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.

In meditation practices that involve focused attention to a specific object, novice practitioners often experience moments of distraction (i.e., mind wandering). Previous studies have investigated the neural correlates of mind wandering during meditation practice through Electroencephalography (EEG) using linear metrics (e.g., oscillatory power). However, their results are not fully consistent. Since the brain is known to be a chaotic/nonlinear system, it is possible that linear metrics cannot fully capture complex dynamics present in the EEG signal. In this study, we assess whether nonlinear EEG signatures can be used to characterize mind wandering during breath focus meditation in novice practitioners. For that purpose, we adopted an experience sampling paradigm in which 25 participants were iteratively interrupted during meditation practice to report whether they were focusing on the breath or thinking about something else. We compared the complexity of EEG signals during mind wandering and breath focus states using three different algorithms: Higuchi\'s fractal dimension (HFD), Lempel-Ziv complexity (LZC), and Sample entropy (SampEn). Our results showed that EEG complexity was generally reduced during mind wandering relative to breath focus states. We conclude that EEG complexity metrics are appropriate to disentangle mind wandering from breath focus states in novice meditation practitioners, and therefore, they could be used in future EEG neurofeedback protocols to facilitate meditation practice.

Detection of incipient cognitive impairment and dementia pathophysiology is critical to identify preclinical populations and target potentially disease modifying interventions towards them. There are currently concerted efforts for such detection for Alzheimer\'s disease (AD). By contrast, the examination of cognitive markers and their relationship to biomarkers for Vascular Cognitive Impairment (VCI) is far less established, despite VCI being highly prevalent and often concomitantly presenting with AD. Critically, vascular risk factors are currently associated with the most viable treatment options via pharmacological and non-pharmacological intervention, hence early identification of vascular factors have important implications for modifying dementia disease trajectories. The aim of this review is to examine the current evidence of cognitive marker correlates to VCI pathology. We begin by examining midlife risk factors that predict VCI. Next, discuss preclinical cognitive hallmarks of VCI informed by insights from neuropsychological assessment, network connectivity and ERP/EEG experimental findings. Finally, we discuss limitations of current cognitive assessments and the need for future cognitive test development to inform diagnostic assessment. As well as, intervention outcome measures for preclinical VCI. In turn, these tests will inform earlier detection of vascular changes and allow implementation of disease intervention approaches.

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.

The Cognitive Avoidance Theory of Worry argues that worry is a cognitive strategy adopted to control the physiological arousal associated with anxiety. According to this theory, pathological worry, as in Generalized Anxiety Disorder (GAD), is verbal in nature, negative and abstract, rather than concrete. Neuroimaging studies link the expression of worry to characteristic modes of brain functional connectivity, especially in relation to the amygdala. However, the distinctive features of worry (verbal, abstract, negative), and their relationship to physiological arousal, have not so far been mapped to brain function.
We addressed this omission by undertaking a resting-state functional magnetic resonance neuroimaging study of 19 patients with GAD and 21 controls, before and after induction of perseverative cognitions, while measuring emotional bodily arousal from heart rate (HR). Seed-based analyses quantified brain changes in whole brain functional connectivity from the amygdala.
In GAD, the induction increased negative thoughts and their verbal content. In line with predictions, the verbal expression of worry in GAD was associated with higher HR at baseline and attenuated HR increases after induction of perseverative cognitions. Within brain, the increased use of words during worry, and the associated dampening of HR after induction were mediated by the strength of functional connectivity between the amygdala and default mode network \'hubs\' and the opercular cortex. The negative content of worry was further related to functional communication between amygdala and cingulo-opercular and temporal cortices.
Findings provide a neurobiological basis for the impact of verbal worry on HR in GAD.

It has been proposed that pain competes with other attention-demanding stimuli for cognitive resources, and many chronic pain patients display significant attention and mental flexibility deficits. These alterations may result from disruptions in the functioning of the default mode network (DMN) which plays a critical role in attention, memory, prospection and self-processing, and recent investigations have found alterations in DMN function in multiple chronic pain conditions. Whilst it has been proposed that these DMN alterations are a characteristic of pain that is chronic in nature, we recently reported altered oscillatory activity in the DMN during an acute, 5  minute noxious stimulus in healthy control subjects. We therefore hypothesize that altered DMN activity patterns will not be restricted to those in chronic pain but instead will also occur in healthy individuals during tonic noxious stimuli. We used functional magnetic resonance imaging to measure resting state infra-slow oscillatory activity and functional connectivity in patients with chronic orofacial pain at rest and in healthy controls during a 20-minute tonic pain stimulus. We found decreases in oscillatory activity in key regions of the DMN in patients with chronic pain, as well as in healthy controls during tonic pain in addition to changes in functional connectivity between the posterior cingulate cortex and areas of the DMN in both groups. The results show that similar alterations in DMN function occur in healthy individuals during acute noxious stimuli as well as in individuals with chronic pain. These DMN changes may reflect the presence of pain per se and may underlie alterations in attentional processes that occur in the presence of pain.

This prospective study explored whether an approach combining structural [cortical thickness and white matter (WM) microstructure] and resting state functional MRI can aid differentiation between 62 early onset Alzheimer\'s disease (EOAD) and 27 behavioural variant of frontotemporal dementia (bvFTD) patients. Random forest and receiver operator characteristic curve analyses assessed the ability of MRI in classifying the two clinical syndromes. All patients showed a distributed pattern of brain alterations relative to controls. Compared to bvFTD, EOAD patients showed bilateral inferior parietal cortical thinning and decreased default mode network functional connectivity. Compared to EOAD, bvFTD patients showed bilateral orbitofrontal and temporal cortical thinning, and WM damage of the corpus callosum, bilateral uncinate fasciculus, and left superior longitudinal fasciculus. Random forest analysis revealed that left inferior parietal cortical thickness (accuracy 0.78, specificity 0.76, sensitivity 0.83) and WM integrity of the right uncinate fasciculus (accuracy 0.81, specificity 0.96, sensitivity 0.43) were the best predictors of clinical diagnosis. The combination of cortical thickness and DT MRI measures was able to distinguish patients with EOAD and bvFTD with accuracy 0.82, specificity 0.76, and sensitivity 0.96. The diagnostic ability of MRI models was confirmed in a subsample of patients with biomarker-based clinical diagnosis. Multiparametric MRI is useful to identify brain alterations which are specific to EOAD and bvFTD. A severe cortical involvement is suggestive of EOAD, while a prominent WM damage is indicative of bvFTD.

Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes reflect distinct aberrations in underlying brain organization. We imaged 34 ADHD participants defined using DSM-IV criteria as ADHD-I (n = 16) or as ADHD-C (n = 18) and 28 matched typically developing controls, aged 8-17 years, using high-resolution T1 MRI. To quantify neuroanatomical organization we used graph theoretical analysis to assess properties of structural covariance between ADHD subtypes and controls (global network measures: path length, clustering coefficient, and regional network measures: nodal degree). As a context for interpreting network organization differences, we also quantified gray matter volume using voxel-based morphometry. Each ADHD subtype was distinguished by a different organizational profile of the degree to which specific regions were anatomically connected with other regions (i.e., in \"nodal degree\"). For ADHD-I (compared to both ADHD-C and controls) the nodal degree was higher in the hippocampus. ADHD-I also had a higher nodal degree in the supramarginal gyrus, calcarine sulcus, and superior occipital cortex compared to ADHD-C and in the amygdala compared to controls. By contrast, the nodal degree was higher in the cerebellum for ADHD-C compared to ADHD-I and in the anterior cingulate, middle frontal gyrus and putamen compared to controls. ADHD-C also had reduced nodal degree in the rolandic operculum and middle temporal pole compared to controls. These regional profiles were observed in the context of no differences in gray matter volume or global network organization. Our results suggest that the clinical distinction between the Inattentive and Combined subtypes of ADHD may also be reflected in distinct aberrations in underlying brain organization.

Conventional MRI studies showed that radiation-induced brain necrosis in patients with nasopharyngeal carcinoma (NPC) in years after radiotherapy (RT) could involve brain gray matter (GM) and impair brain function. However, it is still unclear the radiation-induced brain morphological changes in NPC patients with normal-appearing GM in the early period after RT. In this study, we acquired high-resolution brain structural MRI data from three groups of patients, 22 before radiotherapy (pre-RT) NPC patients with newly diagnosed but not yet medically treated, 22 NPC patients in the early-delayed stage after radiotherapy (post-RT-ED), and 20 NPC patients in the late-delayed stage after radiotherapy (post-RT-LD), and then analyzed the radiation-induced cortical thickness alteration in NPC patients after RT. Using a vertex-wise surface-based morphometry (SBM) approach, we detected significantly decreased cortical thickness in the precentral gyrus (PreCG) in the post-RT-ED group compared to the pre-RT group. And the post-RT-LD group showed significantly increased cortical thickness in widespread brain regions, including the bilateral inferior parietal, left isthmus of the cingulate, left bank of the superior temporal sulcus and left lateral occipital regions, compared to the pre-RT group, and in the bilateral PreCG compared to the post-RT-ED group. Similar analysis with ROI-wise SBM method also found the consistent results. These results indicated that radiation-induced brain injury mainly occurred in the post-RT-LD group and the cortical thickness alterations after RT were dynamic in different periods. Our findings may reflect the pathogenesis of radiation-induced brain injury in NPC patients with normal-appearing GM and an early intervention is necessary for protecting GM during RT.