Social reward processing in depressed and healthy individuals across the lifespan: A systematic review and a preliminary coordinate-based meta-analysis of fMRI studies.

BACKGROUND: Social rewards (e.g., social feedback, praise, and social interactions) are fundamental to social learning and relationships across the life span. Exposure to social rewards is linked to activation in key brain regions, that are impaired in major depression. This is the first summary of neuroimaging literature on social reward processing in depressed and healthy individuals. METHOD: We screened 409 studies and identified 25 investigating task-based fMRI activation during exposure to social stimuli in depressed and healthy populations across the lifespan. We conducted a systematic review followed by an Activation Likelihood Estimation (ALE) analysis of three main contrasts: a) positive social feedback vs. neutral stimuli; b) negative social feedback vs. neutral stimuli; c) positive vs. negative social feedback. We also compared activation patterns in depressed versus healthy controls. RESULTS: Systematic review revealed that social rewards elicit increased activation in subcortical reward regions (NAcc, amygdala, ventral striatum, thalamus) in healthy and depressed individuals; and decreased activation in prefrontal reward regions (medial prefrontal cortex, orbitofrontal cortex) among depressed persons. Our meta-analysis showed, in both depressed and healthy individuals, increased cluster activation of the putamen and caudate in response to negative social stimuli vs. positive stimuli. We also found increased cluster activation in the inferior frontal gyrus (IFG) and the medial frontal gyrus (MFG) in healthy controls vs. depressed individuals, in response to negative social stimuli. CONCLUSIONS: Processing of social stimuli elicits activation of key brain regions involved in affective and social information processing. Interventions for depression can increase social reward responsivity to improve outcomes.

Stress-Induced Auto-Cannibalism in Patients With a History of Moderate Traumatic Brain Injury.

A traumatic brain injury (TBI) is a significant factor in injury-related deaths in the United States and may lead to complex psychological disorders. Auto-cannibalism as a sequela of a TBI has yet to be reported in the literature. The current literature regarding such behavior is often associated with psychosis, intellectual disability, or substance use. A 35-year-old male had a past medical history significant for a TBI a decade ago. He was transferred to the emergency department due to a self-inflicted wound. The patient had been scratching his arms and legs for the last few months and displayed an intense new pattern of self-destructive behavior in the past week. He went through surgical wound debridement and psychiatric evaluation before he was discharged home. This case depicts the importance of regular, long-term psychiatric, and neurological follow-up for patients sustaining TBIs, regardless of whether or not they were previously deemed stable. A greater understanding of many factors leading to self-destructive behavior following TBIs is needed to improve patient outcomes.

Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the Cerebral Cortex of Sanfilippo Syndrome IIIA Mice.

Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The accumulation of heparan sulfate results in neurological symptoms, culminating in extensive neurodegeneration and early death. To study the impact of storage in postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the enzyme sulfamidase. We show that changes occur in excitatory postsynaptic structure and function in the somatosensory cortex prior to signs of neurodegeneration. These changes coincide with accumulation of heparan sulfate with characteristic non-reducing ends, which is present at birth in the mutant mice. Accumulation of heparan sulfate was also detected in primary cultures of cortical neural cells, especially astrocytes. Accumulation of heparan sulfate in cultured astrocytes corresponded with augmented extracellular heparan sulfate and glypican 4 levels. Heparan sulfate from the cerebral cortex of MPS IIIA mice showed enhanced ability to increase glutamate AMPA receptor subunits at the cell surface of wild type neurons. These data support the idea that abnormalities in heparan sulfate content and distribution contribute to alterations in postsynaptic function. Our findings identify a disease-induced developmental phenotype that temporally overlaps with the onset of behavioral changes in a mouse model of MPS IIIA.

Modeling multiple infection of cells by viruses: Challenges and insights.

The multiple infection of cells with several copies of a given virus has been demonstrated in experimental systems, and has been subject to previous mathematical modeling approaches. Such models, especially those based on ordinary differential equations, can be characterized by difficulties and pitfalls. One such difficulty arises from what we refer to as multiple infection cascades. That is, such models subdivide the infected cell population into sub-populations that are carry i viruses, and each sub-population can in principle always be further infected to contain i + 1 viruses. In order to study the model with numerical simulations, the infection cascade needs to be cut artificially, and this can influence the results. This is shown here in the context of the simplest setting that involves a single, homogeneous virus population. If the viral replication rate is sufficiently fast, then most infected cells will accumulate in the last member of the infection cascade, leading to incorrect numerical results. This can be observed even with relatively long infection cascades, and in this case computational costs associated with a sufficiently long infection cascade can render this approach impractical. We subsequently examine a more complex scenario where two virus types/strains with different fitness are allowed to compete. Again, we find that the length of the infection cascade can have a crucial influence on the results. Competitive exclusion can be observed for shorter infection cascades, while coexistence can be observed for longer infection cascades. More subtly, the length of the infection cascade can influence the equilibrium level of the populations in numerical simulations. Studying the model in a parameter regime where an increase in the infection cascade length does not influence the results, we examine the effect of multiple infection on the outcome of competition. We find that multiple infection can promote coexistence of virus types if there is a degree of intracellular niche separation. If this is not the case, the only outcome is competitive exclusion, similar to equivalent models that do not take into account multiple infection of cells. We further find that multiple infection has a reduced ability to allow coexistence if virus spread is spatially restricted compared to a well-mixed system. These results provide important insights when analyzing and interpreting multiple infection models.