Search

ObjectivesSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer’s disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function.MethodsThis study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed.ResultsCross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged.ConclusionThis study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum.Clinical Trial Registrationhttp://www.chictr.org.cn, ChiCTR2000034533.

ObjectiveImpaired interhemispheric connectivity and corpus callosum atrophy have been linked to cognitive impairment in Alzheimer’s disease (AD). Existing evidence indicates that repetitive transcranial magnetic stimulation (rTMS) targeting the bilateral precuneus may enhance cognitive function in AD. This study aims to investigate the effects of precuneus rTMS on cognitive function, as well as alterations in interhemispheric functional connectivity (FC) and its structural basis in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI).MethodsA total of 14 patients with SCD and 16 patients with MCI were enrolled in this study and received 10 Hz rTMS intervention on the bilateral precuneus for 2 weeks. Neurocognitive scales, structural and functional magnetic resonance imaging were collected at enrollment and after the rTMS intervention. Interhemispheric FC was assessed using mirror homotopic functional connectivity (VMHC), while the structural equation modeling (SEM) was employed to analyze the relationship between corpus callosum volume, interhemispheric connectivity, and cognitive function after rTMS intervention.ResultsThe precuneus rTMS not only enhanced episodic memory in SCD, but also improved multiple cognitive domains in MCI. Post-rTMS intervention, decreased VMHC values in the lingual cortex, middle occipital gyrus, putamen, and fusiform gyrus were observed in SCD, and an increased VMHC value in the postcentral gyrus along with reduced VMHC value in the cerebellum and putamen in MCI. After intervention, more brain regions show decreased FC in SCD and MCI patients, suggesting that precuneus rTMS may protect cerebral cortical plasticity by reducing excessive functional compensation, and thus improve cognitive function. The SEM indicated that the corpus callosum serves as the structural foundation for rTMS regulation of interhemispheric FC to further improve cognitive function.Conclusion10 Hz rTMS in the bilateral precuneus could be a promising strategy to improve cognitive function in patients with SCD and MCI. Our study implies that improvements in cognition brought about by precuneus rTMS may result from the remodeling of interhemispheric FC, with the corpus callosum possibly acting as the anatomical basis for functional modulation.

Abstract Background Amnestic mild cognitive impairment (aMCI) is considered to be the prodromal stage of Alzheimer's disease (AD). The precuneus (PCUN) may be an imaging marker for monitoring the progression of AD. Meanwhile, cognitive impairment in AD patients is closely related to functional connectivity (FC) changes in the salience network (SN). We hypothesize that there are specific neuroimaging biomarkers in the SN and that FC changes in aMCI patients after repetitive transcranial magnetic stimulation (rTMS) intervention are associated with cognitive function. The purpose of this study was to first investigate the pattern of functional changes in aMCI patients and healthy controls (HCs) and then compare the functional changes in aMCI patients before and after rTMS targeting to PCUN and its correlation with cognitive function. Methods Thirty‐six HCs and 61 aMCIs were recruited for our study. Eleven people in the aMCI group received rTMS intervention 5 days a week for 4 weeks. Using the right anterior insula as the seed‐of‐interest, we first compared FC changes in HC and aMCI patients and then compared cognitive function in aMCI patients before and after rTMS. The above is the functional connection analysis of seed‐to‐voxel. Moreover, we investigated the FC changes in aMCI patients after rTMS intervention and its correlation with cognitive function. Results Compared with HC, the aMCI group showed altered FC in bilateral parahippocampal gyrus, bilateral inferior parietal lobule, left middle frontal gyrus, and left middle temporal gyrus. Moreover, rTMS at PCUN improved the cognitive function of aMCI patients, which was related to the altered FC in posterior cerebellar lobes (CPL). Conclusions Our findings suggest that rTMS targeting PCUN is a promising, noninvasive approach to ameliorating cognitive dysfunction in aMCI patients, and that this cognitive improvement is accompanied by brain connectivity modulation.

BackgroundMild cognitive impairment (MCI) depicts a transitory phase between healthy elderly and the onset of Alzheimer's disease (AD) with worsening cognitive impairment. Some functional MRI (fMRI) research indicated that the frontoparietal network (FPN) could be an essential part of the pathophysiological mechanism of MCI. However, damaged FPN regions were not consistently reported, especially their interactions with other brain networks. We assessed the fMRI-specific anomalies of the FPN in MCI by analyzing brain regions with functional alterations.MethodsPubMed, Embase, and Web of Science were searched to screen neuroimaging studies exploring brain function alterations in the FPN in MCI using fMRI-related indexes, including the amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity. We integrated distinctive coordinates by activating likelihood estimation, visualizing abnormal functional regions, and concluding functional alterations of the FPN.ResultsWe selected 29 studies and found specific changes in some brain regions of the FPN. These included the bilateral dorsolateral prefrontal cortex, insula, precuneus cortex, anterior cingulate cortex, inferior parietal lobule, middle temporal gyrus, superior frontal gyrus, and parahippocampal gyrus. Any abnormal alterations in these regions depicted interactions between the FPN and other networks.ConclusionThe study demonstrates specific fMRI neuroimaging alterations in brain regions of the FPN in MCI patients. This could provide a new perspective on identifying early-stage patients with targeted treatment programs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432042, identifier: CRD42023432042.

Perceived stress, which refers to people's evaluation of a stressful event and their ability to cope with it, has emerged as a stable predictor for physical and mental health outcomes. Increasing evidence has suggested the buffering effect of social support on perceived stress. Although previous studies have investigated the brain structural features (e.g., gray matter volume) associated with perceived stress, less is known about the association between perceived chronic stress and intra-cortical myelin (ICM), which is an important microstructure of brain and is essential for healthy brain functions, and the role of social support in this association. Using a sample of 1076 healthy young adults drawn from the Human Connectome Project, we quantified the ICMby the contrast of T1w and T2w images and examined its association with perceived chronic stress during the last month and social support. Behavioral results showed that perceived chronic stress was negatively associated with both emotional support and instrumental support. Vertex-wise multiple regression analyses revealed that higher level of perceived chronic stress was significantly associated with lower ICM content of a cluster in the right supramarginal gyrus (rSMG). Interestingly, the emotional support, but not the instrumental support, significantly mediated the association of perceived chronic stress with ICM in the rSMG. Overall, the present study provides novel evidence for the cortical myelination of perceived chronic stress in humans and highlights the essential role of the rSMG in perceived chronic stress and emotional support.

BackgroundSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered part of the early progression continuum of Alzheimer’s disease (AD). The anterior cingulate cortex (ACC), a hub of information processing and regulation in the brain, plays an essential role in AD pathophysiology. In the present study, we aimed to systematically identify changes in the functional connectivity (FC) of ACC subregions in patients with SCD and aMCI and evaluate the association of these changes with cognition.Materials and methodsFunctional connectivity (FC) analysis of ACC sub-regions was performed among 66 patients with SCD, 71 patients with aMCI, and 78 healthy controls (HCs). Correlation analyses were performed to examine the relationship between FC of altered ACC subnetworks and cognition.ResultsCompared to HCs, SCD patients showed increased FC of the bilateral precuneus (PCUN) and caudal ACC, left superior frontal gyrus (SFG) and subgenual ACC, left inferior parietal lobule (IPL) and dorsal ACC, left middle occipital gyrus (MOG) and dorsal ACC, and left middle temporal gyrus (MTG) and subgenual ACC, while aMCI patients showed increased FC of the left inferior frontal gyrus (IFG) and dorsal ACC and left medial frontal gyrus (MFG) and subgenual ACC. Compared to patients with SCD, patients with aMCI showed increased FC of the right MFG and dorsal ACC and left ACC and subgenual ACC, while the left posterior cingulate cortex (PCC) showed decreased FC with the caudal ACC. Moreover, some FC values among the altered ACC subnetworks were significantly correlated with episodic memory and executive function.ConclusionSCD and aMCI, part of the spectrum of pre-clinical AD, share some convergent and divergent altered intrinsic connectivity of ACC subregions. These results may serve as neuroimaging biomarkers of the preclinical phase of AD and provide new insights into the design of preclinical interventions.

Increasing evidence indicates that neuroinflammation contributes to and exacerbates the pathogenesis of Alzheimer’s disease (AD). Neuroinflammation is thought to be primarily driven by glial cells (microglia and astrocytes) and escalates with neurodegenerative progression in AD. However, the spatiotemporal change patterns of glial reactivity and neuroinflammatory response during different stages of neurodegeneration, especially early in disease, remain unknown. Here we found that gliosis and the up-regulation of substantial neuroinflammatory genes were primarily initiated in the cortex of presenilin 1/2 conditional double knockout (cDKO) mice, rather than in the hippocampus. Specifically, astrocyte activation preceding microglial activation was found in the somatosensory cortex (SS) of cDKO mice at 6 weeks of age. Over time, both astrocyte and microglial activation were found in the whole cortex, and age-related increases in gliosis activation were more pronounced in the cortex compared to hippocampus. Moreover, the age-associated increase in glial activation was accompanied by a gradual increase in the expression of cell chemokines Ccl3 and Ccl4, complement related factors C1qb, C3 and C4, and lysosomal proteases cathepsin S and Z. These findings suggest that astrocyte and microglial activation with a concurrent increase in inflammatory mediators such as chemokines might be an early event and contribute to the pathogenesis of neurodegeneration due to presenilin deficiency.

Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in prevention and treatment strategies as well as drug development. This review discusses the classification and pathological characteristics of cerebral edema, the possible relationship of the development of cerebral edema after ischemic stroke with aquaporin 4, the SUR1-TRPM4 channel, matrix metalloproteinase 9, microRNA, cerebral venous reflux, inflammatory reactions, and cerebral ischemia/reperfusion injury. It also summarizes research on new therapeutic drugs for post-stroke cerebral edema. Thus, this review provides a reference for further studies and for clinical treatment of cerebral edema after ischemic stroke.

A central aim of neuroethological research is to discover the mechanisms of natural behaviors in controlled laboratory studies. This goal, however, comes with challenges, namely the selection of experimental paradigms that allow full expression of natural behaviors. Here, we explore this problem in echolocating bats that evolved Doppler shift compensation (DSC) of sonar vocalizations to yield close matching between echo frequency and hearing sensitivity. We ask if behavioral tasks influence the precision of DSC in Pratt’s roundleaf bat, Hipposideros pratti, in three classic laboratory paradigms evoking audio-vocal adjustments: Stationary bats listening to echo playbacks, bats transported on a moving pendulum, and bats flying freely. We found that experimental conditions had a strong influence on the expression of the audiovocal frequency adjustments in bats. H. pratti exhibited robust DSC in both free-flying and moving-pendulum experiments but did not exhibit consistent audiovocal adjustments in echo playback experiments. H. pratti featured a maximum compensation magnitude of 87% and a compensation precision of 0.27% in the free flight experiment. Interestingly, in the moving pendulum experiment H. pratti displayed surprisingly high-precision DSC, with an 84% maximum compensation magnitude and a 0.27% compensation precision. Such DSC performance places H. pratti among the bat species exhibiting the most precise audio-vocal control of echo frequency. These data support the emerging view that Hipposiderid bats have a high-precision DSC system and highlight the importance of selecting experimental paradigms that yield the expression of robust natural behaviors.

BackgroundMild cognitive impairment (MCI) is considered to be an intermediate stage between normal aging and Alzheimer's disease (AD). The earliest and most common symptom of MCI is impaired episodic memory. When episodic memory is impaired in MCI patients, specific functional changes occur in related brain areas. However, there is currently a lack of a unified conclusion on this change. Therefore, the purpose of this meta-analysis is to find MRI-specific functional changes in episodic memory in MCI patients.MethodsBased on three commonly used indicators of brain function: functional connectivity (FC), the amplitude of low-frequency fluctuation /fractional amplitude of low-frequency fluctuation (ALFF/fALFF), and regional homogeneity (ReHo), we systematically searched PubMed, Web of Science and Ovid related literature and conducted the strict screening. Then we use the activation likelihood estimation (ALE) algorithm to perform the coordinate-based meta-analysis.ResultsThrough strict screening, this meta-analysis finally included 21 related functional neuroimaging research articles. The final result displays that functional changes of episodic memory in MCI patients are mainly located in the parahippocampal gyrus, precuneus, posterior cingulate gyrus, cuneus, middle temporal gyrus, middle frontal gyrus, lingual gyrus, and thalamus.ConclusionsThere are specific functional changes in episodic memory brain regions in MCI patients, and the brain functional network can regulate episodic memory through these brain regions. And these specific changes can assist in the early diagnosis of MCI, providing new ideas and directions for early identification and intervention in the process of MCI.

BackgroundBoth subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) have a high risk of progression to Alzheimer's disease (AD). While most of the available evidence described changes in functional connectivity (FC) in SCD and aMCI, there was no confirmation of changes in functional connectivity density (FCD) that have not been confirmed. Therefore, the purpose of this study was to investigate the specific alterations in resting-state FCD in SCD and aMCI and further assess the extent to which these changes can distinguish the preclinical and early-stage AD.MethodsA total of 57 patients with SCD, 59 patients with aMCI, and 78 healthy controls (HC) were included. The global FCD, local FCD, and long-range FCD were calculated for each voxel to identify brain regions with significant FCD alterations. The brain regions with abnormal FCD were then used as regions of interest for FC analysis. In addition, we calculated correlations between neuroimaging alterations and cognitive function and performed receiver-operating characteristic analyses to assess the diagnostic effect of the FCD and FC alterations on SCD and aMCI.ResultsFCD mapping revealed significantly increased global FCD in the left parahippocampal gyrus (PHG.L) and increased long-range FCD in the left hippocampus for patients with SCD when compared to HCs. However, when compared to SCD, patients with aMCI showed significantly decreased global FCD and long-range FCD in the PHG.L. The follow-up FC analysis further revealed significant variations between the PHG.L and the occipital lobe in patients with SCD and aMCI. In addition, patients with SCD also presented significant changes in FC between the left hippocampus, the left cerebellum anterior lobe, and the inferior temporal gyrus. Moreover, changes in abnormal indicators in the SCD and aMCI groups were significantly associated with cognitive function. Finally, combining FCD and FC abnormalities allowed for a more precise differentiation of the clinical stages.ConclusionTo our knowledge, this study is the first to investigate specific alterations in FCD and FC for both patients with SCD and aMCI and confirms differential abnormalities that can serve as potential imaging markers for preclinical and early-stage Alzheimer's disease (AD). Also, it adds a new dimension of understanding to the diagnosis of SCD and aMCI as well as the evaluation of disease progression.

BackgroundMild cognitive impairment (MCI) is known as the prodromal stage of the Alzheimer’s disease (AD) spectrum. The recent studies have advised that functional alterations in the dorsal attention network (DAN) could be used as a sensitive marker to forecast the progression from MCI to AD. Therefore, our aim was to investigate specific functional alterations in the DAN in MCI.MethodsWe systematically searched PubMed, EMBASE, and Web of Science and chose relevant articles based on the three functional indicators, the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the DAN in MCI. Based on the activation likelihood estimation, we accomplished the aggregation of specific coordinates and the analysis of functional alterations.ResultsA total of 38 studies were involved in our meta-analysis. By summing up included articles, we acquired specific brain region alterations in the DAN mainly in the superior temporal gyrus (STG), middle temporal gyrus (MTG), superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), precentral gyrus (preCG), inferior parietal lobule (IPL), superior parietal lobule (SPL). At the same time, the key area that shows anti-interaction with default mode network included the IPL in the DAN. The one showing interactions with executive control network was mainly in the MFG. Finally, the frontoparietal network showed a close connection with DAN especially in the IPL and IFG.ConclusionThis study demonstrated abnormal functional markers in the DAN and its interactions with other networks in MCI group, respectively. It provided the foundation for future targeted interventions in preventing the progression of AD.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021287958].

The present study aimed to explore the effect of intermittent theta-burst stimulation (iTBS) on visual working memory for people suffering from methamphetamine use disorder (MUD). Five sessions of iTBS were carried over the left dorsolateral prefrontal cortex (DLPFC) or the vertex as a sham control, with each session in one day. Orientation free-recall tasks were conducted before the iTBS stimulation, after the first and fifth sessions of stimulation. Results showed that when compared with the sham group, a single session of iTBS over the left DLPFC improved participants’ working memory performance. Specifically, iTBS over the left DLPFC increased the working memory capacity and such effects enlarged with multiple sessions. The present finding suggested that iTBS over DLPFC could be a promising intervention method to enhance the cognitive function of addicts with MUD.

We have developed a low-cost electromagnetic vibrotactile stimulator that uses the magnetic field of an MR scanner as a permanent magnet to power a vibrating motor. A simple variable current power supply is controlled by software using a USB data acquisition controller. In our study, the function of our novel stimulator was verified in a vibration frequency discrimination working memory task, in which various ranges of frequencies and amplitudes are delivered in MRI scanner. Furthermore, our functional MRI study revealed activations of the primary and secondary somatosensory cortices during the perception of tactile stimulation. Therefore, the new designed electromagnetic vibrotactile stimulator is capable of generating various frequencies of tactile stimuli and represents a powerful and useful tool for studying somatosensory functions with functional MRI.

Histone acetylation has been shown to play a crucial role in memory formation, and histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) has been demonstrated to improve memory performance and rescue the neurodegeneration of several Alzheimer’s Disease (AD) mouse models. The forebrain presenilin-1 and presenilin-2 conditional double knockout (cDKO) mice showed memory impairment, forebrain degeneration, tau hyperphosphorylation and inflammation that closely mimics AD-like phenotypes. In this article, we have investigated the effects of systemic administration of NaB on neurodegenerative phenotypes in cDKO mice. We found that chronic NaB treatment significantly restored contextual memory but did not alter cued memory in cDKO mice while such an effect was not permanent after treatment withdrawal. We further revealed that NaB treatment did not rescue reduced synaptic numbers and cortical shrinkage in cDKO mice, but significantly increased the neurogenesis in subgranular zone of dentate gyrus (DG). We also observed that tau hyperphosphorylation and inflammation related protein glial fibrillary acidic protein (GFAP) level were decreased in cDKO mice by NaB. Furthermore, GO and pathway analysis for the RNA-Seq data demonstrated that NaB treatment induced enrichment of transcripts associated with inflammation/immune processes and cytokine-cytokine receptor interactions. RT-PCR confirmed that NaB treatment inhibited the expression of inflammation related genes such as S100a9 and Ccl4 found upregulated in the brain of cDKO mice. Surprisingly, the level of brain histone acetylation in cDKO mice was dramatically increased and was decreased by the administration of NaB, which may reflect dysregulation of histone acetylation underlying memory impairment in cDKO mice. These results shed some lights on the possible molecular mechanisms of HDAC inhibitor in alleviating the neurodegenerative phenotypes of cDKO mice and provide a promising target for treating AD.

Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group.