Functional connectivity in complex regional pain syndrome: A bicentric study.

Brain imaging studies in complex regional pain syndrome (CRPS) have found mixed evidence for functional and structural changes in CRPS. In this cross-sectional study, we evaluated two patient cohorts from different centers and examined functional connectivity (rsFC) in 51 CRPS patients and 50 matched controls. rsFC was compared in predefined ROI pairs, but also in non-hypothesis driven analyses. Resting state (rs)fMRI changes in default mode network (DMN) and the degree rank order disruption index (kD) were additionally evaluated. Finally, imaging parameters were correlated with clinical severity and somatosensory function. Among predefined pairs, we found only weakly to moderately lower functional connectivity between the right nucleus accumbens and bilateral ventromedial prefrontal cortex in the infra-slow oscillations (ISO) band. The unconstrained ROI-to-ROI analysis revealed lower rsFC between the periaqueductal gray matter (PAG) and left anterior insula, and higher rsFC between the right sensorimotor thalamus and nucleus accumbens. In the correlation analysis, pain was positively associated with insulo-prefrontal rsFC, whereas sensorimotor thalamo-cortical rsFC was positively associated with tactile spatial resolution of the affected side. In contrast to previous reports, we found no group differences for kD or rsFC in the DMN, but detected overall lower data quality in patients. In summary, while some of the previous results were not replicated despite the larger sample size, novel findings from two independent cohorts point to potential down-regulated antinociceptive modulation by the PAG and increased connectivity within the reward system as pathophysiological mechanisms in CRPS. However, in light of the detected systematic differences in data quality between patients and healthy subjects, validity of rsFC abnormalities in CRPS should be carefully scrutinized in future replication studies.

Global functional connectivity reorganization reflects cognitive processing speed deficits and fatigue in multiple sclerosis.

BACKGROUND AND PURPOSE: Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. METHODS: Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. RESULTS: Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. CONCLUSIONS: kD is a potential biomarker of CI and fatigue warranting further validation.

White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy.

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Event-based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data.

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multicenter cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1-weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1625 healthy controls from 25 centers. Features with a moderate case-control effect size (Cohen d ≥ .5) were used to train an event-based model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman ρ = .293, p = 7.03 × 10-16 ), age at onset (ρ = -.18, p = 9.82 × 10-7 ), and ASM resistance (area under the curve = .59, p = .043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE-HS with mild or nondetectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features.

White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study.

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.

Do Belonging and Social Exclusion at School Affect Structural Brain Development During Adolescence?

Students' sense of belonging presents an essential resource for academic and health outcomes, whereas social exclusion at school negatively impacts students' well-being and academic performance. Aiming to understand how feelings of school-related belonging and exclusion shape the structural brain development, this study applied longitudinal questionnaire-based data and MRI data from 71 adolescent students (37 females, Mage at t1 = 15.0; t2 = 16.1 years). All were white participants from Germany. Voxel-based morphometry revealed only an association of social exclusion (and not of belonging) and gray matter volume in the left anterior insula: From t1 to t2, there was less gray matter decrease, the more social exclusion students perceived. School-related social exclusion and disturbed neurodevelopment are thus significantly associated.

The ENIGMA-Epilepsy working group: Mapping disease from large data sets.

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller-scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well-established by the ENIGMA Consortium, ENIGMA-Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event-based modeling analysis. We explore age of onset- and duration-related features, as well as phenomena-specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA-Epilepsy.

Effects of centric mandibular splint therapy on orofacial pain and cerebral activation patterns.

OBJECTIVES: To investigate the effects on pain, movement kinematics, and cerebral representation by a 3-month mandibular splint therapy. MATERIAL AND METHODS: Thirteen patients with temporo-mandibular joint disease (TMD) and moderate pain intensity were investigated before (PRE), within (after 2 weeks, POST1) and after a period of 12 weeks (POST2) using functional magnetic resonance imaging (fMRI) of representation of occlusal movements on natural teeth and on an individually fitted mandibular splint. In addition, kinematic investigations of jaw movements, muscle electromyography and pain ratings using a pain diary (VAS-scale 0-100) were measured. RESULTS: Although the patient's pain ratings decreased about 60%, kinematic and electromyographic characteristics over therapy were not significantly altered. Over therapy, we observed a decrease of fMRI activation magnitude in the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) and insular cortex during occlusion. Left hemispheric anterior insula and the cerebellar fMRI activation decrease were associated with decrease in pain over time. CONCLUSIONS: Within the limitations of this pilot study, a reduction in both discriminative (primary and secondary somatosensory cortex) and affective (anterior insula) areas for pain processing suggest that altered pain anticipation is critical for the therapeutic effects of mandibular splint therapy after TMD. CLINICAL RELEVANCE: A 3-month mandibular splint therapy moderately decreases pain and anticipatory anterior insular activation.

The association of health-related quality of life and cerebral gray matter volume in the context of aging: A voxel-based morphometry study with a general population sample.

Health-related quality of life is likely associated with the brain via processes relating to physiology, behavior, cognition, emotion and stress. Previous studies with small student or clinical samples have identified associations with gray matter volume in the anterior cingulate cortex, prefrontal cortex, insular cortex, (para)hippocampal area, amygdala, and precuneus. The present study investigated the association of gray matter volume of these brain areas with mental and physical components of health, as well as general health perception, measured with the 12-item Short Form Health Survey, in a large sample of 3027 participants from the Study of Health in Pomerania, using voxel-based morphometry for T1-weighted magnetic resonance imaging. Higher physical, but not mental, health-related quality of life and general health perception were associated with larger gray matter volume of the anterior cingulate cortex, medial prefrontal cortex, insular cortex, and the precuneus with a substantial decrease when controlling for lifestyle, comorbidity and symptoms. Age-stratified analyses revealed significantly higher partial correlations of physical health and left insular gray matter volume in the oldest age group. Our study emphasizes the importance of high medial prefrontal and anterior insula gray matter volume for health-related quality of life on the basis of a large sample size.

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study.

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. We ranked brain structures in order of greatest differences between patients and controls, by meta-analysing effect sizes across 16 subcortical and 68 cortical brain regions. We also tested effects of duration of disease, age at onset, and age-by-diagnosis interactions on structural measures. We observed widespread patterns of altered subcortical volume and reduced cortical grey matter thickness. Compared to controls, all epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to -0.73; P < 1.49 × 10-4), and lower thickness in the precentral gyri bilaterally (d = -0.34 to -0.52; P < 4.31 × 10-6). Both MTLE subgroups showed profound volume reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 × 10-19), and lower thickness in extrahippocampal cortical regions, including the precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P < 1.49 × 10-4). Thickness differences of the ipsilateral temporopolar, parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis, and bilateral precuneus, superior frontal and caudal middle frontal gyri were observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 × 10-4). Contrastingly, thickness differences of the ipsilateral pars opercularis, and contralateral transverse temporal gyrus, were observed in right, but not left, MTLE (d = -0.27 to -0.51; P < 1.49 × 10-4). Lower subcortical volume and cortical thickness associated with a longer duration of epilepsy in the all-epilepsies, all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 × 10-4). In the largest neuroimaging study of epilepsy to date, we provide information on the common epilepsies that could not be realistically acquired in any other way. Our study provides a robust ranking of brain measures that can be further targeted for study in genetic and neuropathological studies. This worldwide initiative identifies patterns of shared grey matter reduction across epilepsy syndromes, and distinctive abnormalities between epilepsy syndromes, which inform our understanding of epilepsy as a network disorder, and indicate that certain epilepsy syndromes involve more widespread structural compromise than previously assumed.

Voxel-based morphometry in creative writers: Grey matter increase in a prefronto-thalamic-cerebellar network.

Continuous practice modulates those features of brain anatomy specifically associated with requirements of the respective training task. This study aimed to highlight brain structural changes going along with long-term experience in creative writing. To this end, we investigated the grey matter volume of 23 expert writers with voxel-based morphometry and compared it to 28 matched nonexpert controls. Expert writers had higher grey matter volume in the right superior frontal and middle frontal gyri (BA 9,10) as well as left middle frontal gyrus (BA 9, 10, 46), the bilateral medial dorsal nuclei of the thalamus and left posterior cerebellum. A regression analysis confirmed the association of enhanced grey matter volume in the right superior frontal gyrus (BA 10) with practice index of writing. In region-of-interest based regression analyses, we found associations of grey matter volume in the right Broca's analogue (BA 44) and right primary visual cortex (BA 17) with creativity ratings of the texts written during scanning, but not with a standardised verbal creativity test. Creative writing thus seems to be strongly connected to a prefronto-thalamic-cerebellar network that supports the continuous generation, organisation and revision of ideas that is necessary to write literary texts.

Motor imagery training: Kinesthetic imagery strategy and inferior parietal fMRI activation.

Motor imagery (MI) is the mental simulation of action frequently used by professionals in different fields. However, with respect to performance, well-controlled functional imaging studies on MI training are sparse. We investigated changes in fMRI representation going along with performance changes of a finger sequence (error and velocity) after MI training in 48 healthy young volunteers. Before training, we tested the vividness of kinesthetic and visual imagery. During tests, participants were instructed to move or to imagine moving the fingers of the right hand in a specific order. During MI training, participants repeatedly imagined the sequence for 15 min. Imaging analysis was performed using a full-factorial design to assess brain changes due to imagery training. We also used regression analyses to identify those who profited from training (performance outcome and gain) with initial imagery scores (vividness) and fMRI activation magnitude during MI at pre-test (MIpre ). After training, error rate decreased and velocity increased. We combined both parameters into a common performance index. FMRI activation in the left inferior parietal lobe (IPL) was associated with MI and increased over time. In addition, fMRI activation in the right IPL during MIpre was associated with high initial kinesthetic vividness. High kinesthetic imagery vividness predicted a high performance after training. In contrast, occipital activation, associated with visual imagery strategies, showed a negative predictive value for performance. Our data echo the importance of high kinesthetic vividness for MI training outcome and consider IPL as a key area during MI and through MI training.

Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images-a voxel-based whole brain analysis.

OBJECTIVES: To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. METHODS: In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the "Diffeomorphic Anatomical Registration using Exponentiated Lie algebra" (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. RESULTS: Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. CONCLUSION: Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. KEY POINTS: • Repeated administration of gadobutrol does not lead to increased signal intensity. • Voxel-based whole-brain analysis allows assessment of subtle changes in signal intensity. • Macrocyclic contrast agents in a proven dosage are safe.

I can't keep your face and voice out of my head: neural correlates of an attentional bias toward nonverbal emotional cues.

Emotional information can be conveyed by verbal and nonverbal cues with the latter often suggested to exert a greater influence in shaping our perceptions of others. The present functional magnetic resonance imaging study sought to explore attentional biases toward nonverbal signals by investigating the interaction of verbal and nonverbal cues. Results obtained in this study underline the previous suggestions of a "nonverbal dominance" in emotion communication by evidencing implicit effects of nonverbal cues on emotion judgements even when attention is directed away from nonverbal signals and focused on verbal cues. Attentional biases toward nonverbal signals appeared to be reflected in increasing activation of the dorsolateral prefrontal cortex (DLPFC) assumed to reflect increasing difficulties to suppress nonverbal cues during task conditions that asked to shift attention away from nonverbal signals. Aside the DLPFC, results suggest the right amygdala to play a role in attention control mechanisms related to the processing of emotional cues. Analyses conducted to determine the cerebral correlates of the individual ability to shift attention between verbal and nonverbal sources of information indicated that higher task-switching abilities seem to be associated with the up-regulation of right amygdala activation during explicit judgments of nonverbal cues, whereas difficulties in task-switching seem to be related to a down-regulation.

Gray matter volume of limbic brain structures during the development of chronic back pain: a longitudinal cohort study.

ABSTRACT: This study set out to investigate in a population-based longitudinal cohort, whether chronification of back pain (BP) is related to structural gray matter changes in corticolimbic brain structures. Gray matter volume (GMV) was measured in participants with chronic BP (CBP, n = 168) and controls without chronic pain (n = 323) at 2 time points with an interval of 7 years (baseline t1, follow-up t2). Over this time period, participants with CBP showed an increase of GMV in the left ventral striatum, whereas controls showed a decrease. By contrast, participants with CBP had a GMV decrease in the left parahippocampal gyrus. Within the CBP group, pain duration was negatively associated with GMV in the left caudate. Those with emerging CBP had less GMV in the right entorhinal area, right amygdala, and left medial frontal cortex. Additional variables differing between those who had BP at t1 and later developed CBP or not were pain intensity, body mass index, and depression score. In sum, these findings are in accordance with the notion that limbic brain properties are both predisposing risk factors and drivers of brain reorganization during the development of CBP.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

Chronic pain is associated with less grey matter volume in the anterior cingulum, anterior and posterior insula and hippocampus across three different chronic pain conditions.

BACKGROUND: Chronic pain of different aetiologies and localization has been associated with less grey matter volume (GMV) in several cortical and subcortical brain areas. Recent meta-analyses reported low reproducibility of GMV alterations between studies and pain syndromes. METHODS: To investigate GMV in common chronic pain conditions defined by body location (chronic back pain, n = 174; migraine, n = 92; craniomandibular disorder, n = 39) compared to controls (n = 296), we conducted voxel-based morphometry and determined GMV from high-resolution cranial MRIs obtained in an epidemiologic survey. Mediation analyses were performed between the presence of chronic pain and GMV testing the mediators stress and mild depression. The predictability of chronic pain was investigated with binomial logistic regression. RESULTS: Whole-brain analyses yielded reduced GMV within the left anterior insula and the anterior cingulate cortex, for a ROI approach additionally the left posterior insula and left hippocampus showing less GMV across all patients with chronic pain. The relationship of pain with GMV in the left hippocampus was mediated by self-reported stressors in the last 12 months. Binomial logistic regression revealed a predictive effect for GMV in the left hippocampus and left anterior insula/temporal pole for the presence of chronic pain. CONCLUSIONS: Chronic pain across three different pain conditions was characterized by less GMV in brain regions consistently described for different chronic pain conditions before. Less GMV in the left hippocampus mediated by experienced stress during the last year might be related to altered pain learning mechanisms in chronic pain patients. SIGNIFICANCE: Grey matter reorganization could serve as a diagnostic biomarker for chronic pain. In a large cohort, we here replicated findings of less grey matter volume across three pain conditions in the left anterior and posterior insula, anterior cingulate and left hippocampus. Less hippocampal grey matter was mediated by experienced stress.

One Year of Outpatient Dialectical Behavioral Therapy and Its Impact on Neuronal Correlates of Attachment Representation in Patients with Borderline Personality Disorder Using a Personalized fMRI Task.

(1) Background: BPD is characterized by affect dysregulation, interpersonal problems, and disturbances in attachment, but neuroimaging studies investigating attachment representations in BPD are rare. No study has examined longitudinal neural changes associated with interventions targeting these impairments. (2) Methods: We aimed to address this gap by performing a longitudinal neuroimaging study on n = 26 patients with BPD treated with Dialectic Behavioral Therapy (DBT) and n = 26 matched healthy controls (HCs; post intervention point: n = 18 BPD and n = 23 HCs). For functional imaging, we applied an attachment paradigm presenting attachment related scenes represented in drawings paired with related neutral or personalized sentences from one's own attachment narratives. In a prior cross-sectional investigation, we identified increased fMRI-activation in the human attachment network, in areas related to fear response and the conflict monitoring network in BPD patients. These were especially evident for scenes from the context of loneliness (monadic pictures paired with individual narrative sentences). Here, we tested whether these correlates of attachment representation show a near-to-normal development over one year of DBT intervention. In addition, we were interested in possible associations between fMRI-activation in these regions-of-interest (ROI) and clinical scores. (3) Results: Patients improved clinically, showing decreased symptoms of borderline personality organization (BPI) and increased self-directedness (Temperament and Character Inventory, TCI) over treatment. fMRI-activation was increased in the anterior medial cingulate cortex (aMCC) and left amygdala in BPD patients at baseline which was absent after intervention. When investigating associations between scores (BPI, TCI) and functional activation, we found significant effects in the bilateral amygdala. In contrast, aMCC activation at baseline was negatively associated with treatment outcome, indicating less effective treatment effects for those with higher aMCC activation at baseline. (4) Conclusions: Monadic attachment scenes with personalized sentences presented in an fMRI setup are capable of identifying increased activation magnitude in BPD. After successful DBT treatment, these increased activations tend to normalize which could be interpreted as signs of a better capability to regulate intensive emotions in the context of "social pain" towards a more organized/secure attachment representation. Amygdala activation, however, indicates high correlations with pre-treatment scores; activation in the aMCC is predictive for treatment gain. Functional activation of the amygdala and the aMCC as a response to attachment scenes representing loneness at baseline might be relevant influencing factors for DBT-intervention outcomes.