant underactivity of contralateral primary motor cortex, contralateral posterior putamen (sensorimotor territory), ipsilateral anterior cerebellum / cerebellar vermis, along with underactivity in supplementary motor area (based on ROI analyses only), corroborating previous findings in Parkinson's Disease. During motor planning, Parkinson's Disease patients showed a significant relative overactivity in dorsolateral prefrontal cortex (DLPFC), suggesting a compensatory overactivity. To a variable extent this relative overactivity in the DLPFC went along with a relative overactivity in the precuneus and the ipsilateral anterior cerebellum/cerebellar vermis Our study illustrates that a refined view of disturbances in motor function and compensatory processes can be gained from experimental designs that try to dissociate motor planning from motor execution, emphasizing that compensatory mechanisms are triggered in Parkinson's Disease when voluntary movements are conceptualized for action.

Automated quantitative evaluation of brain MRI may be more accurate for discriminating preterm born adults.

OBJECTIVE: To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults. METHODS: We analyzed 3-T MRIs acquired in 2011-2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves. RESULTS: Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more "dirty" white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect. CONCLUSION: Enlarged and deformed lateral ventricles, thinner corpus callosum, and "dirty" white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations. KEY POINTS: • Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood. • In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and "dirty" white matter are visible on MRI, ask for prematurity before considering other diagnoses. • Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.

Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study.

OBJECTIVE: To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs. METHODS: This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls. RESULTS: No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1ß was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p < 0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p > 0.05]. No severe device-/stimulation-related adverse events occurred. CONCLUSION: 2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1ß plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics].