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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.

Magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus is a novel incisionless ablative treatment for essential tremor (ET).The aim was to study the structural and functional network changes induced by unilateral sonication of the ventral intermediate nucleus in ET.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.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.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.

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.

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.The objective of this study was to identify structural differences of brain gray and white matter between both patient groups.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.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.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.

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-1 beta 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]. 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-1 beta plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-alpha, 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]. (C) 2019 Elsevier Inc. All rights reserved.

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

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], Hedderich et al. report unspecific reductions of hippocampus subfield volumes in premature‐born adults. However, they found reduced dentate gyrus volumes to mediate the effect of low gestational age on adult full‐scale intelligence quotient suggesting functional relevance in premature‐born adults.

Background There is growing evidence in the literature that the cholinergic basal forebrain might be one of the earliest affected structures in Alzheimer’s disease (AD). Recent data suggest that individuals with preclinical Alzheimer’s pathology already show atrophy of the posterior nucleus basalis of Meynert and that this even precedes the atrophy of the entorhinal cortex. Here we investigated whether basal forebrain volume reductions might not only be detectable in the mild cognitive impairment (MCI) and dementia stage of AD, but also in subjective cognitive decline (SCD) individuals who represent an at-risk population for preclinical AD, and examine the relationship with cognitive performance and amyloid-beta pathology. Methods Basal forebrain volumes of 341 participants from the multi-center German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study, including 135 healthy controls, 110 SCD, 60 MCI, and 36 AD, were analyzed using high-resolution T1-weighted images. Healthy controls and SCD participants were further grouped into amyloid-positive and amyloid-negative cases according to their cerebrospinal fluid Aβ42/40 ratio. Associations between basal forebrain volume, neuropsychological performance, and amyloid load were evaluated. Results Apart from confirming progressive basal forebrain atrophy from MCI to AD, atrophy of the posterior of nucleus basalis of Meynert was also observed in subjective cognitive decline with confirmed evidence for preclinical Alzheimer’s pathology, based on the Aβ42/40 ratio. This atrophy was neither evident in subjects with SCD without amyloid pathology nor in healthy controls with amyloid pathology. Additionally, the volume of the posterior of nucleus basalis of Meynert was significantly correlated with amyloid Aβ42/40 ratio in SCD but not in healthy controls. Conclusion Our results confirm that basal forebrain atrophy occurs early along the Alzheimer’s disease trajectory. The observed volume reduction of the cholinergic basal forebrain in Aβ-positive participants with subjective cognitive complains and the absence of any volume reductions in the Aβ-positive healthy controls suggests that these ‘subjective cognitive decline’ symptoms reflect progression from stage 1 (asymptomatic) to stage 2 (transitional cognitive impairment) of the Alzheimer’s continuum (according to the recent National Institute on Aging-Alzheimer’s Association Research Framework), revealing the beginning neurodegeneration on a macroscopic level.

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.\ud \ud One-hundred-and-one very premature-born adults (gestational age

Background: While cerebral beta-amyloid accumulation was found in many studies to alter precuneus-based functional connectivity (FC) in mild cognitive impairment and demented Alzheimer’s disease (AD) patients, its impact is less well understood in subjective cognitive decline (SCD), which in the presence of underlying AD pathologic change corresponds to a progression to stage 2 of the clinical Alzheimer’s continuum in the 2018 National Institute on Aging and Alzheimer’s Association research framework, and represents the earliest clinical manifestation of AD. Methods: From the DELCODE (DZNE – Longitudinal Cognitive Impairment and Dementia Study) cohort, two groups of 24 age- and gender-matched amyloid-positive SCD (SCDAβ+) and amyloid-negative SCD (SCDAβ-) patients were selected according to visual [18F]-Florbetaben PET readings, and studied with resting-state BOLD fMRI. Local (regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF)) and global (degree centrality (DC), precuneus seed-based FC maps) measures were calculated and compared between both groups. Furthermore, follow-up correlation analyses probed linear relationships of observed group differences with global as well as precuneal amyloid load measured by Florbetaben standard uptake value ratios (SUVRFBB). Results: For the local measures, ReHo was significantly higher in the bilateral precuneus for the SCDAβ+ group, whereas ALFF and fALFF measures were not altered between groups. For the global measures, relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in the SCDAβ+ group. Moreover, the FC differences between precuneus and occipital areas were positively correlated with global (SCDAβ+) and local precuneus SUVRFBB (both groups). Conclusions: While confounding influences due to a higher ratio of APOE e4 carriers in the SCDAβ+ group cannot be excluded, results indicate functional alterations in the precuneus hub region that were linearly related to beta-amyloid load, highlighting incipient pathology and possible compensatory mechanisms in stage 2 of the AD continuum.

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.

Purpose The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences.Methods The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 +/- 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging.Results No between-leg differences in triceps surae muscle strength were identified between dominant (2798 +/- 566 N) and non-dominant limb (2667 +/- 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P Conclusions These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size.

Cardiovascular training has been associated with neuroimaging correlates of executive control functions (ECF) in seniors and children/adolescents, while complementary studies in middle-aged populations are lacking. Ascribing a prominent role to cardiorespiratory fitness improvements, most studies concentrated on training-induced gains in maximal oxygen uptake (VO2max), although other fitness indices may provide complementary information. Here, we investigated the impact of long-term sub-maximal exercise training on interference control, considering individual training-induced shifts in blood lactate profile curves (BLC) and VO2max. Twenty-three middle-aged sedentary males (M = 49 years) underwent a six-month exercise program (intervention group, IG). Additionally, 14 individuals without exercise training were recruited (control group, CG, M = 52 years). Interference control was assessed before and after the intervention, using a functional magnetic resonance imaging (fMRI) flanker paradigm. Task performance and brain activations showed no significant group-by-time interactions. However, regression analyses in the IG revealed significant associations between individual fitness gains and brain activation changes in frontal regions, which were not evident for VO2max, but for BLC. In conclusion, training-induced plasticity of ECF-related brain activity can be observed in late middle adulthood, but depends on individual fitness gains. For moderate training intensities, BLC shifts may provide sensitive markers for training-induced adaptations linked to ECF-related brain function.

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 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.

Sporadic adult-onset ataxia of unknown etiology (SAOA) is a non-genetic neurodegenerative disorder of the cerebellum of unknown cause which manifests with progressive ataxia without severe autonomic failure. Although SAOA is associated with cerebellar degeneration, little is known about the specific cerebellar atrophy pattern in SAOA. Thirty-seven SAOA patients and 49 healthy controls (HCs) were included at two centers. We investigated the structural and functional characteristics of SAOA brains using voxel-based morphometry (VBM) and resting-state functional imaging (rs-fMRI). In order to examine the functional consequence of structural cerebellar alterations, the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and then assessed their relation with disease severity, disease duration, and age of onset within these regions. Group differences were investigated using two-sample t tests, controlling for age, gender, site, and the total intracranial volume. The VBM analysis revealed a significant, mostly bilateral reduction of local gray matter (GM) volume in lobules I–V, V, VI, IX, X, and vermis VIII a/b in SAOA patients, compared with HCs. The GM volume loss in these regions was significantly associated with disease severity, disease duration, and age of onset. The disease-related atrophy regions did not show any functional alternations compared with HCs but were functionally characterized by high ALFF and poor DC compared with intact cerebellar regions. Our data revealed volume reduction in SAOA in cerebellar regions that are known to be involved in motor and somatosensory processing, corresponding with the clinical phenotype of SAOA. Our data suggest that the atrophy occurs in those cerebellar regions which are characterized by high ALFF and poor DC. Further studies have to show if these findings are specific for SAOA, and if they can be used to predict disease progression.

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.

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. 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. 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

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term-born and 56 very preterm and/or low birth weight (VP/VLBW, < 32 weeks of gestation and/or birth weight < 1,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity--AD, RD, MD, fractional anisotropy--FA) in the whole CST and slice-wise along the CST. Additionally, we used the automatic, tract-based-spatial-statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice-wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long-term structural WM changes induced by premature birth.

Background\ud \ud Premature-born individuals have an increased risk for long-term neurocognitive impairments. In animal models, the development of the cholinergic basal forebrain (cBF) is selectively vulnerable to adverse effects of perinatal stressors, and impaired cBF integrity results in lasting cognitive deficits. We hypothesized that in premature-born individuals cBF integrity is impaired and mediates adult cognitive impairments associated with prematurity.\ud \ud Methods\ud \ud We used MRI-based volumetric assessments of a cytoarchitectonically defined cBF region-of-interest to determine differences in cBF integrity between 99 adults who were born very preterm and/or with very low birth weight (VP/VLBW) and 106 term born controls from the same birth cohort. MRI-derived cBF volumes were studied in relation to neonatal clinical complications after delivery as well as intelligence measures (IQ) in adulthood.\ud \ud Results\ud \ud In VP/VLBW adults, cBF volumes were significantly reduced compared to term-born adults (-4.5%, F(1, 202) = 11.82, p = 0.001). Lower cBF volume in VP/VLBW adults was specifically associated with both neonatal complications (rpart(92) = -0.35, p < 0.001) and adult IQ (rpart(88) = 0.33, p = 0.001) even after controlling for global gray matter and white matter volume. In an additional path analytic model, cBF volume significantly mediated the association between neonatal complications and adult cognitive deficits.\ud \ud Conclusions\ud \ud Results provide first time evidence in humans that cBF integrity is impaired after premature birth and links neonatal complications with long-term cognitive outcome. Data suggest that cholinergic system abnormalities may play a relevant role for long-term neurocognitive impairments associated with premature delivery.

Premature birth is associated with an increased risk of cognitive performance deficits that are dependent on working memory (WM) load in childhood. Less clear is whether preterm-born adults show similar WM impairments, or develop compensatory brain mechanisms that help to overcome prematurity-related functional deficits, for example, by a workload-dependent over-recruitment of WM-typical areas, and/or engagement of alternative brain networks. In this functional magnetic resonance imaging study, 73 adults born very preterm and/or with very low birth weight (VP/VLBW) and 73 term-born controls (CON, mean age: 26.5 years) performed a verbal N-Back paradigm with varying workload (0-back, 1-back, 2-back). Generally, both groups showed similar performance accuracy and task-typical patterns of brain activations (especially in fronto-cingulo-parietal, thalamic, and cerebellar areas) and deactivations (especially in mesial frontal and parietal aspects of the default mode network [DMN]). However, VP/VLBW adults showed significantly stronger deactivations (P 2-back) in the parahippocampal/cerebellar cluster also presented a greater slowing of response latencies with increasing WM load (2-back > 1-back), indicative of higher effort. In conclusion, VP/VLBW adults recruited similar anatomical networks as controls during N-back performance, but showed an enhanced suppression of posterior DMN regions during higher workload, which may reflect a temporary suppression of stimulus-independent thoughts that helps to maintain adequate task performance with increasing attentional demands.

Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM.

Background Individuals with subjective memory impairment (SMI) report worsening of memory without impairment in cognitive tests. Despite normal cognitive performance, they may be at higher risk of cognitive decline compared with individuals without SMI. Methods We used a discriminative function (a support vector machine) trained on an independent data set of 226 healthy control subjects and 191 patients with probable Alzheimer's disease (AD) dementia to characterize the baseline gray matter patterns of 24 individuals with SMI and 53 control subjects. We tested for associations of these gray matter patterns with SMI presence, cognitive performance at baseline, and cognitive decline at follow-up. Results Individuals with SMI showed greater similarity to an AD gray matter pattern compared with control subjects without SMI. In addition, episodic memory decline was associated with an AD gray matter pattern in the SMI group. Conclusions Our results indicate a link between the gray matter atrophy pattern of patients with AD and the presence of SMI. Furthermore, multivariate pattern recognition approaches seem to be a sensitive method for identifying subtle brain changes that correspond to future memory decline in SMI.

PLoS ONE, 12 (1), ISSN:1932-6203

Reexposure to trauma reminders is an integral element of trauma-focused cognitive behavioral therapy (Roberts et al., 2009), but little is known about the physiological processes underlying the therapeutic progress. While it is well established that amygdala, prefrontal cortex and hippocampus are key brain structures in fear memory processing (McGaugh, 2004; Herry et al., 2008; Likhtik et al., 2008), it is not well known which neurotransmitters or neuromodulators are involved. Here with a translational approach we investigated the role of dynorphins in the formation and extinction of fear memories in mice and in humans. Mice lacking dynorphin showed an enhanced cue-dependent fear conditioning, as well as delayed extinction in contextual conditioning/extinction paradigms. The pharmacological blockade of κ-opioid receptors before the extinction trials but not before or after the conditioning produced a similar effect. Analysis of neuronal activity, using the immediate early gene c-fos, demonstrated a reduced neuronal activity in key limbic structures during extinction in the absence of dynorphin. Translating these findings into the human domain, fear conditioning and extinction, coupled with functional MRI was then performed in volunteers preselected for a functionally relevant polymorphism in the dynorphin gene. Human volunteers bearing the (T) allele of PDYN (prodynorphin) at rs1997794 showed reduced fear extinction and a significantly diminished functional connectivity between amygdala and ventromedial prefrontal cortex. Our findings establish a role of dynorphin κ-opioid receptor signaling in fear extinction.

Major depressive disorder (MDD) is accompanied by morphological changes of brain structures which are of great importance in the neural circuitry mediating depression like the hippocampus and the amygdala. Hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system resulting in enhanced glucocorticoid secretion can often be observed during depression and has been thought to play an important role in inducing these morphological changes. We used magnetic resonance imaging to investigate alterations of amygdala and hippocampal volumes in 86 in-patients with unipolar depression and 87 healthy controls, and we then correlated amygdala and hippocampal volumes of 76 in-patients with the area under the curve of cortisol secretion in the dexamethasone/corticotropin releasing hormone (Dex/CRH) test at baseline and during short-term antidepressant therapy. In line with recently published studies both left and right amygdala volumes of patients in a first depressive episode were smaller than those of healthy controls. Patients with recurrent depressive episodes showed a reduction of hippocampal volumes, while amygdala volumes were normal. Larger left and right amygdala volumes correlated with a more pronounced reduction of HPA activity, measured by the cortisol secretion in the combined DEX/CRH test, during antidepressant therapy in patients with recurrent depressive episodes.

BackgroundThe apolipoprotein E4 allele (ApoE4) is an established genetic risk factor for Alzheimer's disease (AD). However, its effects on cognitive performance and brain structure in healthy individuals are complex. We investigated the effect of ApoE4 on cognitive performance and medial temporal lobe volumetric measures in cognitively unimpaired young elderly with and without subjective memory impairment (SMI), which is an at-risk condition for dementia.MethodAltogether, 40 individuals with SMI and 62 without were tested on episodic memory and on tasks of speed and executive function. All participants were ApoE genotyped. 21 subjects with SMI and 47 without received additional structural magnetic resonance imaging. Volumetric measures of the hippocampus, the entorhinal cortex and the amygdala were obtained manually.ResultsIn the SMI group, ApoE4 carriers performed worse on the episodic memory (p=0.049) and showed smaller left hippocampal volumes (p=0.030). In the individuals without SMI, the ApoE4 carriers performed better on episodic memory (p=0.018) and had larger right hippocampal volumes (p=0.039). The interaction of group (SMI/no SMI) and ApoE genotype was significant for episodic memory (p=0.005) and right and left hippocampal volumes (p=0.042; p=0.035). There were no within-group differences or interaction effects on speed and executive function composite measures or other volumetric measures.ConclusionsThe negative effect of ApoE4 on episodic memory and hippocampal volume in SMI supports SMI as a prodromal condition of AD. The positive effects of ApoE4 in subjects without SMI adds to a number of reports on positive ApoE4 effects in young and very old individuals.

Alterations of regional cerebral blood flow (rCBF) in prefrontal cortex and the anterior cingulate cortex are conspicuous imaging findings in patients with major depression (MD). While these rCBF changes have been suggested as functional disease markers, data in large patient samples examining treatment response prediction to antidepressant therapy are limited. This study examined the predictive value of Tc-99m-HMPAO-SPECT for subsequent treatment response to antidepressant therapy with citalopram in an unprecedented large collective of patients. Ninety-three patients with MD were examined with Tc-99m-HMPAO-SPECT twice, at the beginning of citalopram-treatment (T1) and after 4 weeks of treatment (T2). To determine the impact of rCBF changes associated with treatment response, the patient sample was divided into two subgroups: responders (44 patients) and non-responders (49 patients). A two-sample t-test was used to determine group-specific rCBF-differences. Age, gender and initial Hamilton Rating Scale for Depression (HRSD) were treated as regressors of no interest. The responder group revealed significant relative rCBF increases at T1 in a large region en-compassing predominantly prefrontal and temporal cortices as well as subgenual cingulate cortex. No relative rCBF decreases were detected in this group. The comparison between T1 and T2 revealed trends of rCBF decreases in inferior frontal gyrus and rCBF increases in premotor cortex in the responder group. Our data show that rCBF measurements with TC-99M-HMPAO-SPECT provide a predictor estimate for subsequent treatment response in depressed patients undergoing antidepressant therapy with citalopram. This effect is highly significant and, most notably, independent of the initial HRSD score.

OBJECTIVE. Preterm birth at PATIENTS AND METHODS. Eight patients (median gestational age: 26.5 weeks; median birth weight: 885 g) were included. The functional MRI was performed at term-equivalent age (median: 39 weeks' postconceptional age) under chloral hydrate (50 mg/kg) sedation. In 5 of 8 patients, functional MRI data acquisition was successful. This resulted in 10 functional data sets (5 for passive stimulation of each forearm).RESULTS. Unilateral stimulation was associated with mainly bilateral activation of the primary sensorimotor cortex (n = 7 of 10 data sets), the prevailing hemodynamic response being a negative blood oxygenation level–dependent signal. Positive blood oxygenation level–dependent response or failure to activate the sensorimotor cortex (n = 3 of 10 data sets) were seen in those patients with aberrant structural/behavioral indices.CONCLUSIONS. Our data show the feasibility of passive unilateral sensorimotor stimulation during neonatal clinical MRI protocols. The bilateral activation pattern observed at this age is compatible with a bilaterally distributed sensorimotor system. Our data validate initial accounts for a raised incidence of negative blood oxygenation level–dependent responses in the primary sensorimotor cortex at this developmental stage. The negative blood oxygenation level–dependent response is likely to reflect a reduction of the oxy/deoxy–hemoglobin ratio during a maturational stage characterized by rapid formation of synapses, yet ineffective processing. Positive blood oxygenation level–dependent responses or failure to activate the sensorimotor cortex may be an early indicator of abnormal development and will have to be followed up carefully.

Currently, a paradigm shift towards expanded early use of cranial MRI in newborns at risk and infants in the first year of life can be observed in neonatology. Beyond clinical MRI applications, there is progressive use of functional MRI (fMRI) in this age group. On the one hand, fMRI allows monitoring of functional developmental processes depending on maturational stage; on the other hand, this technique may provide the basis for early detection of pathophysiological processes as a prerequisite for functionally guided therapeutic interventions. This article provides a comprehensive review of current fMRI applications in neonates and infants during the first year of life and focuses on the associated methodological issues (e. g. signal physiology, sedation, safety aspects).

Glucocorticoid receptor (GR) plays a major role in regulation of the hypothalamic–pituitary–adrenocortical (HPA) system; HPA dysregulation represents the most consistent biological pattern of depression. Multiple functional polymorphisms are known for the GR gene, which might influence the development of unipolar depression. Previous studies reported associations to some variants in this gene but not consistently so. We investigated seven genetic polymorphisms in the GR gene (NR3C1) located in the putative promoter, exon 2 and intron 2 region. Study populations were 322 German inpatients with recurrent unipolar depression, and 298 German controls recruited from the general population. The relationships between intermediate phenotypes (hippocampal and amygdala volumes) and NR3C1 DNA sequence variants were additionally explored in a subpopulation of patients. We found association between the diagnosis of depression and DNA sequence variants in intron 2 as well as in the 5′ region of the NR3C1 gene but not for the previously studied exon 2 and putative promoter variants (global test after control of multiple testing, P = 0.02). In patients, diagnosis-related alleles were also associated to hippocampal volume reduction and amygdala volume variation. Unipolar depression is associated with DNA variants of the NR3C1 gene in our population. Neurobiological underpinnings of depression as volumetric reductions of the hippocampus may also be mediated by variants in this gene. © 2008 Wiley-Liss, Inc.

The last few years have proven that high field magnetic resonance imaging (MRI) is superior in nearly every way to conventional equipment up to 1.5 tesla (T). Following the global success of 3T-scanners in research institutes and medical practices, a new generation of MRI devices with field strengths of 7T and higher is now on the horizon. The introduction of ultra high fields has brought MRI technology closer to the physical limitations and increasingly greater costs are required to achieve this goal. This article provides a critical overview of the advantages and problems of functional neuroimaging using ultra high field strengths. This review is principally limited to T2*-based functional imaging techniques not dependent on contrast agents. The main issues include the significance of high field technology with respect to SNR, CNR, resolution, and sequences, as well as artifacts, noise exposure, and SAR. Of great relevance is the discussion of parallel imaging, which will presumably determine the further development of high and ultra high field strengths. Finally, the importance of high field strengths for functional neuroimaging is explained by selected publications.