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Substance use disorders (SUD) have been shown to be associated with gray matter (GM) loss, particularly in the frontal cortex. However, unclear is to what degree these regional GM alterations are substance-specific or shared across different substances, and if these regional GM alterations are independent of each other or the result of system-level processes at the intrinsic connectivity network level. The T1 weighted MRI data of 65 treated patients with alcohol use disorder (AUD), 27 patients with opioid use disorder (OUD) on maintenance therapy, 21 treated patients with stimulant use disorder comorbid with alcohol use disorder (polysubstance use disorder patients, PSU), and 21 healthy controls were examined via data-driven vertex-wise and voxel-wise GM analyses. Then, structural covariance analyses and open-access fMRI database analyses were used to map the cortical thinning patterns found in the three SUD groups onto intrinsic functional systems. Among AUD and OUD, we identified both common cortical thinning in right anterior brain regions as well as SUD-specific regional GM alterations that were not present in the PSU group. Furthermore, AUD patients had not only the most extended regional thinning but also significantly smaller subcortical structures and cerebellum relative to controls, OUD and PSU individuals. The system-level analyses revealed that AUD and OUD showed cortical thinning in several functional systems. In the AUD group the default mode network was clearly most affected, followed by the salience and executive control networks, whereas the salience and somatomotor network were highlighted as critical for understanding OUD. Structural brain alterations in groups with different SUDs are largely unique in their spatial extent and functional network correlates.

Background Prenatal maternal depression (PMD) and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with increased developmental risk in infants. Reports suggest that PMD is associated with hyperconnectivity of the insula and the amygdala, while SSRI exposure is associated with hyperconnectivity of the auditory network in the infant brain. However, associations between functional brain organization and PMD and/or SSRI exposure are not well understood. Methods We examined the relation between PMD or SSRI exposure and neonatal brain functional organization. Infants of control (n = 17), depressed SSRI-treated (n = 20) and depressed-only (HAM-D ≥ 8) (n = 16) women, underwent resting-state functional magnetic resonance imaging at postnatal Day 6. At 6 months, temperament was assessed using Infant Behavioral Questionnaire (IBQ). We applied GTA and partial least square regression (PLSR) to the resting-state time series to assess group differences in modularity, and connector and provincial hubs. Results Modularity was similar across all groups. The depressed-only group showed higher connector hub values in the left anterior cingulate, insula, and caudate as well as higher provincial hub values in the amygdala compared to the control group. The SSRI group showed higher provincial hub values in Heschl's gyrus relative to the depressed-only group. PLSR showed that newborns' hub values predicted 10% of the variability in infant temperament at 6 months, suggesting different developmental patterns between groups. Conclusions Prenatal exposures to maternal depression and SSRIs have differential impacts on neonatal functional brain organization. Hub values at 6 days predict variance in temperament between infant groups at 6 months of age.

The diffuse and continually evolving secondary changes after mild traumatic brain injury (mTBI) make it challenging to assess alterations in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic mTBI and persistent symptoms and measured their cognitive status using the NIH Toolbox Cognitive Battery. Fifteen adults with mTBI with persistent symptoms and twelve age, gender and education matched healthy controls took part in this study. We found a significant decrease in global white matter MWF in patients compared to the healthy controls. Significantly lower MWF was evident in most white matter region of interest (ROIs) examined including the corpus callosum (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. Although patients showed lower cognitive functioning, no significant correlations were found between MWF and cognitive measures. These results suggest that individuals with chronic mTBI who have persistent symptoms have reduced MWF., magnetic resonance imaging; mild traumatic brain injury; cognition; myelin water fraction; chronic injury

Abstinence is a lifelong endeavor, and the risk of a relapse is always present for patients with Alcohol Use Disorder (AUD). The aim of the study was to better understand specific characteristics of the intrinsic whole‐brain‐network architecture of 34 AUD patients that may support abstinence or relapse. We used Graph Theory Analysis (GTA) of resting‐state fMRI data from treatment seekers at 1 month of abstinence and their follow‐up data as abstainers or relapsers 3 months later, together with data from 30 light/non‐drinking controls scanned at the same interval. We determined the group‐specific intrinsic community configurations at both timepoints as well as the corresponding modularity Q, a GTA measure that quantifies how well individual network communities are separated from each other. Both AUD groups at both timepoints had community configurations significantly different from those of controls, but the three groups did not significantly differ in their Q values. However, relapsers showed a maladaptive community configuration at baseline, which became more similar to the controls’ community organization after the relapsers had started consuming alcohol again during the study interval. Additionally, successful recovery from AUD was not associated with re‐gaining the intrinsic brain organization found in light/non‐drinkers, but with a re‐configuration resulting in a new brain organization distinctly different from that of healthy controls. Resting‐state fMRI provides useful measures reflecting neuroplastic adaptations related to AUD treatment outcome., At one month into treatment, future relapsers showed a maladaptive community configuration, which became more similar to the controls’ community organization after they had started consuming alcohol again. Successful recovery from AUD was not associated with re‐gaining the intrinsic brain organization found in healthy controls, but with a re‐configuration resulting in a new brain organization distinctly different from that of controls.

A fine-tuned interplay of highly synchronized activity within and between the brain's communities is a crucial feature of the brain's functional organization. We wanted to investigate in individuals with alcohol use disorder (AUD) the degree to which the interplay of the brain's community-architecture and the extended brain reward system (eBRS) is affected by drinking status (relapse or abstinence). We used Graph Theory Analysis of resting-state fMRI data from treatment seekers at 1 month of abstinence to model the brain's intrinsic community configuration and their follow-up data as abstainers or relapsers 3 months later to quantify the degree of global across-community interaction between the eBRS and the intrinsic communities at both timepoints. After 1 month of abstinence, the ventromedial PFC in particular showed a significantly higher global across-community interaction in the 22 future relapsers when compared to 30 light/non-drinking controls. These differences were no longer present 3 months later when the relapsers had resumed drinking. We found no significant differences between abstainers and controls at either timepoint. Post hoc tests revealed that one eBRS region, the ventromedial PFC, showed a significant global across-community interaction with a community comprising the visual cortex in relapsers at baseline. In contrast, abstainers showed a significant negative association of the ventromedial PFC with the visual cortex. The increased across-community interaction of the ventromedial PFC and the visual cortex in relapsers at timepoint 1 may be an early indicator for treatment failure in a subgroup of AUD patients.

The increased incidence of reported traumatic brain injury (TBI) and its potentially serious long-term consequences have enormous clinical and societal impacts. The diffuse and continually evolving secondary changes after TBI make it challenging to evaluate the changes in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic brain injury and evaluated their cognitive status using the NIH Toolbox Cognitive Battery. Twenty-two adults with mild or severe brain injury and twelve age, gender and education matched healthy controls took part in this study. We found a significant decrease in global white matter MWF in individuals with mild TBI compared to the healthy controls. Significantly lower MWF was evident in most white matter ROIs examined including the corpus callosum (separated into genu, body and splenium), minor forceps, right anterior thalamic radiation, left inferior longitudinal fasciculus; and right and left superior longitudinal fasciculus and corticospinal tract. No significant correlations were found between MWF in mild TBI and the cognitive measures. These results show for the first time the loss of myelin in chronic mild TBI.

Objectives Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with impaired recognition of emotional facial expressions. Correspondingly, imaging studies showed decreased activity of the amygdala and cortical face processing regions in response to emotional faces. However, functional connectivity among regions involved in emotion perception has not been studied so far. Methods To address this, we examined intrinsic functional connectivity (FC) modulated by the perception of dynamic fearful faces among the amygdala and limbic, frontal, temporal and brainstem regions. Regions of interest were identified in an activation analysis by presenting a block-design with dynamic fearful faces and dynamic landscapes to 15 healthy individuals. This led to 10 predominately right-hemispheric regions. Functional connectivity between these regions during the perception of fearful faces was examined in drug-refractory patients with left- ( n =16) or right-sided ( n =17) MTLE, epilepsy patients with extratemporal seizure onset ( n =15) and a second group of 15 healthy controls. Results Healthy controls showed a widespread functional network modulated by the perception of fearful faces that encompassed bilateral amygdalae, limbic, cortical, subcortical and brainstem regions. In patients with left MTLE, a downsized network of frontal and temporal regions centered on the right amygdala was present. Patients with right MTLE showed almost no significant functional connectivity. A maintained network in the epilepsy control group indicates that findings in mesial temporal lobe epilepsy could not be explained by clinical factors such as seizures and antiepileptic medication. Conclusion Functional networks underlying facial emotion perception are considerably changed in left and right MTLE. Alterations are present for both hemispheres in either MTLE group, but are more pronounced in right MTLE. Disruption of the functional network architecture possibly contributes to deficits in facial emotion recognition frequently reported in MTLE.

A major contribution to our understanding of the aging brain comes either from studies comparing young with older adults or from studies investigating pathological aging and using the healthy aging older adults as control group. In consequence, we know relatively well, what distinguishes young from old brains or pathological aging from healthy but that does not mean that we really understand the structural and functional transformations characterizing the healthy aging brain. By analyzing task-free fMRI data from a large cross-sectional sample of 186 older adults (mean age = 70.4, 97 female), we aimed to elucidate age-related changes in the intrinsically active functional architecture of the brain in our study group covering an age range from 65 to 85 years. First, we conducted an intrinsic connectivity contrast analysis (ICC) in order to detect the brain regions whose degree of connectedness was significantly correlated with increasing age. Secondly, using connectivity analyses we investigated how the clusters highlighted by the ICC analysis functionally related to the other major resting-state networks. The most important finding was the right anterior insula's loss of connectedness in the older participants of the study group because of the region's causal role in the switching from the task-negative to the task-positive state of the brain. Further, we found a higher functional dedifferentiation of two of the brain's major intrinsic connectivity networks, the DMN, and the cingulo-opercular network, caused by a reduction of functional connection strength, especially in the frontal regions. At last, we showed that all these age-related changes have the potential to impair older adult's performance of working memory tasks.

One of the great challenges in surgical tendon rupture repair is to minimize peritendinous adhesions. In order to reduce adhesion formation, a physical barrier was applied to a sutured rabbit Achilles tendon, with two different immobilization protocols used postoperatively. Methods. Thirty New Zealand white rabbits received a laceration on the Achilles tendon, sutured with a 4-strand Becker suture, and half of the rabbits got a DegraPol tube at the repair site. While fifteen rabbits had their treated hind leg in a 180° stretched position during 6 weeks (adhesion provoking immobilization), the other fifteen rabbits were recasted with a 150° position after 3 weeks (adhesion inhibiting immobilization). Adhesion extent was analysed macroscopically, via ultrasound and histology. Inflammation was determined histologically. Biomechanical properties were analysed. Results. Application of a DegraPol tube reduced adhesion formation by approximately 20%—independently of the immobilization protocol. Biomechanical properties of extracted specimen were not affected by the tube application. There was no serious inflammatory reaction towards the implant material. Conclusions. Implantation of a DegraPol tube tightly set around a sutured tendon acts as a beneficial physical barrier and prevents adhesion formation significantly—without affecting the tendon healing process., BioMed Research International, 2014, ISSN:2314-6133, ISSN:2314-6141

In humans, the most obvious functional lateralization is the specialization of the left hemisphere for language. Therefore, the involvement of the right hemisphere in language is one of the most remarkable findings during the last two decades of fMRI research. However, the importance of this finding continues to be underestimated. We examined the interaction between the two hemispheres and also the role of the right hemisphere in language. From two seeds representing Broca's area, we conducted a seed correlation analysis (SCA) of resting state fMRI data and could identify a resting state network (RSN) overlapping to significant extent with a language network that was generated by an automated meta-analysis tool. To elucidate the relationship between the clusters of this RSN, we then performed graph theoretical analyses (GTA) using the same resting state dataset. We show that the right hemisphere is clearly involved in language. A modularity analysis revealed that the interaction between the two hemispheres is mediated by three partitions: A bilateral frontal partition consists of nodes representing the classical left sided language regions as well as two right-sided homologs. The second bilateral partition consists of nodes from the right frontal, the left inferior parietal cortex as well as of two nodes within the posterior cerebellum. The third partition is also bilateral and comprises five regions from the posterior midline parts of the brain to the temporal and frontal cortex, two of the nodes are prominent default mode nodes. The involvement of this last partition in a language relevant function is a novel finding.

In humans, the most obvious functional lateralization is the specialization of the left hemisphere for language. Therefore, the involvement of the right hemisphere in language is one of the most remarkable findings during the last two decades of fMRI research. However, the importance of this finding continues to be underestimated. We examined the interaction between the two hemispheres and also the role of the right hemisphere in language. From two seeds representing Broca’s area, we conducted a seed correlation analysis of resting state fMRI data and could identify an intrinsic connectivity network (ICN) overlapping to significant extent with a language network that was generated by an automated meta-analysis tool. To elucidate the relationship between the clusters of this ICN, we then performed graph theoretical analyses using the same resting state dataset. We show that the right hemisphere is clearly involved in language. A modularity analysis revealed that the interaction between the two hemispheres is mediated by three partitions: A bilateral frontal partition consists of nodes representing the classical left sided language regions as well as two right-sided homologues. The second bilateral partition consists of nodes from the right frontal, the left inferior parietal cortex as well as of two nodes within the posterior cerebellum. The third partition is also bilateral and comprises five regions from the posterior midline parts of the brain to the temporal and frontal cortex, two of the nodes are prominent default mode nodes. The involvement of this last partition in a language relevant function is a novel finding.

For the prevention of re-rupture during early healing phase, the primary repair strength of repaired lacerated tendons in hand surgery should be maximal and the reconstructed diameter minimal. Two new repair methods (small hook thread and internal splint) were assessed for strength and reconstructed diameter characteristics.Achilles tendons of 43 female New Zealand White rabbits were sectioned 2 cm above the calcaneus. Specimens were divided into 7 groups and repaired as follows: Kirchmayr method 2-strand with 4.0 polypropylene thread; Becker method 4-strand; 6-strand; internal splint; Kirchmayr method small hook 2-strand; Becker method small hook 4-strand, non-modified tendon. Load until failure, load until gap formation, gap length, cross-sectional area and failure stress were determined.The small hook 2-strand suture had 1.3 fold higher loads until failure compared to a conventional 2-strand suture, P0.05. The internal splint had a similar load until failure (22 N (SD 6)) as the conventional 2-strand suture (23 N (SD 4)); around half the load until failure of the conventional 4-strand suture (38 N (SD 9)). Load until gap formation correlated positively with load until failure (y=0.65+3.6; r(2)=0.72). The running suture increased the cross-sectional area at the repair site by a factor of 1.3.Using a small hook thread instead of a 4.0 polypropylene thread significantly increases the primary repair strength with the same number of strands. Internal splints may be an alternative to conventional 2-strand sutures for bridging large gaps.