Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Repetitive negative thinking (RNT) symptoms, which are characterized by pervasive, uncontrollable negative thoughts, are common in individuals with mood, anxiety, and traumatic stress disorders. Inability to regulate the contents of working memory is a hypothesized etiological factor in RNT, which suggests that training to improve working memory may be beneficial. This study examined the effects of working memory training on resting-state functional connectivity (rsFC) in individuals with elevated RNT and whether such changes would be associated with clinical improvement.

Methods: We conducted a secondary analysis of pre-post resting-state data collected as part of a randomized controlled trial (NCT04912089) of working memory training interventions (n = 42) compared with a waitlist control group (n = 23). We hypothesized that individuals who completed training would show increased rsFC between the 2 key intrinsic connectivity networks-the default mode network (posterior cingulate cortex) and the frontoparietal network (dorsolateral prefrontal cortex). We explored whether the magnitude of rsFC change was associated with change in RNT symptom severity.

Results: rsFC increased between the posterior cingulate cortex and regions including the frontal and parietal cortex in the training group compared with the waitlist group. Increased connectivity between the posterior cingulate cortex and superior frontal cortex was associated with RNT symptom reduction.

Conclusions: These data provide evidence that working memory training can modulate neural circuitry at rest in individuals with RNT. Results are consistent with accounts of working memory training effects on large-scale neurocircuitry changes and suggest that these changes may contribute to clinical promise of this type of intervention on transdiagnostic RNT symptoms.

Background: While the amygdala receives early tau deposition in Alzheimer's disease (AD) and is involved in social and emotional processing, the relationship between amygdalar tau and early neuropsychiatric symptoms in AD is unknown. We sought to determine whether focal tau binding in the amygdala and abnormal amygdalar connectivity were detectable in a preclinical AD cohort and identify relationships between these and self-reported mood symptoms.

Methods: We examined 598 individuals (347 amyloid positive [58% female], 251 amyloid negative [62% female] subset in tau positron emission tomography and functional magnetic resonance imaging cohorts) from the A4 (Anti-Amyloid Treatment in Asymptomatic AD) Study. In the tau positron emission tomography cohort, we used amygdalar segmentations to examine representative nuclei from 3 functional divisions of the amygdala. We analyzed between-group differences in division-specific tau binding in the amygdala in preclinical AD. We conducted seed-based functional connectivity analyses from each division in the functional magnetic resonance imaging cohort. Finally, we conducted exploratory post hoc correlation analyses between neuroimaging biomarkers of interest and anxiety and depression scores.

Results: Amyloid-positive individuals demonstrated increased tau binding in the medial and lateral amygdala, and tau binding in these regions was associated with mood symptoms. Across amygdalar divisions, amyloid-positive individuals had relatively higher regional connectivity from the amygdala to other temporal regions, the insula, and the orbitofrontal cortex, but medial amygdala to retrosplenial cortex connectivity was lower. Medial amygdala to retrosplenial connectivity was negatively associated with anxiety symptoms, as was retrosplenial tau.

Conclusions: Our findings suggest that preclinical tau deposition in the amygdala and associated changes in functional connectivity may be related to early mood symptoms in AD.

Background: Symptoms of depression are associated with impaired interoceptive processing of bodily sensation. The antidepressant effects of subcallosal cingulate deep brain stimulation (SCC DBS) include acute change in bodily sensation, and the SCC target is connected to cortical regions critically involved in interoception. This study tested whether cortical interoceptive processing is modulated by SCC DBS for treatment-resistant depression.

Methods: In 8 patients receiving SCC DBS for treatment-resistant depression, we used electroencephalography to measure the heartbeat-evoked potential (HEP), a putative readout of neural interoception, before surgery and over 6 months of treatment with DBS. We also examined the immediate effect of DBS on the HEP and correlated HEP change over time with outcomes of treatment for depression.

Results: HEP amplitude increased from baseline to 6 months of DBS treatment, and this increase was associated with faster antidepressant response. Recording with stimulation on (vs. off) had an immediate effect on HEP in the laboratory. Overall, modulation of the HEP was most pronounced in sensors over the left parietal cortex.

Conclusions: Brain-based evidence implies an interoceptive element in the mechanism of treatment efficacy with DBS for treatment-resistant depression and substantiates a theorized connection between interoception and depression.

Background: Adolescent substance use is a significant predictor of future addiction and related disorders. Understanding neural mechanisms underlying substance use initiation and frequency during adolescence is critical for early prevention and intervention.

Methods: The current longitudinal study followed 91 substance-naïve adolescents annually for seven years from ages 14 to 21 to identify potential neural precursors that predict substance use initiation and frequency. Cognitive control processes were examined using the Multi-Source Interference Task to assess functional neural connectivity. A questionnaire assessed substance use frequency.

Results: Stronger connectivity between the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC) at Time 1 predicted a delayed onset of substance use, indicative of a protective effect. A notable decline in this dACC-dlPFC connectivity was observed one year prior to substance use initiation. Conversely, lower connectivity of the dACC with the supplementary motor area and heightened connectivity of the aINS with the dorsal medial prefrontal cortex and Angular gyrus were predictive of greater frequency of future substance use. These findings remained after controlling for demographic and socioeconomic covariates.

Conclusions: This study highlights the critical role of cognitive control-related neural connectivity in forecasting substance use initiation and frequency during adolescence. The results imply that efforts to strengthen and monitor the development of the top-down cognitive control system in the brain from early adolescence can be protective and deter progression into problematic substance use. Furthermore, for adolescents with heightened frequency of substance use, interventions may prove more effective by targeting interoceptive processes in cognitive control training.

Background: As people live longer, maintaining brain health becomes essential for extending health span and preserving independence. Brain degeneration and cognitive decline are major contributors to disability. In this study, we investigated how metabolic health influences the brain age gap estimate (brainAGE), which measures the difference between neuroimaging-predicted brain age and chronological age.

Methods: K-means clustering was applied to fasting metabolic markers including insulin, glucose, leptin, cortisol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol, steady-state plasma glucose, and body mass index of 114 physically and cognitively healthy adults. The homeostatic model assessment for insulin resistance served as a reference. T1-weighted brain magnetic resonance imaging was used to calculate voxel-level and global brainAGE. Longitudinal data were available for 53 participants over a 3-year interval.

Results: K-means clustering divided the sample into 2 groups, those with favorable (n = 58) and those with suboptimal (n = 56) metabolic health. The suboptimal group showed signs of insulin resistance and dyslipidemia (false discovery rate-corrected p < .05) and had older global brainAGE and local brainAGE, with deviations most prominent in cerebellar, ventromedial prefrontal, and medial temporal regions (familywise error-corrected p < .05). Longitudinal analysis revealed group differences but no significant time or interaction effects on brainAGE measures.

Conclusions: Suboptimal metabolic status is linked to accelerated brain aging, particularly in brain regions rich in insulin receptors. These findings highlight the importance of metabolic health in maintaining brain function and suggest that promoting metabolic well-being may help extend health span.

Background: We examined the acute effects of intranasal insulin on cognitive function and brain glutathione, a central factor in resistance to oxidative stress, in both participants with early psychosis and healthy participants.

Methods: Twenty-one patients with early-stage psychotic disorders and 18 healthy controls underwent magnetic resonance spectroscopy (MRS) scans and cognitive assessments pre- and post- administration of intranasal insulin 40 IU. We conducted ¹H-magnetic resonance spectroscopy (MRS) in the prefrontal cortex at 4T to measure glutathione (GSH) and glutamate metabolites. We assessed cognition using the Brief Assessment of Cognition in Schizophrenia (BACS) symbol coding, digit sequencing, and verbal fluency tasks, in addition to Stroop Task.

Results: The mean (SD) age of participants was 25.7(4.6); 51.3% were female. There were no significant group differences at baseline in age, sex, body mass index, homeostatic model assessment of insulin resistance (HOMA-IR), or cognition. Patients had higher baseline GSH (p<0.001) and glutamate (p=0.007). After insulin administration, GSH increased in controls (Mean change 0.15;95%CI 0.03, 0.26; p=0.015), but not in patients. Symbol coding improved in both patients (0.74;95%CI 0.37,1.11;p<0.001) and controls (0.83;95%CI 0.58,1.09;p<0.001) and verbal fluency improved in controls (0.43;95%CI 0.14, 0.72; p=0.006). Lower baseline HOMA-IR was associated with greater change in GSH (Coeff -0.22; 95%CI -0.40, -0.04; p=0.017).

Conclusions: Intranasal insulin increases brain GSH in healthy participants, but not in early psychotic disorders. These novel findings demonstrate that intranasal insulin enhances antioxidant capacity and resilience to oxidative stress in healthy individuals, in contrast to an absent antioxidant response in those with early psychotic disorders.

Background: Borderline Personality Disorder (BPD) is a serious psychiatric condition, associated with a high risk for suicide attempts and death by suicide. However, relatively little is known about the pathophysiology of BPD. The metabotropic glutamate receptor type 5 (mGlu5) has been specifically implicated in the pathophysiology of BPD and suicide attempts, with more general roles in emotion regulation, social and cognitive functioning, and pain processing. Here, we examined the relationship between mGlu5 availability, BPD, and suicide attempts in vivo for the first time.

Methods: Eighteen individuals with BPD, and 18 age-, sex-, and smoking-status matched healthy (HC) and 18 clinical comparison controls with major depressive disorder (MDD) completed comprehensive clinical assessments and participated in an [¹⁸F]FPEB positron emission tomography (PET) scan to measure mGlu5 availability. Volume of distribution (V_T) in the frontolimbic circuit implicated in BPD pathophysiology was the PET outcome measure.

Results: We observed significantly higher frontolimbic mGlu5 availability in BPD compared to both HC (p=.009, d=0.84, 18.43% difference), and MDD (p=.03, d=0.69, 15.21% difference). In the BPD, but not MDD group, higher mGlu5 availability was also associated with history of suicide attempts (SA; 19-25% higher, p's=.005-.02). Further, mGlu5 availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in BPD-SA group.

Conclusions: Results show higher mGlu5 availability in BPD and suicide attempt for the first time. Our preliminary findings suggest mGlu5 may be a critical treatment target for BPD symptoms, including suicide attempts, and warrant further investigation in larger samples.