Hippocampus-Based Dynamic Functional Connectivity Mapping in the Early Stages of Alzheimer’s Disease

Background: The hippocampus with varying degrees of atrophy was a crucial neuroimaging feature resulting in the declining memory and cognitive function in Alzheimer’s disease (AD). However, the abnormal dynamic functional connectivity (DFC) in both white matter (WM) and gray matter (GM) from the left and right hippocampus remains unclear. Objective: To explore the abnormal DFC within WM and GM from the left and right hippocampus across the different stages of AD. Methods: Current study employed the OASIS-3 dataset including 43 mild cognitive impairment (MCI), 71 pre-mild cognitive impairment (pre-MCI), and matched 87 normal cognitive (NC). Adopting the FMRIB’s Integrated Registration and Segmentation Tool, we obtained the left and right hippocampus mask. Based on above hippocampus mask as seed point, we calculated the DFC between left/right hippocampus and all voxel time series within whole brain. One-way ANOVA analysis was performed to estimate the abnormal DFC among MCI, pre-MCI, and NC groups. Results: We found that MCI and pre-MCI groups showed the common abnormalities of DFC in the Temporal_Mid_L, Cingulum_Mid_L, and Thalamus_L. Specific abnormalities were found in the Cerebelum_9_L and Precuneus of MCI group and Vermis_8 and Caudate_L of pre-MCI group. In addition, we found that DFC within WM regions also showed the common low DFC for the Cerebellum anterior lobe-WM, Corpus callosum, and Frontal lobe-WM in MCI and pre-MCI group. Conclusion: Our findings provided a novel information for discover the pathophysiological mechanisms of AD and indicate WM lesions were also an important cause of cognitive decline in AD.

Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression

Background Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. Methods Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. Results Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. Conclusions These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Altered Patterns of Amplitude of Low-Frequency Fluctuations and Fractional Amplitude of Low-Frequency Fluctuations Between Amnestic and Vascular Mild Cognitive Impairment: An ALE-Based Comparative Meta-Analysis

Background: Changes in the amplitude of low-frequency fluctuations (ALFF) and the fractional amplitude of low-frequency fluctuations (fALFF) have provided stronger evidence for the pathophysiology of cognitive impairment. Whether the altered patterns of ALFF and fALFF differ in amnestic cognitive impairment (aMCI) and vascular mild cognitive impairment (vMCI) is largely unknown. The purpose of this study was to explore the ALFF/fALFF changes in the two diseases and to further explore whether they contribute to the diagnosis and differentiation of these diseases.Methods: We searched PubMed, Ovid, and Web of Science databases for articles on studies using the ALFF/fALFF method in patients with aMCI and vMCI. Based on the activation likelihood estimation (ALE) method, connectivity modeling based on coordinate meta-analysis and functional meta-analysis was carried out.Results: Compared with healthy controls (HCs), patients with aMCI showed increased ALFF/fALFF in the bilateral parahippocampal gyrus/hippocampus (PHG/HG), right amygdala, right cerebellum anterior lobe (CAL), left middle temporal gyrus (MTG), left cerebrum temporal lobe sub-gyral, left inferior temporal gyrus (ITG), and left cerebrum limbic lobe uncus. Meanwhile, decreased ALFF/fALFF values were also revealed in the bilateral precuneus (PCUN), bilateral cuneus (CUN), and bilateral posterior cingulate (PC) in patients with aMCI. Compared with HCs, patients with vMCI predominantly showed decreased ALFF/fALFF in the bilateral CUN, left PCUN, left PC, and right cingulate gyrus (CG).Conclusions: The present findings suggest that ALFF and fALFF displayed remarkable altered patterns between aMCI and vMCI when compared with HCs. Thus, the findings of this study may serve as a reliable tool for distinguishing aMCI from vMCI, which may help understand the pathophysiological mechanisms of these diseases.

Mechanisms of Ethanol-Induced Cerebellar Ataxia: Underpinnings of Neuronal Death in the Cerebellum

Ethanol consumption remains a major concern at a world scale in terms of transient or irreversible neurological consequences, with motor, cognitive, or social consequences. Cerebellum is particularly vulnerable to ethanol, both during development and at the adult stage. In adults, chronic alcoholism elicits, in particular, cerebellar vermis atrophy, the anterior lobe of the cerebellum being highly vulnerable. Alcohol-dependent patients develop gait ataxia and lower limb postural tremor. Prenatal exposure to ethanol causes fetal alcohol spectrum disorder (FASD), characterized by permanent congenital disabilities in both motor and cognitive domains, including deficits in general intelligence, attention, executive function, language, memory, visual perception, and communication/social skills. Children with FASD show volume deficits in the anterior lobules related to sensorimotor functions (Lobules I, II, IV, V, and VI), and lobules related to cognitive functions (Crus II and Lobule VIIB). Various mechanisms underlie ethanol-induced cell death, with oxidative stress and endoplasmic reticulum (ER) stress being the main pro-apoptotic mechanisms in alcohol abuse and FASD. Oxidative and ER stresses are induced by thiamine deficiency, especially in alcohol abuse, and are exacerbated by neuroinflammation, particularly in fetal ethanol exposure. Furthermore, exposure to ethanol during the prenatal period interferes with neurotransmission, neurotrophic factors and retinoic acid-mediated signaling, and reduces the number of microglia, which diminishes expected cerebellar development. We highlight the spectrum of cerebellar damage induced by ethanol, emphasizing physiological-based clinical profiles and biological mechanisms leading to cell death and disorganized development.

Investigation of changes in activity and function in acute unilateral open globe injury–associated brain regions based on percent amplitude of fluctuation method: a resting-state functional MRI study

Background Open globe injury (OGI) is a serious condition that can lead to visual impairment and lifelong sequelae, brain activity of some brain regions would change in patients with OGI. Purpose To evaluate changes in brain activity associated with unilateral OGI by resting-state functional magnetic resonance imaging (rs-fMRI) and analysis of percentage amplitude of fluctuation (PerAF). Material and Methods A total of 22 patients with OGI (12 men, 10 women) and 22 healthy controls (HCs) matched for sex, age, and body weight were enrolled. All patients underwent rs-fMRI scans. Brain activity in the relevant brain regions was assessed with the PerAF method. The ability of PerAF to distinguish patients with OGI from HCs was assessed by receiver operating characteristic (ROC) curve analysis. We also examined the relationship between Hospital Anxiety and Depression Scale (HADS) scores and PerAF signals by Pearson’s correlation analysis. Results PerAF values in amygdala_R and Frontal_Inf_Orb_L/Frontal_Inf_Oper_L were increased whereas that in Cerebellum Anterior Lobe/Cerebelum_8_L was decreased in patients with OGI compared to HCs. The areas under the ROC curve showed that these brain regions could distinguish between patients with OGI and HCs. The PerAF value of amygdala_R was positively correlated with HADS scores. Conclusion Changes in PerAF in the amygdala_R, Frontal_inferior_Orb_L/Frontal_Inf_Oper_L, and Cerebellum Anterior Lobe/Cerebelum_8_L in patients with OGI may be related to an increased risk of developing psychiatric disorders such as anxiety and depression. PerAF can be used to investigate the neural basis of complications associated with OGI and monitor disease progression.

Brain Activation of College Students in China With Premenstrual Syndrome Localized by BOLD-fMRI

Background: Most studies on the mechanism behind premenstrual syndrome (PMS) have focused on fluctuating hormones, but little evidence exists regarding functional abnormalities in the affected brain regions of college students. Thus, the aim of this study is to localize PMS's abnormal brain regions by BOLD-fMRI in college students.Methods: Thirteen PMS patients and fifteen healthy control (HC) subjects underwent a BOLD-fMRI scan during the luteal phase induced by depressive emotion pictures. The BOLD-fMRI data were processed by SPM 8 software and rest software based on MATLAB platform. Each cluster volume threshold (cluster) was greater than 389 continuous voxels, and the brain area with single voxel threshold P < 0.05 (after correction) was defined as the area with a significant difference. The emotion report form and the instruction implementation checklist were used to evaluate the emotion induced by picture.Results: Compared to the HC, right inferior occipital gyrus, right middle occipital gyrus, right lingual gyrus, right fusiform gyrus, right inferior temporal gyrus, cerebelum_crus1_R，cerebelum_6_R, culmen, the cerebellum anterior lobe, tuber, cerebellar tonsil of PMS patients were enhanced activation. Sub-lobar，sub-gyral，extra-nuclear，right orbit part of superior frontal gyrus, right middle temporal gyrus, right Orbit part of inferior frontal gyrus, limbic lobe, right insula, bilateral anterior and adjacent cingulate gyrus, bilateral caudate, caudate head, bilateral putamen, left globus pallidus were decreased activation.Conclusion: Our findings may improve our understanding of the neural mechanisms involved in PMS.

Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations

ObjectiveCerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition.MethodsA prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying an intermediate-length repeat expansion in ATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography.ResultsCerebellar pathology was confined to lobules I–V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified in C9orf72 mutation carriers. Patients with intermediate ATXN2 expansions did not exhibit significant cerebellar pathology.ConclusionsFocal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.

Neural Response to High and Low Energy Food Images in Anorexia Nervosa

To compare neural responses to high and low-energy food images in patients with Anorexia Nervosa (AN) and an age-matched Healthy Control (HC) group. 25 adolescents with AN and 21 HCs completed a diagnostic interview, self-report questionnaires and fMRI, during which they viewed food images evoking responses of disgust, happiness, or fear. Following whole brain analyses, neural responses in six regions of interest were examined in a series of between-group contrasts, across the three emotive categories. Compared to the HCs, people in the AN group showed increased responsivity to high-energy (1) disgust images in temporal lobe, frontal lobe, insula, and cerebellum anterior lobe; (2) fear images in occipital lobe, temporal, and frontal lobes and (3) happy images in frontal lobe, cerebellum anterior lobe, sub-lobar, and cuneus. More activity was observed in response to low-energy (1) disgust food images in the temporal lobe, frontal lobe, insula, cerebellum anterior and posterior lobes, parietal lobe, occipital lobe, and limbic lobe; (2) and happy food images in frontal lobes. Few correlations were found with levels of eating disorder symptoms. The findings highlight the emotional impact of diverse high and low-energy foods for people with AN. People without AN may have a better capacity to filter salient from non-salient information relating to the current task when viewing high energy foods. In summary, for those with AN, it would seem their ability to efficiently ‘sort-out’ information (especially information pertaining to disorder-relevant stimuli such as food images) to complete the task at hand, may be diminished.

Single-Dose Toxicity Study on ML171, a Selective NOX1 Inhibitor, in Mice

Background. ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. Methods. The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. Results. Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. Conclusion. Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.