MRI resting-state signature of the propensity to experience meaningful coincidences: a functional coupling analysis.

The propensity to experience meaningful patterns in random arrangements and unrelated events shows considerable interindividual differences. Reduced inhibitory control (over sensory processes) and decreased working memory capacities are associated with this trait, which implies that the activation of frontal as well as posterior brain regions may be altered during rest and working memory tasks. In addition, people experiencing more meaningful coincidences showed reduced gray matter of the left inferior frontal gyrus (IFG), which is linked to the inhibition of irrelevant information in working memory and the control and integration of multisensory information. To study deviations in the functional connectivity of the IFG with posterior associative areas, the present study investigated the fMRI resting state in a large sample of n = 101 participants. We applied seed-to-voxel analysis and found that people who perceive more meaningful coincidences showed negative functional connectivity of the left IFG (i.e. pars triangularis) with areas of the left posterior associative cortex (e.g. superior parietal cortex). A data-driven multivoxel pattern analysis further indicated that functional connectivity of a cluster located in the right cerebellum with a cluster including parts of the left middle frontal gyrus, left precentral gyrus, and the left IFG (pars opercularis) was associated with meaningful coincidences. These findings add evidence to the neurocognitive foundations of the propensity to experience meaningful coincidences, which strengthens the idea that deviations of working memory functions and inhibition of sensory and motor information explain why people experience more meaning in meaningless noise.

Differential patterns of functional connectivity in tremor dominant Parkinson's disease and essential tremor plus.

Tremor dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.

Alterations of Functional Connectivity in Autism and Attention-Deficit/Hyperactivity Disorder Revealed by Multi-Voxel Pattern Analysis.

Background: Autism and attention-deficit/hyperactivity disorder (ADHD) are comorbid neurodevelopmental disorders that share common and distinct neurobiological mechanisms, with disrupted brain connectivity patterns being a hallmark feature of both conditions. It is challenging to gain a mechanistic understanding of the underlying disorder, because brain connectivity changes in autism and ADHD are heterogeneous. Objectives: The present resting state functional MRI (rs-fMRI) study focuses on investigating the shared and distinct resting state-fMRI connectivity (rsFC) patterns in autistic and ADHD adults using multi-voxel pattern analysis (MVPA). By identifying spatial patterns of fMRI activity across a given time course, MVPA is an innovative and powerful method for generating seed regions of interest (ROIs) without a priori hypotheses. Methods: We performed a data-driven, whole-brain, connectome-wide MVPA on rs-fMRI data collected from 15 autistic, 19 ADHD, and 15 neurotypical (NT) young adults. Results: MVPA identified cerebellar vermis 9, precuneus, and the right cerebellum VI for autistic versus NT, right inferior frontal gyrus and vermis 9 for ADHD versus NT, and right dorsolateral prefrontal cortex for autistic versus ADHD as significant clusters. Post hoc seed-to-voxel analyses using these clusters as seed ROIs were performed for further characterization of group differences. The cerebellum VI, vermis, and precuneus in autistic adults, and the vermis and frontal regions in ADHD showed different connectivity patterns in comparison with NT. Conclusions: The study characterizes the rsFC profile of cerebellum with key cortical areas in autism and ADHD, and it emphasizes the importance of studying the role of the functional connectivity of the cerebellum in neurodevelopmental disorders.

The association of genetic variation in CACNA1C with resting-state functional connectivity in youth bipolar disorder.

BACKGROUND: CACNA1C rs1006737 A allele, identified as a genetic risk variant for bipolar disorder (BD), is associated with anomalous functional connectivity in adults with and without BD. Studies have yet to investigate the association of CACNA1C rs1006737 with resting-state functional connectivity (rsFC) in youth BD. METHODS: Participants included 139 youth with BD-I, -II, or -not otherwise specified, ages 13-20 years, including 27 BD A-carriers, 41 BD non-carriers, 32 healthy controls (HC) A-carriers, and 39 HC non-carriers. Anterior cingulate cortex (ACC), amygdala, and orbitofrontal cortex (OFC) were examined as regions-of-interest in seed-to-voxel analyses. General linear models included main effects of diagnosis and rs1006737, and an interaction term, controlling for age, sex, and race. RESULTS: We observed a main effect of BD diagnosis on rsFC between the right amygdala and the right occipital pole (p = 0.02), and a main effect of rs1006737 genotypes on rsFC between the right OFC and bilateral occipital cortex (p < 0.001). Two significant BD diagnosis-by-CACNA1C rs1006737 interactions were also identified. The A allele was associated with positive rsFC between the right ACC and right amygdala in BD but negative rsFC in HC (p = 0.01), and negative rsFC between the left OFC and left putamen in BD but positive rsFC in HC (p = 0.01). CONCLUSION: This study found that the rs1006737 A allele, identified as a genetic risk variant for BD in adults, was differentially associated with rsFC in youth with BD in regions relevant to emotion, executive function, and reward. Future task-based approaches are warranted to better understand brain connectivity in relation to CACNA1C in BD.

Cingulate-Prefrontal Connectivity During Dynamic Cognitive Control Mediates Association Between p Factor and Adaptive Functioning in a Transdiagnostic Pediatric Sample.

BACKGROUND: Covariation among psychiatric symptoms is being actively pursued for transdiagnostic dimensions of psychopathology with predictive utility. A superordinate dimension, the p factor, reflects overall psychopathology burden and has support from genetic and neuroimaging correlates. However, the neurocognitive correlates that link an elevated p factor to maladaptive outcomes are unknown. We tested the mediating potential of dynamic adjustments in cognitive control rooted in functional connections anchored by the dorsal anterior cingulate cortex (dACC) in a transdiagnostic pediatric sample. METHODS: A multiple mediation model tested the association between the p factor (derived by principal component analysis of Child Behavior Checklist syndrome scales) and outcome measured with the Vineland Adaptive Behavior Scale-II in 89 children ages 8 to 13 years (23 female) with a variety of primary neurodevelopmental diagnoses who underwent functional magnetic resonance imaging during a socioaffective Stroop-like task with eye gaze as distractor. Mediators included functional connectivity of frontoparietal- and salience network-affiliated dACC seeds during conflict adaptation. RESULTS: Higher p factor scores were related to worse adaptive functioning. This effect was partially mediated by conflict adaptation-dependent functional connectivity between the frontoparietal network-affiliated dACC seed and the right dorsolateral prefrontal cortex. Post hoc follow-up indicated that the p factor was related to all Vineland Adaptive Behaviors Scale-II domains; the association was strongest for socialization followed by daily living skills and then communication. Mediation results remained significant for socialization only. CONCLUSIONS: Higher psychopathology burden was associated with worse adaptive functioning in early adolescence. This association was mediated by weaker dACC-dorsolateral prefrontal cortex functional connectivity underlying modulation of cognitive control in response to contextual contingencies. Our results contribute to the identification of transdiagnostic and developmentally relevant neurocognitive endophenotypes of psychopathology.

Functional connectivity of brain networks during semantic processing in older adults.

The neural systems underlying semantic processing have been characterized with functional neuroimaging in young adults. Whether the integrity of these systems degrade with advanced age remains unresolved. The current study examined functional connectivity during abstract and concrete word processing. Thirty-eight adults, aged 55-91, engaged in semantic association decision tasks during a mixed event-related block functional magnetic resonance imaging (fMRI) paradigm. During the semantic trials, the task required participants to make a judgment as to whether pairs were semantically associated. During the rhyme trials, the task required participants to determine if non-word pairs rhymed. Seeds were placed in putative semantic hubs of the left anterior middle temporal gyrus (aMTG) and the angular gyrus (AG), and also in the left inferior frontal gyrus (IFG), an area considered important for semantic control. Greater connectivity between aMTG, AG, and IFG and multiple cortical areas occurred during semantic processing. Connectivity from the three seeds differed during semantic processing: the left AG and aMTG were strongly connected with frontal, parietal, and occipital areas bilaterally, whereas the IFG was most strongly connected with other frontal cortical areas and the AG in the ipsilateral left hemisphere. Notably, the strength and extent of connectivity differed for abstract and concrete semantic processing; connectivity from the left aMTG and AG to bilateral cortical areas was greater during abstract processing, whereas IFG connectivity with left cortical areas was greater during concrete processing. With advanced age, greater connectivity occurred only between the left AG and supramarginal gyrus during the processing of concrete word-pairs, but not abstract word-pairs. Among older adults, robust functional connectivity of the aMTG, AG, and IFG to widely distributed bilateral cortical areas occurs during abstract and concrete semantic processing in a manner consistent with reports from past studies of young adults. There was not a significant degradation of functional connectivity during semantic processing between the ages of 55 and 85 years. As the study focused on semantic functioning in older adults, a comparison group of young adults was not included, limiting generalizability. Future longitudinal neuroimaging studies that compare functional connectivity of young and older adults under different semantic demands will be valuable.

Resting-state functional connectivity in medication-naïve adolescents with major depressive disorder.

Adolescence is a vulnerable period for major depressive disorder (MDD). The aim of our study was to investigate resting-state functional connectivity (RSFC) in first-episode, medication-naïve adolescent MDD patients. Twenty-three drug-naïve adolescents diagnosed with first-episode MDD and 27 healthy participants were enrolled. Seed-to-voxel RSFC analyses were performed. The frontolimbic circuit regions of interest included the amygdala, anterior cingulate cortex, insula, and hippocampus. A correlation analysis between the RSFC and Children's Depression Inventory, Hamilton depression rating scale, and duration of episodes was performed. The adolescents with MDD exhibited the following characteristics: a lower RSFC between the right amygdala and right superior frontal gyrus; a lower RSFC between the right hippocampus and clusters including the right insula and right middle frontal gyrus; a higher RSFC between the left insula and clusters including the bilateral middle frontal gyrus, right superior frontal gyrus, and right frontal pole; and a higher RSFC between the left dorsal anterior cingulate cortex and a cluster including the left insula. Medication-naïve adolescents with depression display lower connectivity of several brain regions implicated in processing, regulation, and memory of emotions. Higher connectivity was observed in brain regions that potentially explain rumination, impaired concentration, and physiological arousal.

Disentangling phonological and articulatory processing: A neuroanatomical study in aphasia.

Phonological and articulatory programming impairments may co-occur in aphasic patients and previous research does not offer a clear-cut picture of their anatomical counterparts. Hickok and Poeppel (2007) put forward a seminal model of speech processes. The ventral stream (mostly bilateral) would be involved in speech recognition and phonological-lexical processing, whereas the dorsal stream (largely lateralized to the left hemisphere) would map phonological representations onto articulatory motor patterns. In this study we analyzed repetition errors for single words and spontaneous speech ratings on the Italian version of the Aachen Aphasia Test. Through a VLSM procedure we aimed at discriminating the neuroanatomical substrates of the phonological and articulatory impairment (and of their normal functional processing). We also estimated functional connectivity networks related to articulation and phonology using seed-to-voxel connectivity analysis with resting state fMRI data. Results indicate that repetition deficit of single words is associated with lesions in a network of left perisylvian areas including the central operculum, the Heschl's gyrus, the angular gyrus, and the supramarginal gyrus (posterior part). Articulatory impairment is associated with lesions in a number of areas in the left dorsal stream, such as the insula (anterior portion), the pars opercularis of the inferior frontal gyrus, the central operculum and the precentral gyrus. On the contrary, phonological impairment is underpinned by lesions of the Heschl's gyrus, and of the posterior portion of the superior temporal and supramarginal gyri. Anatomo-clinical correlative results partly support Hickok and Poeppel's functional model of phonological and articulatory processing.

Pharmacological fMRI: Effects of subanesthetic ketamine on resting-state functional connectivity in the default mode network, salience network, dorsal attention network and executive control network.

Background: Subanesthetic dosages of the NMDAR antagonist, S-Ketamine, can cause changes in behavior in healthy subjects, which are similar to the state acute psychosis and are relevant in translational schizophrenia research. Functional magnetic resonance imaging (fMRI) can be used for non-hypothesis-driven analysis of brain connectivity. The correlation between clinical behavioral scores and neuroimaging can help to characterize ketamine effects on healthy brains in resting state. Method: seventeen healthy, male subjects (mean: 27.42 years, SD: 4.42) were administered an infusion with S-Ketamine (initial bolus 1 mg/kg and continuous infusion of 0.015625 mg/kg/min with dosage reduction -10%/10 min) or saline in a randomized, double-blind, cross-over study. During infusion, resting state connectivity was measured and analyzed with a seed-to-voxel fMRI analysis approach. The seed regions were located in the posterior cingulate cortex, intraparietal sulcus, dorsolateral prefrontal cortex and fronto-insular cortex. Receiver operating characteristics (ROC) were calculated to assess the accuracy of the ketamine-induced functional connectivity changes. Bivariate Pearson correlation was used for correlation testing of functional connectivity changes with changes of clinical scores (PANSS, 5D-ASC). Results: In the executive network (ECN), ketamine significantly increases the functional connectivity with parts of the anterior cingulum and superior frontal gyrus, but no significant correlations with clinical symptoms were found. Decreased connectivity between the salience network (SN) and the calcarine fissure was found, which is significantly correlated with negative symptoms (PANSS) (R2 > 0.4). Conclusion: Decreased ketamine-induced functional connectivity in the salience network may qualify as accurate and highly predictive biomarkers for ketamine induced negative symptoms.