تاثیر حواس پرتی عاطفی بر روی حافظه کاری کلامی: بررسی مقایسه FMRI افراد مبتلا به اسکیزوفرنی و بزرگسالان سالم
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|38785||2011||10 صفحه PDF||سفارش دهید||محاسبه نشده|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Journal of Psychiatric Research, Volume 45, Issue 9, September 2011, Pages 1184–1193
Abstract The ability to maintain information over short periods of time (i.e., working memory) is critically important in a variety of cognitive functions including language, planning, and decision-making. Recent functional Magnetic Resonance Imaging (fMRI) research with healthy adults has shown that brain activations evoked during the delay interval of working memory tasks can be reduced by the presentation of distracting emotional events, suggesting that emotional events may take working-memory processes momentarily offline. Both executive function and emotional processing are disrupted in schizophrenia, and here we sought to elucidate the effect of emotional distraction upon brain activity in schizophrenic and healthy adults performing a verbal working memory task. During the delay period between the memoranda and memory probe items, emotional and neutral distractors differentially influenced brain activity in these groups. In healthy adults, the hemodynamic response from posterior cingulate, orbital frontal cortex, and the parietal lobe strongly differentiated emotional from neutral distractors. In striking contrast, schizophrenic adults showed no significant differences in brain activation when processing emotional and neutral distractors. Moreover, the influence of emotional distractors extended into the memory probe period in healthy, but not schizophrenic, adults. The results suggest that although emotional items are highly salient for healthy adults, emotional items are no more distracting than neutral ones to individuals with schizophrenia.
1. Introduction Schizophrenia is a disorder characterized by disruptions in perception. Individuals with schizophrenia may perceive stimuli that are not present (e.g., auditory or visual hallucinations) or may respond to stimuli in an uncharacteristic manner (e.g., lack of affective response to emotional stimuli). In addition, schizophrenia can profoundly impair cognitive functioning. Some have suggested that a primary deficit in working memory may underlie many of the cognitive deficits seen in schizophrenia (Goldman-Rakic, 1994). For example, verbal dysfluencies (Conklin et al., 2000 and Heinrichs and Zakzanis, 1998) may persist due to an inability to maintain an ordered progression of thoughts or words. A focus on external stimuli may indicate a lack of ability to maintain an internal list of thoughts or goals (Goldman-Rakic, 1994). Working memory, the ability to maintain and manipulate information over brief periods of time, is vital to many cognitive processes including language, planning, and decision-making. Verbal working memory, working memory in sentences, words, and letters, relies heavily on prefrontal cortices (Cohen et al., 1994, Cohen et al., 1997, McCarthy et al., 1994 and Petrides et al., 1993). Middle frontal gyrus has been shown to be engaged by several working memory tasks including spatial working memory (McCarthy et al., 1994), number generation and number memory (Petrides et al., 1993), and letter memory (Sweet et al., 2008). Activation in inferior frontal gyrus (IFG) has been observed during a variety of linguistic tasks such as memory for letters (Cohen et al., 1997), semantic categorization (Kapur et al., 1994 and Roskies et al., 2001), semantic association (Noppenney et al., 2004), semantic priming (Copland et al., 2007, Demb et al., 1995 and Gold et al., 2006), rhyme judgments (Paulesu et al., 1993 and Roskies et al., 2001), pseudo-homophone naming (Owen et al., 2004), and phoneme monitoring (Demonet et al., 1992 and Zatorre et al., 1996). The neural infrastructure of working memory is of considerable relevance to clinical disorders in which executive function is impaired, such as schizophrenia. Several studies suggest that individuals with schizophrenia elicit less brain activation compared to healthy adults during working memory tasks. Using a two-back task with Korean alphabetical letters, individuals with schizophrenia elicited decreased activation in inferior frontal, middle frontal, and superior temporal gyri compared to healthy controls (Pae et al., 2008). Similarly, during an N-back task using English letters patients elicited less activation in right dorsolateral prefrontal cortex (DLPFC) than healthy adults ( Perlstein et al., 2003). Decreased activation in DLPFC for patients compared to healthy controls has also been observed during continuous performance tasks ( Barch et al., 2001 and Perlstein et al., 2003). Children of schizophrenic individuals (high risk offspring) have also been found to elicit less activation in DLPFC and inferior parietal cortex compared to healthy controls during a spatial working memory task ( Keshavan et al., 2002). In addition to differences in levels of activation, the extent of activation may be influenced by task difficulty. At lower difficulty levels (e.g., 0-back, 1-back) activation was similar among patients and controls, but at more difficult loads, activation continued to increase linearly for healthy adults, but declined in patients (Perlstein et al., 2001). Moreover, they found that load-dependent increases in prefrontal activation were negatively correlated with the severity of disorganized symptoms in the patients. In a separate study, although load-dependent increases in activation were found for all participants, the magnitudes of the increases were significantly smaller in patients compared with healthy controls (Perlstein et al., 2003). Beyond DLPFC, others have reported reduced activation for adults with schizophrenia. During a spatial working memory task, although there were no differences in fMRI activation in DLPFC, patients elicited less activation in left anterior cingulate and bilateral parietal cortex compared to healthy controls (Kindermann et al., 2004). Similarly, Schneider and colleagues found that patients elicited decreased activation in the precuneus during an N-back task compared to healthy controls, although they also reported increased activation in ventrolateral prefrontal cortex ( Schneider et al., 2007). However, others have reported no significant differences in brain activation comparing individuals with schizophrenia and control participants. Honey and colleagues (Honey et al., 2002) found that both patients and healthy controls strongly activated the frontal–parietal network during a verbal N-back task, with no significant differences between groups. Interestingly, activation in posterior parietal cortex was positively correlated with reaction time in healthy adults, but not in patients. There have been several reports of differences in brain activation between patients and controls that indicate increases in activation in dorsolateral prefrontal cortex (DLPFC) for patients (Manoach et al., 2000, Manoach et al., 1999 and Potkin et al., 2009). In a recent study, both groups showed significant activation in DLPFC during a Sternberg Item Recognition Paradigm (SIRP), however, patients elicited significantly greater activation than healthy controls (Potkin et al., 2009). Moreover, the pattern of increased activation remained when performance was matched across a subset of participants from the two groups. The authors characterized these changes as inefficiencies in processing because the increased activation did not correspond to performance improvements. Van Raalten and colleagues examined the role of familiarity in working memory processes by comparing activation during the SIRP with practiced and novel stimuli. With novel stimuli, patients elicited larger patterns of activation in left prefrontal regions than healthy controls. Although both groups showed decreases in activation with practiced stimuli, only in healthy controls did the magnitude of this decrease correspond to improvements in performance (van Raalten et al., 2008). Increased brain activation was also found among first-degree relatives of individuals with schizophrenia during a verbal auditory continuous performance task (Thermenos et al., 2004). Relatives elicited greater task-related activation in prefrontal regions, as well as in thalamus and anterior cingulate compared to healthy adults. These findings suggest that neurocognitive dysfunction associated with schizophrenia extends across a variety of cognitive tasks and may extend to close relatives. Additionally, the behavioral (Honey et al., 2002) and functional differences in individuals with first-episode schizophrenia (Barch et al., 2001, Perlstein et al., 2001 and Schneider et al., 2007), and in relatives (Keshavan et al., 2002 and Thermenos et al., 2004) suggest that neurocognitive changes may be at least partially independent of symptom duration. While these studies have examined executive function in patient and control participants, they have not examined the interaction of emotional processing and executive function in individuals with schizophrenia. Previous research has suggested that different networks are involved in executive function and emotional processing. Several lines of research have proposed a dorsal–ventral distinction such that a dorsal network including middle frontal gyrus, parietal cortex, and posterior cingulate is involved in executive tasks, while ventral brain regions such as inferior frontal gyrus, orbital frontal cortex, and the amygdala are involved in emotional processing (Anticevic et al., 2010, Fichtenholtz et al., 2004, Phan et al., 2002, Phan et al., 2004, Phelps and Ledoux, 2005, Wang et al., 2006, Wang et al., 2005 and Yamaskai et al., 2002). Others have suggested that the insula, in particular anterior insular cortex, is involved in interoceptive and emotional sensation, and that the insula along with anterior cingulate cortex may underlie consciousness (Craig, 2002 and Craig, 2009). More recently, research has probed how emotion and distraction interact in working memory among individuals with schizophrenia. Dichter and colleagues investigated the role of emotional and neutral distractors during a visual oddball task in individuals with schizophrenia and healthy control participants (Dichter et al., 2009). Consistent with previous results, healthy control participants elicited activation in dorsolateral prefrontal regions to target stimuli, while emotional stimuli elicited activation in ventral–frontal brain regions. However, individuals with schizophrenia elicited less activation to target stimuli in dorsolateral prefrontal regions and less activation to emotional distractors in ventral–frontal brain regions. In addition, the schizophrenic patients also showed less deactivation within these brain regions when compared to healthy adults. These results suggest that brain regions involved in both emotional processing and executive function may be dysfunctional in schizophrenia. In the present study, we utilized a verbal working memory task that incorporated emotional and neutral distractors. Participants were instructed to remember a series of eight words that were followed by a delay period that contained either emotional or neutral distracting photographs (International Affective Picture System: IAPS). Following the delay period, participants were shown eight pairs of words and asked to decide which word in each pair was presented in the initial memoranda. Of greatest interest is the comparison between emotional and neutral trials in patients and controls. We hypothesized that healthy adults, would show greater activation to emotional distractors compared to neutral distractors in ventral brain regions, such as amygdala, and orbital frontal cortex. Moreover, we predicted that patients would not differentiate emotional and neutral distractors as strongly as healthy adults. With respect to the executive network, previous research suggests that patients inefficiently activate the frontal–parietal network, as evidenced by reduced activations (Barch et al., 2001, Dichter et al., 2009, Pae et al., 2008, Perlstein et al., 2001 and Perlstein et al., 2003), and activations that are unrelated to performance measures (Honey et al., 2002 and van Raalten et al., 2008). Based on those results we expected that patients would show reduced patterns of activation in the executive frontal–parietal network compared to healthy adults, and that these patterns of activation would not be strongly related to behavioral performance.
نتیجه گیری انگلیسی
3. Results 3.1. Behavioral results We examined the response times and accuracies using two-way Analyses of Variance (ANOVAs) with group (healthy controls, patients) and trial type (neutral, emotional) as factors. For response times during the forced-choice task, there was a main effect of group (F = 8.66(1), p < .005; patients = 1130 ms; healthy adults = 1010 ms), but no main effect of trial type (F = .01 (1), p = .921), nor a group by trial type interaction (F = .001 (1), p = .973). For accuracies during the forced-choice task, there was again a main effect of group (F = 12.95 (1), p < .001; patients = 59.3%, healthy controls = 79.5%), but no main effect of trial type (F = .037 (1), p = .849), nor trial type by group interaction (F = .086(1), p = .771). We also examined the response times and accuracy information from the secondary face-detection task that half of the participants performed during the maintenance period to assess task-compliance. There was a significant main effect of group in the response time data (F = 8.1 (1), p = .013; patients = 956.10 ms, healthy controls = 806.71 ms), but no main effect of trial type (F = .018 (1), p = .894), nor group by trial type interaction (F = 2.5 (1), p = .13). There were no differences in accuracy for any of the comparisons (F = .009 (3), p = .999). Behavioral data from 3 patients was lost due to computer error. 3.2. fMRI results 3.2.1. Encode period Both groups elicited activation in bilateral inferior frontal gyrus, which extended through the insula and precentral gyrus. Both groups also elicited activation in bilateral occipital and fusiform gyri, left parietal cortex, and a midline activation that extended into right and left medial frontal gyrus. There were no significant differences in brain activation between trial types or groups during this period, and there were no significant interactions between group and trial type (see Fig. 2). Cluster coordinates from the overall activation during the Encode period are provided in Table 2. Results from the two groups during this period were collapsed into one Table because of the lack of differences between groups and trial types. Activation During the Encode Period. Overall activation to emotional and neutral ... Fig. 2. Activation During the Encode Period. Overall activation to emotional and neutral trials during the encode period is displayed. There were no significant differences between groups or between trial types within groups. Largely overlapping patterns of activation for healthy controls (red) and patients (blue) can be seen. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). Figure options Table 2. Coordinates for clusters of activation during the encode period for all participants. Regions of activation during the encode period Region Hemisphere X Y Z Max Z value # Voxels Inferior frontal gyrus/insula Right 38 16 2 4.59 1314 Left −32 18 2 4.68 3022 Precentral gyrus Right 40 4 30 4.11 461 Left −46 −2 36 4.68a 3022a Occipital/Fusiform gyrus Right 36 −88 2 4.87 1928 Left −38 −76 0 5.17 3311 Parietal cortex Left −28 −52 48 6.05 617 Medial frontal gyrus Bilateral −2 6 52 4.41 1047 a The left inferior frontal gyrus and left precentral gyrus activations formed a single contiguous region. Table options 3.2.2. Maintenance (distractor) period The primary comparisons examined the difference between Emotional and Neutral trials for each participant group, and the interaction between trial type and participant group. During the maintenance period, healthy controls showed extensive patterns of activation. Significant differences between Emotional and Neutral trials in healthy adults were found in bilateral occipital and fusiform gyri (Right: 50, −72, 4; Left: −48, −78, 12), bilateral orbital and medial frontal cortices (Right: 4, 38, −20; Left: −4, 38, −22), bilateral cerebellum (Right: 16, −74, −32; Left: −14, −72, −32), left middle temporal gyrus (−48, −16, −16), and bilateral middle frontal and precentral gyri (Right: 40, 8, 26; Left: −42, 12, 20). Schizophrenic patients elicited a larger response to emotional trials compared with neutral trials in bilateral occipital cortex (Right: 48, −66, 0; Left: −44, −66, 2). This cluster of activation extended through posterior temporal gyri. A significant interaction effect of group and distractor type was found during the maintenance period. In regions where emotional stimuli elicited greater activation compared to neutral stimuli, healthy control participants elicited significantly greater differences in activation than adults with schizophrenia in bilateral posterior cingulate, right parietal cortex, and bilateral orbital frontal cortex (Fig. 3). The MNI coordinates for these activations are provided in Table 3. In posterior cingulate and orbital frontal cortex healthy adults elicited a larger hemodynamic response to emotional trials compared to neutral trials, but in patients this region did not significantly respond to either trial type. In parietal cortex both groups elicited a significant hemodynamic response to both trial types; however, only in healthy controls was the magnitude of the response differentiated by trial type. There were no regions in which the patient group elicited greater activation than healthy controls. Activation During the Maintenance Period. a. Areas in red indicate regions where ... Fig. 3. Activation During the Maintenance Period. a. Areas in red indicate regions where the difference between emotional and neutral trials (emotional > neutral) was greater for healthy control participants compared to schizophrenic patients. These differences can be seen in three regions: bilateral posterior cingulate, right parietal cortex, and bilateral orbital frontal cortex. b. The corresponding hemodynamic responses (HDRs) for emotional (red) and neutral (blue) trials for healthy controls and schizophrenic patients (emotional = orange, neutral = green) are shown. HDRs shown are for the entire trial. Encode, maintenance, and probe periods are denoted by the gray and white bars in the background. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). Figure options Table 3. Cluster Coordinates for regions in which there was a significant interaction between Group (healthy adults and schizophrenic patients) and Trial type (emotional and neutral). Significant interactions between group and trial type during the distractor period Region Hemisphere X Y Z Max Z value # Voxels Posterior cingulate Right 12 −58 18 3.13 661 Left −4 −50 10 3.24 661a Parietal cortex Right 38 −76 38 3.4 740 Orbital frontal cortex Right 8 42 −14 2.66 324 Left −8 48 −14 2.78 324a a Bilateral posterior cingulate and bilateral orbital frontal activations each extended to a single contiguous activation across the hemispheres. Table options For those regions in which there was a significant interaction of group and trial type, we also conducted anatomically based region of interest (ROI) analyses. We conducted one additional anatomical ROI analysis based on an a priori region of interest: the amygdala. For each region, we conducted an ANOVA with three factors: group (patient, healthy control), trial type (emotional, neutral), and hemisphere (right, left). In bilateral orbital frontal cortex (OFC), bilateral posterior cingulate (PC), bilateral amygdala, and right parietal cortex there were significant main effects of trial type (OFC: F = 71.66 (1), p < .001; PC: F = 63.3 (1), p < .001; Amygdala: F = 48.8, p < .001; R Parietal: F = 19.06 (1), p < .001) and significant interactions of group and trial type (OFC: F = 113.56 (1), p < .001; PC: F = 187.13, p < .001; Amygdala: F = 22.65 (1), p < .001; R Parietal: F = 71.75 (1), p < .001). Although overall, emotional trials elicited a larger response than neutral trials, this pattern was seen in healthy controls but not patients. Thus the differentiation to emotional and neutral trials seen in healthy controls may be the driving factor behind the main effect of trial type. Additionally, in bilateral posterior cingulate there was a significant main effect of group (F = 9.85, p = .002), in which healthy controls overall elicited larger hemodynamic responses than patients. 3.2.3. Probe (retrieval) period The primary comparisons examined the difference between emotional and neutral trials for each participant group, and the interaction of trial type and participant group. Healthy young adults elicited greater activation to emotional trials compared to neutral trials in bilateral posterior cingulate and precuneus (Right: 8, −52, 30; Left: −8, −58, 30), bilateral orbital and medial frontal gyri (Right: 6, 38, −14; Left: −10, 52, −2) and bilateral middle and superior temporal gyri (Right: 50, −34, 4; Left: −56, −20, −2). Individuals with schizophrenia did not differentiate emotional and neutral trials during the probe period. During the probe period there was a significant interaction of group and trial type in bilateral posterior cingulate (Centroid: 0, −44, 26; Max Z value: 3.11, 561 Voxels), see Fig. 4. Emotional trials elicited a larger response than neutral trials, but only in the healthy control group. See Fig. 3 for hemodynamic responses during the probe period. Activation During the Forced Choice Probe Period. Areas in red indicate regions ... Fig. 4. Activation During the Forced Choice Probe Period. Areas in red indicate regions where healthy controls elicited a significantly greater difference between emotional and neutral trials (emotional > neutral) compared to schizophrenic patients. These differences can be seen in bilateral posterior cingulate. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article). Figure options Again, we conducted anatomical ROI analyses for the region in which there was a significant interaction of group and trial type, posterior cingulate. A 2 × 2 × 2 ANOVA was conducted with group, trial type, and hemisphere as the factors. There were significant main effects of group (healthy control > patient; F = 10.23 (1), p < .001) and trial type (emotional > neutral; F = 105.91 (1), p < .001). In addition there was a significant interaction of group and trial type (F = 85.77 (1), p < .001), where healthy control participants elicited a greater response to emotional trials compared with neutral trials, and patients did not differentiate these trial types. These results may reflect the continued influence of the emotional distractors on the healthy control group’s pattern of activation. Because there was a significant effect of age across groups it is possible that the fMRI effects that we observed during the maintenance and probe periods were due to an effect of age. To assess this possibility we conducted a separate analysis including age as a covariate. We did not observe a significant main effect of age or significant differences in the effect of age between the two groups. 3.2.4. Secondary task There were no significant differences in activation during any of the task periods when we examined the influence of the secondary task (face-detection).