Individuals who see the good in the bad engage distinctive default network coordination during post-encoding rest.

Focusing on the upside of negative events often promotes resilience. Yet, the underlying mechanisms that allow some people to spontaneously see the good in the bad remain unclear. The broaden-and-build theory of positive emotion has long suggested that positive affect, including positivity in the face of negative events, is linked to idiosyncratic thought patterns (i.e., atypical cognitive responses). Yet, evidence in support of this view has been limited, in part, due to difficulty in measuring idiosyncratic cognitive processes as they unfold. To overcome this barrier, we applied Inter-Subject Representational Similarity Analysis to test whether and how idiosyncratic neural responding supports positive reactions to negative experience. We found that idiosyncratic functional connectivity patterns in the brain's default network while resting after a negative experience predicts more positive descriptions of the event. This effect persisted when controlling for connectivity 1) before and during the negative experience, 2) before, during, and after a neutral experience, and 3) between other relevant brain regions (i.e., the limbic system). The relationship between idiosyncratic default network responding and positive affect was largely driven by functional connectivity patterns between the ventromedial prefrontal cortex and the rest of the default network and occurred relatively quickly during rest. We identified post-encoding rest as a key moment and the default network as a key brain system in which idiosyncratic responses correspond with seeing the good in the bad.

In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth.

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.

Noninvasive modulation of human corticostriatal activity.

Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.

Hemodynamic transient and functional connectivity follow structural connectivity and cell type over the brain hierarchy.

The neural circuit of the brain is organized as a hierarchy of functional units with wide-ranging connections that support information flow and functional connectivity. Studies using MRI indicate a moderate coupling between structural and functional connectivity at the system level. However, how do connections of different directions (feedforward and feedback) and regions with different excitatory and inhibitory (E/I) neurons shape the hemodynamic activity and functional connectivity over the hierarchy are unknown. Here, we used functional MRI to detect optogenetic-evoked and resting-state activities over a somatosensory pathway in the mouse brain in relation to axonal projection and E/I distribution. Using a highly sensitive ultrafast imaging, we identified extensive activation in regions up to the third order of axonal projections following optogenetic excitation of the ventral posteriomedial nucleus of the thalamus. The evoked response and functional connectivity correlated with feedforward projections more than feedback projections and weakened with the hierarchy. The hemodynamic response exhibited regional and hierarchical differences, with slower and more variable responses in high-order areas and bipolar response predominantly in the contralateral cortex. Electrophysiological recordings suggest that these reflect differences in neural activity rather than neurovascular coupling. Importantly, the positive and negative parts of the hemodynamic response correlated with E/I neuronal densities, respectively. Furthermore, resting-state functional connectivity was more associated with E/I distribution, whereas stimulus-evoked effective connectivity followed structural wiring. These findings indicate that the structure-function relationship is projection-, cell-type- and hierarchy-dependent. Hemodynamic transients could reflect E/I activity and the increased complexity of hierarchical processing.

Co-representation of Functional Brain Networks Is Shaped by Cortical Myeloarchitecture and Reveals Individual Behavioral Ability.

Large-scale functional networks are spatially distributed in the human brain. Despite recent progress in differentiating their functional roles, how the brain navigates the spatial coordination among them and the biological relevance of this coordination is still not fully understood. Capitalizing on canonical individualized networks derived from functional MRI data, we proposed a new concept, that is, co-representation of functional brain networks, to delineate the spatial coordination among them. To further quantify the co-representation pattern, we defined two indexes, that is, the co-representation specificity (CoRS) and intensity (CoRI), for separately measuring the extent of specific and average expression of functional networks at each brain location by using the data from both sexes. We found that the identified pattern of co-representation was anchored by cortical regions with three types of cytoarchitectural classes along a sensory-fugal axis, including, at the first end, primary (idiotypic) regions showing high CoRS, at the second end, heteromodal regions showing low CoRS and high CoRI, at the third end, paralimbic regions showing low CoRI. Importantly, we demonstrated the critical role of myeloarchitecture in sculpting the spatial distribution of co-representation by assessing the association with the myelin-related neuroanatomical and transcriptomic profiles. Furthermore, the significance of manifesting the co-representation was revealed in its prediction of individual behavioral ability. Our findings indicated that the spatial coordination among functional networks was built upon an anatomically configured blueprint to facilitate neural information processing, while advancing our understanding of the topographical organization of the brain by emphasizing the assembly of functional networks.

Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

Human Sensorimotor Beta Event Characteristics and Aperiodic Signal Are Highly Heritable.

Individuals' phenotypes, including the brain's structure and function, are largely determined by genes and their interplay. The resting brain generates salient rhythmic patterns that can be characterized noninvasively using functional neuroimaging such as magnetoencephalography (MEG). One of these rhythms, the somatomotor (rolandic) beta rhythm, shows intermittent high amplitude "events" that predict behavior across tasks and species. Beta rhythm is altered in neurological disease. The aperiodic (1/f) signal present in electrophysiological recordings is also modulated by some neurological conditions and aging. Both sensorimotor beta and aperiodic signal could thus serve as biomarkers of sensorimotor function. Knowledge about the extent to which these brain functional measures are heritable could shed light on the mechanisms underlying their generation. We investigated the heritability and variability of human spontaneous sensorimotor beta rhythm events and aperiodic activity in 210 healthy male and female adult siblings' spontaneous MEG activity. The most heritable trait was the aperiodic 1/f signal, with a heritability of 0.87 in the right hemisphere. Time-resolved beta event amplitude parameters were also highly heritable, whereas the heritabilities for overall beta power, peak frequency, and measures of event duration remained nonsignificant. Human sensorimotor neural activity can thus be dissected into different components with variable heritability. We postulate that these differences partially reflect different underlying signal-generating mechanisms. The 1/f signal and beta event amplitude measures may depend more on fixed, anatomical parameters, whereas beta event duration and its modulation reflect dynamic characteristics, guiding their use as potential disease biomarkers.

Encoding Manual Dexterity through Modulation of Intrinsic α Band Connectivity.

The human hand possesses both consolidated motor skills and remarkable flexibility in adapting to ongoing task demands. However, the underlying mechanisms by which the brain balances stability and flexibility remain unknown. In the absence of external input or behavior, spontaneous (intrinsic) brain connectivity is thought to represent a prior of stored memories. In this study, we investigated how manual dexterity modulates spontaneous functional connectivity in the motor cortex during hand movement. Using magnetoencephalography, in 47 human participants (both sexes), we examined connectivity modulations in the α and ß frequency bands at rest and during two motor tasks (i.e., finger tapping or toe squeezing). The flexibility and stability of such modulations allowed us to identify two groups of participants with different levels of performance (high and low performers) on the nine-hole peg test, a test of manual dexterity. In the α band, participants with higher manual dexterity showed distributed decreases of connectivity, specifically in the motor cortex, increased segregation, and reduced nodal centrality. Participants with lower manual dexterity showed an opposite pattern. Notably, these patterns from the brain to behavior are mirrored by results from behavior to the brain. Indeed, when participants were divided using the median split of the dexterity score, we found the same connectivity patterns. In summary, this experiment shows that a long-term motor skill-manual dexterity-influences the way the motor systems respond during movements.

The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity.

Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia. Using multiple behavioural tests, we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172 and accelerated in mGluR5 knock-out mice compared with wild-type mice. After stroke, multisensory stimulation by enriched environments enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in enriched environment-mediated recovery. Additionally, MTEP treatment in conjunction with enriched environment housing provided an additive recovery enhancement compared to either MTEP or enriched environment alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke. We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy.

Abnormal higher-order network interactions in Parkinson's disease visual hallucinations.

Visual hallucinations in Parkinson's disease can be viewed from a systems-level perspective, whereby dysfunctional communication between brain networks responsible for perception predisposes a person to hallucinate. To this end, abnormal functional interactions between higher-order and primary sensory networks have been implicated in the pathophysiology of visual hallucinations in Parkinson's disease, however the precise signatures remain to be determined. Dimensionality reduction techniques offer a novel means for simplifying the interpretation of multidimensional brain imaging data, identifying hierarchical patterns in the data that are driven by both within- and between-functional network changes. Here, we applied two complementary non-linear dimensionality reduction techniques-diffusion-map embedding and t-distributed stochastic neighbour embedding (t-SNE)-to resting state functional MRI data, in order to characterize the altered functional hierarchy associated with susceptibility to visual hallucinations. Our study involved 77 people with Parkinson's disease (31 with hallucinations; 46 without hallucinations) and 19 age-matched healthy control subjects. In patients with visual hallucinations, we found compression of the unimodal-heteromodal gradient consistent with increased functional integration between sensory and higher order networks. This was mirrored in a traditional functional connectivity analysis, which showed increased connectivity between the visual and default mode networks in the hallucinating group. Together, these results suggest a route by which higher-order regions may have excessive influence over earlier sensory processes, as proposed by theoretical models of hallucinations across disorders. By contrast, the t-SNE analysis identified distinct alterations in prefrontal regions, suggesting an additional layer of complexity in the functional brain network abnormalities implicated in hallucinations, which was not apparent in traditional functional connectivity analyses. Together, the results confirm abnormal brain organization associated with the hallucinating phenotype in Parkinson's disease and highlight the utility of applying convergent dimensionality reduction techniques to investigate complex clinical symptoms. In addition, the patterns we describe in Parkinson's disease converge with those seen in other conditions, suggesting that reduced hierarchical differentiation across sensory-perceptual systems may be a common transdiagnostic vulnerability in neuropsychiatric disorders with perceptual disturbances.

Quantification of mediation effects of white matter functional characteristics on cognitive decline in aging.

Cognitive decline with aging involves multifactorial processes, including changes in brain structure and function. This study focuses on the role of white matter functional characteristics, as reflected in blood oxygenation level-dependent signals, in age-related cognitive deterioration. Building on previous research confirming the reproducibility and age-dependence of blood oxygenation level-dependent signals acquired via functional magnetic resonance imaging, we here employ mediation analysis to test if aging affects cognition through white matter blood oxygenation level-dependent signal changes, impacting various cognitive domains and specific white matter regions. We used independent component analysis of resting-state blood oxygenation level-dependent signals to segment white matter into coherent hubs, offering a data-driven view of white matter's functional architecture. Through correlation analysis, we constructed a graph network and derived metrics to quantitatively assess regional functional properties based on resting-state blood oxygenation level-dependent fluctuations. Our analysis identified significant mediators in the age-cognition relationship, indicating that aging differentially influences cognitive functions by altering the functional characteristics of distinct white matter regions. These findings enhance our understanding of the neurobiological basis of cognitive aging, highlighting the critical role of white matter in maintaining cognitive integrity and proposing new approaches to assess interventions targeting cognitive decline in older populations.

Multi-scale spiking network model of human cerebral cortex.

Although the structure of cortical networks provides the necessary substrate for their neuronal activity, the structure alone does not suffice to understand the activity. Leveraging the increasing availability of human data, we developed a multi-scale, spiking network model of human cortex to investigate the relationship between structure and dynamics. In this model, each area in one hemisphere of the Desikan-Killiany parcellation is represented by a $1\,\mathrm{mm^{2}}$ column with a layered structure. The model aggregates data across multiple modalities, including electron microscopy, electrophysiology, morphological reconstructions, and diffusion tensor imaging, into a coherent framework. It predicts activity on all scales from the single-neuron spiking activity to the area-level functional connectivity. We compared the model activity with human electrophysiological data and human resting-state functional magnetic resonance imaging (fMRI) data. This comparison reveals that the model can reproduce aspects of both spiking statistics and fMRI correlations if the inter-areal connections are sufficiently strong. Furthermore, we study the propagation of a single-spike perturbation and macroscopic fluctuations through the network. The open-source model serves as an integrative platform for further refinements and future in silico studies of human cortical structure, dynamics, and function.

Modular brain network in volitional eyes closing: enhanced integration with a marked impact on hubs.

Volitional eyes closing would shift brain's information processing modes from the "exteroceptive" to "interoceptive" state. This transition induced by the eyes closing is underpinned by a large-scale reconfiguration of brain network, which is still not fully comprehended. Here, we investigated the eyes-closing-relevant network reconfiguration by examining the functional integration among intrinsic modules. Our investigation utilized a publicly available dataset with 48 subjects being scanned in both eyes closed and eyes open conditions. It was found that the modular integration was significantly enhanced during the eyes closing, including lower modularity index, higher participation coefficient, less provincial hubs, and more connector hubs. Moreover, the eyes-closing-enhanced integration was particularly noticeable in the hubs of network, mainly located in the default-mode network. Finally, the hub-dominant modular enhancement was positively correlated to the eyes-closing-reduced entropy of BOLD signal, suggesting a close connection to the diminished consciousness of individuals. Collectively, our findings strongly suggested that the enhanced modular integration with substantially reorganized hubs characterized the large-scale cortical underpinning of the volitional eyes closing.

Prediction of individual brain age using movie and resting-state fMRI.

Brain age is a promising biomarker for predicting chronological age based on brain imaging data. Although movie and resting-state functional MRI techniques have attracted much research interest for the investigation of brain function, whether the 2 different imaging paradigms show similarities and differences in terms of their capabilities and properties for predicting brain age remains largely unexplored. Here, we used movie and resting-state functional MRI data from 528 participants aged from 18 to 87 years old in the Cambridge Centre for Ageing and Neuroscience data set for functional network construction and further used elastic net for age prediction model building. The connectivity properties of movie and resting-state functional MRI were evaluated based on the connections supporting predictive model building. We found comparable predictive abilities of movie and resting-state connectivity in estimating brain age of individuals, as evidenced by correlation coefficients of 0.868 and 0.862 between actual and predicted age, respectively. Despite some similarities, notable differences in connectivity properties were observed between the predictive models using movie and resting-state functional MRI data, primarily involving components of the default mode network. Our results highlight that both movie and resting-state functional MRI are effective and promising techniques for predicting brain age. Leveraging its data acquisition advantages, such as improved child and patient compliance resulting in reduced motion artifacts, movie functional MRI is emerging as an important paradigm for studying brain function in pediatric and clinical populations.

Multilayer analysis of dynamic network reconfiguration in pediatric posttraumatic stress disorder.

Neuroimage studies have reported functional connectome abnormalities in posttraumatic stress disorder (PTSD), especially in adults. However, these studies often treated the brain as a static network, and time-variance of connectome topology in pediatric posttraumatic stress disorder remain unclear. To explore case-control differences in dynamic connectome topology, resting-state functional magnetic resonance imaging data were acquired from 24 treatment-naïve non-comorbid pediatric posttraumatic stress disorder patients and 24 demographically matched trauma-exposed non-posttraumatic stress disorder controls. A graph-theoretic analysis was applied to construct time-varying modular structure of whole-brain networks by maximizing the multilayer modularity. Network switching rate at the global, subnetwork, and nodal levels were calculated and compared between posttraumatic stress disorder and trauma-exposed non-posttraumatic stress disorder groups, and their associations with posttraumatic stress disorder symptom severity and sex interactions were explored. At the global level, individuals with posttraumatic stress disorder exhibited significantly lower network switching rates compared to trauma-exposed non-posttraumatic stress disorder controls. This difference was mainly involved in default-mode and dorsal attention subnetworks, as well as in inferior temporal and parietal brain nodes. Posttraumatic stress disorder symptom severity was negatively correlated with switching rate in the global network and default mode network. No significant differences were observed in the interaction between diagnosis and sex/age. Pediatric posttraumatic stress disorder is associated with dynamic reconfiguration of brain networks, which may provide insights into the biological basis of this disorder.

Functional brain networks in Developmental Topographical Disorientation.

Despite a decade-long study on Developmental Topographical Disorientation, the underlying mechanism behind this neurological condition remains unknown. This lifelong selective inability in orientation, which causes these individuals to get lost even in familiar surroundings, is present in the absence of any other neurological disorder or acquired brain damage. Herein, we report an analysis of the functional brain network of individuals with Developmental Topographical Disorientation ($n = 19$) compared against that of healthy controls ($n = 21$), all of whom underwent resting-state functional magnetic resonance imaging, to identify if and how their underlying functional brain network is altered. While the established resting-state networks (RSNs) are confirmed in both groups, there is, on average, a greater connectivity and connectivity strength, in addition to increased global and local efficiency in the overall functional network of the Developmental Topographical Disorientation group. In particular, there is an enhanced connectivity between some RSNs facilitated through indirect functional paths. We identify a handful of nodes that encode part of these differences. Overall, our findings provide strong evidence that the brain networks of individuals suffering from Developmental Topographical Disorientation are modified by compensatory mechanisms, which might open the door for new diagnostic tools.

The significance and limited influence of cerebrovascular reactivity on age and sex effects in task- and resting-state brain activity.

Functional MRI measures the blood-oxygen-level dependent signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state blood-oxygen-level dependent activity and may confound inter-individual effects, such as those related to aging and biological sex. We examined a large dataset containing breath-holding, checkerboard, and resting-state tasks. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and quantified resting-state activity with amplitude of low-frequency fluctuations and regional homogeneity. We hypothesized that cerebrovascular reactivity would be correlated with blood-oxygen-level dependent measures and that accounting for these correlations would result in better estimates of age and sex effects. We found that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with amplitude of low-frequency fluctuations and regional homogeneity in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in amplitude of low-frequency fluctuations and regional homogeneity. However, correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

Shared and differing functional connectivity abnormalities of the default mode network in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia.

Cortical and subcortical substrates of minutes and days-long object value memory in humans.

Obtaining valuable objects motivates many of our daily decisions. However, the neural underpinnings of object processing based on human value memory are not yet fully understood. Here, we used whole-brain functional magnetic resonance imaging (fMRI) to examine activations due to value memory as participants passively viewed objects before, minutes after, and 1-70 days following value training. Significant value memory for objects was evident in the behavioral performance, which nevertheless faded over the days following training. Minutes after training, the occipital, ventral temporal, interparietal, and frontal areas showed strong value discrimination. Days after training, activation in the frontal, temporal, and occipital regions decreased, whereas the parietal areas showed sustained activation. In addition, days-long value responses emerged in certain subcortical regions, including the caudate, ventral striatum, and thalamus. Resting-state analysis revealed that these subcortical areas were functionally connected. Furthermore, the activation in the striatal cluster was positively correlated with participants' performance in days-long value memory. These findings shed light on the neural basis of value memory in humans with implications for object habit formation and cross-species comparisons.