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PubMed2026

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans↗
PubMed2026

Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent↗
PubMed2026

Combining neuromelanin-sensitive MRI and quantitative susceptibility mapping for enhanced diagnosis and differentiation of parkinson's disease: A systematic review.

BACKGROUND: Loss of dopaminergic neurones and iron deposition in the substantia nigra pars compacta (SNpc) are two major pathological hallmarks of Parkinson's disease (PD). Such changes can be visualised by advanced techniques including neuromelanin-sensitive MRI (NM-MRI) and quantitative susceptibility mapping (QSM). This systematic review investigates the diagnostic performance and methodological development of the integrated use of NM-MRI and QSM in PD. METHODS: The systematic search was performed in four databases (Scopus, PubMed, ScienceDirect, and Web of Science) according to the PRISMA 2020 guidelines until July 2026. Bias was assessed using QUADAS-2 and certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies with 2228 participants were included. Combined NM-MRI and QSM consistently showed reduced neuromelanin volume/contrast and increased iron deposition in the SNpc of PD patients compared to healthy controls. Multimodal integration yielded a significant improvement in diagnostic accuracy (AUC values 0.86-0.99), and was able to successfully differentiate PD. Recent methodological advances included simultaneous acquisition sequences (e.g. MTC-GRE, STAGE, setMag) and AI-driven automated segmentation, which led to significantly reduced scan times and improved reproducibility. CONCLUSION: The combination of NM-MRI and QSM has a synergistic effect and provides powerful complementary biomarkers for the diagnosis and differential diagnosis of PD.

Humans↗
PubMed2026

Subtle cortical thinning in the temporal pole in middle-aged APOE-ε4 and PICALM (rs3851179) AA/AG carriers without dementia.

The symptoms of Alzheimer's disease (AD) are caused by neurodegeneration and atrophy in particular brain regions, especially in the temporal lobe. However, the influence of genetic risk on cortical thickness prior to dementia onset, remains unclear. This study aimed to explore the relationship between AD genetic risk (related to APOE and PICALM genes) and cortical thickness in selected regions of interest (ROIs) in middle-aged individuals without dementia. Sixty-nine (N = 69) participants (34 females, 35 males; age: 55.45 ± 3.19) underwent magnetic resonance imaging (MRI). They were divided into three groups based on their genetic AD risk: A+ P+ (APOE/PICALM risk variants), A+P- (APOE risk variant, PICALM neutral variants), and the N group (APOE/PICALM neutral alleles). Cortical thickness was analyzed using CAT12 software (surface-based morphometry with the Destrieux atlas) based on T1-weighted MR images in five ROIs referred to as "the cortical signature of AD" in previous studies. The A+P- group had a thinner right temporal pole cortex than non-carriers after controlling for sex, age, and Raven's Progressive Matrices scores. Although this finding did not survive FDR correction across the 10 tested regions, it is consistent with our hypotheses and prior literature. No other differences in cortical thickness were found in the analyzed regions of AD "signature". The observed effect was restricted to single-risk APOE carriers without PICALM risk alleles. Therefore, further research is needed to understand the genetic interplay between these two genes in conferring AD risk.

Humans↗
PubMed2026

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans↗
PubMed2026

Complexity in disguise: a systematic review of fractal analysis in psychiatric neuroimaging.

OBJECTIVES: Psychiatric diagnosis and fractal studies are complex processes that extend beyond clinical evaluation and require careful methodological considerations in neuroimaging. Over the years, fractals have helped reduce these complexities in research, but they still cannot grant clinical diagnoses. Thus, the main objective was a systematic review exploring the potential applications of fractal analysis in characterizing psychiatric conditions through neuroimaging techniques-including both functional and structural MRI. MATERIALS AND METHODS: A systematic literature review was conducted on PubMed, identifying thirty-nine original studies that met the inclusion criteria. Areas showing statistical significance (p&#x2009;<&#x2009;0.05) were reported. These studies were categorized according to DSM-V classification and examined for the description of psychiatric conditions through the fractal analysis. RESULTS: The review primarily focuses on young adults with psychiatric conditions compared to control groups. Schizophrenia and Autism Spectrum Disorder are major areas of investigation, and fractal dimension (FD) is the primary analysis method used to reflect brain patterns. Studies that calculated whole-brain FD may have underestimated local abnormalities due to the inclusion of a high percentage of tissue, potentially resulting in overlooked findings. Notably, abnormalities in the frontal cortex represent a common neurobiological feature across several psychiatric conditions. CONCLUSIONS: The findings from this systematic review shed light on the use of fractal analysis to quantify complex brain patterns in both psychiatric patients and healthy individuals. However, it is essential to recognize the need for further research to elucidate a fractal analysis protocol that allows for optimal extraction of psychiatric insights. KEY POINTS: Question Fractal analysis applied to structural and functional MRI help characterize brain alterations across psychiatric conditions. Findings This review shows consistent fractal patterns across multiple psychiatric disorders, especially in frontal regions. Despite heterogeneous methodologies, results highlight shared structural and functional abnormalities. Clinical relevance Fractal analysis may offer complementary characterization of subtle brain organization across psychiatric disorders. Its potential clinical utility-such as improving diagnostic characterization, earlier detection, among others-remains limited by the current absence of a standardized protocol.

Humans↗