A critical challenge in current research on Alzheimer\'s disease (AD) is to clarify the relationship between network dysfunction and the emergence of subtle memory deficits in itspreclinical stage. The AppNL-F/MAPT double knock-in (dKI) model with humanized β-amyloid peptide (Aβ) and tau was used to investigate both memory and network dysfunctions at an early stage. Young male dKI mice (2 to 6 months) were tested in three tasks taxing different aspects of recognition memory affected in preclinical AD. An early deficit first appeared in the object-place association task at the age of 4 months, when increased levels of β-CTF and Aβ were detected in both the hippocampus and the medial temporal cortex, and tau pathology was found only in the medial temporal cortex. Object-place task-dependent c-Fos activation was then analyzed in 22 subregions across the medial prefrontal cortex, claustrum, retrosplenial cortex, and medial temporal lobe. Increased c-Fos activation was detected in the entorhinal cortex and the claustrum of dKI mice. During recall, network efficiency was reduced across cingulate regions with a major disruption of information flow through the retrosplenial cortex. Our findings suggest that early perirhinal-entorhinal pathology is associated with abnormal activity which may spread to downstream regions such as the claustrum, the medial prefrontal cortex and ultimately the key retrosplenial hub which relays information from frontal to temporal lobes. The similarity between our findings and those reported in preclinical stages of AD suggests that the AppNL-F/MAPT dKI model has a high potential for providing key insights into preclinical AD.

UNASSIGNED: Although homeostasis of the cardiovascular system is regulated by the cerebral cortex via the autonomic nervous system, the role of abnormal brain functional connectivity (FC) networks in patients with cardiac dysfunction remains unclear. Here, we report thalamus-based FC alterations and their relationship with clinical characteristics in patients with coronary heart disease (CHD).
UNASSIGNED: We employed resting-state functional magnetic resonance imaging (rs-fMRI) to acquire imaging data in twenty-six patients with CHD alongside sixteen healthy controls (HCs). Next, we performed a thalamus-based FC analysis to profile abnormal FC patterns in the whole brain. Subsequently, the mean time series of the brain regions that survived in the FC analysis were used to determine correlations with clinical parameters in patients with CHD.
UNASSIGNED: We found no statistically significant differences in demographic and clinical data between patients with CHD and HCs. Patients with CHD showed decreased FC patterns between bilateral thalami and left hemisphere, encompassing supplementary motor area, superior frontal gyrus, superior parietal gyrus, inferior parietal gyrus, middle cingulate cortex, lingual gyrus and calcarine sulcus.
UNASSIGNED: These findings not only have implications in clarifying the relationship between cerebral functional imbalance and cardiovascular system, but also provide valuable insights to guide future evaluation and management of cardiac autonomic regulation via the brain-heart axis.

UNASSIGNED: The underlying pathophysiology of slight cognitive dysfunction in Parkinson\'s disease-related mild cognitive impairment (PD-MCI) is yet to be elucidated. Our study aimed to evaluate the association between cognitive function and brain functional connectivity (FC) in patients with PD-MCI.
UNASSIGNED: Twenty patients with sporadic PD-MCI were evaluated for FC in the brain network. Further, electroencephalography (EEG) coherence analysis in the whole-brain and quantified regional coherence using phase coupling were performed for each frequency, and motor and cognitive function were assessed in the whole-brain.
UNASSIGNED: The degree of cognitive impairment was related to a decrease in the coherence in the alpha ranges. The regional coherence in the left frontal-left parietal region rather than the right frontal-right parietal region showed a higher correlation with the cognitive function scores.
UNASSIGNED: The differences in EEG coherence across different types of cognitive dysfunction reflect a compensatory response to the heterogeneous and complex clinical presentation of PD-MCI. Our findings indicate decreased brain efficiency and impaired neural synchronization in PD-MCI; these results may be crucial in elucidating the pathological exacerbation of PD-MCI.

Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied.
Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes).
Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities.
Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results.
Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

UNASSIGNED: To examine the role of the hippocampus in stress regulation in older adults with amnestic mild cognitive impairment (aMCI).
UNASSIGNED: This study combined resting-state functional MRI, structural MRI, self-reported chronic stress exposure, and an electrocardiography-based acute stress protocol to compare aMCI group (n = 17) to their cognitively healthy counterparts (HC, n = 22).
UNASSIGNED: For the entire sample, there was a positive correlation between chronic stress exposure and acute stress regulation. The aMCI group showed significantly smaller volumes in the right hippocampus than HC. The two groups did not differ in chronic stress exposure or acute stress regulation. In the HC group, the left hippocampal connectivity with inferior parietal lobe was significantly correlated with both the chronic stress and acute stress. In the aMCI group, the left hippocampal connectivity with both the right insula and the left precentral gyrus was significantly correlated to chronic stress exposure and acute stress regulation. Additionally, the left hippocampal connectivity with right insula significantly mediated the relationship between chronic stress exposure and acute stress regulation in aMCI group.
UNASSIGNED: Extra hippocampal networks may be recruited as compensation to attend the maintenance of relatively normal stress regulation in aMCI by alleviating the detrimental effects of chronic stress exposure on acute stress regulation.

Synchronization of neural activity as measured with functional connectivity (FC) is increasingly used to study the neural basis of brain disease and to develop new treatment targets. However, solid evidence for a causal role of FC in disease and therapy is lacking. Here, we manipulated FC of the ipsilesional primary motor cortex in ten chronic human stroke patients through brain-computer interface technology with visual neurofeedback. We conducted a double-blind controlled crossover study to test whether manipulation of FC through neurofeedback had a behavioral effect on motor performance. Patients succeeded in increasing FC in the motor cortex. This led to improvement in motor function that was significantly greater than during neurofeedback training of a control brain area and proportional to the degree of FC enhancement. This result provides evidence that FC has a causal role in neurological function and that it can be effectively targeted with therapy.

Auditory hallucinations (AH), typically hearing voices, are a core symptom in schizophrenia. They may result from deficits in dynamic functional connectivity (FC) between cortical regions supporting speech production and language perception that interfere with the ability to recognize self-generated speech as not coming from external sources. We tested this hypothesis by investigating dynamic connectivity between the frontal cortex region related to language production and the temporal cortex region related to auditory processing.
Resting-state fMRI scans were acquired from 18 schizophrenia patients with AH (AH+), 17 schizophrenia patients without AH (AH-) and 22 healthy controls. A multiband sequence with TR = 427 ms was adopted to provide relatively high temporal resolution data for characterizing dynamic FC. Analysis focused on connectivity between speech production and language comprehension areas, eloquent language cortex in the left hemisphere. Two frequency bands of brain oscillatory activity were evaluated (0.01-0.027 Hz, 0.027-0.08 Hz) in which differential alterations that have been previously linked to schizophrenia. Conventional static FC maps of these seeds were also calculated.
Dynamic connectivity analysis indicated that AH+ patients showed not only less temporal variability but transient lower strength in connectivity between speech and auditory areas than healthy controls, while AH- patients not. These findings were restricted to 0.027-0.08 Hz activity. In static connectivity analysis, no significant differences were observed in connectivity between speech production and language comprehension areas in either frequency band.
Reduced temporal variability and connectivity strength between key regions of eloquent language cortex may represent a mechanism for AH in schizophrenia.

BACKGROUND: Writer\'s cramp is a task-specific dystonia impairing writing and sometimes other fine motor tasks. Neuroimaging studies using manifold designs have shown varying results regarding the nature of changes in the disease.
OBJECTIVE: To clarify and extend the knowledge of underlying changes by investigating functional connectivity (FC) in intrinsic connectivity networks with putative sensorimotor function at rest in an increased number of study subjects.
METHODS: Resting-state functional magnetic resonance imaging with independent component analysis was performed in 26/27 writer\'s cramp patients/healthy controls, and FC within and between resting state networks with putative sensorimotor function was compared. Additionally, voxel-based morphometry was carried out on the subjects\' structural images.
RESULTS: Patients displayed increased left- and reduced right-hemispheric primary sensorimotor FC in the premotor-parietal network. Mostly bilaterally altered dorsal/ventral premotor FC, as well as altered parietal FC were observed within multiple sensorimotor networks and showed differing network-dependent directionality. Beyond within-network FC changes and reduced right cerebellar grey matter volume in the structural analysis, the positive between-network FC of the cerebellar network and the basal ganglia network was reduced.
CONCLUSIONS: Abnormal resting-state FC in multiple networks with putative sensorimotor function may act as basis of preexisting observations made during task-related neuroimaging. Further, altered connectivity between the cerebellar and basal ganglia network underlines the important role of these structures in the disease.

New neuroimaging techniques have led to significant advancements in our understanding of cerebral mechanisms of primary insomnia. However, the neuronal low-frequency oscillation remains largely uncharacterized in chronic primary insomnia (CPI). In this study, the amplitude of low-frequency fluctuation (ALFF), a data-driven method based on resting-state functional MRI, was used to examine local intrinsic activity in 27 patients with CPI and 27 age-, sex-, and education-matched healthy controls. We examined neural activity in two frequency bands, slow-4 (between 0.027 and 0.073 Hz) and slow-5 (0.010-0.027 Hz), because blood-oxygen level dependent (BOLD) fluctuations in different low-frequency bands may present different neurophysiological manifestations that pertain to a spatiotemporal organization. The ALFF associated with the primary disease effect was widely distributed in the cerebellum posterior lobe (CPL), dorsal and ventral prefrontal cortex, anterior cingulate cortex, precuneus, somatosensory cortex, and several default-mode sub-regions. Several brain regions (i.e., the right cerebellum, anterior lobe, and left putamen) exhibited an interaction between the frequency band and patient group. In the slow-5 band, increased ALFF of the right postcentral gyrus/inferior parietal lobule (PoCG/IPL) was enhanced in association with the sleep quality (ρ = 0.414, P = 0.044) and anxiety index (ρ = 0.406, P = 0.049) of the CPI patients. These findings suggest that during chronic insomnia, the intrinsic functional plasticity primarily responds to the hyperarousal state, which is the loss of inhibition in sensory-informational processing. Our findings regarding an abnormal sensory input and intrinsic processing mechanism might provide novel insight into the pathophysiology of CPI. Furthermore, the frequency factor should be taken into consideration when exploring ALFF-related clinical manifestations.

Attention dysfunction is a common but often undiagnosed cognitive impairment in Parkinson\'s disease that significantly reduces quality of life. We sought to increase understanding of the mechanisms underlying attention dysfunction using functional neuroimaging. Functional MRI was acquired at two repeated sessions in the resting state and during the Attention Network Test, for 25 non-demented subjects with Parkinson\'s disease and 21 healthy controls. Behavioral and MRI contrasts were calculated for alerting, orienting, and executive control components of attention. Brain regions showing group differences in attention processing were used as seeds in a functional connectivity analysis of a separate resting state run. Parkinson\'s disease subjects showed more activation during increased executive challenge in four regions of the dorsal attention and frontoparietal networks, namely right frontal eye field, left and right intraparietal sulcus, and precuneus. In three regions we saw reduced resting state connectivity to the default mode network. Further, whereas higher task activation in the right intraparietal sulcus correlated with reduced resting state connectivity between right intraparietal sulcus and the precuneus in healthy controls, this relationship was absent in Parkinson\'s disease subjects. Our results suggest that a weakened interaction between the default mode and task positive networks might alter the way in which the executive response is processed in PD.