Developmental synchrony of thalamocortical circuits in the neonatal brain

10.1016/j.neuroimage.2015.03.039Neuroimage116168-176GUSTO (Growing up towards Healthy Outcomes

Lack of Evidence for Regional Brain Volume or Cortical Thickness Abnormalities in Youths at Clinical High Risk for Psychosis:Findings From the Longitudinal Youth at Risk Study

There is cumulative evidence that young people in an “at-risk mental state” (ARMS) for psychosis show structural brain abnormalities in frontolimbic areas, comparable to, but less extensive than those reported in established schizophrenia. However, most available data come from ARMS samples from Australia, Europe, and North America while large studies from other populations are missing. We conducted a structural brain magnetic resonance imaging study from a relatively large sample of 69 ARMS individuals and 32 matched healthy controls (HC) recruited from Singapore as part of the Longitudinal Youth At-Risk Study (LYRIKS). We used 2 complementary approaches: a voxel-based morphometry and a surface-based morphometry analysis to extract regional gray and white matter volumes (GMV and WMV) and cortical thickness (CT). At the whole-brain level, we did not find any statistically significant difference between ARMS and HC groups concerning total GMV and WMV or regional GMV, WMV, and CT. The additional comparison of 2 regions of interest, hippocampal, and ventricular volumes, did not return any significant difference either. Several characteristics of the LYRIKS sample like Asian origins or the absence of current illicit drug use could explain, alone or in conjunction, the negative findings and suggest that there may be no dramatic volumetric or CT abnormalities in ARMS

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Cortical graph neural network for AD and MCI diagnosis and transfer learning across populations

10.1016/j.nicl.2019.101929NeuroImage: Clinical101929-10192

Long-term Influences of Prenatal Maternal Depressive Symptoms on the Amygdala-Prefrontal Circuitry of the Offspring from Birth to Childhood

10.1016/j.bpsc.2019.05.006Biological Psychiatry: Cognitive Neuroscience and Neuroimagin

Fronto-parietal numerical networks in relation with early numeracy in young children

Early numeracy provides the foundation of acquiring mathematical skills that is essential for future academic success. This study examined numerical functional networks in relation to counting and number relational skills in preschoolers at 4 and 6 years of age. The counting and number relational skills were assessed using school readiness test (SRT). Resting-state fMRI (rs-fMRI) was acquired in 123 4-year-olds and 146 6-year-olds. Among them, 61 were scanned twice over the course of 2 years. Meta-analysis on existing task-based numeracy fMRI studies identified the left parietal-dominant network for both counting and number relational skills and the right parietal-dominant network only for number relational skills in adults. We showed that the fronto-parietal numerical networks, observed in adults, already exist in 4-year and 6-year-olds. The counting skills were associated with the bilateral fronto-parietal network in 4-year-olds and with the right parietal-dominant network in 6-year-olds. Moreover, the number relational skills were related to the bilateral fronto-parietal and right parietal-dominant networks in 4-year-olds and had a trend of the significant relationship with the right parietal-dominant network in 6-year-olds. Our findings suggested that neural fine-tuning of the fronto-parietal numerical networks may subserve the maturation of numeracy in early childhood

Functional and structural networks of lateral and medial orbitofrontal cortex as potential neural pathways for depression in childhood

Background: Converging evidence suggests that the lateral and medial orbitofrontal cortices (lOFC and mOFC) may contribute distinct neural mechanisms in depression. This study investigated the relations of their functional and structural organizations with postnatal maternal depressive symptoms in young children. Methods: Resting-state functional magnetic resonance imaging and structural magnetic resonance imaging were acquired in children at age 4 (n = 199) and 6 years (n = 234). Child's withdrawal behavior problems were assessed using Child's Behavior Checklist. Results: In 4-year-old girls, postnatal maternal depressive symptoms were positively associated with the lOFC functional connectivity with the visual network but negatively with the cognitive control network. The lOFC functional connectivity with the visual network and cerebellum, which was influenced by postnatal maternal depressive symptoms, was also associated with child's withdrawal behavior problems in 6-year-old girls. Moreover, postnatal maternal depressive symptoms were also negatively associated with the mOFC functional connectivity with the cognitive control and motor networks in 4-year-old girls. Furthermore, postnatal maternal depressive symptoms influenced the structural connectivity of left mOFC with the right middle frontal cortex and left inferior temporal cortex in 4-year-old girls. Unlike girls, boys showed that postnatal maternal depressive symptoms selectively impacted the mOFC functional connectivity with the memory system at age 6 years. Conclusion: Our study provided novel evidence on the distinct neural mechanisms of the lOFC and mOFC structural and functional organizations for intergenerational transmission of maternal depression to the offspring. Boys and girls may potentially employ different neural mechanisms to adapt to maternal environment at different timings of early life

Sex-Dependent Associations among Maternal Depressive Symptoms, Child Reward Network, and Behaviors in Early Childhood

Maternal depression is associated with disrupted neurodevelopment in offspring. This study examined relationships among postnatal maternal depressive symptoms, the functional reward network and behavioral problems in 4.5-year-old boys (57) and girls (65). We employed canonical correlation analysis to evaluate whether the resting-state functional connectivity within a reward network, identified through an activation likelihood estimation (ALE) meta-analysis of fMRI studies, was associated with postnatal maternal depressive symptoms and child behaviors. The functional reward network consisted of three subnetworks, that is, the mesolimbic, mesocortical, and amygdala-hippocampus reward subnetworks. Postnatal maternal depressive symptoms were associated with the functional connectivity of the mesocortical subnetwork with the mesolimbic and amygdala-hippocampus complex subnetworks in girls and with the functional connectivity within the mesocortical subnetwork in boys. The functional connectivity of the amygdala-hippocampus subnetwork with the mesocortical and mesolimbic subnetworks was associated with both internalizing and externalizing problems in girls, while in boys, the functional connectivity of the mesocortical subnetwork with the amygdala-hippocampus complex and the mesolimbic subnetworks was associated with the internalizing and externalizing problems, respectively. Our findings suggest that the functional reward network might be a promising neural phenotype for effects of maternal depression and potential intervention to nurture child behavioral development