Acute and chronic effects of betel quid chewing on brain functional connectivity

Background: The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dependence, is not clear. Methods: In this observational study, functional magnetic resonance imaging in a resting-state was performed in 24 male betel quid-dependent chewers and 28 male controls prior to and promptly after betel quid chewing. Network-based statistics were employed to determine significant differences in functional connectivity between brain networks for both acute effects and in long-term betel users versus controls. A support vector machine was employed for pattern classification analysis. Results: Before chewing betel quid, higher functional connectivity in betel quid-dependent chewers than in controls was found between the temporal, parietal and frontal brain regions (right medial orbitofrontal cortex, right lateral orbital frontal cortex, right angular gyrus, bilateral inferior temporal gyrus, superior parietal gyrus, and right medial superior frontal gyrus). In controls, the effect of betel quid chewing was significantly increased functional connectivity between the subcortical regions (caudate, putamen, pallidum, and thalamus), and the visual cortex (superior occipital gyrus and right middle occipital gyrus). Conclusion: These findings show that individuals who chronically use betel quid have higher functional connectivity than controls of the orbitofrontal cortex, and inferior temporal and angular gyri. Acute effects of betel quid are to increase the functional connectivity of some visual cortical areas (which may relate to the acute symptoms) and the basal ganglia and thalamus

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortexPrevious studies have observed reduced suppression of the default mode network (DMN) when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia

Reduced cortical thickness in right Heschl’s gyrus associated with auditory verbal hallucinations severity in first-episode schizophrenia

BACKGROUND: Auditory verbal hallucinations (AVHs) represent one of the most intriguing phenomena in schizophrenia, however, brain abnormalities underlying AVHs remain unclear. The present study examined the association between cortical thickness and AVHs in first-episode schizophrenia. METHOD: High-resolution MR images were obtained in 49 first-episode schizophrenia (FES) patients and 50 well-matched healthy controls (HCs). Among the FES patients, 18 suffered persistent AVHs (“auditory hallucination” AH group), and 31 never experienced AVHs (“no hallucination” NH group). The severity of AVHs was rated by the Auditory Hallucinations Rating Scale (AHRS). Cortical thickness differences among the three groups and their association with AVHs severity were examined. RESULTS: Compared to both HCs and NH patients, AH patients showed lower cortical thickness in the right Heschl’s gyrus. The degree of reduction in the cortical thickness was correlated with AVH severity in the AH patients. CONCLUSIONS: Abnormalities of cortical thickness in the Heschl’s gyrus may be a physiological factor underlying auditory verbal hallucinations in schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-015-0546-2) contains supplementary material, which is available to authorized users

Structural and Functional Alterations in Betel-Quid Chewers: A Systematic Review of Neuroimaging Findings

Background: A number of neuroimaging studies have investigated structural, metabolic, and functional connectivity changes in betel quid (BQ) chewers. We present a systematic review of neuroimaging studies with emphasis on key brain systems affected by BQ chewing to bring a better understanding on the neuro mechanisms involved in BQD.Methods: All BQ neuroimaging studies were identified by searching PubMed, EMBASE, and Google scholar for English articles published until March 2018 using the key words: Betel-quid, resting state, functional MRI, structural MRI, diffusion tensor imaging (DTI), and betel quid dependence basing on the PRISMA criteria. We also sought unpublished studies, and the rest were obtained from reference lists of the retrieved articles. All neuroimaging studies investigating brain structural, and functional alterations related to BQ chewing and BQ dependence were included. Our systematic review registration number is CRD42018092669.Results: A review of 12 studies showed that several systems in the brain of BQ chewers exhibited structural, metabolic, and functional alterations. BQ chewing was associated with alterations in the reward [areas in the midbrain, and prefrontal cortex (PFC)], impulsivity (anterior cingulate cortex, PFC) and cognitive (PFC, the default mode, frontotemporal, frontoparietal, occipital/temporal, occipital/parietal, temporal/limbic networks, hippocampal/hypothalamus, and the cerebellum) systems in the brain. BQ duration and severity of betel quid dependence were associated with majority of alterations in BQ chewers.Conclusion: Betel quid chewing is associated with brain alterations in structure, metabolism and function in the cognitive, reward, and impulsivity circuits which are greatly influenced by duration and severity of betel quid dependence

Associations Among Suicidal Ideation, White Matter Integrity and Cognitive Deficit in First-Episode Schizophrenia

Objective: The study was aimed to investigate the possible associations among suicidal ideation, brain white matter (WM) integrity and cognitive deficit in first-episode schizophrenia (FES) using diffusion tensor imaging.Methods: The sample contained 18 FES patients with suicidal ideation (SI+), 45 FES patients without suicidal ideation (SI–) and 44 healthy controls. The Calgary Depression Scale for Schizophrenia was used to measure the suicidal ideation and depression symptoms. The whole brain WM integrity and three domains of cognitive function: working memory, verbal comprehension as well as processing speed were compared between the three groups.Results: Compared with SI–, SI+ showed preserved WM integrity as indicated by significantly higher factional anisotropy (FA) or lower mean diffusivity (MD) in multiple WM tracts, and higher FA coupled with lower MD in bilateral posterior corona radiata. Compared with SI−, SI+ were more depressed and had less cognitive deficit in working memory and verbal comprehension. The fiber tracts in bilateral posterior corona radiata connect to the precuneus as shown by probabilistic tractography, and their WM integrity disruptions were found to be positively associated with the cognitive deficits in the FES patients.Discussion: Preserved WM integrity may be a risk factor for suicidal ideation in FES patients. One possible explanation is that it contributes to preserved cognitive function, especially in working memory and verbal comprehension, which may be associated with greater insight and could lead to increased depression and suicidal ideation. The posterior corona radiata and the precuneus may be linked to the related biological processes

Altered functional connectivity links in neuroleptic-naïve and neuroleptic-treated patients with schizophrenia, and their relation to symptoms including volition

In order to analyze functional connectivity in untreated and treated patients with schizophrenia, resting-state fMRI data were obtained for whole-brain functional connectivity analysis from 22 first-episode neuroleptic-naïve schizophrenia (NNS), 61 first-episode neuroleptic-treated schizophrenia (NTS) patients, and 60 healthy controls (HC). Reductions were found in untreated and treated patients in the functional connectivity between the posterior cingulate gyrus and precuneus, and this was correlated with the reduction in volition from the Positive and Negative Symptoms Scale (PANSS), that is in the willful initiation, sustenance, and control of thoughts, behavior, movements, and speech, and with the general and negative symptoms. In addition in both patient groups interhemispheric functional connectivity was weaker between the orbitofrontal cortex, amygdala and temporal pole. These functional connectivity changes and the related symptoms were not treated by the neuroleptics. Differences between the patient groups were that there were more strong functional connectivity links in the NNS patients (including in hippocampal, frontal, and striatal circuits) than in the NTS patients. These findings with a whole brain analysis in untreated and treated patients with schizophrenia provide evidence on some of the brain regions implicated in the volitional, other general, and negative symptoms, of schizophrenia that are not treated by neuroleptics so have implications for the development of other treatments; and provide evidence on some brain systems in which neuroleptics do alter the functional connectivity

Connectomic underpinnings of working memory deficits in schizophrenia: Evidence from a replication fMRI study

Background: Working memory (WM) deficit is a key feature of schizophrenia that relates to a generalized neural inefficiency of extensive brain areas. To date, it remains unknown how these distributed regions are systemically organized at the connectome level and how the disruption of such organization brings about the WM impairment seen in schizophrenia. Methods: We used graph theory to examine the neural efficiency of the functional connectome in different granularity in 155 patients with schizophrenia and 96 healthy controls during a WM task. These analyses were repeated in another independent dataset (81 patients and 54 controls). Linear regression analysis was used to test associations of altered graph properties, clinical symptoms, and WM accuracy in patients. A machine-learning approach was adopted to study the ability of multivariate connectome features from one dataset to discriminate patients from controls in the second dataset. Results: Small-worldness of the whole-brain connectome was significantly increased in schizophrenia during the WM task; this increase is related to better (though subpar) WM accuracy in patients with more severe negative symptom burden. There was a shift in the degree distribution to a more homogeneous form in patients. The machine-learning approach classified a new set of patients from controls with 84.3% true-positivity rate for schizophrenia and 71.6% overall accuracy. Conclusions: We demonstrate a putative mechanistic link between connectome topology, hub redistribution, and impaired n-back performance in schizophrenia. The task-dependent modulation of the connectome relates to, but remains inefficient in, improving the performance above par in the presence of severe negative symptoms