Anhedonia as a potential transdiagnostic phenotype with immune-related changes in recent onset mental health disorders.

BACKGROUND: Chronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes - reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in those with enduring illness, with few exploring inflammatory changes. We sought to identify an inflammatory signal and associated brain function underlying anhedonia among young people with recent onset psychosis (ROP) and recent onset depression (ROD). METHOD: Resting-state functional magnetic resonance imaging, inflammatory markers, and anhedonia symptoms were collected from N=108 (M age=26.2[SD 6.2]years; Female =50) participants with ROP (n=53) and ROD (n=55) from the EU-FP7-funded PRONIA study. Time-series were extracted using the Schaefer atlas, defining 100 cortical regions of interest. Using advanced multimodal machine learning, an inflammatory marker model and functional connectivity model were developed to classify an anhedonic group, compared to a normal hedonic group. RESULTS: A repeated nested cross-validation model using inflammatory markers classified normal hedonic and anhedonic ROP/ROD groups with a balanced accuracy (BAC) of 63.9%, and an area under the curve (AUC) of 0.61. The functional connectivity model produced a BAC of 55.2% and an AUC of 0.57. Anhedonic group assignment was driven by higher levels of Interleukin-6, S100B, and Interleukin-1 receptor antagonist, and lower levels of Interferon gamma, in addition to connectivity within the precuneus and posterior cingulate. CONCLUSION: We identified a potential transdiagnostic anhedonic subtype that was accounted for by an inflammatory profile and functional connectivity. Results have implications for anhedonia as an emerging transdiagnostic target across emerging mental disorders.

Pattern of frustration formation in the functional brain network.

The brain is a frustrated system that contains conflictual link arrangements named frustration. The frustration as a source of disorder prevents the system from settling into low-energy states and provides flexibility for brain network organization. In this research, we tried to identify the pattern of frustration formation in the brain at the levels of region, connection, canonical network, and hemisphere. We found that frustration formation has no uniform pattern. Some subcortical elements have an active role in frustration formation, despite low contributions from many cortical elements. Frustrating connections are mostly between-network connections, and triadic frustrations are mainly formed between three regions from three distinct canonical networks. We did not find any significant differences between brain hemispheres or any robust differences between the frustration formation patterns of various life-span stages. Our results may be interesting for those who study the organization of brain links and promising for those who want to manipulate brain networks.

Brain network analysis approaches commonly ignore the signs of links. Frustration is a fascinating phenomenon referring to the conflictual arrangements of signed links. As a source of instability, it can give valuable information on altering components of a network. It can specify which brain network elements intend to drive brain network alterations. Accordingly, we tried to identify the pattern of frustration formation in the brain network, which brain network elements are more frustrated and which ones are less frustrated. We provided some maps for frustration formation in the levels of region, connection, canonical network, and hemisphere. The introduced concept of frustration and our results may be interesting for brain network scientists.

Requirement to change of functional brain network across the lifespan.

Many studies have focused on neural changes and neuroplasticity, while the signaling demand for neural modification needs to be explored. In this study, we traced this issue in the organization of brain functional links where the conflictual arrangement of signed links makes a request to change. We introduced the number of frustrations (unsatisfied closed triadic interactions) as a measure for assessing "requirement to change" of functional brain network. We revealed that the requirement to change of the resting-state network has a u-shape functionality over the lifespan with a minimum in early adulthood, and it's correlated with the presence of negative links. Also, we discovered that brain negative subnetwork has a special topology with a log-normal degree distribution in all stages, however, its global measures are altered by adulthood. Our results highlight the study of collective behavior of functional negative links as the source of the brain's between-regions conflicts and we propose exploring the attribute of the requirement to change besides other neural change factors.

Topological impact of negative links on the stability of resting-state brain network.

Stability is a physical attribute that stands opposite the change. However, it is still unclear how the arrangement of links called topology affects network stability. In this study, we tackled this issue in the resting-state brain network using structural balance. Structural balance theory employs the quality of triadic associations between signed links to determine the network stability. In this study, we showed that negative links of the resting-state network make hubs to reduce balance-energy and push the network into a more stable state compared to null-networks with trivial topologies. In this regard, we created a global measure entitled 'tendency to make hub' to assess the hubness of the network. Besides, we revealed nodal degrees of negative links have an exponential distribution that confirms the existence of negative hubs. Our findings indicate that the arrangement of negative links plays an important role in the balance (stability) of the resting-state brain network.

Odorant receptors of Drosophila are sensitive to the molecular volume of odorants.

Which properties of a molecule define its odor? This is a basic yet unanswered question regarding the olfactory system. The olfactory system of Drosophila has a repertoire of approximately 60 odorant receptors. Molecules bind to odorant receptors with different affinities and activate them with different efficacies, thus providing a combinatorial code that identifies odorants. We hypothesized that the binding affinity of an odorant-receptor pair is affected by their relative sizes. The maximum affinity can be attained when the molecular volume of an odorant matches the volume of the binding pocket. The affinity drops to zero when the sizes are too different, thus obscuring the effects of other molecular properties. We developed a mathematical formulation of this hypothesis and verified it using Drosophila data. We also predicted the volume and structural flexibility of the binding site of each odorant receptor; these features significantly differ between odorant receptors. The differences in the volumes and structural flexibilities of different odorant receptor binding sites may explain the difference in the scents of similar molecules with different sizes.