Biological psychiatry. Cognitive neuroscience and neuroimaging最新文献

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: While the last decade of extensive research revealed the prominent role of the claustrum for mammalian forebrain organization, i.e., widely distributed claustral-cortical circuits coordinate basic cognitive functions such as attention, it is poorly understood whether the claustrum is relevant for schizophrenia and related cognitive symptoms. We hypothesized firstly, that claustrum volumes are lower in schizophrenia and secondarily, that potentially lower volumes mediate patients' attention deficits.

Methods: Based on T1-weighted MRI, advanced automated claustrum segmentation, and attention symbol coding task (SCT) in 90 patients with schizophrenia and 96 healthy controls from two independent sites, the COBRE open-source database and MUNICH dataset, we compared total-intracranial-volume-normalized claustrum volumes and SCT scores across groups via ANCOVA and related variables via correlation and mediation analysis.

Results: Patients had lower claustrum volumes of about 13 % (p<0.001, Hedges g=0.63), which not only correlated with (r=0.24, p=0.014) but also mediated lower SCT scores (indirect effect ab = -1.30 ± 0.69; CI [-3.73; -1.04]). Results were not confounded by age, sex, global and claustrum-adjacent gray matter changes, scanner site, smoking, and medication.

Conclusions: Results demonstrate lower claustrum volumes that mediate patients' attention deficits in schizophrenia. Data indicate the claustrum as being relevant for schizophrenia pathophysiology and cognitive functioning.

Background: The present study examined EEG microstate alterations and their neural generators during resting state in children with ADHD to explore a potential state biomarker.

Methods: A total of seventy-six participants, thirty-eight each, combined type ADHD, and neurotypical children (NC) participated in the study. Five-minute resting (eyes open) 128 channel eeg data were acquired and two-minute clean EEG data were analyzed for microstates, its sources and connectivity in both the groups. Between groups comparisons were done for microstate parameters using modified k means clustering in Cartool software. Further, the cortical sources and functional connectivity of significant microstate maps were explored using LORETA software. Subsequently microstate parameters were correlated with the behavioral scores from Conner's parent rating scale.

Results: Among the microstate parameters examined, children with ADHD displayed significant difference (p<0.05) in time frames and time coverage of map B (decreased) and transition probability of map D (increased) respectively. Interestingly, source analysis of both microstate maps showed hypoactivation of frontal areas predominantly while functional connectivity showed hyperconnectivity between medial frontal gyrus and anterior cingulate gyrus (executive function area) for map B and hypoconnectivity between medial frontal gyrus and middle temporal gyrus (both are suggested to be part of DMN areas) for map D. Further CSD values of map B was found to be correlated with executive function scores of conners questionnaire.

Conclusion: EEG microstate features, alongside source and connectivity measures, could discern children with ADHD from neurotypical controls. The hypoactivation of predominantly frontal areas and its connectivity was found to determine microstate maps.

Background: Modafinil is primarily employed to treat narcolepsy but also as an off-label cognitive enhancer. Functional Magnetic Resonance Imaging (fMRI) 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 fMRI (rs-fMRI) connectivity were estimated in 50 participants from scans acquired pre- and post-administration of a single (100 mg) dose of modafinil (n=25) or placebo (n=25). Using specific cerebellar regions as seeds for voxel-wise analyses, we examined modafinil's modulation on 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.

Conclusion: 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 and serotonin transporters.

There is a renewed interest in taking phenomenology seriously in consciousness research, contemporary psychiatry, and neurocomputation. The neurophenomenology research program, pioneered by Varela (1996), rigorously examines subjective experience using first-person methodologies, inspired by phenomenology and contemplative practices. This review explores recent advancements in neurophenomenological approaches, particularly their application to meditation practices and potential clinical research translations. We first examine innovative multi-dimensional phenomenological assessment tools designed to capture subtle, dynamic shifts in experiential contents and structures of consciousness during meditation. These experience sampling approaches allow shedding new light on the mechanisms and dynamic trajectories of meditation practice and retreat. Secondly, we highlight how empirical studies in neurophenomenology leverage the expertise of experienced meditators to deconstruct aversive and self-related processes, providing detailed first-person reports that guide researchers in identifying novel behavioral and neurodynamic markers associated with pain regulation, self-dissolution and acceptance of mortality. Finally, we discuss a recent framework, deep computational neurophenomenology, which updates the theoretical ambitions of neurophenomenology to "naturalize phenomenology" (Varela, 1997). This framework uses the formalism of deep parametric active inference, where parametric depth refers to a property of generative models that can form beliefs about the parameters of their own modeling process. Collectively, these methodological innovations, centered around rigorous first-person investigation, highlight the potential of epistemologically beneficial mutual constraints among phenomenological, computational, and neurophysiological domains. This could contribute to an integrated understanding of the biological basis of mental illness, its treatment and its tight connections to the lived experience of the patient.

Background: Adolescent depression is a growing public health concern, and neuroimaging offers a promising approach to its pathology. We focused on the functional connectivity of the amygdala and subgenual anterior cingulate cortex (sgACC), which is theoretically important in major depressive disorder (MDD), but empirical evidence has remained inconsistent. This discrepancy is likely due to the limited statistical power of small sample sizes.

Methods: We rigorously examined sgACC-amygdala connectivity in depressed adolescents and adults using data from the Healthy Brain Network (n=321; 170 females), the Adolescent Brain Cognitive Development study (n=141; 56 females), the Boston Adolescent Neuroimaging of Depression and Anxiety study (n=108; 75 females), and the REST-meta-MDD project (n=1436; 880 females). Linear mixed models, Bayesian factor analyses, and meta-analysis were employed to assess connectivity.

Results: Our analyses revealed that sgACC-amygdala connectivity in adolescents with MDD was comparable to that in healthy controls, whereas adults with recurrent MDD exhibited reduced connectivity. Resampling analysis demonstrated that small sample sizes (i.e., n<30 MDDs) tend to inflate effects, potentially leading to misinterpretations.

Conclusions: These findings clarify the state of sgACC-amygdala connectivity in MDD and underscore the importance of refining neurocognitive models separately for adolescents and adults. The study also highlights the necessity for large-scale replication studies to ensure robust and reliable findings.

Background: Adolescence is a time of increased risk for the onset of internalising problems, particularly in females. However, how individual differences in brain maturation relate to the increased vulnerability for internalising problems in adolescence remains poorly understood due to a scarcity of longitudinal studies.

Methods: Using Adolescent Brain Cognitive Development (ABCD) Study data, we examined longitudinal associations between multimodal brain age and youth internalising problems. Brain age models were trained, validated, and tested independently on T1-weighted (T1; N=9523), diffusion tensor (DTI; N=8834), and resting-state functional (rs-fMRI; N=8233) MRI data at baseline (M_age= 9.9 years) and 2-year follow-up (M_age= 11.9 years). Self-reported internalising problems were measured at 3-year follow-up (M_age= 12.9 years) using the Brief Problem Monitor.

Results: Latent change score models demonstrated that although brain age gap (BAG) at baseline was not related to later internalising problems, an increase in BAG between timepoints was positively associated with internalising problems at 3-year follow-up in females but not males. This association between an increasing BAG and higher internalising problems was observed in the T1 (β = 0.067, SE = 0.050, p_FDR = 0.020) and rs-fMRI β = 0.090, SE = 0.025, p_FDR = 0.007) models but not DTI (β=-0.002, SE=0.053, p_FDR = 0.932), and remained significant when accounting for earlier internalising problems.

Conclusions: A greater increase in BAG in early adolescence may reflect the heightened vulnerability shown by female youth to internalising problems. Longitudinal research is necessary to understand if this increasing BAG signifies accelerated brain development and its relationship to the trajectory of internalising problems throughout adolescence.

Background: The pathophysiology of attention-deficit/hyperactivity disorder (ADHD) is characterized by atypical brain network organization and dynamics. Although functional brain networks adaptively reconfigure across cognitive contexts, previous studies have largely focused on network dysfunction during the resting-state. This preliminary study examined how functional brain network organization and dynamics flexibly reconfigure across rest and two cognitive control tasks with different cognitive demands in 30 children with ADHD and 36 typically developing (TD) children (8-12 years).

Methods: We leveraged graph theoretical analyses to interrogate the segregation (modularity, within-module degree) and integration (global efficiency, node dissociation index) of fronto-parietal, cingulo-opercular/salience, default mode, somatomotor, and visual networks. We also conducted edge timeseries analyses to quantify connectivity dynamics within and between these networks.

Results: Across resting and task-based states, children with ADHD demonstrated significantly lower whole-graph modularity and greater node dissociation index between default mode and visual networks. Further, a significant task-by-diagnosis interaction was observed for fronto-parietal network within-module degree, which decreased from rest to task in children with ADHD but increased in TD children. Finally, children with ADHD displayed significantly more dynamic connectivity within and across cingulo-opercular/salience, default mode, and somatomotor networks, especially during task performance. Exploratory analyses revealed associations between network dynamics, cognitive performance, and ADHD symptoms.

Conclusions: By integrating static and dynamic network analyses across changing cognitive demands, this study provides novel insight into how context-specific, context-general, and timescale-dependent network connectivity is altered in children with ADHD. Our findings highlight the involvement and clinical relevance of both association and sensory/motor systems in ADHD.

Background: The Reward Positivity (RewP) is a sensitive and specific electrophysiological marker of reward receipt. These characteristics make it a compelling candidate marker of dysfunctional reward processing in Major Depressive Disorder (MDD). We previously proposed that the RewP is a temporal nexus for multiple dimensions of reward value, and that a diminished RewP in depression might only reflect a deficit in some of these features. Specifically, we predicted a diminished ventromedial contribution in depression in the context of maintained reward learning.

Methods: We collected magnetoencephalographic (MEG) recordings of reward receipt in 43 individuals with MDD (35 female) and 38 healthy controls (21 female). MEG allows effective source estimation due to the absence of volume conduction that compromises electroencephalographic recordings.

Results: The MEG RewP analogue was generated by a broad set of cortical areas, yet only right ventromedial and right ventral temporal areas were diminished in MDD. These areas correlated with a principal component of anhedonia derived from multiple questionnaires. Compellingly, BA25 was the frontal region with the largest representation in both of these effects.

Conclusions: These findings not only advance our understanding underlying the computation of the RewP, but they also dovetail with convergent findings from other types of functional source imaging in depression, as well as from deep brain stimulation treatments. Together, these discoveries suggest that the RewP may be a valuable marker for objective assessment of reward affect and its disruption in anhedonia.

Background: Repetitive transcranial magnetic stimulation (rTMS), combined with exposure and response prevention (ERP), is a promising treatment modality for treatment-refractory obsessive-compulsive disorder (OCD). Yet, not all patients respond sufficiently to this treatment. We investigated whether brain activation during a symptom provocation task could predict treatment response.

Methods: Sixty-one adults with OCD (22 male/ 39 female) underwent symptom provocation with OCD- and fear-related visual stimuli during fMRI prior to an 8-week combined rTMS and ERP treatment regimen. Participants received one of the three following rTMS treatments as part of a randomized controlled trial: (1) 10Hz rTMS (110% resting motor threshold (RMT)) to the left dorsolateral prefrontal cortex (DLPFC); (2) 10Hz rTMS (110% RMT) to the left pre-supplementary motor area (preSMA); or (3) 10Hz control rTMS (60% RMT) to the vertex. Multiple regression and correlation were used to examine the predictive value of task-related brain activation for treatment response in the following ROIs: dorsomedial prefrontal cortex, amygdala, DLPFC, and preSMA.

Results: The different treatment groups responded equally to treatment. Higher pre-treatment task-related activation of the right amygdala to OCD-related stimuli showed a positive association with treatment response in all groups. Exploratory whole-brain analyses showed positive associations between activation in multiple task-relevant regions and treatment response. Only dorsal anterior cingulate cortex activation to fear-related stimuli showed a negative association with treatment outcome.

Conclusions: Higher pre-treatment right amygdala activation during symptom provocation predicts better treatment response to combined rTMS and ERP in OCD.