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Background and ObjectivesWhile there is growing evidence that physical activity promotes neuronal health, studies examining the relation between physical activity and brain morphology remain inconclusive. We therefore examined whether objectively quantified physical activity is related to brain volume, cortical thickness, and gray matter density in a large cohort study. In addition, we assessed molecular pathways that may underlie the effects of physical activity on brain morphology.MethodsWe used cross-sectional baseline data from 2,550 eligible participants (57.6% women; mean age: 54.7 years, range: 30–94 years) of a prospective cohort study. Physical activity dose (metabolic equivalent hours and step counts) and intensity (sedentary and light-intensity and moderate-to-vigorous intensity activities) were recorded with accelerometers. Brain volumetric, gray matter density, and cortical thickness measures were obtained from 3T MRI scans using FreeSurfer and Statistical Parametric Mapping. The relation of physical activity (independent variable) and brain structure (outcome) was examined with polynomial multivariable regression, while adjusting for age, sex, intracranial volume, education, and smoking. Using gene expression profiles from the Allen Brain Atlas, we extracted molecular signatures associated with the effects of physical activity on brain morphology.ResultsPhysical activity dose and intensity were independently associated with larger brain volumes, gray matter density, and cortical thickness of several brain regions. The effects of physical activity on brain volume were most pronounced at low physical activity quantities and differed between men and women and across age. For example, more time spent in moderate-to-vigorous intensity activities was associated with greater total gray matter volume, but the relation leveled off with more activity (standardized β [95% CIs]: 1.37 [0.35–2.39] and −0.70 [−1.25 to −0.15] for the linear and quadratic terms, respectively). The strongest effects of physical activity were observed in motor regions and cortical regions enriched for genes involved in mitochondrial respiration.DiscussionOur findings suggest that physical activity benefits brain health, with the strongest effects in motor regions and regions with a high oxidative demand. While young adults may particularly profit from additional high-intensity activities, older adults may already benefit from light-intensity activities. Physical activity and reduced sedentary time may be critical in the prevention of age-associated brain atrophy and neurodegenerative diseases.

Metabolic syndrome (MetS) is a major public health burden worldwide and associated with brain abnormalities. Although insulin resistance is considered a pivotal feature of MetS, its role in the pathogenesis of MetS‐related brain alterations in the general population is unclear. Therefore, in 973 participants (mean age 52.5 years) of the population‐based Rhineland Study, we assessed brain morphology in relation to MetS and insulin resistance, and evaluated to what extent the pattern of structural brain changes seen in MetS overlap with those associated with insulin resistance. Cortical reconstruction and volumetric segmentation were obtained from high‐resolution brain images at 3 Tesla using FreeSurfer. The relations between metabolic measures and brain structure were assessed through (generalized) linear models. Both MetS and insulin resistance were associated with smaller cortical gray matter volume and thickness, but not with white matter or subcortical gray matter volume. Age‐ and sex‐adjusted vertex‐based brain morphometry demonstrated that MetS and insulin resistance were related to cortical thinning in a similar spatial pattern. Importantly, no independent effect of MetS on cortical gray matter was observed beyond the effect of insulin resistance. Our findings suggest that addressing insulin resistance is critical in the prevention of MetS‐related brain changes in later life., Both MetS and insulin resistance were associated with smaller cortical gray matter volume and thickness, and related to cortical thinning in a similar spatial pattern. Importantly, no independent effect of MetS on cortical gray matter was observed beyond the effect of insulin resistance. Our findings suggest that addressing insulin resistance is critical in the prevention of MetS‐related brain changes in later life.

Subregions in the medial temporal lobe (MTL) are affected early by Alzheimer’s disease (AD) pathology and subject to grey matter atrophy. Measuring the earliest AD-related atrophy in the hippocampus is challenging as region-of-interest (ROI) analyses of hippocampal subregional volumes collapse across voxels within anatomical subregions. PET imaging studies, however, report accumulation of tau pathology between anatomical subregions in the earliest disease stages (Berron et al., 2021) fitting reports from the neuropathological literature (Lace et al., 2019; Ravikumar et al., 2021). Thus, sensitive in vivo methods of point-wise structural measures are needed in order to detect the earliest hippocampal thinning in AD along the anterior-posterior as well as the medial-lateral hippocampal axis.MethodHere we analyzed data from 76 amyloid-beta negative (Ab-) cognitively normal (CN), 46 Ab+ CN individuals and 25 Ab+ patients with mild cognitive impairment (MCI) from the BioFINDER-2 study, who underwent 7 Tesla T2-weighted structural magnetic resonance imaging, tau positron emission tomography imaging (using 18F-RO-948) and cognitive assessments. First, we segmented hippocampal subfields and extrahippocampal subregions. Second, we calculated point-wise hippocampal thickness estimates (Diers et al.) of hippocampal subfields subiculum, cornu ammonis (CA)1, CA2 and CA3 on the level of the hippocampal body. Thirdly, we extracted local tau-PET SUVR from Area 35 (A35), entorhinal cortex and amygdala. Finally, we assessed relationships between hippocampal local thickness and tau accumulation as well as cognitive performance.ResultOur analyses revealed earliest hippocampal thinning associated with tau accumulation in an area spanning the boundary of subiculum and CA1 at the level of the anterior hippocampal body. Ab+ MCI patients showed more posterior thinning in comparison to Ab- CU participants. Median thickness in an ROI comprising vertices with A35 tau-related thinning (A35-TauThinning-ROI) was significantly lower in MCI Ab+ and tended to be lower in CU Ab+ compared to CU Ab-. Higher median thickness in the hippocampal A35-TauThinning-ROI, but not whole CA1 nor subiculum thickness, was associated with better 10-Word-Delayed-Recall and higher PACC scores.ConclusionOur results suggest that tau-related thinning of hippocampal subregions can be observed already in early disease stages. Tau-related point-wise thickness measures were more sensitive compared to volumetric measures of anatomical subregions.

We introduce a new and time-efficient memory-encoding paradigm for functional magnetic resonance imaging (fMRI). This paradigm is optimized for mapping multiple contrasts using a mixed design, using auditory (environmental/vocal) and visual (scene/face) stimuli. We demonstrate that the paradigm evokes robust neuronal activity in typical sensory and memory networks. We were able to detect auditory and visual sensory-specific encoding activities in auditory and visual cortices. Also, we detected stimulus-selective activation in environmental-, voice-, scene-, and face-selective brain regions (parahippocampal place and fusiform face area). A subsequent recognition task allowed the detection of sensory-specific encoding success activity (ESA) in both auditory and visual cortices, as well as sensory-unspecific positive ESA in the hippocampus. Further, sensory-unspecific negative ESA was observed in the precuneus. Among others, the parallel mixed design enabled sustained and transient activity comparison in contrast to rest blocks. Sustained and transient activations showed great overlap in most sensory brain regions, whereas several regions, typically associated with the default-mode network, showed transient rather than sustained deactivation. We also show that the use of a parallel mixed model had relatively little influence on positive or negative ESA. Together, these results demonstrate a feasible, versatile, and brief memory-encoding task, which includes multiple sensory stimuli to guarantee a comprehensive measurement. This task is especially suitable for large-scale clinical or population studies, which aim to test task-evoked sensory-specific and sensory-unspecific memory-encoding performance as well as broad sensory activity across the life span within a very limited time frame.

Highlights • First publicly available deep learning pipeline to segment the olfactory bulbs (OBs) in sub-millimeter T2-weighted whole-brain MRI. • Rigorous validation in the Rhineland Study - an ongoing large population-based cohort study - in terms of segmentation accuracy, stability and reliability of volume estimates, as well as sensitivity to replicate known OB volume associations (e.g. age effects). • Good generalizability to an unseen heterogeneous independent dataset (the Human Connectome Project). • Robustness even for individuals without apparent OBs, as can be encountered in large cohort studies., The neuroimage analysis community has neglected the automated segmentation of the olfactory bulb (OB) despite its crucial role in olfactory function. The lack of an automatic processing method for the OB can be explained by its challenging properties (small size, location, and poor visibility on traditional MRI scans). Nonetheless, recent advances in MRI acquisition techniques and resolution have allowed raters to generate more reliable manual annotations. Furthermore, the high accuracy of deep learning methods for solving semantic segmentation problems provides us with an option to reliably assess even small structures. In this work, we introduce a novel, fast, and fully automated deep learning pipeline to accurately segment OB tissue on sub-millimeter T2-weighted (T2w) whole-brain MR images. To this end, we designed a three-stage pipeline: (1) Localization of a region containing both OBs using FastSurferCNN, (2) Segmentation of OB tissue within the localized region through four independent AttFastSurferCNN - a novel deep learning architecture with a self-attention mechanism to improve modeling of contextual information, and (3) Ensemble of the predicted label maps. For this work, both OBs were manually annotated in a total of 620 T2w images for training (n=357) and testing. The OB pipeline exhibits high performance in terms of boundary delineation, OB localization, and volume estimation across a wide range of ages in 203 participants of the Rhineland Study (Dice Score (Dice): 0.852, Volume Similarity (VS): 0.910, and Average Hausdorff Distance (AVD): 0.215 mm). Moreover, it also generalizes to scans of an independent dataset never encountered during training, the Human Connectome Project (HCP), with different acquisition parameters and demographics, evaluated in 30 cases at the native 0.7 mm HCP resolution (Dice: 0.738, VS: 0.790, and AVD: 0.340 mm), and the default 0.8 mm pipeline resolution (Dice: 0.782, VS: 0.858, and AVD: 0.268 mm). We extensively validated our pipeline not only with respect to segmentation accuracy but also to known OB volume effects, where it can sensitively replicate age effects (β=−0.232, p

Traditional neuroimage analysis pipelines involve computationally intensive, time-consuming optimization steps, and thus, do not scale well to large cohort studies with thousands or tens of thousands of individuals. In this work we propose a fast and accurate deep learning based neuroimaging pipeline for the automated processing of structural human brain MRI scans, replicating FreeSurfer's anatomical segmentation including surface reconstruction and cortical parcellation. To this end, we introduce an advanced deep learning architecture capable of whole brain segmentation into 95 classes. The network architecture incorporates local and global competition via competitive dense blocks and competitive skip pathways, as well as multi-slice information aggregation that specifically tailor network performance towards accurate segmentation of both cortical and sub-cortical structures. Further, we perform fast cortical surface reconstruction and thickness analysis by introducing a spectral spherical embedding and by directly mapping the cortical labels from the image to the surface. This approach provides a full FreeSurfer alternative for volumetric analysis (in under 1 minute) and surface-based thickness analysis (within only around 1h runtime). For sustainability of this approach we perform extensive validation: we assert high segmentation accuracy on several unseen datasets, measure generalizability and demonstrate increased test-retest reliability, and high sensitivity to group differences in dementia., Comment: Submitted to NeuroImage

Emotion regulation is an indispensable part of mental health and adaptive behavior. Research into emotion regulation processes has largely focused on the concurrent effects of volitional emotion regulation. However, there is scarce evidence considering post-regulatory effects with regard to neural mechanisms and emotional experiences. Therefore, we compared concurrent effects of cognitive emotion regulation with effects at different (immediate, short- and long-term) time intervals. In an fMRI study with N=46 (N=30 at re-exposure) young healthy adults, we compared neuronal responses to negative and neutral pictures while participants had to distance themselves from or to actively permit emotions in response to these pictures. We investigated the temporal dynamics of activation changes related to regulation in cognitive control brain networks as well as in the amygdala during stimulation (concurrent effects, timepoint 1) and post-stimulation (immediate, timepoint 2), as well as during re-exposure with the same pictures after short (10 minutes, timepoint 3) and long (1 week, timepoint 4) time intervals. At timepoint 1, negative pictures (versus neutral pictures) elicited a strong response in regions of affective processing, including the amygdala. Distancing (as compared to permit) led to a decrease of this response, and to an increase of activation in the right middle frontal and inferior parietal cortex. We observed an interaction effect of time (stimulation vs. post-stimulation) and regulation (distance vs. permit), indicating a partial reversal of regulation effects during the post-stimulation phase (timepoint 2). Similarly, after 10 minutes (timepoint 3) and after 1 week (timepoint 4), activation in the amygdala was higher during pictures that participants were previously instructed to distance from as compared to permit. These results show that the temporal dynamics are highly variable both within experimental trials and across brain regions. This can even take the form of paradoxical aftereffects at immediate and persistent effects at prolonged time scales.

Shape-based markers have entered the field of morphometric neuroimaging analysis as a second mainstay alongside conventional volumetric approaches. We aimed to assess the added value of shape description for the analysis of lesional and autoimmune temporal lobe epilepsy (TLE) focusing on hippocampus and amygdala. We retrospectively investigated MRI and clinical data from 65 patients with lesional TLE (hippocampal sclerosis (HS) and astrogliosis) and from 62 patients with limbic encephalitis (LE) with serologically proven autoantibodies. Surface reconstruction and volumetric segmentation were performed with FreeSurfer. For the shape analysis, we used BrainPrint, a tool that utilizes eigenvalues of the Laplace-Beltrami operator on triangular meshes to calculate intra-subject asymmetry. Psychometric tests of memory performance were ascertained, to evaluate clinical relevance of the shape descriptor. The potential benefit of shape in addition to volumetric information for classification was assessed by five-fold repeated cross validation and logistic regression. For the LE group, the best performing classification model consisted of a combination of volume and shape asymmetry (mean AUC = 0.728), the logistic regression model was significantly improved considering both modalities instead of just volume asymmetry. For lesional TLE, the best model only considered volumetric information (mean AUC = 0.867). Shape asymmetry of the hippocampus was largely associated with verbal memory performance only in LE patients (OR = 1.07, p = 0.02). For lesional TLE, shape description is robust, but redundant when compared to volumetric approaches. For LE, in contrast, shape asymmetry as a complementary modality significantly improves the detection of subtle morphometric changes and is further associated with memory performance, which underscores the clinical relevance of shape asymmetry as a novel imaging biomarker.

Recent translational studies identified a common endocannabinoid polymorphism, FAAH C385A, in the gene for the fatty acid amide hydrolase (FAAH). This polymorphism alters endocannabinoid anandamide levels, which are known to be involved in the fronto-amygdala circuitry implicated in mood regulation and anxiety-like behaviors. While it has been shown that the variant that selectively enhances fronto-amygdala connectivity at rest is associated with decreased anxiety-like behaviors, no study so far has investigated whether this finding of FAAH-related differential plasticity extends to task-related differential functional expression and regulation during negative emotional processing. Using an imaging genetics approach, this study aimed to replicate and extend prior findings by examining functional activity and task-related connectivity in fronto-amygdala regions during emotion reactivity and emotional down-regulation of negative affect. Therefore, 48 healthy young adults underwent a functional MRI resting state measurement, completed an emotion regulation paradigm and provided self-reports on anxiety and use of emotion regulation strategies. In line with previous studies, preliminary evidence suggests that A-allele carriers demonstrate stronger fronto-amygdala connectivity during rest. In addition, exploratory whole-brain analyses indicate differential functional activity of A-allele carriers during emotion reactivity and emotion regulation. There were no associations with anxiety-related self-reports and use of emotional regulation strategies. Further research using larger samples and polygenic approaches is indicated to clarify the precise role and its underlying mechanisms in emotion processing.

Regulation of emotions is necessary for successful attainment of short-term and long-term goals. However, over-regulation may also have its costs. In anorexia nervosa (AN), forgoing food intake despite emaciation and endocrine signals that promote eating is an example of “too much” self-control. Here we investigated whether voluntary emotion regulation in AN patients comes with associated disorder-relevant costs. Thirty-five patients with acute AN and thirty-five age-matched healthy controls (HCs) performed an established emotion regulation paradigm during functional magnetic resonance imaging after an overnight fast. The task required reducing emotions induced by positively valenced pictures via distancing. We calculated a neural regulation score from responses recorded in a reward-related brain region of interest (ventral striatum; VS) by subtracting activation measured on “positive distance” trials from that elicited under the “positive watch” (baseline) condition. Complementing the imaging data, we used ecological momentary assessment (EMA) to probe disorder-related rumination and affect six times/day for 2 weeks following the scanning session. The neural regulation score indicating reduced VS activation during emotion regulation was used as a predictor in hierarchical linear models with EMA measures as outcomes. No group differences in neural activity were found for the main contrasts of the task. However, regulation of VS activity was associated with increased body-related rumination and increased negative affect in AN, but not in HC. In line with this finding, correlational analysis with longitudinal BMI measurements revealed a link between greater VS regulation and poorer treatment outcome after 60 and 90 days. Together, these results identify a neural correlate of altered emotion regulation in AN, which seems to be detrimental to psychological well-being and may interfere with recovery.

Amyloid-β (Aβ) deposition is known to starts decades before the onset of clinical symptoms of Alzheimer’s disease (AD), however, the detailed pathophysiological processes underlying this preclinical period are not well understood. This study aimed to investigate functional network alterations in cognitively intact elderly individuals at risk for AD, and assessed the association between these network alterations and changes in Aβ deposition, glucose metabolism, and brain structure. Forty-five cognitively normal elderly subjects, who were classified into Aβ-positive (CN+) and Aβ-negative (CN−) groups using 11C-Pittsburgh compound B PET, underwent resting state magnetoencephalography measurements, 18F-fluorodeoxyglucose PET (FDG-PET) and structural MRI. Results demonstrated that in the CN+ group, functional connectivity (FC) within the precuneus was significantly decreased, whereas it was significantly enhanced between the precuneus and the bilateral inferior parietal lobules in the low-frequency bands (theta and delta). These changes were suggested to be associated with local cerebral Aβ deposition. Most of Aβ+ individuals in this study did not show any metabolic or anatomical changes, and there were no significant correlations between FC values and FDG-PET or MRI volumetry data. These results demonstrate that functional network alterations, which occur in association with Aβ deposition, are detectable using magnetoencephalography before metabolic and anatomical changes are seen.

A common and mostly effective emotion regulation strategy is reappraisal. During reappraisal, activity in cognitive control brain regions increases and activity in brain regions associated with emotion responding (e.g., the amygdala) diminishes. Immediately after reappraisal, it has been observed that activity in the amygdala increases again, which might reflect a paradoxical aftereffect. While there is extensive empirical evidence for these neural correlates of emotion regulation, only few studies targeted the association with individual differences in personality traits. The aim of this study is to investigate these associations more thoroughly. Seventy-six healthy participants completed measures of broad personality traits (Big Five, Positive and Negative Affect) as well as of more narrow traits (habitual use of emotion regulation) and performed an experimental fMRI reappraisal task. Participants were instructed to either permit their emotions or to detach themselves from the presented negative and neutral pictures. After each picture, a relaxation period was included. Reappraisal success was determined by arousal ratings and activity in the amygdala. During reappraisal, we found activation in the prefrontal cortex and deactivation in the left amygdala. During the relaxation period, an immediate aftereffect was found in occipital regions and marginally in the amygdala. Neither personality traits nor habitual use of emotion regulation predicted reappraisal success or the magnitude of the aftereffect. We replicated typical activation and deactivation patterns during intentional emotion regulation and partially replicated the immediate aftereffect in the amygdala. However, there was no association between personality traits and emotion regulation success.

Purpose: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population.Design: Cross-sectional meta-analysis.Participants: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9 +/- 12.3-82.1 +/- 4.2 years) of the European Eye Epidemiology (E3) consortium.Methods: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis.Main Outcome Measures: Determinants of pRNFLT.Results: Mean pRNFLT ranged from 86.8 +/- 21.4 mu m in the Rotterdam Study I to 104.7 +/- 12.5 mu m in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mu m/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (10P) (beta = -0.36 mu m/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mu m; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mu m; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mu m; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mu m; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mu m/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mu m; 95% CI, 1.00-2.06 for current smokers compared with never-smokers).Conclusions: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. (C) 2018 by the American Academy of Ophthalmology

Biomarkers relevant to the pre-dementia stages of Alzheimer’s disease are needed. Using MEG, PET, and MRI, Nakamura et al. disentangle resting state regional spectral patterns in cognitively normal subjects and individuals with mild cognitive impairment into MEG signatures related to Aβ deposition, disease progression, or changes non-specific to Alzheimer’s disease., Biomarkers useful for the predementia stages of Alzheimer’s disease are needed. Electroencephalography and magnetoencephalography (MEG) are expected to provide potential biomarker candidates for evaluating the predementia stages of Alzheimer’s disease. However, the physiological relevance of EEG/MEG signal changes and their role in pathophysiological processes such as amyloid-β deposition and neurodegeneration need to be elucidated. We evaluated 28 individuals with mild cognitive impairment and 38 cognitively normal individuals, all of whom were further classified into amyloid-β-positive mild cognitive impairment (n = 17, mean age 74.7 ± 5.4 years, nine males), amyloid-β-negative mild cognitive impairment (n = 11, mean age 73.8 ± 8.8 years, eight males), amyloid-β-positive cognitively normal (n = 13, mean age 71.8 ± 4.4 years, seven males), and amyloid-β-negative cognitively normal (n = 25, mean age 72.5 ± 3.4 years, 11 males) individuals using Pittsburgh compound B-PET. We measured resting state MEG for 5 min with the eyes closed, and investigated regional spectral patterns of MEG signals using atlas-based region of interest analysis. Then, the relevance of the regional spectral patterns and their associations with pathophysiological backgrounds were analysed by integrating information from Pittsburgh compound B-PET, fluorodeoxyglucose-PET, structural MRI, and cognitive tests. The results demonstrated that regional spectral patterns of resting state activity could be separated into several types of MEG signatures as follows: (i) the effects of amyloid-β deposition were expressed as the alpha band power augmentation in medial frontal areas; (ii) the delta band power increase in the same region was associated with disease progression within the Alzheimer’s disease continuum and was correlated with entorhinal atrophy and an Alzheimer’s disease-like regional decrease in glucose metabolism; and (iii) the global theta power augmentation, which was previously considered to be an Alzheimer’s disease-related EEG/MEG signature, was associated with general cognitive decline and hippocampal atrophy, but was not specific to Alzheimer’s disease because these changes could be observed in the absence of amyloid-β deposition. The results suggest that these MEG signatures may be useful as unique biomarkers for the predementia stages of Alzheimer’s disease.

Psychopathy is characterized by severe deficits in emotion processing and empathy. These emotional deficits might not only affect the feeling of own emotions, but also the understanding of others' emotional and mental states. The present study aims on identifying the neurobiological correlates of social-cognitive related alterations in psychopathy.We applied a social-cognitive paradigm for the investigation of face processing, emotion recognition, and affective Theory of Mind (ToM) to 11 imprisoned psychopaths and 18 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation.While showing no overall behavioural deficit, psychopathy was associated with altered brain activation. Psychopaths had reduced fusiform activation related to face processing. Related to affective ToM, psychopaths had hypoactivation in amygdala, inferior prefrontal gyrus and superior temporal sulcus, areas associated with embodied simulation of emotions and intentions. Furthermore, psychopaths lacked connectivity between superior temporal sulcus and amygdala during affective ToM.These results replicate findings of alterations in basal face processing in psychopathy. In addition, they provide evidence for reduced embodied simulation in psychopathy in concert with a lack of communication between motor areas and amygdala which might provide the neural substrate of reduced feeling with others during social cognition.

The Implicit Association Test (IAT) is a widely used latency-based categorization task that indirectly measures the strength of automatic associations between target and attribute concepts. So far, little is known about the perceptual and cognitive processes underlying personality IATs. Thus, the present study examined event-related potential indices during the execution of an IAT measuring neuroticism (N = 70). The IAT effect was strongly modulated by the P1 component indicating early facilitation of relevant visual input and by a P3b-like late positive component reflecting the efficacy of stimulus categorization. Both components covaried, and larger amplitudes led to faster responses. The results suggest a relationship between early perceptual and semantic processes operating at a more automatic, implicit level and later decision-related categorization of self-relevant stimuli contributing to the IAT effect.

The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI).

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task. Compared to HC, rMDD patients showed diminished DMN deactivation with strongest differences in the anterior-medial prefrontal cortex (amPFC), which was further linked to increased rumination response style. On a brain systems level, rMDD patients showed an increased FC between the amPFC and the dorsolateral prefrontal cortex, which constitutes a key region of the antagonistic working-memory network. Both whole-brain analyses revealed significant differences between adolescent-onset rMDD patients and HC, while adult-onset rMDD patients showed no significant effects. Results of this study demonstrate that reduced DMN suppression exists even after full recovery of depressive symptoms, which appears to be specifically pronounced in adolescent-onset MDD patients. Our results encourage the investigation of DMN suppression as a putative predictor of relapse in clinical trials, which might eventually lead to important implications for antidepressant maintenance treatment., Highlights • Reduced default mode network suppression persists even after remission of MDD symptoms. • Adolescent-onset rMDD patients show stronger alterations likely reflecting the more severe disease course. • The anterior-medial prefrontal cortex appears to be the mediator of these brain network changes in rMDD patients. • Reduced default mode network suppression is related to increased rumination.

PLoS one 5(9), (2010). doi:10.1371/journal.pone.0012514, Published by PLoS [u.a.], Lawrence, Kan.

Prepulse inhibition (PPI) is the attenuation of the startle response towards an instantaneous and intense stimulus when preceded by a weaker non-startling stimulus. Deficits in this sensorimotor gating process have been associated with the pathophysiology of schizophrenia and other psychiatric disorders. Among the neurotransmitters involved in PPI modulation, serotonin (5-HT) has so far received comparably little attention. While a recent pharmacological study suggests an important role of different 5-HT receptor (5-HTR) subtypes in PPI modulation, the mechanisms by which 5-HTR impact on PPI remain to be further elucidated. Therefore, we employed a molecular genetic approach in order to examine whether PPI is associated with two functional 5-HTR gene polymorphisms, 5-HTR1A C−1019G and 5-HTR2A T102C. In a sample of 81 healthy volunteers, we found no significant main effects of the polymorphisms, but a significant interaction effect on PPI at short (50 ms) and mid-long (150 ms) pulse–prepulse intervals. The presence of the 5-HTR2A T allele (reported to result in higher 5-HTR2A expression) led to attenuated PPI only in the absence of the 5-HTR1A G allele (reported to result in reduced 5-HTR1A autoreceptor expression). Our results may indicate that a higher 5-HTR2A expression together with a reduced 5-HTR1A autoreceptor expression and consequently, elevated firing rates of serotonergic neurons results in elevated 5-HTR2A activation by serotonin which could potently attenuate PPI. While further research into the molecular mechanisms underlying this interaction is needed, our results underscore the role of 5-HTR in PPI modulation and further implicate the 5-HTR1A G−1019C and the 5-HTR2A T102C polymorphisms in the pathophysiology of schizophrenia.

IntroductionThe natural course of Major Depressive Disorder (MDD) encompasses the occurrence of alternating intervals of major depressive episodes and remission. While several abnormalities in neural circuits related to acute MDD have been identified, the neural mechanisms underlying stable remission remain obscure.ObjectivesAcute MDD is characterized by increased amygdala and subgenual anterior cingulate cortex (sACC) activation and decreased connectivity between the amygdala and the sACC. Consequently, we expect those regions to be affected during remission.AimsTo determine whether active counter-regulatory mechanisms are implicated in the maintenance of full remission once antidepressant treatment has been discontinued.MethodsFunctional and structural magnetic resonance imaging was used to measure brain activation and volume of the amygdala and the sACC. Images were obtained from 38 healthy subjects without any psychiatric life-time diagnosis and 38 gender-matched drug-free remitted MDD patients. Furthermore, correlation analyses were performed with clinical variables.ResultsPatients with rMDD exhibited lower activation in the amygdala and the sACC and increased functional coupling between the amygdala and sACC compared to controls. This connectivity was particularly pronounced in patients characterized by a long cumulated time of depressive episodes. Similarly, structural connectivity results showed increased association between the amygdala and sACC volume in rMDD patients compared to controls.ConclusionsRemitted MDD is related to neural alterations within a neural circuit encompassing the amygdala and the sACC compared to controls. These findings suggest active counter-regulatory mechanisms likely contributing to the maintenance of remission once treatment has been discontinued.