Cognitive control dysfunctions in the compulsive-impulsive spectrum: unveiling subclinical cognitive and neurofunctional markers

The aim of this thesis was to investigate neurofunctional and cognitive endophenotypes associated with subclinical transdiagnostic traits found in different clinical conditions. We focused on compulsivity (tendency towards stereotyped behaviors without adaptive functions) and impulsivity (tendency to act on the spur of the moment), given evidence of their role in distinguishable clinical entities. We were interested in characterizing intrinsic neural and task-related behavioral markers underlying the implementation of cognitive control (i.e., ability to coordinate information processing and actions according to behavioral goals). Firstly, we conducted a systematic review of the literature on the intrinsic functional connectivity of brain networks (resting-state fMRI) in obsessive-compulsive disorder and its associations with symptom severity(Chapter 2). Specific intrinsic neurofunctional abnormalities, involving both default-mode and executive networks, were consistently reported. Afterwards, we hypothesized that compulsivity might stem from a deficit in the implementation of proactive control (i.e., ability to maintain active task-relevant representations and goals in an anticipatory fashion). Therefore, we investigated the association between subclinical compulsivity and performance on a spatial Stroop task, in which requirements for proactive control were manipulated (Chapter 3). Results showed that subclinical compulsivity was not associated with abnormalities in implementing proactive control. Secondly, we focused on investigating the intrinsic neurofunctional abnormalities associated with impulsivity (Chapter 4). Specifically, we directly examined topological abnormalities of neurofunctional brain networks (characterized with resting-state fMRI) typically associated with impulsivity in healthy younger and older adults. Results showed that impulsivity was associated with a more widespread and less segregated/efficient functional topology of fronto-striatal and fronto-limbic circuits in younger – but not older – healthy individuals. Subsequently, we hypothesized that different impulsivity traits (i.e., attentional and motor) might be associated with selective deficits in reactive control modes (i.e., phasic reactivation of task-relevant representations on a moment-by-moment basis), implemented at different temporal scales (i.e., early and late reactive control). Using a similar approach to that used for compulsivity, we found a reduced effect of early reactive control requirements for attentional impulsive individuals. Moreover, an augmented effect of late reactive control was found for motor and generally impulsive individuals. Such results were consistent with neurofunctional topology associated with impulsivity. Finally, we further explored the fundamental intrinsic topology of functional brain networks associated with impulsivity using a novel methodological approach: the Minimum Spanning Tree. Specifically, we hypothesized that the essential topological features of neurofunctional networks (studied with resting-state EEG) associated with impulsivity might be consistent with both fMRI-based topology (see Chapter 3) and with behavioral correlates (see Chapter 5) found in our previous studies, as well as with typical clinical manifestations. Results revealed an increased amplitude-based connectivity in the alpha and beta bands for high impulsive individuals, as well as positive associations between integration indices. In conclusion, by exploiting a plethora of different approaches, the present thesis attempted to detail the neurofunctional and behavioral correlates that may (and may not) be associated with subclinical transdiagnostic traits. Our findings may shed light on prodromic endophenotypes predisposing to the development of severe psychiatric conditions, possibly paving the way for developing more tailored and effective preventive strategies.