Top-down and bottom-up processes in the extrastriate cortex of cirrhotic patients: An ERP study
Introduction
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome occurring in acute or chronic liver failure. In its subclinical or minimal expression, HE is characterized by the presence of cognitive and neurophysiological abnormalities in cirrhotic patients with normal or near-normal neurological and mental status (Gitlin et al., 1986, Rikkers et al., 1978, Tarter et al., 1984).
Minimal hepatic encephalopathy (MHE) is detectable in 20–60% of cirrhotic patients (Amodio et al., 2004, Ferenci et al., 2002). This neuropsychiatric syndrome is characterized by many neuropsychological dysfunctions concerning visual-constructive abilities, orienting of visual attention, psychomotor speed, inhibitory processes and executive functions (Amodio et al., 1995, Amodio et al., 1998, Amodio et al., 2005, Osman et al., 1995, Schiff et al., 2005, Weissenborn et al., 2001). Chronometric studies showed that in patients without overt HE (patient with or without MHE), the delay of simple reaction times (RTs) tasks is smaller compared to the delay of choice RTs tasks. Furthermore, there are evidences that MHE patients fail in cognitive tasks, which need higher levels of control and inhibition of non-relevant information (Amodio et al., 1999a, Amodio et al., 2005, Rikkers et al., 1978, Schiff et al., 2005, Schomerus et al., 1981). These data suggest that when performance need the control of incoming information (top-down processes), patients show a worse performance.
Additional information about brain dysfunctions in cirrhotic patients come from brain imaging studies. Reduced brain metabolism was observed in MHE patients in the following associative cortical areas: the anterior cingulate cortex, the dorsolateral prefrontal cortex, the occipito-parietal cortex, the medial temporal cortex and the extrastriate cortex (Lockwood, 2000, Lockwood et al., 1993, Lockwood et al., 2002, Zafiris et al., 2004).
These neuropsychological and brain imaging findings suggest a correlation between the alterations observed in cirrhotic patients and top-down processes involved in stimulus discrimination and response selection during goal-directed behaviour (Corbetta and Shulman, 2002). Information inside the brain can travel from sensory input, through perceptual analysis, towards motor output, or from ‘higher’ associative cortices to ‘lower’ primary cortices involving feedback or re-entrant connections. The former types of processes are called bottom-up processes and are exogenous in nature (stimulus-driven); the latter are called top-down processes and are endogenous (goal-directed) in nature. Since, the control of visual and spatial selective attention affect information processing in extrastriate cortex (Corbetta and Shulman, 2002, Desimone and Duncan, 1995, Luck et al., 1997), it may be expected that a dissociation between the efficiency of top-down and bottom-up processes in cirrhotic patients with MHE may be detected in this area using event-related potentials techniques.
Event-related brain potentials (ERPs) are useful for the temporal analysis of cognitive processes (Rugg and Coles, 1995). ERPs reflect phasic modulations of brain activity, which are time-locked to the onset of an external or internal event. The abrupt onset of a visual stimulus evokes, independently of any task demand, two early ERP components named P1 and N1. Many reports claim that the origin of the P1/N1 lies in the extrastriate pathway and they represent the early multi- level analysis of visual information coming from V1 (Eimer, 1998, Heinze et al., 1994; Hillyard and Anllo-Vento, 1998; Hopfinger and Maxwell, 2005, Johannes et al., 1995, Mangun and Hillyard, 1995) However, a minority of reports claim that their origin, at least P1, lie in the striate pathway (Hashimoto et al., 1999, Hoshiyama and Kakigi, 2001).
Even if the amplitude of these two components can be modulated by selective attention, their nature is mainly exogenous (Eimer, 1998). Spatial attention can have an effect on P1 and N1 components in trial-by-trial cueing situations (Mangun et al., 1993), which indicates a spatially selective modulation of processing in the V1–IT pathway. When the stimulus located in the unattended visual field, these components are markedly attenuated.
In multi-stimulus array visual search tasks, it has recently been described a negative ERP component that occurs in the N2 latency-window in the posterior sites contralateral to target position. This location-specific processing modulations in the ventral pathway was called N2pc (Luck and Hillyard, 1994a, Luck and Hillyard, 1994b). N2pc can be also observed when a target stimulus is laterally displayed and only a single irrelevant stimulus is presented simultaneously in the opposite visual field (Eimer, 1996; Oostenveld et al., 2001, Valle-Inclán, 1996, Wascher and Wauschkuhn, 1996, Wijers et al., 1997). From a functional point of view, the N2pc seems to reflect the spatial filtering of irrelevant information (Luck and Hillyard, 1994b). An alternative possibility is that the N2pc reflects the detection and the selection of the task-relevant information (Eimer, 1996). In any case, it is an index of visuospatial selective attention (Eimer, 1996, Eimer, 1998). The most probable generator of the N2pc seems to be located in the ventro-lateral temporal cortex (Oostenveld et al., 2001, Praamstra and Oostenveld, 2003, Wijers et al., 1997, Woldorff et al., 2002), even if a small early contribute to this component was detected in the parietal cortex (Hopf et al., 2000). In recent models regarding the enhanced neural activity induced by selective attention in the extrastriate cortex, it was suggested that, during visual search tasks, the interaction between bottom-up and top-down processes can start early in the P1–N1 latency-window, but the N2pc is evoked only when target location is selected (Woldorff et al., 2002). For this reason, the latency of this attentional modulation can vary depending on the difficulty of the target localization (Shedden and Nordgaard, 2001, Wascher, 2005). Many authors, indeed, prefer to use the term posterior contralateral negativity (PCN) to dissociate this lateralized endogenous component from the N2 component (van der Lubbe et al., 2001, Wascher et al., 2001).
Albeit many studies (Amodio et al., 1999a, Amodio et al., 2005, Rikkers et al., 1978, Schiff et al., 2005, Schomerus et al., 1981) suggest an impairment of top-down processes in MHE, there is not yet direct evidence for a clear dissociation between the efficiency of top-down and bottom-up processes in the extrastriate cortex of cirrhotic patients. In the present study we tested the integrity of these two kinds of processes in the extrastriate cortex in a group of cirrhotic patients with no signs of overt HE, in order to clarify this still unknown characteristic of MHE. For their obligatory nature, we used the P1 and N1 components as indexes of bottom-up (i.e. stimulus-driven) perceptual processing in the extrastriate cortex, and the N2pc, given its selective nature (Eimer, 1996), was used as an index of top-down (i.e. goal-directed) post-perceptual processing.
We used a choice RTs task involving visual discrimination. It is known that in a choice RTs task, if target stimuli are presented laterally with respect to a central fixation point, RTs are faster when the position of the responding hand corresponds, spatially to the position of the target (Fitts and Deininger, 1954, Fitts and Seeger, 1953). This effect occurs even if the spatial position of the target is not relevant for the task. In this case it is called Simon effect (Simon and Rudell, 1967). In the Simon task it is assumed that stimulus localization process automatically activates a response code ipsilateral to the stimulus position (De Jong et al., 1994, Wascher et al., 2001). If the automatic activated response corresponds to the appropriate response, faster RTs follow. If the automatic activated response does not corresponds to the appropriate response, it has to be inhibited. This inhibitory process requires additional time that slows RTs down in the non-corresponding condition. Moreover, the response automatically activated by the irrelevant position of the target stimulus is assumed to be transient in nature. Many studies, using the distributional analysis of RTs, showed that the automatically generated response decays with time. Therefore, with the longest RTs the Simon effect tends to disappear (De Jong et al., 1994, Hommel, 1993, Hommel, 1994, Nicoletti and Umiltà, 1994) at least under some conditions (Ansorge, 2003, Vallesi et al., 2005, Wascher et al., 2001, Wiegand and Wascher, 2005).
The first aim of the present study was to demonstrate a clear dissociation in the efficiency of bottom-up and top-down processing of cirrhotic patients in the extrastriate cortex using ERP correlates of early stimulus-driven processing, indexed by the P1 and N1, and of late goal-directed processing, expressed by the N2pc. To avoid exogenous perceptual asymmetries in the EEG signal an irrelevant distracter was displayed in the opposite visual field together with the target stimulus (Valle-Inclán, 1996). Under these conditions P1, N1 and the N2pc are frequently described (Eimer, 1996, Praamstra and Oostenveld, 2003, Valle-Inclán, 1996, Wascher and Wauschkuhn, 1996, Wascher et al., 2001). A second aim of the study was to evaluate the presence of any difference between controls and patients with regard to the Simon effect and its time-course. Distribution analysis of RTs provide a measure of RTs dispersion. In a previous study, Elssas and co-workers (1985) showed that this dispersion in RTs distribution in cirrhotic patients with overt HE was higher both compared to healthy controls and patients with brain damage. If this effect is associated with the presence of motor alteration in HE patients, this effect may be detectable also in patients with less severe motor or cognitive alteration.
Section snippets
Subjects
The population study comprised of 17 patients (4 females) with non-alcoholic cirrhosis and without evidence of overt HE and 10 healthy matched control participants (3 females) The mean age of the patients was 50±10 years and the mean age of the controls was 48±7 years (see Table 1).
The diagnosis of cirrhosis was made on the basis of historical, clinical, laboratory, endoscopic and ultrasonographic findings; histological confirmation was obtained when needed (12 patients). With one exception,
Behavioural data
Behavioural results are summarized in Table 2. The Simon effect (i.e. slower RTs in the non-corresponding condition) was observed both in cirrhotic patients (P<0.0001) and healthy controls (P<0.005). Accuracy in non-corresponding trials was found significantly lower than the corresponding one in control subjects (P<0.005), but not in cirrhotic patients. In cirrhotic patients, RTs for both the corresponding and non-corresponding conditions were significantly delayed compared to healthy controls (
Discussion
In this study, the efficiency of bottom-up and top-down mechanisms involved in perceptual and post-perceptual selective processes of the extrastriate cortex of cirrhotic patients without overt HE was explored. To that purpose, ERPs were recorded during the execution of a visual discrimination Simon task. The analysis of the ERPs revealed that the early stages of visual information processing (P1 and N1 components) are maintained even when target selection processes are altered (N2pc), and that
Acknowledgements
The authors would like to thanks Prof. Carlo Alberto Marzi from University of Verona for his helpfully suggestions about data interpretation. This research was supported in part by grants from MIUR and from the University of Padua to P.A. and C.U.
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