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Adolescence is characterized by significant brain development and marks a period of the life span with an increased incidence of mood disorders, especially in females. The risk of developing mood disorders is also higher in individuals scoring high on neuroticism, a personality trait characterized by a tendency to experience negative and anxious emotions. We previously found in a cross-sectional study that neuroticism is associated with microstructural left–right asymmetry of the fronto-limbic white matter involved in emotional processing, with opposite effects in female and male adolescents. We now have extended this work collecting longitudinal data in 76 typically developing children and adolescents aged 7–18 years, including repeated MRI sampling up to 11 times. This enabled us, for the first time, to address the critical question, whether the association between neuroticism and frontal-limbic white matter asymmetry changes or remains stable across late childhood and adolescence. Neuroticism was assessed up to four times and showed good intraindividual stability and did not significantly change with age. Conforming our cross-sectional results, females scoring high on neuroticism displayed increased left–right cingulum fractional anisotropy (FA), while males showed decreased left–right cingulum FA asymmetry. Despite ongoing age-related increases in FA in cingulum, the association between neuroticism and cingulum FA asymmetry was already expressed in females in late childhood and remained stable across adolescence. In males, the association appeared to become more prominent during adolescence. Future longitudinal studies need to cover an earlier age span to elucidate the time point at which the relationship between neuroticism and cingulum FA asymmetry arises.

Contains fulltext : 248857.pdf (Publisher’s version ) (Open Access) Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.

Background Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. Methods We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. Results Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. Conclusions Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. Impact It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.

Contains fulltext : 292515.pdf (Publisher’s version ) (Open Access) It is well documented that some brain regions, such as association cortices, caudate, and hippocampus, are particularly prone to age-related atrophy, but it has been hypothesized that there are individual differences in atrophy profiles. Here, we document heterogeneity in regional-atrophy patterns using latent-profile analysis of 1,482 longitudinal magnetic resonance imaging observations. The results supported a 2-group solution reflecting differences in atrophy rates in cortical regions and hippocampus along with comparable caudate atrophy. The higher-atrophy group had the most marked atrophy in hippocampus and also lower episodic memory, and their normal caudate atrophy rate was accompanied by larger baseline volumes. Our findings support and refine models of heterogeneity in brain aging and suggest distinct mechanisms of atrophy in striatal versus hippocampal-cortical systems.

Highlights • Verbal fluency associated with superior longitudinal fasciculus (SLF/AF) in children. • Semantic fluency was positively related to right SLF/AF fractional anisotropy (FA). • Better phonemic fluency was related to higher right and lower left SLF/AF FA. • Verbal fluency performance in children may rely on right hemisphere structure., Verbal fluency is the ability to retrieve lexical knowledge quickly and efficiently and develops during childhood and adolescence. Few studies have investigated associations between verbal fluency performance and brain structural variation in children. Here we examined associations of verbal fluency performance with structural measures of frontal and temporal language-related brain regions and their connections in 73 typically-developing children aged 7–13 years. Tract-based spatial statistics was used to extract fractional anisotropy (FA) from the superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and the white matter underlying frontal and temporal language-related regions. FreeSurfer was used to extract cortical thickness and surface area. Better semantic and phonemic fluency performance was associated with higher right SLF/AF FA, and phonemic fluency was also modestly associated with lower left SLF/AF FA. Explorative voxelwise analyses for semantic fluency suggested associations with FA in other fiber tracts, including corpus callosum and right inferior fronto-occipital fasciculus. Overall, our results suggest that verbal fluency performance in children may rely on right hemisphere structures, possibly involving both language and executive function networks, and less on solely left hemisphere structures as often is observed in adults. Longitudinal studies are needed to clarify whether these associations are mediated by maturational processes, stable characteristics and/or experience.

Contains fulltext : 235420.pdf (Publisher’s version ) (Open Access) Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.

Background and Objectives A healthy brain is central to physical and mental well-being. In this multi-site, qualitative study, we investigated views and attitudes of adult participants in brain research studies on the brain and personalized brain health as well as interest in maintaining a healthy brain. Design and Methods We conducted individual interviews with 44 adult participants in brain research cohorts of the Lifebrain consortium in Spain, Norway, Germany, and the United Kingdom. The interviews were audio recorded, transcribed, and coded using a cross-country codebook. The interview data were analyzed using qualitative content analysis. Results Most participants did not focus on their own brain health and expressed uncertainty regarding how to maintain it. Those actively focusing on brain health often picked one specific strategy like diet or memory training. The participants were interested in taking brain health tests to learn about their individual risk of developing brain diseases, and were willing to take measures to maintain their brain health if personalized follow-up was provided and the measures had proven impact. The participants were interested in more information on brain health. No differences in responses were identified between age groups, sex, or countries. Discussion and Implications Concise, practical, personalized, and evidence-based information about the brain may promote brain health. Based on our findings, we have launched an ongoing global brain health survey to acquire more extensive, quantitative, and representative data on public perception of personalized brain health.

The ability to effectively suppress motor response tendencies is essential for focused and goal-directed behavior. Here, we tested the hypothesis that developmental improvement in the ability to cancel a motor response is reflected by maturational changes in the white matter underlying the right presupplementary motor area (preSMA) and posterior inferior frontal gyrus (IFG), two cortical key areas of the fronto-basal ganglia “stopping” network. Eighty-eight typically-developing children and adolescents, aged 7-19 years, were longitudinally assessed with the stop-signal task (SST) and diffusion tensor imaging (DTI) of the brain over a period of six years. Participants were examined from two to nine times with an average of 6.6 times, resulting in 576 SST-DTI datasets. We applied tract-based spatial statistics to extract mean fractional anisotropy (FA) from regions-of-interest in the white matter underlying the right IFG (IFGFA) and right preSMA (preSMAFA) at each time point. Motor response cancelation performance, estimated with the stop-signal reaction time (SSRT), improved with age. Initially well performing children plateaued around the age of 11 years, while initially poor performers caught up at the age of 13-14 years. White matter microstructure continued to mature across the investigated age range. Males generally displayed linear maturational trajectories, while females displayed more curvilinear trajectories that leveled off around 12-14 years of age. Maturational increases in right preSMAFA but not right IFGFA were associated with developmental improvements in SSRT. This association differed depending on the mean right preSMAFA across the individual maturational trajectory. Children with lower mean right preSMAFA exhibited poorer SSRT performance at younger ages but steeper developmental trajectories of SSRT improvement. Children with higher mean right preSMAFA exhibited flatter trajectories of SSRT improvement along with faster SSRT already at the first assessments. The results suggest that no further improvement in motor response cancellation is achieved once a certain level of maturity in the white matter underlying the right preSMA is reached. Similar dynamics may apply to other behavioral read-outs and brain structures and, thus, need to be considered in longitudinal MRI studies designed to map brain structural correlates of behavioral changes during development.HighlightsMotor response cancellation, i.e. SSRT, improvement plateaued at 13-14 years of ageFractional anisotropy (FA) captured maturation of white matter (WM) microstructureFA in the WM underlying right preSMA (preSMAFA) reflected SSRT improvement with ageIndividual SSRT improvement depended on mean right preSMAFA across all DTI sessionsChildren with lower mean right preSMAFA had the steepest improvements in SSRT

We have recently shown that the emergence and severity of seasonal affective disorder (SAD) symptoms in the winter is associated with an increase in cerebral serotonin (5-HT) transporter (SERT) binding. Intriguingly, we also found that individuals resilient to SAD downregulate their cerebral SERT binding in the winter. In the present paper, we provide an analysis of the SERT- and 5-HT dynamics as indexed by 5-HT4 receptor (5-HT4R) binding related to successful stress coping. We included 46 11C-DASB positron emission tomography (PET) scans (N = 23, 13 women, age: 26 ± 6 years) and 14 11C-SB207145 PET scans (7 participants, 3 women, age: 25 ± 3 years) from 23 SAD-resilient Danes. Data was collected longitudinally in summer and winter. We found that compared to the summer, raphe nuclei and global brain SERT binding decreased significantly in the winter (praphe = 0.003 and pglobal = 0.003) and the two measures were positively correlated across seasons (summer: R2 = 0.33, p = .004, winter: R2 = 0.24, p = .018). A voxel-based analysis revealed prominent changes in SERT in clusters covering both angular gyri (0.0005

Background Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD and healthy controls (HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of SAD. We hypothesized increased amygdala activation to aversive stimuli in the winter in SAD individuals (season-by-group interaction). Methods Seventeen SAD individuals and 15 HCs completed an implicit emotional faces BOLD-fMRI paradigm during summer and winter. We computed amygdala activation (SPM5) to an aversive contrast (angry & fearful minus neutral) and angry, fearful and neutral faces, separately. Season-by-group and main effects were evaluated using Generalized Least Squares. In SAD individuals, we correlated change in symptom severity, assessed with The Hamilton Rating Scale for Depression – Seasonal Affective Disorder version (SIGH-SAD), with change in amygdala activation. Results We found no season-by-group, season or group effect on our aversive contrast. Independent of season, SAD individuals showed significantly lower amygdala activation to all faces compared to healthy controls, with no evidence for a season-by-group interaction. Seasonal change in amygdala activation was unrelated to change in SIGH-SAD. Limitations Small sample size, lack of positive valence stimuli. Conclusions Amygdala activation to aversive faces is not increased in symptomatic SAD individuals. Instead, we observed decreased amygdala activation across faces, independent of season. Our findings suggest that amygdala activation to angry, fearful and neutral faces is altered in SAD individuals, independent of the presence of depressive symptoms.

The human sense of smell is closely associated with morphological differences of the fronto-limbic system, specifically the piriform cortex and medial orbitofrontal cortex (mOFC). Still it is unclear whether cortical volume in the core olfactory areas and connected brain regions are shaped differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI) matched with sixteen normosmic controls. All subjects underwent whole-brain magnetic resonance imaging, and voxel-based morphometry was used to estimate regional variations in grey matter volume. The analyses showed that relative to controls, COI subjects had significantly larger grey matter volumes in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks" test, was positively associated with larger grey matter volume in right posterior cingulate and parahippocampal cortices whereas the opposite relationship was observed in controls. Across COI subjects and controls, better olfactory detection threshold was associated with smaller volume in right piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory.

Neuroticism is a fundamental personality trait that reflects a tendency to experience heightened negative affect and susceptibility to stress. Negative emotionality has been associated with fronto-limbic brain structures and connecting fibre tracts. The major fibre tracts connecting the frontal and limbic brain regions are the cingulum bundle and uncinate fasciculus. We previously found that healthy adults with higher neuroticism scores had decreased left relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and uncinate fasciculus FA increases throughout childhood and into early adulthood. Since adolescence is associated with an increased incidence of anxiety and mood disorders, for which neuroticism is a known risk factor, the question arises whether the association between neuroticism and fronto-limbic white matter microstructure asymmetry is already present in children and adolescents or whether such relationship emerges during this age period. To address this question, we assessed 72 typically-developing 10-to-15 year-olds with diffusion-weighted imaging on a 3 T magnetic resonance scanner. Neuroticism was assessed with the Junior Eysenck Personality Questionnaire. FA and parallel and perpendicular diffusivity measures were extracted for cingulum, uncinate fasciculus as well as the white matter underlying the ventromedial prefrontal cortex. Higher neuroticism scores were associated with decreased left relative to right cingulum FA in boys, while in girls, higher neuroticism scores were associated with increased left relative to right cingulum and ventromedial prefrontal white matter FA, indicating that there are sex differences in the neural correlates of neuroticism. Our findings suggest that the link between neuroticism and frontal-limbic white matter microstructure asymmetry likely predates early adolescence. Future studies need to elucidate the significance of the observed sex differences in the neural correlates of neuroticism.

Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.

We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.

Aim Perinatal exposure to glucocorticoids has been associated with adverse cerebral effects, but little is known about their effect on cognitive development and exposure later in childhood. This study examined intellectual abilities, memory and behavioural problems in children previously treated with glucocorticoids. Methods We evaluated 38 children aged from seven to 16 years, who had been treated with glucocorticoids for rheumatic disease or nephrotic syndrome, together with 42 healthy controls matched for age, gender and parental education. The median cumulative dose of prednisolone equivalents was 158 mg/kg (range 21–723) and the mean time that had elapsed since treatment was three-and-a-half (standard deviation 2.2) years. Intellectual abilities were assessed with the Wechsler Intelligence Scale for Children and memory performance and behavioural problems with a pattern recognition memory task and the Child Behaviour Check List. Results There were no significant differences between the groups in pattern recognition memory, perceptual organisation index or behavioural problems, but patients had a significantly lower verbal comprehension index and this difference was present in both disease groups. There were no significant dose–response relationships regarding verbal intellectual abilities. Conclusion Children and adolescents previously treated with glucocorticoids seemed to have lower intellectual verbal abilities than healthy controls.

We have recently shown that the emergence and severity of seasonal affective disorder (SAD) symptoms in the winter is associated with an increase in cerebral serotonin (5-HT) transporter (SERT) binding. Intriguingly, we also found that individuals resilient to SAD downregulate their cerebral SERT binding in the winter. In the present paper, we provide an analysis of the SERT- and 5-HT dynamics as indexed by 5-HT

BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.

Background Major depression and bipolar disorders aggregates in families and are linked with a wide range of neurobiological abnormalities including cortical gray matter (GM) alterations. Prospective studies of individuals at familial risk may expose the neural mechanisms underlying risk transmission. Methods We used voxel based morphometry to investigate changes in regional GM brain volume, over a seven-year period, in 37 initially healthy individuals having a mono- or di-zygotic twin diagnosed with major depression or bipolar disorder (high-risk group; mean age 41.6 yrs.) as compared to 36 individuals with no history of affective disorders in the index twin and first-degree relatives (low-risk group; mean age 38.5 yrs.). Results Groups did not differ in regional GM volume changes over time. However, independent of time, high-risk twins had significantly greater GM volumes in bilateral dorsal anterior cingulate, inferior frontal gyrus and temporoparietal regions as compared to low-risk twins. Further, individuals who developed an affective disorder at follow-up (n = 12), had relatively the largest GM volumes, both at baseline and follow-up, in the right dorsal anterior cingulate cortex and right inferior frontal cortex compared to high- and low-risk twins who remained well at follow-up. Conclusion This pattern of apparently stable grater regional GM volume may constitute a neural marker of an increased risk for developing an affective disorder in individuals at familial risk., Highlights • We explored the neural markers of increased risk for developing affective disorders. • Healthy twins of affective disorder patients show greater PFC gray matter volume. • Twins with subsequent disorder onset had the greatest gray matter volumes.

Brain-derived neurotrophic factor (BDNF) has been implicated in multiple aspects of brain function including regulation of serotonin signaling. The BDNF val66met polymorphism (rs6265) has been linked to aspects of serotonin signaling in humans but its effects are not well understood. To address this, we evaluated whether BDNF val66met was predictive of a putative marker of brain serotonin levels, serotonin 4 receptor (5-HT4) binding assessed with [11C]SB207145 positron emission tomography, which has also been associated with the serotonin-transporter-linked polymorphic region (5-HTTLPR) polymorphism. We applied a linear latent variable model (LVM) using regional 5-HT4 binding values (neocortex, amygdala, caudate, hippocampus, and putamen) from 68 healthy humans, allowing us to explicitly model brain-wide and region-specific genotype effects on 5-HT4 binding. Our data supported an LVM wherein BDNF val66met significantly predicted a LV reflecting [11C]SB207145 binding across regions (P = 0.005). BDNF val66met met-carriers showed 2–9% higher binding relative to val/val homozygotes. In contrast, 5-HTTLPR did not predict the LV but S-carriers showed 7% lower neocortical binding relative to LL homozygotes (P = 7.3 × 10−6). We observed no evidence for genetic interaction. Our findings indicate that BDNF val66met significantly predicts a common regulator of brain [11C]SB207145 binding, which we hypothesize reflects brain serotonin levels. In contrast, our data indicate that 5-HTTLPR specifically affects 5-HT4 binding in the neocortex. These findings implicate serotonin signaling as an important molecular mediator underlying the effects of BDNF val66met and 5-HTTLPR on behavior and related risk for neuropsychiatric illness in humans. Hum Brain Mapp, 36:313–323, 2015. © 2014 Wiley Periodicals, Inc.

Background: Glucocorticoids are widely used in the treatment of several pediatric diseases with undisputed disease-related benefits. Perinatal exposure to high levels of glucocorticoids can have long-term adverse cerebral effects. In adults, glucocorticoid treatment has been associated with smaller volumes of subcortical grey matter structures. Recently, we observed smaller total brain volumes in children and adolescents treated with glucocorticoid during childhood compared to healthy controls. The possible long-term effects of glucocorticoid treatment during childhood on subcortical brain volume and microstructure remain unknown. Method: We examined 30 children and adolescents, who had previously been treated with glucocorticoids for nephrotic syndrome or rheumatic disease, and 30 healthy volunteers. Patients and healthy control groups were matched by age, gender, and level of parent education. Participants underwent 3 T magnetic resonance (MR) brain imaging. T1-weighted and diffusion-weighted images were acquired. Volume and mean diffusivity (MD) measures were extracted for hippocampus, amygdala, nucleus accumbens, caudate nucleus and putamen. Multiple linear regression analyses were used to assess differences between patients and controls, and to evaluate possible dose-response relationships. A priori, we expected patients to display lower hippocampal and amygdala volumes. Results: While children previously treated with glucocorticoids displayed smaller right hippocampal volumes than controls, this difference did not survive correction for multiple comparisons. Furthermore, patients as compared to controls showed lower right hippocampal MD, which remained when correcting for global changes in MD. The longer the time between the glucocorticoid treatment termination and MR-scan, the more right hippocampal MD values resembled that of healthy controls. Patient and controls did not differ in amygdala volume or MD. Analyses of the nucleus accumbens, caudate nucleus and putamen only revealed smaller putamen volumes in patients compared to controls, which remained significant when controlling for total brain volume. Conclusion: The results suggest that extra-cerebral diseases during childhood treated with glucocorticoids may be associated with reduced subcortical grey matter volumes and lower right hippocampal mean diffusivity later in life. Our findings warrant replication and elaboration in larger, preferably prospective and longitudinal studies. Such studies may also allow disentangling disease-specific effects from possible glucocorticoid treatment effects. Keywords: Glucocorticoid treatment, Brain structure, Subcortical, MRI, Childhood, Adolescence

© 2016, The Author(s). Most humans show a strong preference to use their right hand, but strong preference for the right hand does not necessarily imply a strong right–left asymmetry in manual proficiency (i.e., dexterity). Here we tested the hypothesis that intra-individual asymmetry of manual proficiency would be reflected in microstructural differences between the right and left corticospinal tract (CST) in a cohort of 52 right-handed typically-developing adolescents (11–16 years). Participants were asked to fluently draw superimposed circles with their right dominant and left non-dominant hand. Temporal regularity of circle drawing movements was assessed for each hand using a digitizing tablet. Although all participants were right-handed, there was substantial inter-individual variation regarding the relative right-hand advantage for fluent circle drawing. All subjects underwent whole-brain diffusion tensor imaging at 3 Tesla. The right and left CST were defined as regions-of-interest and mean fractional anisotropy (FA) and diffusivity values were calculated for right and left CST. On average, mean FA values were higher in the left CST relative to right CST. The degree of right–left FA asymmetry showed a linear relationship with right–left asymmetry in fluent circle drawing after correction for age and gender. The higher the mean FA values were in the left dominant CST relative to the right non-dominant CST, the stronger was the relative right-hand advantage for regular circle drawing. These findings show that right–left differences in manual proficiency are highly variable in right-handed adolescents and that this variation is associated with a right-left microstructural asymmetry of the CST.

Long-term dopamine DTwenty-two initially antipsychotic-naïve patients underwent magnetic resonance imaging (MRI), [Neither extrastriatal DThe present data do not support an association between extrastriatal D

Udgivelsesdato: 2007-Nov-28 There is evidence from neuroimaging that the prefrontal cortex may be involved in establishing task set activity in advance of presentation of the task itself. To find out whether it plays an essential role, we examined patients with unilateral lesions of the rostral prefrontal cortex. They were first instructed as to whether to perform a spatial or a verbal working memory task and then given spatial and verbal items after a delay of 4-12 s. The patients showed an increase in switch costs, making more errors by repeating what they had done on the previous trial. They were able to establish regional task set activity during the instruction delay, as evidenced by sustained changes in the blood oxygenation level-dependent signal in caudal frontal regions. However, in contrast to healthy controls, they were less able to maintain functional connectivity among the surviving task-related brain regions, as evidenced by reduced correlations between them during instruction delays. The results suggest that the left rostral prefrontal cortex is indeed required for establishing a cognitive set but that the essential function is to support the functional connectivity among the task-related regions.

It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is growing evidence for hemispheric lateralization in brain systems regulating arousal and emotion. Here we tested the hypotheses that individual variations in basal morning and afternoon/evening cortisol levels would be associated with the degree of hemispheric asymmetry in hippocampal microstructure. Fifty healthy adults aged 19 to 86 years were included in the analyses. Diffusion-weighted imaging was acquired from all subjects. Hippocampal mean diffusivity (MD) and volume was extracted. Cortisol measures were based on 5 morning and 3 afternoon/evening saliva samples. Higher left relative to right hippocampus MD was associated with higher basal cortisol levels. Associations were anatomically specific and not attributable to hippocampal volume asymmetry. No correlation between hippocampal volume and MD was observed, suggesting that MD and volume index distinct biological properties of the hippocampus. Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point to an important relationship between the limbic system and neuroendocrine function in terms of left-right asymmetries, raising additional questions about how the limbic system is related to neuroendocrine functions.

Serotonin (5-HT) is a neuromodulator affecting myriad aspects of personality and behavior and has been implicated in the pathophysiology of affective disorders including depression and anxiety. The 5-HTTLPR is a common genetic polymorphism within the promoter region of the gene coding for the serotonin transporter such that the S allele is associated with reduced transcriptional efficacy compared to the L allele, potentially contributing to increased serotonin levels. In humans, this genetic variant has been linked to inter-individual variability in risk for affective disorders, related aspects of personality and brain function including response to threat. However, its effects on aspects of serotonin signaling in humans are not fully understood. Studies in animals suggest that the 5-HT 4 receptor (5-HT(4)) shows a monotonic inverse association with long-term changes in serotonin levels indicating that it may be a useful measure for identifying differences in serotonergic neurotransmission. In 47 healthy adults we evaluated the association between 5-HTTLPR status and in vivo 5-HT(4) receptor binding assessed with [(11)C]SB207145 positron emission tomography (PET). We observed a significant association within the neocortex where [(11)C]SB207145 binding was 9% lower in S carriers compared to LL homozygotes. We did not find evidence for an effect of season or a season-by-5-HTTLPR interaction effect on regional [(11)C]SB207145 binding. Our findings are consistent with a model wherein the 5-HTTLPR S allele is associated with relatively increased serotonin levels. These findings provide novel evidence supporting an effect of 5-HTTLPR status on serotonergic neurotransmission in adult humans. There were no indications of seasonal effects on serotonergic neurotransmission.