Applicazione della neurodiagnostica avanzata allo studio dei disturbi psicologici nelle malattie infiammatorie croniche intestinali

Background and aim Ulcerative Colitis (UC) and Crohn’s Disease (CD), collectively labelled as inflammatory bowel disease (IBD), are idiopathic, chronic inflammatory disorder of the bowel with a remitting and relapsing course. IBD are associated to poor emotional functioning and psychological distress. We have investigated the brain involvement in patients with IBD using functional magnetic resonance imaging (fMRI). Materials and methods We developed an emotional visual task to investigate the emotional functioning in 10 UC patients and 10 healthy controls (HC). Furthermore, we have compared the brain stress response between a group of 20 CD patients and a group of 18 HC. Finally, we evaluated potential morphological differences between 18 CD patients and 18 HC in a voxel based morphometry (VBM) study. Results We found brain functional changes in UC patients characterized by decreased activity in the amygdala in response to positive emotional stimuli. Moreover, in CD patients, the brain stress response and habituation to stressful stimuli were significantly different in the medial temporal lobe (including the amygdala and hippocampus), the insula and cerebellum. Finally, in CD patients there were morphological abnormalities in the anterior mid cingulated cortex (aMCC). Conclusion IBD are associated to functional and morphological brain abnormalities. The previous intestinal inflammatory activity in IBD patients might have contributed to determine the functional and morphological changes we found. On the other hand, the dysfunctions of the brain structures we found may influence the course of the disease. Our findings might have clinical implications. The differences in the emotional processing may play a role in the development of psychological disorders in UC patients. Furthermore, in CD patients, the different habituation to stress might contribute to stress related inflammatory exacerbations. Finally, the structural changes in the aMCC might be involved in the pain symptoms associated to the bowel disorder.

Functional and neural mechanisms of intertemporal choice

People are daily faced with intertemporal choice, i.e., choices differing in the timing of their consequences, frequently preferring smaller-sooner rewards over larger-delayed ones, reflecting temporal discounting of the value of future outcomes. This dissertation addresses two main goals. New evidence about the neural bases of intertemporal choice is provided. Following the disruption of either the medial orbitofrontal cortex or the insula, the willingness to wait for larger-delayed outcomes is affected in odd directions, suggesting the causal involvement of these areas in regulating the value computation of rewards available with different timings. These findings were also supported by a reported imaging study. Moreover, this dissertation provides new evidence about how temporal discounting can be modulated at a behavioral level through different manipulations, e.g., allowing individuals to think about the distant time, pairing rewards with aversive events, or changing their perceived spatial position. A relationship between intertemporal choice, moral judgements and aging is also discussed. All these findings link together to support a unitary neural model of temporal discounting according to which signals coming from several cortical (i.e., medial orbitofrontal cortex, insula) and subcortical regions (i.e., amygdala, ventral striatum) are integrated to represent the subjective value of both earlier and later rewards, under the top-down regulation of dorsolateral prefrontal cortex. The present findings also support the idea that the process of outcome evaluation is strictly related to the ability to pre-experience and envision future events through self-projection, the anticipation of visceral feelings associated with receiving rewards, and the psychological distance from rewards. Furthermore, taking into account the emotions and the state of arousal at the time of decision seems necessary to understand impulsivity associated with preferring smaller-sooner goods in place of larger-later goods.

The role of medial parieto occipital cortex in visuospatial attention and reach planning: electrophysiological studies in human and non-human primates

We usually perform actions in a dynamic environment and changes in the location of a target for an upcoming action require both covert shifts of attention and motor planning update. In this study we tested whether, similarly to oculomotor areas that provide signals for overt and covert attention shifts, covert attention shifts modulate activity in cortical area V6A, which provides a bridge between visual signals and arm-motor control. We performed single cell recordings in monkeys trained to fixate straight-ahead while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention demonstrating that visual, motor, and attentional responses can occur in combination in single neurons of V6A. This modulation in an area primarily involved in visuo-motor transformation for reaching suggests that also reach-related regions could directly contribute in the shifts of spatial attention necessary to plan and control goal-directed arm movements. Moreover, to test whether V6A is causally involved in these processes, we have performed a human study using on-line repetitive transcranial magnetic stimulation over the putative human V6A (pV6A) during an attention and a reaching task requiring covert shifts of attention and reaching movements towards cued targets in space. We demonstrate that the pV6A is causally involved in attention reorienting to target detection and that this process interferes with the execution of reaching movements towards unattended targets. The current findings suggest the direct involvement of the action-related dorso-medial visual stream in attentional processes, and a more specific role of V6A in attention reorienting. Therefore, we propose that attention signals are used by the V6A to rapidly update the current motor plan or the ongoing action when a behaviorally relevant object unexpectedly appears at an unattended location.