The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Significant MRI site and vendor effects (p ​< ​.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p ​< ​1.39E-36). In particular, volumes larger than 200 ​mm3 (for amygdalar nuclei) and 300 ​mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε ​< ​5% and DICE ​> ​0.80). Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Different psychotherapeutic approaches demonstrated their efficacy but the possible neurobiological mechanism underlying the effect of psychotherapy in borderline personality disorder (BPD) patients is poorly investigated. We assessed the effects of metacognitive interpersonal therapy (MIT) on BPD features and other dimensions compared to structured clinical management (SCM). We also assessed changes in amygdala activation by viewing emotional pictures after psychotherapy. One hundred forty-one patients were referred and 78 BPD outpatients were included and randomized to MIT or SCM. Primary outcome was emotional dysregulation assessed with the Difficulties in Emotion Regulation Scale (DERS). We also assessed BPD symptomatology, number of PD criteria, metacognitive abilities, state-psychopathology, depression, impulsiveness, interpersonal functioning, and alexithymia. A subset of 60 patients underwent functional magnetic resonance imaging before and after 1 year of psychotherapy to assess amygdala activation by viewing standardized emotional pictures (secondary outcome). DERS scores decreased in both groups (time effect p < .001). The Cohen's d effect size for change (baseline posttreatment) on DERS was very large (d = 0.84) in MIT, and large (d = 0.76) in SCM. Both groups significantly improved in depressive symptoms, state-psychopathology, alexithymia, and interpersonal functioning. MIT showed larger effect on metacognitive functions than SCM (Time × Group p < .001). Both interventions showed a significant effect on BPD symptomatology although SCM group showed a larger decrease. On the contrary, MIT group showed larger decrease in impulsivity and number of PD criteria. Interestingly, both MIT and SCM modulated amygdala activation in BPD patients. MIT is a valid and effective psychotherapy for BPD with an impact on amygdala activation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Core symptoms of Borderline Personality Disorder (BPD) are associated to aberrant connectivity of the triple network system (salience network [SN], default mode network [DMN], executive control network [ECN]). While functional abnormalities are widely reported, structural connectivity (SC) and anatomical changes have not yet been investigated. Here, we explored the triple network’s SC, structure, and its association with BPD clinical features. Methods: A total of 60 BPD and 26 healthy controls (HC) underwent a multidomain neuropsychological and multimodal MRI (diffusion- and T1-weighted imaging) assessment. Metrics (fractional anisotropy [FA], mean diffusivity [MD], cortical thickness) were extracted from SN, DMN, ECN (triple network), and visual network (control network) using established atlases. Multivariate general linear models were conducted to assess group differences in metrics and associations with clinical features. Results: Patients showed increased MD in the anterior SN, dorsal DMN, and right ECN compared to HC. Diffusivity increases were more pronounced in patients with higher behavioral dysregulation, i.e., suicidal attempting, self-harm, and aggressiveness. No differences were detected in network structure. Conclusions: These results indicate that the triple network system is impaired in BPD at the microstructural level. The preferential involvement of anterior and right-lateralized subsystems and their clinical association suggests that these abnormalities could contribute to behavioral dysregulation.

Objectives: Care for community‐dwelling people with dementia is frequently delegated to relatives, who find themselves in the role of informal caregivers with no practical management knowledge. This situation exposes caregivers to increased risk for emotional wellbeing. The current study aims to test whether the integration of the efficacy of an immersive virtual reality (VR) experience into an online psychoeducational program impacts caregiver empathy and therefore emotional wellbeing.Methods: One‐hundred informal caregivers of mild‐to‐moderate Alzheimer's disease (AD) patients will be enrolled and randomly assigned to (i) an online psychoeducational program (control arm); or (ii) an online psychoeducational program integrated with VR (experimental arm). VR will consist of 360‐degree videos involving the caregivers to an immersive experience of dementia symptoms from the patient's perspective. Before, after the intervention and after 2 months, all participants will complete validated clinical scales for caregiver burden and anxiety (primary outcomes) and sense of competence and dispositional empathy (secondary outcomes). A subsample of 50 participants will also undergo MRI exam, including structural and functional (resting‐state and task‐functional MRI [fMRI]) sequences. The fMRI task paradigm will use emotional stimuli to evaluate the neural correlate of empathy, by stressing its cognitive and affective components. The main outcome will be the change in the clinical assessment; the secondary outcome will be the change in brain connectivity of networks subserving the empathic and emotional functioning.Results: We expect that the psychoeducational program will decrease anxiety and stress, enabling caregivers to perceive themselves capable of managing AD patients at home, educating them on symptom handling and boosting their cognitive empathy. In the experimental intervention, the VR‐based experience will act as an add‐on to psychoeducation, leading to greater improvement in the assessed clinical dimensions. VR should, in fact, enable a deeper understanding of disease symptoms and improve caregivers' cognitive empathy. We expect that the experimental intervention will result in deeper comprehension of disease symptoms and further strengthen caregivers' cognitive empathy. At the neural level, we expect to observe increased activation in circuits subserving cognitive empathy and decreased activation in circuits underlying affective empathy.Conclusions: To the best of our knowledge, this will be the first randomized controlled trial assessing the effect of combining psychoeducational interventions with VR‐based experience in caregivers, and assessing both clinical and imaging outcomes.Trial Registration: Registered in ClinicalTrials.gov (NCT05780476)