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The sense of agency (SoA) is central to human experience. The comparator model, contrasting sensory prediction and action feedback, is influential but limited in explaining SoA. We investigated mechanisms beyond the comparator model, focusing on the processing of unpredictable stimuli, perimotor components of SoA, and their relation to schizotypy. ERPs were recorded from 18 healthy participants engaged in button-pressing tasks while perceiving tones with varying causal relationships with their actions. We investigated the processing of non-causally related tones, contrasted this to causally related tones, and examined perimotor correlates of subjective expectancy and experience of agency. We confirmed N100 attenuation for self-generated stimuli but found similar effects for expectancy-dependent processing of random tones. SoA also correlated with perimotor ERP components, modulated by schizotypy. Thus, neural processes preceding actions contribute to the formation of SoA and are associated with schizotypy. Unpredictable events also undergo sensory attenuation, implying additional mechanisms contributing to SoA.

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The neural underpinnings of selfhood encompass pre-reflective and reflective self-experience. The former refers to a basic, immediate experience of being a self, while the latter involves cognition and introspection. Although neural correlates of reflective self-experience have been studied, the pre-reflective remains underinvestigated. This research aims to bridge this gap by comparatively investigating ERP correlates of reading first- vs. third-person pronouns - approximating pre-reflective self-experience - and self- vs. other-related adjectives - approximating reflective self-experience - in 30 healthy participants. We found differential neural engagement between pre-reflective and reflective self-experience at 254-310 ms post-stimulus onset. Source estimation suggested that our sensor-level results could be plausibly explained by the involvement of cortical midline structures and default mode network in the general sense of self but selective recruitment of anterior cingulate and top-down dorsal attention network in the pre-reflective self. These findings offer a deeper understanding of the experiential self, especially pre-reflective, providing a foundation for investigating self-disorders.

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BACKGROUND: Major depressive disorder (MDD) is a severe psychiatric condition characterized by selective cognitive dysfunctions. In this regard, functional Magnetic Resonance Imaging (fMRI) studies showed, both at resting state and during tasks, alterations in the brain functional networks involved in cognitive processes in MDD patients compared to controls. Among those, it seems that the attention network may have a role in the disease pathophysiology. Therefore, in this review we aim at summarizing the current fMRI evidence investigating sustained attention in MDD patients. METHODS: We conducted a search on PubMed on case-control studies on MDD employing fMRI acquisitions during Go/No-Go and continuous performance tasks. A total of 12 studies have been included in the review. RESULTS: Overall, the majority of fMRI studies reported quantitative alterations in the response to attentive tasks in selective brain regions, including the prefrontal cortex, the cingulate cortex, the temporal and parietal lobes, the insula and the precuneus, which are key nodes of the attention, the executive, and the default mode networks. LIMITATIONS: The heterogeneity in the study designs, fMRI acquisition techniques and processing methods have limited the generalizability of the results. CONCLUSIONS: The results from the included studies showed the presence of alterations in the activation patterns of regions involved in sustained attention in MDD, which are in line with current evidence and seemed to explain some of the key symptoms of depression. However, given the paucity and heterogeneity of studies available, it may be worthwhile to continue investigating the attentional domain in MDD with ad-hoc study designs to retrieve more robust evidence.

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Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex (p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions (p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex (p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD-especially in regions involved in attention processing and in the brain default mode-potentially supporting cognitive and symptom differences between sexes.