Yi Zhang

Preterm infants have a higher risk for developing neurocognitive deficits and behavioral abnormalities across the lifespan, but the individual long-term neurobiological heterogeneity presents a challenge for developmental risk assessment and outcome prediction. Thus, we took advantage of the large sample size of the Adolescent Brain Cognitive Development dataset to investigate neuroanatomical subtypes that were previously unobservable in typical case-control designs, and explored potential neurodevelopmental mechanisms by analyzing the brain maturation of preterm subtypes. Our findings revealed two markedly distinct and reproducible brain structural and behavioral features that differentiated subtypes of preterm adolescents: 1) the “at-risk” subtype had an “average preterm brain pattern” of widespread lower cortical volume/area and subcortical volume and higher cortical thickness, and showed cognitive deficiencies and psychopathological risk; 2) the “resilient” subtype demonstrated more complex brain structural differences including both higher and lower cortical and subcortical volumes in different regions simultaneously, as well as widespread higher cortical area and lower cortical thickness. In addition, the “resilient: subtype showed accelerated brain maturation that may contribute to their normal cognitive function though they still had psychopathological risk. These neurodevelopmental alterations had significant associations with gestational age, birth weight, puberty development levels, psychopathological risk and cognitive deficits. The findings provide mechanistic insights into neurobiological heterogeneities in long-term neurodevelopmental trajectories in preterm adolescents, aiming to guide risk stratification and support healthy development in preterm adolescents.

Background Preterm infants with very low birth weight are at high risk for long-term neurocognitive deficits. However, whether these neurocognitive deficits are improved or worsened in adolescence remains unclear. Methods We took advantage of the large sample from the Adolescent Brain Cognitive Development dataset to investigate alterations in brain structure, behavior, including cognitive function and mental health symptoms, and in puberty among preterm children with very low/normal birth weight (Pre_VLBW/Pre_NBW) and full-term children with normal birth weight (Con_NBW) from baseline to 2-year follow-up. Results Pre_VLBW children relative to the other two groups had higher cortical thickness, lower cortical area and cortical/subcortical volumes in large portions of frontal cortex, temporal and occipital gyrus, insula, thalamus, and cerebellum; and attenuated fiber tract volumes in the fornix and foreceps major at baseline. Pre_VLBW children for their baseline measures also had lower cognitive function, higher pubertal levels and psychopathological risk. Furthermore, there were significant interaction effects on increased adrenarche score and cortical and subcortical volumes in medial orbitofrontal cortex (mOFC) and thalamus from baseline to 2-year follow-up. Pre_VLBW individuals showed higher adrenarche scores and lower volumes in the mOFC and thalamus than the other two groups at 2-year follow-up, but not at baseline. These brain structural changes showed associations with pubertal development levels, psychopathological risk and cognitive deficits. Conclusion These findings support a view that preterm children with VLBW showed distinctive developmental alterations during adolescence, which potentially lead to long-lasting deviations in various brain regions and might be associated with behavioral problems and neurocognitive deficits.

Objective: The aim of this study was to investigate the relationship between obesity (OB) progression and brain structural changes.Methods: T1‐weighted magnetic resonance images were acquired from 258 participants with overweight (OW) or OB and 74 participants with normal weight. Participants with OW or OB were divided into four groups according to BMI grades. Two‐sample t tests compared disparities between the four subgroups and the participants with normal weight. We used causal structural covariance networks to examine the progressive impact of OB on brain structure.Results: With increasing BMI values, reductions in gray matter volume originated in the left caudate nucleus, medial orbitofrontal cortex, and left insula and expanded to the right hippocampus and left lateral orbitofrontal cortex and then to the right parahippocampal gyrus, left precuneus, and left dorsolateral prefrontal cortex (p < 0.05, false discovery rate corrected). The left caudate nucleus and medial orbitofrontal cortex are the primary hubs of the directional network, exhibiting positive causality to the right hippocampus and left dorsolateral prefrontal cortex. Moreover, the right hippocampus is identified as an important transition hub.Conclusions: These findings suggest that changes in gray matter volume in individuals with OB may originate from reward/motivation processing regions, subsequently progressing to inhibitory control/learning memory regions, providing a new reference direction for clinical intervention and treatment of OB.

BACKGROUND: A polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than noncarriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery. METHODS: Resting-state functional magnetic resonance imaging and cue-reactivity functional magnetic resonance imaging with high-/low-caloric food cues were performed before surgery and at 1, 6, and 12 months after surgery to examine brain function in 16 carriers with 1 copy of the rs9939609 A allele (AT) and 26 noncarriers (TT). Behavioral assessments up to 5 years after surgery were also conducted. RESULTS: The AT group relative to the TT group had smaller BMI loss at 12–60 months after surgery and lower resting-state activity in posterior cingulate cortex following laparoscopic sleeve gastrectomy (group-by-time interaction effects). Meanwhile, the AT group relative to the TT group showed greater food cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and insula (group effects). There were negative associations of weight loss with ghrelin and greater activation in DLPFC, DMPFC and insula in the AT but not the TT group. CONCLUSION: These findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight loss. TRIAL REGISTRATION: Chinese Clinical Trial Registry Center, ChiCTR-OOB-15006346. FUNDING: This work was supported by the National Natural Science Foundation of China (grant nos. 82172023, 82202252, 82302292); National Key R&D Program of China (no. 2022YFC3500603); Natural Science Basic Research Program of Shaanxi (grant nos. 2022JC-44, 2022JQ-622, 2023-JC-QN-0922, 2023-ZDLSF-07); Fundamental Research Funds for the Central Universities (grant nos. ZYTS23188, XJSJ23190, XJS221201, QTZX23093); and the Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse (grant no. Y1AA3009).

Time-on-task effect is a common consequence of long-term cognitive demand work, which reflects reduced behavioral performance and increases the risk of accidents. Neurofeedback is a neuromodulation method that can guide individuals to regulate their brain activity and manifest as changes in related symptoms and cognitive behaviors. This study aimed to examine the effects of functional near-infrared spectroscopy-based neurofeedback training on time-on-task effects and sustained cognitive performance. A randomized, single-blind, sham-controlled study was performed: 17 participants received feedback signals of their own dorsolateral prefrontal cortex activity (neurofeedback group), and 16 participants received feedback signals of dorsolateral prefrontal cortex activity from the neurofeedback group (sham-neurofeedback group). All participants received 5 neurofeedback training sessions and completed 2 sustained cognitive tasks, including a 2-back task and a psychomotor vigilance task, to evaluate behavioral performance changes following neurofeedback training. Results showed that neurofeedback relative to the sham-neurofeedback group exhibited increased dorsolateral prefrontal cortex activation, increased accuracy in the 2-back task, and decreased mean response time in the psychomotor vigilance task after neurofeedback training. In addition, the neurofeedback group showed slower decline performance during the sustained 2-back task after neurofeedback training compared with sham-neurofeedback group. These findings demonstrate that neurofeedback training could regulate time-on-task effects on difficult task and enhance performance on sustained cognitive tasks by increasing dorsolateral prefrontal cortex activity.

Children with ADHD show abnormal brain function and structure. Neuroimaging studies found that stimulant medications may improve brain structural abnormalities in children with ADHD. However, prior studies on this topic were conducted with relatively small sample sizes and wide age ranges and showed inconsistent results. In this cross-sectional study, we employed latent class analysis and linear mixed-effects models to estimate the impact of stimulant medications using demographic, clinical measures, and brain structure in a large and diverse sample of children aged 9-11 from the Adolescent Brain and Cognitive Development Study. We studied 273 children with low ADHD symptoms and received stimulant medication (Stim Low-ADHD), 1002 children with high ADHD symptoms and received no medications (No-Med ADHD), and 5378 typically developing controls (TDC). After controlling for the covariates, compared to Stim Low-ADHD and TDC, No-Med ADHD showed lower cortical thickness in the right insula (INS, d = 0.340, P_FDR = 0.003) and subcortical volume in the left nucleus accumbens (NAc, d = 0.371, P_FDR = 0.003), indicating that high ADHD symptoms were associated with structural abnormalities in these brain regions. In addition, there was no difference in brain structural measures between Stim Low-ADHD and TDC children, suggesting that the stimulant effects improved both ADHD symptoms and ADHD-associated brain structural abnormalities. These findings together suggested that children with ADHD appear to have structural abnormalities in brain regions associated with saliency and reward processing, and treatment with stimulant medications not only improve the ADHD symptoms but also normalized these brain structural abnormalities.

Obesity has been linked to abnormal frontal function, including the white matter fibers of anterior portion of the corpus callosum, which is crucial for information exchange within frontal cortex. However, alterations in white matter anatomical connectivity between corpus callosum and cortical regions in patients with obesity have not yet been investigated. Thus, we enrolled 72 obese and 60 age-/gender-matched normal weight participants who underwent clinical measurements and diffusion tensor imaging. Probabilistic tractography with connectivity-based classification was performed to segment the corpus callosum and quantify white matter anatomical connectivity between subregions of corpus callosum and cortical regions, and associations between corpus callosum–cortex white matter anatomical connectivity and clinical behaviors were also assessed. Relative to normal weight individuals, individuals with obesity exhibited significantly greater white matter anatomical connectivity of corpus callosum–orbitofrontal cortex, which was positively correlated with body mass index and self-reported disinhibition of eating behavior, and lower white matter anatomical connectivity of corpus callosum–prefrontal cortex, which was significantly negatively correlated with craving for high-calorie food cues. The findings show that alterations in white matter anatomical connectivity between corpus callosum and frontal regions involved in reward and executive control are associated with abnormal eating behaviors.