The Artificial Brain: A Neuroscience Inspired Architecture for Multimodal AI Systems

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

According to the conflict monitoring hypothesis, conflict monitoring and inhibitory control in cognitive control mainly cause activity in the anterior cingulate cortex (ACC) and control-related prefrontal cortex (PFC) in many cognitive tasks. However, the role of brain regions in the default mode network (DMN) in cognitive control during category induction tasks is unclear. To test the role of the ACC, PFC, and subregions of the DMN elicited by cognitive control during category induction, a modified category induction task was performed using simultaneous fMRI scanning. The results showed that the left middle frontal gyrus (BA9) and bilateral dorsal ACC/medial frontal gyrus (BA8/32) were sensitive to whether conflict information (with/without) appears, but not to the level of conflict. In addition, the bilateral ventral ACC (BA32), especially the right vACC, a part of the DMN, showed significant deactivation with an increase in cognitive effort depending on working memory. These findings not only offer further evidence for the important role of the dorsolateral PFC and dorsal ACC in cognitive control during categorization but also support the functional distinction of the dorsal/ventral ACC in the category induction task.

BackgroundMild behavioral impairment (MBI) is a syndrome that uses later‐life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting‐state functional magnetic resonance imaging (rs‐fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI–).MethodsFrom two harmonized dementia‐free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI– individuals were identified (mean age: 71.7 years; 54.7% female). Seed‐based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p‐value of .05 considered significant.ResultsFor the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI–. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula.ConclusionMBI in dementia‐free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers.HighlightsResting‐state functional magnetic resonance imaging was completed in 95 dementia‐free persons from FAVR and COMPASS‐ND studies.Participants were stratified by informant‐rated Mild Behavioral Impairment Checklist (MBI‐C) score, ≥6 for MBI+.MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network.These FC changes are consistent with those seen in early‐stage Alzheimer's disease.MBI may help identify persons with early‐stage neurodegenerative disease.

Major depressive disorder (MDD) is a prevalent mental disorder characterized by impairments in affect, behaviour and cognition. Previous studies have indicated that the anterior cingulate cortex (ACC) may play an essential role in the pathophysiology of depression. In this study, we systematically identified changes in functional connectivity (FC) for ACC subdivisions that manifest in MDD and further investigated the relationship between these changes and the clinical symptoms of depression. Sub-regional ACC FC was estimated in 41 first-episode medication-naïve MDD patients compared to 43 healthy controls. The relationships between depressive symptom severity and aberrant FC of ACC subdivisions were investigated. In addition, we conducted a meta-analysis to generate the distributions of MDD-related abnormal regions from previously reported results and compared them to FC deficits revealed in this study. In MDD patients, the subgenual and perigenual ACC demonstrated decreased FC with the posterior regions of the default network (DN), including the posterior inferior parietal lobule and posterior cingulate cortex. FC of these regions was negatively associated with the Automatic Thoughts Questionnaire scores and largely overlapped with previously reported abnormal regions. In addition, reduced FC between the caudal ACC and precuneus was negatively correlated with the Hamilton Anxiety Scale scores. We also found increased FC between the rostral ACC and dorsal medial prefrontal cortex. Our findings confirmed that functional interaction changes in different ACC sub-regions are specific and associated with distinct symptoms of depression. Our findings provide new insights into the role of ACC sub-regions and DN in the pathophysiology of MDD.

Intra- and Inter-Network connectivity of the default mode network differentiates Treatment-Resistant depression from Treatment-Sensitive depression

Environmental hyperthermia is a common risk factor for occupational safety in many situations due to decreased vigilance performances. Previously, we have reported that decreased resting-state functional connectivity within the default mode network (DMN) and decreased activations in dorsal attention network (DAN) such as dorsolateral prefrontal cortex (DLPFC) were correlated with selective attention deficits during hyperthermia. However, whether the inherent functionally organized anti-correlation between the DMN and DAN would contribute to the behavioral deficits remains unclear. In this study, we collected the resting-state fMRI data of 25 participants during two simulated thermal conditions: normothermic condition (25°C for 1 h) and hyperthermic condition (50°C for 1 h). Using group independent component analysis (ICA), we investigated the functional connectivity within the DMN and DAN, as well as the anti-correlations between both networks. Paired comparisons revealed that decreased intranetwork functional connectivity in the medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) in the DMN contributed to executive control performance during hyperthermia using multivariate linear regression analysis. Paired comparison on the DAN showed that increased one in the posterior part of the middle and inferior temporal gyrus nearby the temporal–parietal junction area contributed to preserved alerting performance. Lastly but most importantly, we found that decreased correlation between mPFC in the DMN and intraparietal sulcus (IPS) area in the DAN contributed to the executive control deficit, suggesting a weaker intrinsic anti-correlation between DMN and DAN during hyperthermia. These findings indicated that a functional reorganized architecture of DMN and DAN might provide a potential neural basis of the selective deficits for different cognitive-demand attention tasks in high-temperature environments.

Bipolar disorder (BD) is a common psychiatric disorder, but its pathophysiology is not fully elucidated. The current study focused on its electrophysiological characteristics, especially power spectral density (PSD). Resting state with eyes opened magnetoencephalography data were collected from 21 patients with BD and 22 healthy controls. The whole brain's PSD was calculated from source reconstructed waveforms at each frequency band (delta: 1-3 Hz, theta: 4-7 Hz, alpha: 8-12 Hz, low beta: 13-19 Hz, high beta: 20-29 Hz, and gamma: 30-80 Hz). We compared PSD values on the marked vertices at each frequency band between healthy and patient groups using a Mann-Whitney rank test to examine the relationship between significantly different PSD and clinical measures. The PSD in patients with BD was significantly decreased in lower frequency bands, mainly in the default mode network (DMN) areas (bilateral medial prefrontal cortex, bilateral precuneus, left inferior parietal lobe, and right temporal cortex in the alpha band) and salience network areas (SAL; left anterior insula [AI] at the delta band, anterior cingulate cortex at the theta band, and right AI at the alpha band). No significant differences in PSD were observed at low beta and high beta. PSD was not correlated with age or other clinical scales. Altered PSDs of the DMN and SAL were observed in the delta, theta, and alpha bands. These alterations contribute to the vulnerability of BD through the disturbance of self-referential mental activity and switching between the default mode and frontoparietal networks.

Disrupted functional connectivity of default mode and salience networks in chronic pancreatitis patients

The cortical midline structures seem to be involved in the modulation of different resting state networks, such as the default mode network (DMN) and salience network (SN). Alterations in these systems, in particular in the perigenual anterior cingulate cortex (PACC), seem to play a central role in bipolar disorder (BD). However, the exact role of the PACC, and its functional connections to other midline regions (within and outside DMN) still remains unclear in BD. We investigated functional connectivity (FC), standard deviation (SD, as a measure of neuronal variability) and their correlation in bipolar patients (n = 40) versus healthy controls (n = 40), in the PACC and in its connections in different frequency bands (standard: 0.01-0.10 Hz; Slow-5: 0.01-0.027 Hz; Slow-4: 0.027-0.073 Hz). Finally, we studied the correlations between FC alterations and clinical-neuropsychological parameters and we explored whether subgroups of patients in different phases of the illness present different patterns of FC abnormalities. We found in BD decreased FC (especially in Slow-5) from the PACC to other regions located predominantly in the posterior DMN (such as the posterior cingulate cortex (PCC) and inferior temporal gyrus) and in the SN (such as the supragenual anterior cingulate cortex and ventrolateral prefrontal cortex). Second, we found in BD a decoupling between PACC-based FC and variability in the various target regions (without alteration in variability itself). Finally, in our subgroups explorative analysis, we found a decrease in FC between the PACC and supragenual ACC (in depressive phase) and between the PACC and PCC (in manic phase). These findings suggest that in BD the communication, that is, information transfer, between the different cortical midline regions within the cingulate gyrus does not seem to work properly. This may result in dysbalance between different resting state networks like the DMN and SN. A deficit in the anterior DMN-SN connectivity could lead to an abnormal shifting toward the DMN, while a deficit in the anterior DMN-posterior DMN connectivity could lead to an abnormal shifting toward the SN, resulting in excessive focusing on internal contents and reduced transition from idea to action or in excessive focusing on external contents and increased transition from idea to action, respectively, which could represent central dimensions of depression and mania. If confirmed, they could represent diagnostic markers in BD.

Episodic memory depends on interactions between the hippocampus and interconnected neocortical regions. Here, using data-driven analyses of resting-state functional magnetic resonance imaging (fMRI) data, we identified the networks that interact with the hippocampus-the default mode network (DMN) and a "medial temporal network" (MTN) that included regions in the medial temporal lobe (MTL) and precuneus. We observed that the MTN plays a critical role in connecting the visual network to the DMN and hippocampus. The DMN could be further divided into 3 subnetworks: a "posterior medial" (PM) subnetwork comprised of posterior cingulate and lateral parietal cortices; an "anterior temporal" (AT) subnetwork comprised of regions in the temporopolar and dorsomedial prefrontal cortex; and a "medial prefrontal" (MP) subnetwork comprised of regions primarily in the medial prefrontal cortex (mPFC). These networks vary in their functional connectivity (FC) along the hippocampal long axis and represent different kinds of information during memory-guided decision-making. Finally, a Neurosynth meta-analysis of fMRI studies suggests new hypotheses regarding the functions of the MTN and DMN subnetworks, providing a framework to guide future research on the neural architecture of episodic memory.

The default mode network (DMN) is often considered a functionally homogeneous system that is broadly associated with internally directed cognition (e.g. episodic memory, theory of mind, self-evaluation). However, few studies have examined how this network interacts with other networks during putative “default” processes such as episodic memory retrieval. Using fMRI, we investigated the topography and response profile of human parietal regions inside and outside the DMN, independently defined using task-evoked deactivations and resting state functional connectivity, during episodic memory retrieval. Memory retrieval activated posterior nodes of the DMN, particularly the angular gyrus, but also more anterior and dorsal parietal regions that were anatomically separate from the DMN. The two sets of parietal regions showed different resting-state functional connectivity and response profiles. During memory retrieval, responses in DMN regions peaked sooner than non-DMN regions, which in turn showed responses that were sustained until a final memory judgment was reached. Moreover, a parahippocampal region that showed strong resting-state connectivity with parietal DMN regions also exhibited a pattern of task-evoked activity similar to that exhibited by DMN regions. These results suggest that DMN parietal regions directly supported memory retrieval, whereas non-DMN parietal regions were more involved in post-retrieval processes such as memory-based decision making. Finally, a robust functional dissociation within the DMN was observed. While angular gyrus and posterior cingulate/precuneus were significantly activated during memory retrieval, an anterior DMN node in medial prefrontal cortex was strongly deactivated. This latter finding demonstrates functional heterogeneity rather than homogeneity within the DMN during episodic memory retrieval.

Amyloid load, as measured by florbetapir positron emission tomography (PET) standardized uptake value ratio (SUVr), has high specificity in the diagnosis of Alzheimer disease (AD). As the posterior cingulate cortex (PCC) represents densely amyloid-affected regions early in AD, we hypothesized that amyloid load within the key hubs of the default mode networks (DMN) may result in local or distant interconnected gray matter (GM) volume atrophy, thereby affecting cognitive performance. Thirty AD patients with a clinical dementia rating sum of box score ≤2 were enrolled and underwent cognitive evaluation, 3-dimensional T1-weighted imaging and florbetapir PET. Volumes of interest (VOIs) included the hippocampus, lateral temporal region, and key hubs of the DMN [anterior cingulate cortex (ACC), PCC, posterior parietal, and precuneus]. The SUVr was calculated by florbetapir standard uptake value (SUV) within the T1-weighted image segmented GM VOIs divided by the cerebellar GM SUV. Our results suggested inverse correlations between ACC (ρ = −0.444, P = 0.016) and PCC SUVr (ρ = −0.443, P = 0.016) with PCC GM volume. In stepwise regression, the orientation scores were associated with PCC SUVr (β = 2.584, P = 0.02) and posterior parietal volume (β = −0.446, P = 0.04), whereas the word recall score was related to hippocampal volume (β = −0.391, P = 0.04). After removing the patients with a hippocampal VOI below the lowest tertile and adjusting for age, an inverse correlation was found between hippocampal volume and SUVr in the ACC (partial σ = −0.639, P = 0.002), precuneus (partial σ = −0.692, P = 0.002), and lateral temporal SUVr (partial σ = −0.604, P = 0.005). Our results suggest that amyloid burden within the key DMN regions may contribute to local and distant GM atrophy, and that this may explain the cognitive scores.

Serotonin transporter occupancy by the SSRI citalopram predicts default-mode network connectivity

Background: Previous studies have indicated the resting-state default mode network (DMN) related connectivity serving as predictor of sustained attention performance in healthy people. Interestingly, sustained attention deficits as well as DMN-involved functional connectivity (FC) alterations are common in both patients with schizophrenia (SCZ) and with obsessive-compulsive disorder (OCD). Thus, the present study was designed to investigate whether the DMN related resting-state connectivity alterations in these two psychiatric disorders were neural correlates of their sustained attention impairments.Methods: The study included 17 SCZ patients, 35 OCD patients and 36 healthy controls (HCs). Sustained attention to response task was adopted to assess the sustained attention. Resting-state scan was administrated and seed-based whole-brain FC analyses were performed with seeds located in classical DMN regions including bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC).Results: Both SCZ and OCD patients had poorer sustained attention than HCs. Sustained attention deficits in OCD was negatively correlated with their impaired FC of right mPFC-left superior frontal gyrus (SFG) within DMN, and that in SCZ was significantly correlated with their altered FC of left mPFC-bilateral anterior cingulate cortex (ACC) which indicated interaction between DMN and salience network. In addition, the FC between left mPFC and right parietal lobe indicating the interaction between DMN and frontal-parietal network was correlated with sustained attention in both SCZ and OCD.Conclusion: These findings suggest the importance of DMN-involved connectivity, both within and between networks in underlying sustained attention deficits in OCD and SCZ. Results further support the potential of resting-state FC in complementing information for cognitive deficits in psychiatric disorders.