The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here, we use multisite GCaMP (a genetically encoded calcium indicator) fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes-the retrosplenial cortex, cingulate cortex, and prelimbic cortex-as well as the anterior insula node of the salience network, and their association with the rats\' spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and found that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a \"task-negative\" network disengaged from the external world. By illuminating the DMN\'s role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts.

The complexity of the classical inverted U-shaped relationship between cortisol levels and responses transposable to stress reactivity has led to an incomplete understanding of the mechanisms enabling healthy and toxic effects of stress on brain and behavior. A clearer, more detailed, picture of those relationships can be obtained by integrating cortisol effects on large-scale brain networks, in particular, by focusing on neural network configurations from the perspective of inhibition and excitation. A unifying view of Semon and Hebb\'s theories of cellular memory links the biophysical and metabolic changes in neuronal ensembles to the strengthening of collective synapses. In that sense, the neuronal capacity to record, store, and retrieve information directly relates to the adaptive capacity of its connectivity and metabolic reserves. Here, we use task-activated cell ensembles or simply engram cells as an example to demonstrate that the adaptive behavioral responses to stress result from collective synapse strength within and across networks of interneurons and excitatory ones.

Over the past years, different studies provided preliminary evidence that Disorganized Attachment (DA) may have dysregulatory and disintegrative effects on both autonomic arousal regulation and brain connectivity. However, despite the clinical relevance of this construct, few studies have investigated the specific alterations underlying DA using electroencephalography (EEG). Thus, the main aim of the current study was to investigate EEG microstate parameters of DA in a non-clinical sample (N = 50) before (pre) and after (post) the administration of the Adult Attachment Interview (AAI). Two EEG eyes-closed Resting State (RS) recordings were performed before and after the AAI, which was used for classifying the participants [i.e., Disorganized/Unresolved (D/U) or Organized/Resolved (O/R) individuals] and to trigger the attachment system. Microstates parameters (i.e., Mean Duration, Time Coverage and Occurrence) were extracted from each recording using Cartool software. EEG microstates clustering analysis revealed 6 different maps (labeled A, B, C, D, E, F) in both groups (i.e., D/U and O/R individuals) and in both conditions (i.e., pre-AAI and post-AAI). In the pre-AAI condition, compared to O/R individuals, D/U participants showed a shorter Mean Duration and Time Coverage of Map F; in the post-AAI condition, a significant reduction in the Mean Duration of Map E was also observed in D/U individuals. Finally, in the \"within\" statistical analysis (i.e., pre-AAI vs. post-AAI), only the D/U group exhibited a significant increase in Time Coverage of Map F after the AAI. Since these maps are associated with brain networks involved in emotional information processing and mentalization (i.e., Salience Network and Default Mode Network), our result might reflect the deficit in the ability to mentalize caregiver\'s interaction as well as the increased sensitivity to attachment-related stimuli typically observed in individuals with a D/U state of mind.

Type 2 diabetes (T2D) is associated with dyslipidemia and mild cognitive impairment. This study investigated the relationships between serum lipids metabolism, cognition, and functional connectivity (FC) within and between brain networks in T2D patients. The study included 102 T2D patients and 45 healthy controls who underwent functional magnetic resonance imaging, lipid profile tests, and cognitive assessments. Thirteen functional networks were identified using independent component analysis. The statistical analyses included multivariate analysis of covariance, partial correlation, canonical correlation, and mediation analyses. We found widely reduced between-network FCs in T2D, especially between the ventral sensorimotor network (SMN) and dorsal attention network (DAN) (p = 0.001) and between the ventral SMN and lateral visual network (VN) (p < 0.001). Moreover, lower between-network FCs were correlated with worse serum lipids metabolism and poorer cognitive performance (all p < 0.05). Importantly, between-network FCs mediated the relationship between lipid metabolism and cognition (β = -0.3136, 95% CI: -0.7660, -0.0186). Within-network analyses revealed altered FCs within the anterior default mode network, DAN, and lateral VN, each positively correlated with global cognition (all p < 0.01). Our results suggest the potential of improving cognitive function by regulating serum lipids in individuals with T2D.

While there is a wealth of knowledge about core object recognition-our ability to recognize clear, high-contrast object images-how the brain accomplishes object recognition tasks under increased uncertainty remains poorly understood. We investigated the spatiotemporal neural dynamics underlying object recognition under increased uncertainty by combining MEG and 7 Tesla (7T) fMRI in humans during a threshold-level object recognition task. We observed an early, parallel rise of recognition-related signals across ventral visual and frontoparietal regions that preceded the emergence of category-related information. Recognition-related signals in ventral visual regions were best explained by a two-state representational format whereby brain activity bifurcated for recognized and unrecognized images. By contrast, recognition-related signals in frontoparietal regions exhibited a reduced representational space for recognized images, yet with sharper category information. These results provide a spatiotemporally resolved view of neural activity supporting object recognition under uncertainty, revealing a pattern distinct from that underlying core object recognition.

Huntington\'s disease is an autosomal, dominantly inherited neurodegenerative disease caused by an expansion of the CAG repeats in exon 1 of the huntingtin gene. Neuronal degeneration and dysfunction that precedes regional atrophy result in the impairment of striatal and cortical circuits that affect the brain\'s large-scale network functionality. However, the evolution of these disease-driven, large-scale connectivity alterations is still poorly understood. Here we used resting-state fMRI to investigate functional connectivity changes in a mouse model of Huntington\'s disease in several relevant brain networks and how they are affected at different ages that follow a disease-like phenotypic progression. Towards this, we used the heterozygous (HET) form of the zQ175DN Huntington\'s disease mouse model that recapitulates aspects of human disease pathology. Seed- and Region-based analyses were performed at different ages, on 3-, 6-, 10-, and 12-month-old HET and age-matched wild-type mice. Our results demonstrate decreased connectivity starting at 6 months of age, most prominently in regions such as the retrosplenial and cingulate cortices, pertaining to the default mode-like network and auditory and visual cortices, part of the associative cortical network. At 12 months, we observe a shift towards decreased connectivity in regions such as the somatosensory cortices, pertaining to the lateral cortical network, and the caudate putamen, a constituent of the subcortical network. Moreover, we assessed the impact of distinct Huntington\'s Disease-like pathology of the zQ175DN HET mice on age-dependent connectivity between different brain regions and networks where we demonstrate that connectivity strength follows a non-linear, inverted U-shape pattern, a well-known phenomenon of development and normal aging. Conversely, the neuropathologically driven alteration of connectivity, especially in the default mode and associative cortical networks, showed diminished age-dependent evolution of functional connectivity. These findings reveal that in this Huntington\'s disease model, altered connectivity starts with cortical network aberrations which precede striatal connectivity changes, that appear only at a later age. Taken together, these results suggest that the age-dependent cortical network dysfunction seen in rodents could represent a relevant pathological process in Huntington\'s disease progression.

An emerging body of evidence indicates that short-term immersion in cold water facilitates positive affect and reduces negative affect. However, the neural mechanisms underlying these effects remain largely unknown. For the first time, we employed functional magnetic resonance imaging (fMRI) to identify topological clusters of networks coupled with behavioural changes in positive and negative affect after a 5 min cold-water immersion. Perceived changes in positive affect were associated with feeling more active, alert, attentive, proud, and inspired, whilst changes in negative affect reflected reductions in distress and nervousness. The increase in positive affect was supported by a unique component of interacting networks, including the medial prefrontal node of the default mode network, a posterior parietal node of the frontoparietal network, and anterior cingulate and rostral prefrontal parts of the salience network and visual lateral network. This component emerged as a result of a focal effect confined to few connections. Changes in negative affect were associated with a distributed component of interacting networks at a reduced threshold. Affective changes after cold-water immersion occurred independently, supporting the bivalence model of affective processing. Interactions between large-scale networks linked to positive affect indicated the integrative effects of cold-water immersion on brain functioning.

UNASSIGNED: Various approaches have been used to explore different aspects of the regulation of brain activity by acute exercise, but few studies have been conducted on the effects of acute exercise fatigue on large-scale brain functional networks. Therefore, the present study aimed to explore the effects of acute exercise fatigue on resting-state electroencephalogram (EEG) microstates and large-scale brain network rhythm energy.
UNASSIGNED: The Bruce protocol was used as the experimental exercise model with a self-controlled experimental design. Thirty males performed incremental load exercise tests on treadmill until exhaustion. EEG signal acquisition was completed before and after exercise. EEG microstates and resting-state cortical rhythm techniques were used to analyze the EEG signal.
UNASSIGNED: The microstate results showed that the duration, occurrence, and contribution of Microstate C were significantly higher after exhaustive exercise (p\'s < 0.01). There was a significantly lower contribution of Microstate D (p < 0.05), a significant increase in transition probabilities between Microstate A and C (p < 0.05), and a significant decrease in transition probabilities between Microstate B and D (p < 0.05). The results of EEG rhythm energy on the large-scale brain network showed that the energy in the high-frequency β band was significantly higher in the visual network (p < 0.05).
UNASSIGNED: Our results suggest that frequently Microstate C associated with the convexity network are important for the organism to respond to internal and external information stimuli and thus regulate motor behavior in time to protect organism integrity. The decreases in Microstate D parameters, associated with the attentional network, are an important neural mechanism explaining the decrease in attention-related cognitive or behavioral performance due to acute exercise fatigue. The high energy in the high-frequency β band on the visual network can be explained in the sense of the neural efficiency hypothesis, which indicates a decrease in neural efficiency.

Objective.It has been demonstrated that schizophrenia (SZ) is characterized by functional dysconnectivity involving extensive brain networks. However, the majority of previous studies utilizing resting-state functional magnetic resonance imaging (fMRI) to infer abnormal functional connectivity (FC) in patients with SZ have focused on the linear correlation that one brain region may influence another, ignoring the inherently nonlinear properties of fMRI signals.Approach. In this paper, we present a neural Granger causality (NGC) technique for examining the changes in SZ\'s nonlinear causal couplings. We develop static and dynamic NGC-based analyses of large-scale brain networks at several network levels, estimating complicated temporal and causal relationships in SZ patients.Main results. We find that the NGC-based FC matrices can detect large and significant differences between the SZ and healthy control groups at both the regional and subnetwork scales. These differences are persistent and significantly overlapped at various network sparsities regardless of whether the brain networks were built using static or dynamic techniques. In addition, compared to controls, patients with SZ exhibited extensive NGC confusion patterns throughout the entire brain.Significance. These findings imply that the NGC-based FCs may be a useful method for quantifying the abnormalities in the causal influences of patients with SZ, hence shedding fresh light on the pathophysiology of this disorder.

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson\'s disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connectivity reconfiguration starting from the preclinical phase is still lacking. We aimed to investigate shared and disease-specific changes in the large-scale networks across the Lewy Bodies (LB) disorders spectrum using a brain metabolic connectivity approach. We included 30 patients with isolated REM sleep behavior disorder (iRBD), 28 with stable PD, 30 with DLB, and 30 healthy controls for comparison. We applied seed-based interregional correlation analyses (IRCA) to evaluate the metabolic connectivity in the large-scale resting-state networks, as assessed by [18F]FDG-PET, in each clinical group compared to controls. We assessed metabolic connectivity changes by applying the IRCA and specific connectivity metrics, such as the weighted and unweighted Dice similarity coefficients (DC), for the topographical similarities. All the investigated large-scale brain resting-state networks showed metabolic connectivity alterations, supporting the widespread involvement of brain connectivity within the alpha-synuclein spectrum. Connectivity alterations were already evident in iRBD, severely affecting the posterior default mode, attentive and limbic networks. Strong similarities emerged in iRBD and DLB that showed comparable connectivity alterations in most large-scale networks, particularly in the posterior default mode and attentive networks. Contrarily, PD showed the main connectivity alterations limited to motor and somatosensory networks. The present findings reveal that metabolic connectivity alterations in the large-scale networks are already present in the early iRBD phase, resembling the DLB metabolic connectivity changes. This suggests and confirms iRBD as a risk condition for progression to the severe LB disease phenotype. Of note, the neurobiology of stable PD supports its more benign phenotype.