Frontostriatal Circuits Alterations Associated with Cognitive Flexibility Deterioration in Huntington's Disease.

BACKGROUND: Recent resting-state functional magnetic resonance imaging studies have reported abnormal functional connectivity (FC) in the prefrontal cortex (PFC)-striatum circuit in patients with premanifest Huntington's disease (HD). However, there is a lack of evidence showing persistence of abnormal frontostriatal FC and its relation to cognitive flexibility performance in patients with clinically manifest HD. OBJECTIVE: The aim of this study was to evaluate the resting-state FC integrity of the frontostriatal circuit and its relation to cognitive flexibility in HD patients and healthy controls (HCs). METHOD: Eighteen patients with early clinical HD manifestation and 18 HCs matched for age, sex, and education participated in this study. Both groups performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional (IED) set-shift task, which measures cognitive flexibility. Resting-state functional magnetic resonance images were also acquired to examine the FC in specific frontostriatal circuits. Eight regions of interest were preselected based on regions previously associated with extradimensional (ED) shifting in patients with premanifest HD. RESULTS: Significant negative correlations between the number of attentional set-shifting errors and the ventral striatum-ventrolateral PFC FC were found in the HD group. This group also showed negative FC correlations between the total errors and the FC between right ventral striatum-right ventrolateral PFC, left ventral striatum-left ventrolateral PFC, and right ventral striatum-left ventrolateral PFC. Negative correlations between the ED errors and left ventral striatum-left ventrolateral PFC and right ventral striatum-right ventrolateral PFC FC were also found. Finally, a positive correlation between the number of stages completed and left ventral striatum-left ventrolateral PFC FC was found. CONCLUSIONS: Manifest HD patients show significant cognitive flexibility deficits in attentional set-shifting that are associated with FC alterations in the frontostriatal circuit. These results show that FC abnormalities found in the prodromal stage of the disease can also be associated with cognitive flexibility deficits at a later clinical stage, making them good candidates to be explored in longitudinal studies.

Altered brain activity in the bilateral frontal cortices and neural correlation with cognitive impairment in schizophrenia.

Cognitive impairments are core aspects of schizophrenia and are highly related to poor outcomes. However, the effect of therapy on cognitive impairments remains unsatisfactory as its biological mechanisms are not fully understood. The purpose of this study was to investigate the disrupted intrinsic neural activity of the frontal areas and to further examine the functional connectivity of frontal areas related to cognitive impairments in schizophrenia. We collected brain imaging data using a 3T Siemens Prisma MRI system in 32 patients with schizophrenia and 34 age- and sex-matched healthy controls. The mean fractional amplitude of low-frequency fluctuation (mfALFF) in the frontal regions was calculated and analyzed to evaluate regional neural activity alterations in schizophrenia. Seed regions were generated from clusters showing significant changes in mfALFF in schizophrenia, and its resting-state functional connectivity (rs-FC) with other brain regions were estimated to detect possible aberrant rs-FC indicating cognitive impairments in schizophrenia. We found that mfALFF in the bilateral frontal cortices was increased in schizophrenia. mfALFF-based rs-FC revealed that decreased rs-FC between left middle frontal gyrus (MFG) and left medial superior frontal gyrus (MFSG) was associated with poor delayed memory (r = 0.566, Bonferroni-corrected p = 0.012). These findings demonstrate increased neural activity in the frontal cortices in schizophrenia. FC analysis revealed a diminished rs-FC pattern between the left MFG and left MSFG that was associated with cognitive impairments. These findings have provided deeper insight into the alterations in brain function related to specific domains of cognitive impairment and may provide evidence for precise interventions for cognitive deficits in schizophrenia.

Dataset of relationship between longitudinal change in cognitive performance and functional connectivity in cognitively normal older individuals.

The data show an association between measured and predicted changes in cognitive performance in older adults who are cognitively normal. Changes in cognitive performance over two years were assessed using the Cognitive Composite Score. The prediction of change in cognitive function was based on changes in pairwise functional connectivity between 80 gray matter regions examined by resting-state functional magnetic resonance imaging. A feature extraction process based on the Variable Importance Testing Approach (VITA) identified changes in 11 pairs of functional connections associated with the default mode network as features related to changes in cognitive performance. Linear and elastic net regression models were applied to these 11 features to predict changes in cognitive performance over two years. A relationship between the 11 features and the geriatric depression score was also shown. The dataset supplements the research findings in the "Changes in pairwise functional connectivity associated with changes in cognitive performance in cognitively normal older individuals: a two-year observational study" published in Oishi et al. (2022). The raw rs-fMRI correlation matrix and associated clinical data can be accessed upon request from the BIOCARD website (www.biocard-se.org) and can be reused for predictive model building.

Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache.

Background: Migraineurs often exhibited abnormalities in cognition, emotion, and resting-state functional connectivity (rsFC), whereas patients with tension-type headache (TTH) rarely exhibited these abnormalities. The aim of this study is to explore whether rsFC alterations in brain regions related to cognition and emotion could be used to distinguish patients with migraine from patients with TTH. Methods: In this study, Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and rsFC analyses were used to assess the cognition, anxiety, and depression of 24 healthy controls (HCs), 24 migraineurs, and 24 patients with TTH. Due to their important roles in neuropsychological functions, the bilateral amygdala and hippocampus were chosen as seed regions for rsFC analyses. We further assessed the accuracy of the potential rsFC alterations for distinguishing migraineurs from non-migraineurs (including HCs and patients with TTH) by the receiver operating characteristic (ROC) analysis. Associations between headache characteristics and rsFC features were calculated using a multi-linear regression model. This clinical trial protocol has been registered in the Chinese Clinical Trial Registry (registry number: ChiCTR1900024307, Registered: 5 July 2019-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=40817). Results: Migraineurs showed lower MoCA scores (p = 0.010) and higher SAS scores (p = 0.017) than HCs. Migraineurs also showed decreased rsFC in the bilateral calcarine/cuneus, lingual gyrus (seed: left amygdala), and bilateral calcarine/cuneus (seed: left hippocampus) in comparison to HCs and patients with TTH. These rsFC features demonstrated significant distinguishing capabilities and got a sensitivity of 82.6% and specificity of 81.8% with an area under the curve (AUC) of 0.868. rsFC alterations showed a significant correlation with headache frequency in migraineurs (p = 0.001, Pc = 0.020). Conclusion: The rsFC of amygdala and hippocampus with occipital lobe can be used to distinguish patients with migraine from patients with TTH. Clinical Trial Registration: [http://www.chictr.org.cn/showproj.aspx?proj=40817], identifier [ChiCTR1900024307].

Brain 5-HT2A receptor binding and its neural network related to behavioral inhibition system.

The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

Dysconnectivity of the amygdala and dorsal anterior cingulate cortex in drug-naive post-traumatic stress disorder.

Convergent studies have highlighted the amygdala-based and dorsal anterior cingulate cortex (dACC)-based circuit or network dysfunction in post-traumatic stress disorder (PTSD). However, previous studies are often complicated by various traumatic types, psychiatric comorbidities, chronic illness duration, and medication effect on brain function. Besides, little is known whether the functional integration with amygdala-dACC interaction disrupted or not in PTSD. Here, we investigated effective connectivity (EC) between the amygdala-dACC and rest of the cortex by applying psycho-physiological interaction (PPI) approach to resting-state functional magnetic resonance imaging data of 63 drug-naive PTSD patients and 74 matched trauma-exposed non-PTSD controls. Pearson correlation analysis was performed between EC values extracted from regions with between-group difference and clinical profiles in PTSD patients. We observed distinct amygdala-dACC interaction pattern between PTSD group and the control group, which is composed primarily by positive EC in the former and negative in the latter. In addition, compared with non-PTSD controls, PTSD patients showed increased EC between amygdala-dACC and the prefrontal cortex, left inferior parietal lobule, and bilateral ventral occipital cortex, and decreased EC between amygdala-dACC and the left fusiform gyrus. The EC increase between amygdala-dACC and the right middle frontal gyrus was negatively correlated with the clinician-administered PTSD scale scores in PTSD patients. Aberrent communication between amgydala-dACC and brain regions involved in central executive network and visual systems might be associated with the pathophysiology of PTSD. Further, these findings suggested that dysconnectivity of the amygdala and dACC could be adapted as a relatively early course diagnostic biomarker of PTSD.

Effects of TIP treatment on brain network topology of frontolimbic circuit in first-episode, treatment-naïve major depressive disorder.

BACKGROUND: The Low Resistance Thought Induction Psychotherapy (TIP) is a comprehensive psychological treatment which could improve the clinical symptoms of major depressive disorder (MDD). However, the neural mechanisms for TIP treating MDD still remain unclear. This study aimed to investigate the topology of intrinsic connectivity network and the therapeutic effects of TIP in MDD on these topological properties. METHODS: Longitudinal study was conducted in 20 first-episode, treatment-naive MDD patients at baseline and after 6 weeks (12 sessions) of TIP treatment based on resting-state functional magnetic resonance image (rsfMRI) in conjunction with graph theoretical analysis. We constructed functional connectivity matrices and extracted the attribute features of the small-world networks in both MDD and age-, education level-, and gender-matched healthy controls (HCs). The global and local small-world network properties were explored and compared between MDD at baseline and HCs. The therapeutic effect of TIP was examined by comparing alterations in global and local network properties between MDD at baseline and after treatment. RESULTS: At baseline, MDD showed altered small-worldness and aberrant nodal properties in the frontolimbic circuit particularly in the orbital frontal gyrus, insula, precuneus and middle cingulate gyrus as compared with HCs. Following 6 weeks treatment, the abnormalities in the small-worldness and the nodal metrics were modulated, which were accompanied by a significant improvement in the clinical symptoms. CONCLUSIONS: Our findings contributed to the understanding of the abnormal topological patterns in the frontolimbic systems in MDD and implicated that these disruptions may be modified by TIP treatment.

Tracking the Main States of Dynamic Functional Connectivity in Resting State.

Dynamical changes have recently been tracked in functional connectivity (FC) calculated from resting-state functional magnetic resonance imaging (R-fMRI), when a person is conscious but not carrying out a directed task during scanning. Diverse dynamical FC states (dFC) are believed to represent different internal states of the brain, in terms of brain-regional interactions. In this paper, we propose a novel protocol, the signed community clustering with the optimized modularity by two-step procedures, to track dynamical whole brain functional connectivity (dWFC) states. This protocol is assumption free without a priori threshold for the number of clusters. By applying our method on sliding window based dWFC's with automated anatomical labeling 2 (AAL2), three main dWFC states were extracted from R-fMRI datasets in Human Connectome Project, that are independent on window size. Through extracting the FC features of these states, we found the functional links in state 1 (WFC-C1) mainly involved visual, somatomotor, attention and cerebellar (posterior lobe) modules. State 2 (WFC-C2) was similar to WFC-C1, but more FC's linking limbic, default mode, and frontoparietal modules and less linking the cerebellum, sensory and attention modules. State 3 had more FC's linking default mode, limbic, and cerebellum, compared to WFC-C1 and WFC-C2. With tests of robustness and stability, our work provides a solid, hypothesis-free tool to detect dWFC states for the possibility of tracking rapid dynamical change in FCs among large data sets.