Giorgia Cona

Improving the Inhibitory Control Task to Detect Minimal Hepatic Encephalopathy

BACKGROUND & AIMS Quantification of the number of noninhibited responses (lures) in the inhibitory control task (ICT) has been proposed for the diagnosis of minimal hepatic encephalopathy (MHE). We assessed the efficacy of ICT compared with recommended diagnostic standards. METHODS We studied patients with cirrhosis and healthy individuals (controls) who underwent the ICT at 2 centers (center A: n=51 patients and 41 controls, center B: n=24 patients and 14 controls). Subjects were evaluated for MHE by psychometric hepatic encephalopathy score (PHES). Patients from center B also were assessed for MHE by critical flicker frequency and spectral electroencephalogram analyses. RESULTS Patients with cirrhosis had higher ICT lures (23.2+/-12.8 vs 12.9+/-5.8, respectively, P<.01) and lower ICT target accuracy (0.88+/-0.17 vs 0.96+/-0.03, respectively, P<.01) compared with controls. However, lures were comparable (25.2+/-12.5 vs 21.4+/-13.9, respectively, P=.32) among patients with/without altered PHES (center A). There was a reverse, U-shaped relationship between ICT lure and target accuracy; a variable adjusting lures was devised based on target accuracy (weighted lures at center B). This variable differed between patients with and without MHE. The variable weighted lures was then validated from data collected at center A by receiver operator characteristic curve analysis; it discriminated between patients with and without PHES alterations (area under the curve=0.71+/-0.07). However, target accuracy alone was as effective as a stand-alone variable (area under the curve=0.81+/-0.06). CONCLUSIONS The ICT is not useful for the diagnosis of MHE, unless adjusted by target accuracy. Testing inhibition (lures) does not seem to be superior to testing attention (target accuracy) for the detection of MHE.

Electrophysiological Correlates of Strategic Monitoring in Event-Based and Time-Based Prospective Memory

Prospective memory (PM) is the ability to remember to accomplish an action when a particular event occurs (i.e., event-based PM), or at a specific time (i.e., time-based PM) while performing an ongoing activity. Strategic Monitoring is one of the basic cognitive functions supporting PM tasks, and involves two mechanisms: a retrieval mode, which consists of maintaining active the intention in memory; and target checking, engaged for verifying the presence of the PM cue in the environment. The present study is aimed at providing the first evidence of event-related potentials (ERPs) associated with time-based PM, and at examining differences and commonalities in the ERPs related to Strategic Monitoring mechanisms between event- and time-based PM tasks. The addition of an event-based or a time-based PM task to an ongoing activity led to a similar sustained positive modulation of the ERPs in the ongoing trials, mainly expressed over prefrontal and frontal regions. This modulation might index the retrieval mode mechanism, similarly engaged in the two PM tasks. On the other hand, two further ERP modulations were shown specifically in an event-based PM task. An increased positivity was shown at 400–600 ms post-stimulus over occipital and parietal regions, and might be related to target checking. Moreover, an early modulation at 130–180 ms post-stimulus seems to reflect the recruitment of attentional resources for being ready to respond to the event-based PM cue. This latter modulation suggests the existence of a third mechanism specific for the event-based PM; that is, the “readiness mode”.

It’s a Matter of Mind! Cognitive Functioning Predicts the Athletic Performance in Ultra-Marathon Runners

The present study was aimed at exploring the influence of cognitive processes on performance in ultra-marathon runners, providing an overview of the cognitive aspects that characterize outstanding runners. Thirty runners were administered a battery of computerized tests right before their participation in an ultra-marathon. Then, they were split according to the race rank into two groups (i.e., faster runners and slower runners) and their cognitive performance was compared. Faster runners outperformed slower runners in trials requiring motor inhibition and were more effective at performing two tasks together, successfully suppressing the activation of the information for one of the tasks when was not relevant. Furthermore, slower runners took longer to remember to execute pre-defined actions associated with emotional stimuli when such stimuli were presented. These findings suggest that cognitive factors play a key role in running an ultra-marathon. Indeed, if compared with slower runners, faster runners seem to have a better inhibitory control, showing superior ability not only to inhibit motor response but also to suppress processing of irrelevant information. Their cognitive performance also appears to be less influenced by emotional stimuli. This research opens new directions towards understanding which kinds of cognitive and emotional factors can discriminate talented runners from less outstanding runners.

The Effects of Focal and Nonfocal Cues on the Neural Correlates of Prospective Memory: Insights From ERPs

The present study is the first designed to investigate behavioral and event-related potential (ERP) correlates of the processes involved in focal and nonfocal prospective memory (PM) tasks. Focal tasks are those in which the features of the PM cue are easily extracted from the ongoing activity, whereas the process is more indirect in nonfocal tasks. Strategic monitoring was associated with a slowing of reaction times in ongoing trials and with frontal and parietal ERP modulations. These effects were greater in the nonfocal task, whereas they were smaller, or even absent for some individuals, in the focal task. This indicates that strategic monitoring is engaged to a greater extent in nonfocal tasks, whereas it is less extensively recruited, or not recruited at all by some individuals, in focal tasks. Indeed, the recognition of the PM cue might also occur automatically in focal tasks, as suggested by the FN400 increase in focal PM trials. Nonfocal tasks are supported by more controlled resources not only in retrieval, but also in postretrieval monitoring and coordinating processes. This was reflected in the enhancement of the prospective positivity and frontal slow wave observed in nonfocal PM trials. We interpreted these results as supporting the multiprocess view of PM.

Modulation of a fronto-parietal network in event-based prospective memory: an rTMS study.

Event-based prospective memory (PM) is a multi-component process that requires remembering the delayed execution of an intended action in response to a pre-specified PM cue, while being actively engaged in an ongoing task. Some neuroimaging studies have suggested that both prefrontal and parietal areas are involved in the maintenance and realization of delayed intentions. In the present study, transcranial magnetic stimulation (TMS) was used to investigate the causal involvement of frontal and parietal areas in different stages of the PM process (in particular, target checking and intention retrieval), and to determine the specific contribution of these regions to PM performance. Our results demonstrate that repetitive TMS (rTMS) interferes with prospective memory performance when applied at 150-350 ms to the right dorsolateral prefrontal cortex (DLPFC), and at 400-600 ms when applied to the left posterior parietal cortex (PPC). The present study provides clear evidence that the right DLPFC plays a crucial role in early components of the PM process (target checking), while the left PPC seems to be mainly involved in later processes, such as the retrieval of the intended action.

Supplementary motor area as key structure for domain-general sequence processing: A unified account

The Supplementary Motor Area (SMA) is considered as an anatomically and functionally heterogeneous region and is implicated in several functions. We propose that SMA plays a crucial role in domain-general sequence processes, contributing to the integration of sequential elements into higher-order representations regardless of the nature of such elements (e.g., motor, temporal, spatial, numerical, linguistic, etc.). This review emphasizes the domain-general involvement of the SMA, as this region has been found to support sequence operations in a variety of cognitive domains that, albeit different, share an inherent sequence processing. These include action, time and spatial processing, numerical cognition, music and language processing, and working memory. In this light, we reviewed and synthesized recent neuroimaging, stimulation and electrophysiological studies in order to compare and reconcile the distinct sources of data by proposing a unifying account for the role of the SMA. We also discussed the differential contribution of the pre-SMA and SMA-proper in sequence operations, and possible neural mechanisms by which such operations are executed.

Differential effects of emotional cues on components of prospective memory: an ERP study

So far, little is known about the neurocognitive mechanisms associated with emotion effects on prospective memory (PM) performance. Thus, this study aimed at disentangling possible mechanisms for the effects of emotional valence of PM cues on the distinct phases composing PM by investigating event-related potentials (ERPs). Participants were engaged in an ongoing N-back task while being required to perform a PM task. The emotional valence of both the ongoing pictures and the PM cues was manipulated (pleasant, neutral, unpleasant). ERPs were recorded during the PM phases, such as encoding, maintenance, and retrieval of the intention. A recognition task including PM cues and ongoing stimuli was also performed at the end of the sessions. ERP results suggest that emotional PM cues not only trigger an automatic, bottom-up, capture of attention, but also boost a greater allocation of top-down processes. These processes seem to be recruited to hold attention toward the emotional stimuli and to retrieve the intention from memory, likely because of the motivational significance of the emotional stimuli. Moreover, pleasant PM cues seemed to modulate especially the prospective component, as revealed by changes in the amplitude of the ERP correlates of strategic monitoring as a function of the relevance of the valence for the PM task. Unpleasant pictures seemed to modulate especially the retrospective component, as revealed by the largest old/new effect being elicited by unpleasant PM pictures in the recognition task.

Neural dissociation of automatic and controlled temporal preparation by transcranial magnetic stimulation

Recent neuropsychological evidence suggested a role for the right prefrontal cortex in temporal orienting of attention guided by symbolic cues, and the left prefrontal cortex in preparation guided by rhythms. We tested this hypothesis by comparing the effects of 1-Hz repetitive transcranial magnetic stimulation (TMS) over prefrontal regions on the performances of two temporal preparation tasks, one using symbolic cues (short vs. long lines) and the other using regular rhythms (fast vs. slow pace) to indicate when (early vs. late) a target would be most likely to appear. Stimulation site was either the left dorsolateral prefrontal cortex (DLPFC), right DLPFC, or sham condition. The results showed that frontal TMS produced differential effects as a function of type of cuing. In symbolic cuing, TMS on either left or right frontal sites (vs. sham) increased temporal orienting effects by reducing reaction times in valid trials. In rhythmic cuing, however, frontal TMS did not influence performance. This dissociation between two forms of temporal preparation suggests a specific role for the DLPFC in the ability of temporal orienting, but not in preparation guided by rhythms.

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks.

Insight into the relationship between brain/behavioral speed and variability in patients with minimal hepatic encephalopathy

OBJECTIVE Intra-individual variability (IIV) of response reaction times (RTs) and psychomotor slowing were proposed as markers of brain dysfunction in patients with minimal hepatic encephalopathy (MHE), a subclinical disorder of the central nervous system frequently detectable in patients with liver cirrhosis. However, behavioral measures alone do not enable investigations into the neural correlates of these phenomena. The aim of this study was to investigate the electrophysiological correlates of psychomotor slowing and increased IIV of RTs in patients with MHE. METHODS Event-related potentials (ERPs), evoked by a stimulus-response (S-R) conflict task, were recorded from a sample of patients with liver cirrhosis, with and without MHE, and a group of healthy controls. A recently presented Bayesian approach was used to estimate single-trial P300 parameters. RESULTS Patients with MHE, with both psychomotor slowing and higher IIV of RTs, showed higher P300 latency jittering and lower single-trial P300 amplitude compared to healthy controls. In healthy controls, distribution analysis revealed that single-trial P300 latency increased and amplitude decreased as RTs became longer; however, in patients with MHE the linkage between P300 and RTs was weaker or even absent. CONCLUSIONS These findings suggest that in patients with MHE, the loss of the relationship between P300 parameters and RTs is related to both higher IIV of RTs and psychomotor slowing. SIGNIFICANCE This study highlights the utility of investigating the relationship between single-trial ERPs parameters along with RT distributions to explore brain functioning in normal or pathological conditions.