Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Contour integration, the process of joining spatially separated elements into a single unified line, has consistently been found to be impaired in schizophrenia. Recent work suggests that this deficit could be associated with psychotic symptomatology, rather than a specific diagnosis such as schizophrenia.

Methods: Examining a transdiagnostic sample of participants with psychotic psychopathology, we obtained quantitative indices of contour perception in a psychophysical behavioral task. We also measured responses during an analogous task using ultra-high field (7T) functional MRI.

Results: We found impaired contour discrimination performance among people with psychotic psychopathology (PwPP, n = 63) compared to healthy controls (n = 34) and biological relatives of PwPP (n = 44). Participants with schizophrenia (n = 31) showed impaired task performance compared to participants with bipolar disorder (n = 18). FMRI showed higher responses in the lateral occipital cortex of PwPP compared to controls. Using task-based functional connectivity analyses, we observed abnormal connectivity between visual brain areas during contour perception among PwPP. These connectivity differences only emerged when participants had to distinguish the contour object from background distractors, suggesting that a failure to suppress noise elements relative to contour elements may underlie impaired contour processing in PwPP.

Conclusions: Our results are consistent with impaired contour integration in psychotic psychopathology, and especially schizophrenia, that is related to cognitive dysfunction, and may be linked to impaired functional connectivity across visual regions.

Background: Obsessive-compulsive disorder (OCD) is a common and debilitating mental disorder. Neuroimaging studies have highlighted that the dysfunctional default mode network (DMN) plays a key role in the pathophysiology mechanisms of OCD. However, the findings of impaired DMN regions have been inconsistent. We employed meta-analysis to identify the fMRI-specific abnormalities of the DMN in OCD.

Methods: PubMed, Web of science and Embase were searched to screen resting-state functional magnetic resonance imaging (rs-fMRI) studies on the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF) and regional homogeneity (ReHo) of the DMN in OCD patients. Based on the activation likelihood estimation (ALE) algorithm, we compared all patients with OCD and control group in a primary meta-analysis, and analyzed the unmedicated OCD without comorbidities in secondary meta-analyses.

Results: A total of 26 eligible studies with 1219 OCD patients (707men) and 1238 healthy controls (684 men) were included in the primary meta-analysis. We concluded specific changes in brain regions of DMN, mainly in the left medial frontal gurus (MFG), bilateral superior temporal gyrus (STG), bilateral inferior parietal lobule (IPL), bilateral precuneus (PCUN), bilateral posterior cingulate cortex (PCC), and right parahippocampal gyrus (PHG).

Conclusion: OCD patients showed dysfunction in the DMN, including impaired local important nodal brain regions. The PCC/PCUN appear to be the most affected regions within the DMN, providing valuable insights into understanding the potential pathophysiology of OCD and targets for clinical interventions.

Background: Cue-induced craving precipitates relapse in drug and alcohol use disorders. Theta burst stimulation (TBS) to the left frontal pole of the medial prefrontal cortex (MPFC) has previously been shown to reduce drinking and brain reactivity to alcohol cues. This randomized, double-blind, sham-controlled target-engagement study aimed to assess whether TBS has similar effects in individuals with cocaine use disorder (CUD).

Methods: Thirty-three participants in intensive outpatient treatment received either real or sham TBS over 10 sessions across 3 weeks (36,000 pulses total; continuous TBS, 110% resting motor threshold, 3600 pulses/session). TBS was administered on days of behavioral counseling. Twenty-five individuals completed all 10 TBS sessions. Brain reactivity to cocaine cues was measured using fMRI at baseline, 1-month, 2-months, and 3-months.

Results: Cocaine abstinence during the 3-month follow-up period was greater in the real TBS group (1-month: 92.0%, 2-month: 100.0%, 3-month: 85.0%) compared to sham (1-month: 66.6%, 2-month: 66.6%, 3-month: 66.6%), though not statistically significant [1-month: 6.00, p=0.14; 2-month OR=:14.30, p=0.09, and 3-month OR=2.75, p=0.30]. However, there was a significant effect on cocaine cue reactivity (treatment effect: F_1,365= 8.92, p=0.003; time*treatment interaction: F_3,365=12.88, p<0.001). Real TBS reduced cocaine cue reactivity in the MPFC (F_3,72=5.46, p=0.02) overall, and in the anterior cingulate (F_3,72=3.03, p=0.04), and insula (F_3,72=3.60, p=0.02).

Conclusions: This early-stage trial demonstrates TBS to the MPFC reduces brain reactivity to cocaine cues in key nodes of the Salience Network in treatment-seeking cocaine users. Future, well-powered trials are warranted to evaluate clinical efficacy outcomes.

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 (GSH), a central factor in resistance to oxidative stress, in both participants with early psychosis and healthy control (HC) participants.

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

Results: The mean (SD) age of participants was 25.7 (4.6) years; 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 < .001) and glutamate (p = .007). After insulin administration, GSH increased in HC participants (mean change, 0.15; 95% CI 0.03 to 0.26; p = .015), but not in patients. Symbol coding improved in both patients (0.74; 95% CI 0.37 to 1.11; p < .001) and HC participants (0.83; 95% CI 0.58 to 1.09; p < .001), and verbal fluency improved in HC participants (0.43; 95% CI 0.14 to 0.72; p = .006). Lower baseline HOMA-IR was associated with greater change in GSH (coefficient -0.22; 95% CI -0.40 to -0.04; p = .017).

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

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

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

Results: We observed significantly higher frontolimbic mGlu₅ availability in the BPD group than in both the healthy control group (p = .009, d = 0.84, 18.43% difference) and the major depressive disorder group (p = .03, d = 0.69, 15.21% difference). In the BPD, but not the major depressive disorder group, higher mGlu₅ availability was also associated with a history of SAs (19-25% higher, ps = .02-.005). Furthermore, mGlu₅ availability was positively correlated with risk factors for suicide (e.g., sexual victimization, perceived burdensomeness) in individuals with BPD and a history of SA.

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

Background: Impulsivity is a multidimensional construct reflecting poor constraint over one's behaviors. Clinical psychology research identifies separable impulsivity dimensions that are each unique transdiagnostic indicators for psychopathology. Yet, despite this apparent clinical importance, the shared and unique neuroanatomical correlates of these factors remain largely unknown. Concomitantly, neuroimaging research identifies variably present human brain structures implicated in cognition and disorder: the folds (sulci) of the cerebral cortex located in the latest developing and most evolutionarily expanded hominoid-specific association cortices.

Methods: We tethered these two fields to test whether variability in one such structure in anterior cingulate cortex (ACC)-the paracingulate sulcus (PCGS)-was related to individual differences in trait impulsivity. 120 adult participants with internalizing or externalizing psychopathology completed a magnetic resonance imaging scan and the Three-Factor Impulsivity Index. Using precision imaging techniques, we manually identified the PCGS, when present, and acquired quantitative folding metrics (PCGS length and ACC local gyrification index).

Results: Neuroanatomical-behavioral analyses revealed that participants with leftward or symmetrical PCGS patterns had greater severity of Lack of Follow Through (LFT)-which captures inattention and lack of perseverance-than those with rightward asymmetry. Neuroanatomical-functional analyses identified that the PCGS co-localized with a focal locus found in a neuroimaging meta-analysis on a feature underlying LFT. Both quantitative folding metrics did not relate to any impulsivity dimension.

Conclusions: This study advances understanding of the neuroanatomical correlates of impulsivity and establishes the notion that the topographical organization of distinct, hominoid-specific cortical expanses underlie separable impulsivity dimensions with robust, transdiagnostic implications for psychopathology.

Background: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters.

Methods: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases.

Results: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D₂ receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H₃ receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission.

Conclusions: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.