Análisis psicofisiológico de las alteraciones atencionales en pacientes con esclerosis múltiple

Resum

Abstract Background: It is well known that Multiple Sclerosis (MS) is associated with cognitive impairment and it has been shown that up to 70% of MS patients can develop some degree of cognitive dysfunction during the course of their disease. Between these cognitive disturbances, attention remains largely unexplored in MS patients, although it could be impaired early in the course of the disease. Based on the Posner and Petersen model of attention, recent studies using the Attention Network Test (ANT) have shown a behavioral impairment associated with the alerting network in MS patients, with no deterioration in other attention networks. Nevertheless, direct functional or electrophysiology (EEG) evidence of this is still lacking. Other studies, however, have also indicated that event-related potentials (ERP) may be used as index of detecting subtle degrees of cognitive dysfunction, suggesting orienting impairment in MS patients, but it has not been demonstrated so far using the ANT paradigm. Objectives and Methods: The aim of our study was to investigate the neural mechanisms underlying visual attention and information processing during the performance of the ANT, which allowed us to study simultaneously three different attentional networks, i.e., alerting, orienting, and executive. For this purpose, and in a first study, we investigated behavioral and ERP measures elicited during the ANT paradigm in healthy subjects. Cue orientation and response preparation processes were respectively measured by Contingent Negative Variation (CNV) activity, ERP components and behavioral measures. Furthermore, the estimation of cortical sources underlying the CNV was additionally performed for every cue condition. In a second study, a cohort of relapsing-remitting MS patients was evaluated using the same paradigm to examine the psychophysiological correlates of attentional impairment in these patients. Results: In the first study, a progressive increase in the CNV amplitude related to the amount of information provided by the cue conditions of the ANT paradigm was observed. Neural source analysis revealed: i) specific modulations of the CNV related to a task-related expectancy presented in the No Cue (NC) condition, ii) a late modulation triggered by the central cue (CC) condition and probably representing a generic motor preparation, and iii) an early and late modulation for spatial cue (SC) condition suggesting specific motor and sensory preactivation. The analyses of the ERP components following target stimulus revealed attentional modulation of early and late ERP components in response to the different cue conditions. Thus, the P1 amplitude increased following the SC, suggesting an enhanced processing of spatially attended stimuli, whereas modulations of the amplitude and latency of N1 component between conditions may be interpreted as a correlate of the first locus for the interaction between attentional networks in the information processing of target stimuli. Finally, regarding the study with MS patients, behavioral measures of the ANT were highly correlated with the neuropsychological scores related to information processing speed and sustained and divided attention, indicating that the alerting and orienting mechanisms were impaired in MS patients. In addition, the reduced amplitude found for the CNV suggested that this component could be an electrophysiological marker related to the alerting and orienting impairment in relapsing-remitting MS patients. On the other hand, the P1 and N1 delayed latencies evidenced demyelination process causing impairment in the first steps of the visual sensory processing for these patients. Lastly, P3 amplitude showed a general decrease for MS patients probably indexing a more central impairment. Conclusions: Taken together, our findings indicate that the ANT can be a useful tool to study specific attentional mechanisms and their interactions. However, calculation of network effects in this test is based in subtractions with non-comparable experimental conditions, as evidenced by the neural source analysis data. This may induce misinterpretations in the study of the attentional capacity in human subjects and caution is recommended. Importantly, our results also suggest that the ANT paradigm provides evidence of multiple levels of attention impairment, which could help in the assessment and treatment of MS patients.