scholarly journals Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chia-Chun Hung ◽  
Yi-Hsuan Liu ◽  
Chu-Chung Huang ◽  
Cheng-Ying Chou ◽  
Chun-Ming Chen ◽  
...  

Abstract Ketamine has been used for medical purposes, most typically as an anesthetic, and recent studies support its use in the treatment of depression. However, ketamine tends to be abused by adolescents and young adults. In the current study, we examined the effects of early ketamine exposure on brain structure and function. We employed MRI to assess the effects of ketamine abuse on cerebral gray matter volume (GMV) and functional connectivity (FC) in 34 users and 19 non-users, employing covariates. Ketamine users were categorized as adolescent-onset and adult-onset based on when they were first exposed to ketamine. Imaging data were processed by published routines in SPM and AFNI. The results revealed lower GMV in the left precuneus in ketamine users, with a larger decrease in the adolescent-onset group. The results from a seed-based correlation analysis show that both ketamine groups had higher functional connectivity between left precuneus (seed) and right precuneus than the control group. Compared to controls, ketamine users showed decreased GMV in the right insula, left inferior parietal lobule, left dorsolateral prefrontal cortex/superior frontal gyrus, and left medial orbitofrontal cortex. These preliminary results characterize the effects of ketamine misuse on brain structure and function and highlight the influence of earlier exposure to ketamine on the development of the brain. The precuneus, a structure of central importance to cerebral functional organization, may be particularly vulnerable to the influences of early ketamine exposure. How these structural and functional brain changes may relate to the cognitive and affective deficits remains to be determined with a large cohort of participants.

2021 ◽  
Vol 12 ◽  
Author(s):  
Adam C. Raikes ◽  
Natalie S. Dailey ◽  
Brittany Forbeck ◽  
Anna Alkozei ◽  
William D. S. Killgore

Background: Mild traumatic brain injuries (mTBIs) are associated with novel or worsened sleep disruption. Several studies indicate that daily morning blue light therapy (BLT) is effective for reducing post-mTBI daytime sleepiness and fatigue. Studies demonstrating changes in brain structure and function following BLT are limited. The present study's purpose is to identify the effect of daily morning BLT on brain structure and functional connectivity and the association between these changes and self-reported change in post-mTBI daytime sleepiness.Methods: A total of 62 individuals recovering from a mTBI were recruited from two US cities to participate in a double-blind placebo-controlled trial. Eligible individuals were randomly assigned to undergo 6 weeks of 30 min daily morning blue or placebo amber light therapy (ALT). Prior to and following treatment all individuals completed a comprehensive battery that included the Epworth Sleepiness Scale as a measure of self-reported daytime sleepiness. All individuals underwent a multimodal neuroimaging battery that included anatomical and resting-state functional magnetic resonance imaging. Atlas-based regional change in gray matter volume (GMV) and region-to-region functional connectivity from baseline to post-treatment were the primary endpoints for this study.Results: After adjusting for pre-treatment GMV, individuals receiving BLT had greater GMV than those receiving amber light in 15 regions of interest, including the right thalamus and bilateral prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with greater GMV in 74 ROIs, covering many of the same general regions. Likewise, BLT was associated with increased functional connectivity between the thalamus and both prefrontal and orbitofrontal cortices. Improved daytime sleepiness was associated with increased functional connectivity between attention and cognitive control networks as well as decreased connectivity between visual, motor, and attention networks (all FDR corrected p < 0.05).Conclusions: Following daily morning BLT, moderate to large increases in both gray matter volume and functional connectivity were observed in areas and networks previously associated with both sleep regulation and daytime cognitive function, alertness, and attention. Additionally, these findings were associated with improvements in self-reported daytime sleepiness. Further work is needed to identify the personal characteristics that may selectively identify individuals recovering from a mTBI for whom BLT may be optimally beneficial.


2021 ◽  
Author(s):  
Laura M. Hack ◽  
Jacob Brawer ◽  
Megan Chesnut ◽  
Xue Zhang ◽  
Max Wintermark ◽  
...  

AbstractA significant number of individuals experience physical, cognitive, and mental health symptoms in the months after acute infection with SARS-CoV-2, the virus that causes COVID-19. This study assessed depressive and anxious symptoms, cognition, and brain structure and function in participants with symptomatic COVID-19 confirmed by PCR testing (n=100) approximately three months following infection, leveraging self-report questionnaires, objective neurocognitive testing, and structural and functional neuroimaging data. Preliminary results demonstrated that over 1/5 of our cohort endorsed clinically significant depressive and/or anxious symptoms, and >40% of participants had cognitive impairment on objective testing across multiple domains, consistent with ‘brain-fog’. While depression and one domain of quality of life (physical functioning) were significantly different between hospitalized and non-hospitalized participants, anxiety, cognitive impairment, and most domains of functioning were not, suggesting that the severity of SARS-CoV-2 infection does not necessarily relate to the severity of neuropsychiatric outcomes and impaired functioning in the months after infection. Furthermore, we found that the majority of participants in a subset of our cohort who completed structural and functional neuroimaging (n=15) had smaller olfactory bulbs and sulci in conjunction with anosmia. We also showed that this subset of participants had dysfunction in attention network functional connectivity and ventromedial prefrontal cortex seed-based functional connectivity. These functional imaging dysfunctions have been observed previously in depression and correlated with levels of inflammation. Our results support and extend previous findings in the literature concerning the neuropsychiatric sequelae associated with long COVID. Ongoing data collection and analyses within this cohort will allow for a more comprehensive understanding of the longitudinal relationships between neuropsychiatric symptoms, neurocognitive performance, brain structure and function, and inflammatory and immune profiles.


2019 ◽  
Author(s):  
Hongyan Ren ◽  
Yajing Meng ◽  
Yamin Zhang ◽  
Qiang Wang ◽  
Wei Deng ◽  
...  

AbstractBackgroundSchizophrenia is a complex mental disorder with recent evidence suggesting a critical immune component underpinning its pathophysiology. Two-sample Mendelian randomization (MR) provided an opportunity to probe the immune changes in schizophrenia by harnessing the increasing availability of summary-level data from large GWAS consortia.ObjectiveTo map the extensive immune response of schizophrenia in terms of cytokines/chemokines and to explore the effect of cytokines induced by schizophrenia (SCZ-induced cytokines) on the brain structure and functionSources and methodsUsing the summary-level data generated from GWAS of schizophrenia, cytokines in the peripheral blood and imaging-derived phenotypes (IDPs), we performed two rounds of two-sample MR analysis; the identified cytokines from first round of analysis (schizophrenia => cytokines) were modeled for its underlying structure and subsequent clustering analysis further grouped SCZ-induced cytokines based on their genetic similarities. The multi-phenotype summary statistics of each cytokine module were then used as instrumental variables (IVs) for the second round of MR analysis to detect their effect on brain structure and function.ResultsThe first round of MR analysis identified nine cytokines, the highlight of which includes IL18 (OR = 1.292, P = 8.37 × 10−42) and TNFa (OR = 0.721, P = 7.33 × 10−6), to be causally associated with schizophrenia. These SCZ-induced cytokines could be clustered into three modules. The second round of MR analysis (cytokine module => IDPs) indicated that module B (SCGFb-IP10-CTACK-IL6) significantly increased the level of IDPs including IDP_T1_SIENAX_peripheral_grey_normalised_volume (β = 0.0453, P = 4.40×1010), IDP_dMRI_TBSS_MD_Posterior_corona_radiata_R (β= 0.0584, P = 8.89× 10−16) and IDP_dMRI_TBSS_MD_Cingulum_hippocampus_R (β = 0.0563, P = 9.88× 10−15), with module C (IL18-GROa-TNFa) increasing the level of IDP_dMRI_TBSS_L2_Posterior_thalamic_radiation_R (β= 0.0341, P = 2.67× 10−6).ConclusionOur study, for the first time, mapped the causal link from schizophrenia to the comprehensive immune responses, and the findings suggest immune networks play a role in pathophysiology of schizophrenia by mediating the deviations of total gray matter volume and white matter fibers possibly in the mesolimbic system.


2020 ◽  
Author(s):  
Christopher M Lawson ◽  
Kilian FG Rentrup ◽  
Xuezhu Cai ◽  
Praveen P Kulkarni ◽  
Craig Ferris

Abstract Objectives This is an exploratory study using multimodal magnetic resonance imaging (MRI) to interrogate the brain of rats with type 2 diabetes (T2DM) as compared to controls. It was assumed there would be changes in brain structure and function that reflected the human disorder, thus providing a model system by which to follow disease progression with non-invasive MRI. Methods The transgenic BBZDR/Wor rat, an animal model of T2MD, and age-matched controls were studied for changes in brain structure using voxel-based morphometry, alteration in white and gray matter microarchitecture using diffusion weighted imaging with indices of anisotropy, and functional coupling using resting state BOLD functional connectivity. Images from each modality were registered to, and analyzed, using a 3D MRI rat atlas providing site-specific data on over 168 different brain areas. Results There was an overall reduction in brain volume focused primarily on somatosensory cortex, cerebellum and white matter tracts. The putative changes in white and gray matter microarchitecture were pervasive affecting much of the brain and not localized to any region. There was a general increase in connectivity in T2DM rats as compared to controls. The cerebellum presented with strong functional coupling to pons and brainstem in T2DM rats but negative connectivity to hippocampus. Conclusion Are the neuroradiological measures collected in BBBKZ/Wor rats using multimodal imaging methods common to the clinic, similar to those reported in T2DM patents? In comparison to the clinical findings, the data would suggest the BBBKZ/Wor rat is not an appropriate imaging model for T2DM.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shijia Li ◽  
Jie Song ◽  
Pengfei Ke ◽  
Lingyin Kong ◽  
Bingye Lei ◽  
...  

AbstractThe effect of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we used 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZ) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was significantly higher in SZ patients than in NCs. Additionally, the analysis of MRI data revealed that several brain regions showed significantly lower gray matter volume (GMV) and regional homogeneity (ReHo) but significantly higher amplitude of low-frequency fluctuation in SZ patients than in NCs. Moreover, the alpha diversity of the gut microbiota showed a strong linear relationship with the values of both GMV and ReHo. In SZ patients, the ReHo indexes in the right STC (r = − 0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = − 0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = − 0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with the abundance of the genus Roseburia. Our results suggest that the potential role of the gut microbiome in SZ is related to alterations in brain structure and function. This study provides insights into the underlying neuropathology of SZ.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Tao Chen ◽  
Yi Lu ◽  
Yu Wang ◽  
Anna Guo ◽  
Xiaoling Xie ◽  
...  

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP.


2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Chelsea M. Stillman ◽  
Shannon D. Donofry ◽  
Kirk I. Erickson

Aging is associated with changes in brain structure and function with some brain regions showing more age-related deterioration than others. There is evidence that regional changes in brain structure and function may affect the functioning of other, less- age-sensitive brain regions and lead to more global changes in brain efficiency and cognitive functioning. Fortunately, emerging evidence from health neuroscience suggests that age-related brain changes and associated cognitive declines may not be inevitable. In fact, they may even be reversible. Exercise is a particularly promising health behavior known to induce changes in regional brain structure and function in older adults. However, much less is known about how exercise affects the organization of brain networks in late life. The purpose of this review is to summarize what is known to date regarding the relationships between functional connectivity, exercise, fitness, and physical activity in aging. A critical summary of this literature may reveal novel mechanisms by which physical activity influences brain health, which in turn may be leveraged to improve other aspects of functioning, including physical, cognitive, and mental health in late life.


2021 ◽  
Author(s):  
Shijia Li ◽  
Jie Song ◽  
Pengfei Ke ◽  
Lingyin Kong ◽  
Bingye Lei ◽  
...  

Abstract The effects of the gut microbiome on the central nervous system and its possible role in mental disorders have received increasing attention. However, our knowledge about the relationship between the gut microbiome and brain structure and function is still very limited. Here, we leveraged 16S rRNA sequencing with structural magnetic resonance imaging (sMRI) and resting-state functional (rs-fMRI) to investigate differences in fecal microbiota between 38 patients with schizophrenia (SZs) and 38 demographically matched normal controls (NCs) and explored whether such differences were associated with brain structure and function. At the genus level, we found that the relative abundance of Ruminococcus and Roseburia was significantly lower, whereas the abundance of Veillonella was increased in SZs compared to NCs. Additionally, the MRI results revealed that several brain regions showed lower gray matter volume (GMV) and regional homogeneity (ReHo), but increased amplitude of low-frequency fluctuation (ALFF) in SZs than in NCs. Statistical analyses were performed to explore the associations between microbial shifts and brain structure and function. Alpha diversity of gut microbiota showed a strong linear relationship with GMV and ReHo. Moreover, we found that lower ReHo indexes in the right STC (r = -0.35, p = 0.031, FDR corrected p = 0.039), the left cuneus (r = -0.33, p = 0.044, FDR corrected p = 0.053) and the right MTC (r = -0.34, p = 0.03, FDR corrected p = 0.052) were negatively correlated with a lower abundance of the genus Roseburia. This study suggests that the potential role of the gut microbiome in schizophrenia (SZ) is related to the alteration of brain structure and function, suggesting a new direction for studying the pathology of SZ.


2021 ◽  
Vol 13 ◽  
Author(s):  
Célia Domingos ◽  
Maria Picó-Pérez ◽  
Ricardo Magalhães ◽  
Mariana Moreira ◽  
Nuno Sousa ◽  
...  

Several studies using neuroimaging techniques have established a positive relationship between physical activity (PA) and brain structure and function in older populations. However, the use of subjective measures of PA and the lack of multimodal neuroimaging approaches have limited the understanding of this association. This study aims to explore the associations between PA and brain structure and function by objectively evaluating PA. Community-dwelling cognitively healthy older adults (without diagnosed cognitive, neurological or degenerative disease) were recruited from local health centers and local gyms. In a cross-sectional design, participants were evaluated regarding cognitive, clinical, anthropometric, physical performance, and lifestyle characteristics. A 3 T magnetic resonance imaging (MRI) was performed for structural and functional brain measures. PA time and level was assessed via a Xiaomi Mi Band 2® worn for 15 consecutive days. Participants (n = 110, after inclusion/exclusion criteria and completion of all evaluations) were 58 females (56%), with an average age of 68.42 years old (SD = 3.12), most were active. Multiple regression analysis revealed that higher time spent in vigorous PA associated with larger left parahippocampal gyrus and right hippocampus volumes. Furthermore, the analysis of the functional connectome indicated a greater functional connectivity (FC) between the frontal gyrus, cingulate gyrus, occipital inferior lobe for light, moderate, and total PA time, and sedentary time associated with lower FC in the same networks. Overall, the structural and functional findings may provide evidence on the relevant association between PA and brain health in aging.


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