Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

Background: Pain empathy represents a fundamental building block of several social functions, which have been demonstrated to be impaired across various mental disorders by accumulating evidence from case-control functional magnetic resonance imaging studies. However, it remains unclear whether the dysregulations are underpinned by robust neural alterations across mental disorders.

Methods: This study utilized coordinate-based meta-analyses to quantitatively determine robust markers of altered pain empathy across mental disorders. To support the interpretation of the findings, exploratory network-level and behavioral meta-analyses were conducted.

Results: Quantitative analysis of 11 case-control functional magnetic resonance imaging studies with data from 296 patients and 229 control participants revealed that patients with mental disorders exhibited increased pain empathic reactivity in the left anterior cingulate gyrus, adjacent medial prefrontal cortex, and right middle temporal gyrus but decreased activity in the left cerebellum IV/V and left middle occipital gyrus compared with control participants. The hyperactive regions showed network-level interactions with the core default mode network and were associated with affective and social cognitive domains.

Conclusions: The findings suggest that pain empathic alterations across mental disorders are underpinned by excessive empathic reactivity in brain systems involved in empathic distress and social processes, highlighting a shared therapeutic target to normalize basal social dysfunctions in mental disorders.

Background: Schizophrenia Spectrum Disorders (SSDs), which are characterized by social cognitive deficits, have been associated with dysconnectivity in "unimodal" (e.g., visual, auditory) and "multimodal" (e.g., default-mode and frontoparietal) cortical networks. However, little is known regarding how such dysconnectivity relates to social and non-social cognition, and how such brain-behavioral relationships associate with clinical outcomes of SSDs.

Methods: We analyzed cognitive (non-social and social) measures and resting-state functional magnetic resonance imaging data from the 'Social Processes Initiative in Neurobiology of the Schizophrenia(s) (SPINS)' study (247 stable participants with SSDs and 172 healthy controls, ages 18-55). We extracted gradients from parcellated connectomes and examined the association between the first 3 gradients and the cognitive measures using partial least squares correlation (PLSC). We then correlated the PLSC dimensions with functioning and symptoms in the SSDs group.

Results: The SSDs group showed significantly lower differentiation on all three gradients. The first PLSC dimension explained 68.53% (p<.001) of the covariance and showed a significant difference between SSDs and Controls (bootstrap p<.05). PLSC showed that all cognitive measures were associated with gradient scores of unimodal and multimodal networks (Gradient 1), auditory, sensorimotor, and visual networks (Gradient 2), and perceptual networks and striatum (Gradient 3), which were less differentiated in SSDs. Furthermore, the first dimension was positively correlated with negative symptoms and functioning in the SSDs group.

Conclusions: These results suggest a potential role of lower differentiation of brain networks in cognitive and functional impairments in SSDs.

Background: Violence exposure during childhood and adolescence is associated with increased prevalence and severity of psychopathology. Neurobiological correlates suggest that abnormal maturation of emotion-related brain circuitry, such as the amygdala-prefrontal cortex (PFC) circuit, may underlie the development of psychiatric symptoms after exposure. However, it remains unclear how amygdala-PFC circuit maturation is related to psychiatric risk in the context of violence.

Methods: In this study, we analyzed individual differences in amygdala-PFC circuit maturity using data collected from the PNC (Philadelphia Neurodevelopmental Cohort) (n = 1133 youths). Neurodevelopment models of amygdala-PFC resting-state functional connectivity were built using deep learning and trained to predict chronological age in typically developing youths (not violence exposed and without a psychiatric diagnosis). Using the brain age gap estimate, an index of relative circuit maturation, patterns of atypical neurodevelopment were investigated.

Results: Violence exposure was associated with delayed maturation of basolateral amygdala (BLA)-PFC circuits, driven by increased BLA-medial orbitofrontal cortex functional connectivity. In contrast, increased psychiatric symptoms were associated with advanced maturation of BLA-PFC functional connectivity, driven by decreased BLA-dorsolateral PFC functional connectivity.

Conclusions: Delayed frontoamygdala maturation after exposure to violence suggests atypical, but adaptive, development of threat appraisal processes, potentially reflecting a greater threat generalization characteristic of younger children. Advanced circuit maturation with increasing symptoms suggests divergent neurodevelopmental mechanisms underlying illness after emotion circuits have adapted to adversity, exacerbated by preexisting vulnerabilities to early maturation. Disentangling the effects of adversity and psychopathology on neurodevelopment is crucial for helping youths recover from violence and preventing illness from continuing into adulthood.

Background: Reduced social attention-looking at faces-is one of the most common manifestations of social difficulty in autism that is central to social development. Although reduced social attention is well characterized in autism, qualitative differences in how social attention unfolds across time remains unknown.

Methods: We used a computational modeling (i.e., hidden Markov modeling) approach to assess and compare the spatiotemporal dynamics of social attention in a large, well-characterized sample of children with autism (n = 280) and neurotypical children (n = 119) (ages 6-11) who completed 3 social eye-tracking assays at 3 longitudinal time points (baseline, 6 weeks, 24 weeks).

Results: Our analysis supported the existence of 2 common eye movement patterns that emerged across 3 eye-tracking assays. A focused pattern was characterized by small face regions of interest, which had high a probability of capturing fixations early in visual processing. In contrast, an exploratory pattern was characterized by larger face regions of interest, with a lower initial probability of fixation and more nonsocial regions of interest. In the context of social perception, children with autism showed significantly more exploratory eye movement patterns than neurotypical children across all social perception assays and all 3 longitudinal time points. Eye movement patterns were associated with clinical features of autism, including adaptive function, face recognition, and autism symptom severity.

Conclusions: Decreased likelihood of precisely looking at faces early in social visual processing may be an important feature of autism that is associated with autism-related symptomology and may reflect less visual sensitivity to face information.

Background: Quantitative susceptibility mapping is a neuroimaging technique that detects local changes in magnetic susceptibility induced by brain iron. Brain iron and the dopaminergic system are linked because iron is an important cofactor for dopamine synthesis. Attention-deficit/hyperactivity disorder (ADHD) is associated with dysregulation of dopaminergic transmission. Therefore, we applied quantitative susceptibility mapping on subcortical structures to study potential alterations in brain iron and its impact on cognition and mental health in children with ADHD.

Methods: Quantitative susceptibility mapping data (3T) of 111 participants (n_ADHD = 58, mean [SD] age = 13.2 [0.63] years; n_Control = 53, mean [SD] age = 13.2 [0.51] years) were analyzed. Subcortical regional brain iron values were extracted. Analysis of variance was used to examine group differences for each region of interest. For dimensional approaches, Pearson correlation analysis was performed across the cohort to examine the association of brain iron with symptoms, mental health, and cognition.

Results: No significant differences were found in iron susceptibility between children with ADHD and control children, between children with persistent ADHD and those with remitted ADHD, or between medicated and medication-naïve children. An unexpected finding was that children with an internalizing disorder had significantly higher iron susceptibility, but the result did not survive multiple comparison correction. Higher brain iron was associated with sustained attention, but not inhibition, IQ, or working memory.

Conclusions: This is the first study to address brain iron susceptibility and its association with comorbidities and cognition in ADHD. Alterations in brain iron may not fully account for a diagnosis of ADHD but may be an indicator of internalizing problems in children. Alterations in brain iron content in children were linked to detrimental sustained attention and may represent developmental variation in cognition.

Background: Current clinical studies have indicated that major depressive disorder (MDD) concurrent with adverse childhood experiences (ACEs) is associated with greater anhedonia. However, little is known about whether the change in reward sensitivity among young individuals with MDD and ACEs is related to anhedonia.

Methods: We evaluated anhedonia and ACEs in 86 patients with MDD (31 with no or 1 ACE and 55 with 2 or more ACEs) and 44 healthy control participants. Then, participants completed the Iowa Gambling Task during electroencephalography to measure the reward positivity (RewP) and its difference (ΔRewP; gains minus losses). Furthermore, we constructed a mediation model to assess whether aberrant ΔRewP mediated the relationship between ACEs and anhedonia.

Results: Compared with healthy control participants and MDD patients with no or 1 ACE, MDD patients with 2 or more ACEs had the most severe symptoms of anhedonia and impaired decision making and showed significantly reduced reward sensitivity (most blunted ΔRewP). More importantly, ΔRewP mediated the relationship between ACEs and anhedonia in MDD.

Conclusions: We found that the ΔRewP partially mediated the association between ACEs and anhedonia in patients with MDD, which provides evidence for the neurobiological basis of abnormal changes in the reward system in MDD individuals with early adverse experiences.

Background: Treatment-resistant depression affects about 30% of individuals with major depressive disorder. Deep brain stimulation is an investigational intervention for treatment-resistant depression with varied results. We undertook this meta-analysis to synthesize outcome data across trial designs, anatomical targets, and institutions to better establish efficacy and side-effect profiles.

Methods: We conducted a systematic PubMed review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven randomized controlled trials (n = 198) and 8 open-label trials (n = 77) were included spanning 2009 to 2020. Outcome measures included Hamilton Depression Rating Scale or Montgomery-Åsberg Depression Rating Scale scores, as well as response and remission rates over time. Outcomes were tracked at the last follow-up and quantified as a time course using model-based network meta-analysis. Linear mixed models were fit to individual patient data to identify covariates.

Results: Deep brain stimulation achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement of around 23 months. There were no significant subgroup effects of stimulation target, time of last follow-up, sex, age of disease onset, or duration of disease, but open-label trials showed significantly greater treatment effects than randomized controlled trials. Long-term (12-60 month) response and remission rates were 48% and 35%, respectively. The time course of improvement with active stimulation could not be adequately distinguished from that with sham stimulation, when available.

Conclusions: Deep brain stimulation produces significant chronic improvement in symptoms of treatment-resistant depression. However, the limited sham-controlled data do not demonstrate significant improvement over placebo. Future advancements in stimulation optimization and careful blinding and placebo schemes are important next steps for this therapy.

Background: Impaired emotion regulation (ER) contributes to major depression and suicidal ideation and behavior. ER is typically studied by explicitly directing participants to regulate, but this may not capture spontaneous tendencies of individuals with depression to engage ER in daily life.

Methods: In 82 participants with major depressive disorder, we examined the relationship of spontaneous engagement of ER to real-world responses to stress. We used a machine learning-derived neural signature reflecting neural systems that underlie cognitive reappraisal (an ER strategy) to identify reappraisal-related activity while participants recalled negative autobiographical memories under the following conditions: 1) unstructured recall; 2) distanced recall, a form of reappraisal; and 3) immersed recall (comparison condition). Participants also completed a week of ecological momentary assessment measuring daily stressors, suicidal ideation, and negative affect.

Results: Higher reappraisal signature output for the unstructured period, a proxy for the spontaneous tendency to engage ER, was associated with greater increases in suicidal ideation following stressors (b = 0.083, p = .041). Higher signature output for distanced recall, a proxy for the capacity to engage ER when directed, was associated with lower negative affect following stressors (b = -0.085, p = .029). Output for the immerse period was not associated with ecological momentary assessment outcomes.

Conclusions: Findings suggest that in major depressive disorder, the spontaneous tendency to react to negative memories with attempts to reappraise may indicate greater reactivity to negative cues, while intact capacity to use reappraisal when directed may be associated with more adaptive responses to stress. These data have implications for understanding stress-related increases in suicide risk in depression.

Background: Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as a therapeutic intervention in mental health; however, the understanding of its mechanisms is still incomplete. Prior magnetic resonance imaging (MRI) studies have mainly used offline iTBS or short sequences in concurrent transcranial magnetic stimulation (TMS)-functional MRI (fMRI). This study investigated a full 600-stimuli iTBS protocol using interleaved TMS-fMRI in comparison with 2 control conditions in healthy subjects.

Methods: In a crossover design, 18 participants underwent 3 sessions of interleaved iTBS-fMRI: 1) the left DLPFC at 40% resting motor threshold (rMT) intensity, 2) the left DLPFC at 80% rMT intensity, and 3) the left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood oxygen level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS-induced electric field strength at the target sites.

Results: Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, the left DLPFC, as well as the bilateral M1, anterior cingulate cortex, and insula, showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was observed with neither 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and electric field intensities were only correlated for M1 stimulation and not for the DLPFC conditions.

Conclusions: This interleaved TMS-fMRI study showed dosage- and target-specific BOLD activation during a 600-stimuli iTBS protocol in healthy individuals. Future studies may use our approach for investigating target engagement in clinical samples.

Background: Emotion regulation skills are linked to corticolimbic brain activity (e.g., dorsolateral prefrontal cortex [dlPFC] and limbic regions) and enable an individual to control their emotional experiences, thus allowing healthy social functioning. Disruptions in emotion regulation skills are reported in neuropsychiatric disorders, including conduct disorder or oppositional defiant disorder (CD/ODD). Clinically recognized means to ameliorate emotion regulation deficits observed in CD/ODD include cognitive or dialectical behavioral skills therapy as implemented in the START NOW program. However, the role of emotion regulation and its neural substrates in symptom severity and prognosis following treatment of adolescent CD/ODD has not been investigated.

Methods: Cross-sectional data including functional magnetic resonance imaging responses during emotion regulation (N = 114; average age = 15 years), repeated-measures assessments of symptom severity (pretreatment, posttreatment, long-term follow-up), and functional magnetic resonance imaging data collected prior to and following the START NOW randomized controlled trial (n = 44) for female adolescents with CD/ODD were analyzed using group comparisons and multiple regression.

Results: First, behavioral and neural correlates of emotion regulation were disrupted in female adolescents with CD/ODD. Second, ODD symptom severity was negatively associated with dlPFC/precentral gyrus activity during regulation. Third, treatment-related symptom changes were predicted by pretreatment ODD symptom severity and regulatory dlPFC/precentral activity. Additionally, pretreatment dlPFC/precentral activity and ODD symptom severity predicted long-term reductions in symptom severity following treatment for participants who received the START NOW treatment.

Conclusions: Our findings demonstrate the important role that emotion regulation skills play in the characteristics of CD/ODD and show that regulatory dlPFC/precentral activity is positively associated with treatment response in female adolescents with CD/ODD.