No abstract

Sex differences in the structure and organization of the corpus callosum (CC) can be attributed to genetic, hormonal, or environmental effects, or a combination of these factors. To address the role of gonadal hormones on axon myelination functional axon conduction and immunohistochemistry analysis of the CC in intact, gonadectomized, and hormone-replaced gonadectomized animals were used. These groups were subjected to cuprizone diet-induced demyelination followed by remyelination. The myelinated component of callosal compound action potential was significantly decreased in ovariectomized and castrated animals. Compared to gonadally intact cohorts, both gonadectomized groups displayed more severe demyelination and inhibited remyelination. Castration in males was more deleterious than ovariectomy in females. Callosal conduction in estradiol-supplemented ovariectomized females was significantly increased during normal myelination less attenuated during demyelination and increased beyond placebo-treated ovariectomized or intact female levels during remyelination. In castrated males, the non-aromatizing steroid dihydrotestosterone was less efficient than testosterone and estradiol in restoring normal myelination/axon conduction and remyelination to levels of intact males. Furthermore, in both sexes, estradiol supplementation in gonadectomized groups increased the number of oligodendrocytes. These studies suggest an essential role of estradiol to bring forth efficient CC myelination and axon conduction in both sexes.

BACKGROUND: There are robust sex differences in the prevalence of depression. Inflammation and anhedonia may play a role in understanding these sex differences. Indeed, sex differences in inflammation-induced neural responses to reward may provide insight into the sex gaps in depression, but no study has examined this question. METHODS: As such, the current study examined whether there were sex differences in reward-related neural activity (i.e., ventral striatum [VS] activity) in response to an experimental inflammatory challenge. Human participants (N = 115; 69 female) were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammation in a safe, time-limited manner. Two hours after receiving placebo or endotoxin (the height of the inflammatory response to endotoxin), participants completed a task in which they anticipated monetary reward in a functional magnetic resonance imaging scanner. RESULTS: Results demonstrated that endotoxin (vs. placebo) led to reduced VS activity in anticipation of reward and that there were sex differences in this effect. Specifically, in female participants, endotoxin (vs. placebo) led to decreased VS activity in anticipation of reward, but this effect was not present in male participants. In addition, within the endotoxin condition, decreases in VS activity in anticipation of reward were related to increases in inflammation for female but not male participants. CONCLUSIONS: These findings may have implications for understanding how inflammation may contribute to sex differences in rates of depression.

Neuroimaging studies of mentalizing (i.e., theory of mind) consistently implicate the default mode network (DMN). Nevertheless, the social cognitive functions of individual DMN regions remain unclear, perhaps due to limited spatiotemporal resolution in neuroimaging. Here we use electrocorticography (ECoG) to directly record neuronal population activity while 16 human participants judge the psychological traits of themselves and others. Self- and other-mentalizing recruit near-identical cortical sites in a common spatiotemporal sequence. Activations begin in the visual cortex, followed by temporoparietal DMN regions, then finally in medial prefrontal regions. Moreover, regions with later activations exhibit stronger functional specificity for mentalizing, stronger associations with behavioral responses, and stronger self/other differentiation. Specifically, other-mentalizing evokes slower and longer activations than self-mentalizing across successive DMN regions, implying lengthier processing at higher levels of representation. Our results suggest a common neurocognitive pathway for self- and other-mentalizing that follows a complex spatiotemporal gradient of functional specialization across DMN and beyond.

Background: Social cognitive impairments, specifically in mentalizing and emotion recognition, are common and debilitating symptoms of posttraumatic stress disorder (PTSD). Despite this, little is known about the neurobiology of these impairments, as there are currently no published neuroimaging investigations of social inference in PTSD.Methods: Trauma-exposed veterans with and without PTSD (n = 20 each) performed the Why/How social inference task during functional magnetic resonance imaging (fMRI). Patients with PTSD had two fMRI sessions, between which they underwent affect labeling training. We probed the primary networks of the "social brain"-the default mode network (DMN) and mirror neuron system (MNS)-by examining neural activity evoked by mentalizing and action identification prompts, which were paired with emotional and nonemotional targets.Results: Hyperactivation to emotional stimuli differentiated PTSD patients from controls, correlated with symptom severity, and predicted training outcomes.Critically, these effects were nonsignificant or marginal for nonemotional stimuli.Results were generally consistent throughout DMN and MNS. Unexpectedly, effects were nonsignificant in core affect regions, but robust in regions that overlap with the dorsal attention, ventral attention, and frontoparietal control networks. Conclusions:The array of social cognitive processes subserved by DMN and MNS appear to be inordinately selective for emotional stimuli in PTSD. However, core affective processes do not appear to be the primary instigators of such selectivity. Instead, we propose that affective attentional biases may instigate widespread affect-selectivity throughout the social brain. Affect labeling training may inhibit such biases. These accounts align with numerous reports of affect-biased attentional processes in PTSD.