Effects of attention on dichotic listening in elderly and patients with dementia of the Alzheimer type

Brain and Cognition 76 (2011) 286–293

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Effects of attention on dichotic listening in elderly and patients with dementia of the Alzheimer type Anke Bouma a,⇑, Liselotte Gootjes b a b

Department of Clinical and Developmental Neuropsychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS Groningen, The Netherlands Institute of Psychology, Faculty of Social Sciences, Erasmus University Rotterdam, Rotterdam, The Netherlands

a r t i c l e

i n f o

Article history: Available online 22 March 2011 Keywords: Dichotic listening Auditory processing Aging Alzheimer’s disease Attention Laterality Corpus callosum MRI MEG Executive function

a b s t r a c t This article presents an overview of our studies in elderly and Alzheimer patients employing Kimura’s dichotic digits paradigm as a measure for left hemispheric predominance for processing language stimuli. In addition to structural brain mechanisms, we demonstrated that attention modulates the direction and degree of ear asymmetry in dichotic listening. Elderly showed increasingly more difficulties focusing attention on the left ear (LE) with advancing age. Alzheimer patients showed severe deficits to allocate attention to the LE, which could result in a right ear advantage. These results may be attributed to a breakdown of the cortical attentional network which is mediated by frontal (inhibitory control of attention) and parietal regions (spatial attention and ‘disengagement processes’). Both interhemispheric disconnectivity (callosal atrophy) and intrahemispheric disconnectivity (subcortical white matter lesions) appear to be important factors contributing to these findings. Ó 2011 Elsevier Inc. All rights reserved.

1. Introduction Since Kimura has published her influential studies in 1961, the dichotic listening paradigm can be considered as one of the most important, noninvasive behavioral methods for the study of hemispheric specialization in language processes (Kimura, 1961). Kimura employed the ‘classic’ dichotic listening task, in which three pairs of digits were presented simultaneously to the left ear (LE) and right ear (RE), and subjects were asked to report as many digits as possible. Kimura found that verbal stimuli presented to the RE were reported more accurately than verbal stimuli to the LE. According to the structural model, Kimura proposed (1961, 1967) that the RE advantage (REA) is based on the anatomical organization of the auditory system and the hemispheric specialization of language functions. She assumes that stimuli are processed more easily if they are projected directly, via contralateral pathways, to the hemisphere that is specialized for that task. She further assumes that ear asymmetries can be obtained under dichotic stimulation only, since in this condition information transmitted via ipsilateral pathways is suppressed by the stronger contralateral input. Thus, information from the RE is projected directly to the language-dominant left hemisphere, whereas information from the LE

⇑ Corresponding author. E-mail address: [email protected] (A. Bouma). 0278-2626/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.bandc.2011.02.008

is transmitted indirectly – via the right hemisphere and the corpus callosum (CC) – to the left hemisphere. Many clinical and experimental studies have confirmed the structural mechanisms proposed by Kimura. Nevertheless, several research findings cannot be explained by structural models. First, studies have shown that the direction and degree of ear asymmetry may be affected by cerebral injuries at locations which are not involved in structural models, such as brain lesions in the frontal lobe, parietal lobe, thalamus, basal ganglia, and insula (Bamiou et al., 2006; Eslinger & Damasio, 1988; Hugdahl, Bodner, Weiss, & Benke, 2003; Hugdahl, Wester, & Asbjørnsen, 1990; Ogden, 1985; Wester, 2008). Second, studies in clinical and healthy subjects have demonstrated that interhemispheric connectivity between the two hemispheres in dichotic listening tasks is not restricted to the posterior regions of the CC which, according to structural models, would specifically transmit auditory information (Bamiou, Sisodiya, Musiek, & Luxon, 2007; Westerhausen & Hugdahl, 2008). Third, functional brain imaging studies, like PET, fMRI or MEG, not only highlight the importance of temporal regions in dichotic listening, but also point at the contribution of other cerebral areas like prefrontal and parietal brain regions (Gootjes, Bouma, van Strien, Scheltens, & Stam, 2006; Jäncke, Buchanan, Lutz, & Shah, 2001; Lipschutz, Kolinsky, Damhaut, Wikler, & Goldman, 2002; Thomsen et al., 2004). Fourth, it has been found that individual ear asymmetries can easily be modified by instructing subjects to attend to either the LE or RE (Hugdahl, 2003;

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Hugdahl et al., 2009). Due to these research findings, alternative models have been proposed to extend Kimura’s structural model by attentional mechanisms.

2. Attention modulates laterality Kinsbourne (1970, 1973) has developed a more dynamic model of hemispheric asymmetry in which attentional processes contribute to ear asymmetries. Kinsbourne proposed that ear asymmetries are primarily determined by the relative levels of activation of the two hemispheres. Moreover, each hemisphere would have a reciprocally inhibitory relationship with the other. If the left hemisphere is more strongly activated than the right, the directional attention bias shifts to the contralateral right hemispace, resulting in improved processing of stimuli presented to the RE. Vice versa for the right hemisphere and left hemispace. Although different versions of structural and attentional models have been proposed, most researchers assume that a combined model provide the best framework to explain the observed variability of ear asymmetries (Bouma, 1990; Hugdahl, 2003). Kimura’s classic dichotic listening task requires subjects to divide attention between two ears. In this condition, subjects are free to report the digits in any order they choose and typically, they recall the digits presented to one ear before recalling those from the other ear (Bryden, 1982; Bryden, Munhall, & Allard, 1983). Bryden and colleagues have argued that ear asymmetries are influenced by individual differences in strategies to focus attention on either the LE or RE. In order to control for volitional attention shift, focusedattention tasks have been introduced. In simple focused-attention paradigms, subjects are required to focus attention on one ear selectively and to recall the stimuli from the attended ear only or to report only the stimuli from the ear they heard most clearly (Hugdahl, 2003). In more complex focused-attention paradigms, subjects are instructed to focus attention on one ear and to recall the stimuli from this ear first (attended ear) and the stimuli from the other ear second (unattended ear). Subjects are thus asked to direct most of the attention to a designated ear, but at the same time to take notice of the other ear. Neuroimaging studies have indeed found that dichotic listening is not simply a function of temporal lobe activation. Rather, the frontal and parietal lobes appear also to be involved in a cortical network of interacting cerebral regions mediating attention in dichotic listening (Gootjes, Bouma, Van Strien, Scheltens, et al., 2006; Jäncke et al., 2001; Lipschutz et al., 2002; Thomsen et al., 2004). Also, it has been shown that attention to specifically one ear activates more strongly the contralateral hemisphere (Gootjes, Bouma, Van Strien, Scheltens, et al., 2006; Jäncke et al., 2001; Lipschutz et al., 2002). Parietal areas appear to be involved in spatial attention, while frontal areas play an important role in executive control of attention. Moreover, different cognitive processes have been proposed in free- and focused-attention conditions (Hugdahl, 2003; Hugdahl et al., 2009). With free recall procedures, bottom-up (stimulus-driven) processing of verbal stimuli is assumed to rely strongly on structural hemispheric differences in language processing, which normally results in superior performance of the right ear. With focused-attention procedures, ear asymmetries are also affected by top-down (instruction-driven) processes. When attention has to be focused on the RE (forced-right attention, FR), top-down and bottom-up processes are in the same direction, thus both contributing to better performance of the RE. However, when attention has to be focused on the LE (forced-left attention, FL), top-down and bottom-up processes are in opposite direction and have contradictory effects. In this conflicting situation, attention to the dominant RE has to be inhibited so that subjects are able to shift

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their attention to the LE. Such inhibitory, executive functions are supposed to be mediated by frontal areas. There are indications that in this condition the left middle frontal gyrus plays a specific role in executive control of attention (Andersson, Ystad, Lundervold, & Lundervold, 2009; Thomsen et al., 2004). Furthermore, using MEG, we (Gootjes, Bouma, Van Strien, Scheltens, et al., 2006) showed that specifically in the FL condition ear asymmetry was strongly associated with functional connectivity within the left frontal and left parietal areas. This indicates that intrahemispheric connectivity of these regions plays an important role when increased top-down processing is required.

3. Effects of attentional modulation on dichotic listening in elderly The dichotic listening task is an excellent method for examining age-related cognitive decline since it involves different degrees of attentional and memory processes. Research has demonstrated that dichotic listening performance of elderly is decreased compared to younger participants. More specifically, an age-related increase of ear asymmetry has been reported: performance of the LE has been found to decrease more strongly than performance of the RE (Andersson, Reinvang, Wehling, Hugdahl, & Lundervold, 2008; Bellis & Wilber, 2001; Hommet et al., 2010; Hugdahl, 2003; Hugdahl et al., 2009; Martin & Jerger, 2005; Roup, Wiley, & Wilson, 2006; Strouse Carter & Wilson, 2001). However, this finding is still controversial since some studies have failed to find such an effect (Borod & Goodglass, 1980; Hugdahl, Carlsson, & Eichele, 2001; Martini et al., 1988; Takio et al., 2009) or have found that age-effects could only be obtained in focused-attention conditions, particularly in FL conditions (Alden, Harrison, Snyder, & Everhart, 1997; Hällgren, Larsby, Lyxell, & Arlinger, 2001; Thomsen et al., 2004).

3.1. Empirical studies of aging employing Kimura’s dichotic digits paradigm 3.1.1. Age-effects when comparing older and younger adults In one of our studies, dichotic listening performance of 31 older adults (61–80 years) was compared to the performance of 25 younger adults (19–29 years) under free- and focused-attention conditions (Gootjes, Van Strien, & Bouma, 2004). In the free-attention task, we employed Kimura’s 3-digits pairs task, and asked participants to report as many digits as possible, irrespective of the ear in which the digits were heard. In the focused-attention task, attention had to be focused on the LE or RE. In this task, each trial was preceded by a tone which was presented either to the LE or RE, and participants had to report first as many digits as possible from the ear to which the tone was presented and then from the other ear. Moreover, participants had to indicate verbally when they switched reporting digits from the attended ear to reporting digits from the unattended ear. The sequence of tone presentation was random. The focused-attention paradigm allows study of performance of both the ‘attended’ ear which receives most of the attention, and the ‘unattended’ ear which receives less attention. The stimuli from the attended ear have to be reported immediately, thus performance of this ear relies on immediate perception. On the other hand, performance of the unattended ear relies on short-term memory function since stimuli from this ear have to be kept in memory while information from the other ear is being reported. Free-attention task. Fig. 1 illustrates that in the free-attention task, both the younger and older group showed the expected REA. Older subjects showed reduced recall accuracy, but no signif-

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Fig. 1. Mean percentage correct responses and localization errors per age-group in the free-attention and focused-attention conditions (LE = left ear; RE = right ear). (Adapted from Gootjes, Teipei, et al., 2004; Gootjes, Van Strien, et al., 2004).

icant difference in ear asymmetry between the two groups was found. Focused-attention task: correct responses An overall REA was also obtained in the focused-attention condition (Fig. 1). However, attention clearly modulates the direction of ear advantage: a LE advantage (LEA) was observed in the FL condition and a large REA in the FR condition. Older adults showed reduced recall accuracy compared to younger adults. In contrast to the free-attention task, we found decreased recall performance for the unattended ear in the elderly, which was most marked for the unattended LE in the FR condition. Focused-attention task: localization errors A localization error (or intrusion) indicates that a digit was identified correctly, but attributed to the wrong ear. As Fig. 1 shows, the results of localization errors in the focused-attention task are in the opposite direction as those of correct responses. We found more localization errors for the RE than for the LE. Also, attention clearly influenced the direction of ear asymmetry: more localization errors were made for the RE than for the LE in the FL condition, while ear asymmetry was reversed in the FR condition. As can be seen, age-related increase in localization errors was only found for the unattended ear, particularly for the unattended RE in the FL condition. These findings suggest that identifying and localizing digits are different processes mediated predominantly by the left and right hemisphere, respectively. Specifically the right hemisphere is thought to play a dominant role in identifying features of sound stimuli and localizing their spatial position (Rauschecker & Tian, 2000), as has also been observed in neuroimaging studies (Weeks et al., 1999; Zatorre, Bouffard, Ahad, & Belin, 2002). For both recall accuracy and localization errors, decreased performance of specifically the unattended ear with increasing age is in agreement with the view that age-related decline is associated with tasks that require higher cognitive demands on memory. Interestingly, the older group showed specifically decreased recall accuracy for the unattended LE and increased localization errors for the unattended RE. Thus, age-related decline is particularly observed on the ear ipsilateral to the hemisphere which is dominant for that particular function. Age-related decrease of LE recall may be caused by an increasing inability of elderly to inhibit attention to the RE and to intentionally switch their attention from the dominant RE to the non-dominant LE. This increased failure may be due to impaired cognitive flexibility, a function mediated by the executive control functions of the frontal lobes. Based on recent (f)MRI studies, the left middle frontal gyrus is suggested to be responsible for age-related decline in top-down control of executive attention (Andersson et al., 2009; Thomsen et al., 2004). Another factor contributing to age-effects could be increased spatial difficulties to

move attention from one location to another in the contralateral hemispace (‘disengagement operation’) (Posner, Walker, Friedrich, & Rafal, 1984), a function assumed to be mediated by the parietal lobes. With respect to localization errors, we suggest that in a similar way both executive control deficits as well as disengagement problems contribute to the increased difficulties of elderly when localizing digits in the unattended RE. Several researchers have proposed that age-related cognitive decline affects functions of the right hemisphere to a greater degree than those of the left (Dolcos, Rice, & Cabeza, 2002). This socalled hemi-aging hypothesis predicts that the LE is more susceptible for age-related decrease than the RE in dichotic listening performance. The recall accuracy data are in agreement with this prediction, but the localization error findings do not support this hypothesis. We suggest that these results may be attributed to declined CC functioning, which leads to a less efficient interhemispheric transfer of auditory information. This interpretation is in agreement with the corpus callosum deficit theory of Goldstein and Braun (1974) who proposed that callosal size decreased with age. Callosal size has indeed been found to decrease with age and to correlate with dichotic listening performance in patients and healthy subjects (Gootjes, Bouma, Van Strien, Van Schijndel, et al., 2006; Westerhausen & Hugdahl, 2008). As a result, for recall of digits, LE information would be transferred less efficiently to the language-dominant left hemisphere, while for localization of digits, RE information would be transferred less efficiently to the right hemisphere which is dominant for localizing auditory stimuli. 3.1.2. Age-effects when comparing with older adults One could hypothesize that age-related problems would be stronger, the older the individuals are. In order to investigate the aging effect within elderly, 96 subjects received the dichotic digits task under free- and focused-attention conditions (Bouma, 1998). The subjects were divided into three age decades: 60–69 years, 70–79 years, and 80–89 years. Free-attention task. A significant REA was obtained, but there were no significant differences between the three age groups, despite a tendency towards a stronger decline of LE than RE performance with increasing age (see Fig. 2). Focused-attention task. For all age groups, a large REA was observed in the FR condition, but age did not interact with ear asymmetry. However, in the FL condition, we found a stronger performance decrement for the LE than for the RE. As a result, a LEA observed in the 60–69 year group shifted gradually to a slight REA in the 80–89 year group. These findings suggest an increasing attentional bias for RE stimuli with advancing age which may be caused by an increasing inability of older subjects to inhibit the

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Fig. 2. Mean percentage correct responses per age-group in (a) the free-attention task (free LE = left ear; free RE = right ear) and (b) the left and right focused-attention conditions (att LE = attended left ear; att RE = attended right ear; unatt LE = unattended left ear; unatt RE = unattended right ear). (Adapted and extended data from Bouma, 1998).

dominant RE information. Interestingly, increasing difficulties in older subjects to overcome the right attentional bias in the FL condition was also reflected by increased negative correlations between LE and RE scores (60–69 years: r = .09, ns; 70–79 years: r = .30, p < .05; 80–89 year group: r = .46, p < .05). No significant relationships between the two ears were found in the FR condition. Also in the free-attention condition, increased negative correlations between the ears were observed as a function of age, although the strength of the relations was somewhat smaller (60–69 years: r = .09, ns; 70–79 years: r = .25, ns; 80–89 year group (r = .37, p < .05). These results support the idea that also within elderly age-related decline is most strongly observed when attention has to be focused on the LE, that is, when top-down and bottom-up processes are in the opposite direction and have contradictory effects. In this conflicting situation, the correlations between the LE and RE become more negative as a function of advanced age. Decreased ability to overcome bottom-up processes in favor of top-down processes was most marked in the oldest group, who even showed a slight REA. As stated before, age-related difficulties may additionally be attributed to increased problems in spatial disengagement processes mediated by the parietal lobe, and reduced interhemispheric interaction.

3.1.3. Intrahemispheric disconnectivity and aging in dichotic listening Cortical ‘disconnectivity’ involving disruptions of white matter tracts in the brain has been hypothesized as a mechanism of agerelated cognitive decline (Moseley, 2002; Wozniak & Lim, 2006). Several MRI studies found age-related increase of diffuse hyperintensities in the deep subcortical white matter (so-called white matter hyperintensities, WMH). These WMH are considered to represent ischemic damage of the subcortical fiber system and age-related increase of vascular changes may underlie the relation with age (Christiansen, Larsson, Thomsen, Wieslander, & Henriksen, 1994). Lesions of the subcortical fiber system may reduce intrahemispheric connectivity, and they may thus be associated with reduced dichotic listening performance in elderly. In order to investigate the influence of WMH on dichotic listening, the free- and the focused-attention task were presented to 36 healthy, older adults (Gootjes, Scheltens, Van Strien, & Bouma, 2007). The participants were equally divided in a younger group (50–68 years) and an older group (72–81 years). The results of the free-attention task showed a stronger REA for the older elderly group than for the younger elderly, particularly due to a stronger decrease of LE compared to RE performance. In the focused-attention task, an overall REA was obtained in both

groups. As in previous studies, a LEA was obtained in the FL condition, and a REA was found in the FR condition. Also, we found reduced performance for the unattended ears with increasing age. The older group showed increased total and regional WMH in both hemispheres (frontal, parietal, temporal and occipital regions) compared to the younger group. Hierarchical regression analyses for the free-attention task revealed that the age-effect on decreased LE performance is mediated for 7% by WHM in the left hemisphere. For the focused-attention task, we found that the age-effect on decreased performance of the unattended LE is mediated for 40% by left hemisphere WMH. Furthermore, the age-effect on decreased performance of the unattended RE is mediated for 19% by right hemisphere WMH and for 5% by left hemisphere WMH. These results revealed that WMH mediate a substantial part of age-effects in performance of specifically the unattended ears in the focused-attention task. We suggest that WMH in the hemisphere contralateral to the attended ear contribute to this age-effect. Increased WMH reduces connectivity within that hemisphere, which might have a strong effect on processing of specifically the unattended ears since they involve more effortful processes and are more likely to be affected by reduced integrity of white matter tracts than performance of the attended ear. Our findings underline the idea that cortical disconnectivity is involved in age-related decline in dichotic listening and that both structural cerebral changes and dynamic processes like attention play an important role.

4. Effects of attentional modulation on dichotic listening in Alzheimer’s disease Most dichotic listening studies in patients with neurodegenerative diseases have been carried out in Alzheimer’s disease (AD). Alzheimer patients showed decreased performance on dichotic listening tasks compared to age matched elderly (Claus & Mohr, 1996; Duchek & Balota, 2005; Grady et al., 1989; Grimes, Grady, Foster, Sunderland, & Patronas, 1985; Mohr, Cox, Williams, Chase, & Fedio, 1990; Strouse, Hall, & Burger, 1995). Moreover, LE performance is found to decrease more strongly than RE performance, which results in increased REA in this group (Claus & Mohr, 1996; Mohr et al., 1990; Strouse et al., 1995). Claus and Mohr (1996) have reported that Alzheimer patients showed even a REA when they were instructed to pay attention to the LE. Decreased dichotic performance in AD has been associated with cortical atrophy, especially in the temporal lobe (Grady et al., 1989; Grimes et al., 1985), but also other brain dysfunctions may

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contribute. AD is generally considered to involve predominantly degeneration of gray matter; however, neuropathological studies revealed that also white matter pathology is involved. Several studies found increased lesions of the subcortical fiber system, seen as WMH on MRIs, in Alzheimer patients compared to age matched healthy elderly. Specifically frontal and parietal areas seem to be most strongly affected in subcortical white matter pathology in AD (Gootjes, Teipel, et al., 2004). Since subcortical WMH is an important factor mediating age-effects of especially the unattended ear in dichotic listening in healthy elderly, one could expect that WMH pathology would have strong effects on ear asymmetry in Alzheimer patients also. Increased ear asymmetry may further be related to reduced CC size in Alzheimer patients, which has been shown to occur independently of subcortical fiber degeneration (Hampel et al., 1998, 2000). 4.1. Empirical studies in patients with Alzheimer’s disease 4.1.1. Effects of attentional modulation on dichotic listening in Alzheimer’s patients As in previous studies, the influence of attention was investigated by means of the free- and focused-attention task. In the focused-attention task, focus of attention on the LE or RE was randomly instructed across the trials. According to Kinsbourne’s attentional model, one could expect that it is easier to activate the appropriate hemisphere when subjects are allowed to consistently focus attention on the same ear than when they are required to focus attention unpredictable on the LE or RE. The focusedattention task consisted of two conditions: ‘random-ordered’ and ‘blocked’ attention condition. In the random-ordered attention condition, the instruction to focus attention on the left or right was randomized across the trials. In the blocked attention condition, subjects were required to focus on the LE during the first half of the task and to focus on the RE during the other half, or vice versa. We expected stronger ear asymmetries in the blocked attention condition than in the random-ordered attention task condition. As a control condition, also a monaural task was administered in which six digits were presented to either the LE (half of the trials) or RE (other half of the trials). The sequence of ear presentation was random. Twenty-five patients (70–98 years) with the clinical diagnosis of probable AD according to NINCDS-ADRDA criteria (McKhann et al., 1984), and 25 normal healthy controls (71–90 years) participated. Monaural task versus free-attention task. Compared to the controls, Alzheimer patients showed decreased performance in the monaural task. The Alzheimer group revealed a small, but signifi-

cant REA which did not differ from that of controls. These findings suggest that dichotic stimulation is not a necessary condition for obtaining a REA. However, in the free-attention task a large REA was obtained. As Fig. 3 shows, the REA was much larger for the Alzheimer patients than for controls, specifically due to decreased LE performance in the AD group. Interestingly, as Table 1 shows, we observed in the free-attention task a highly negative correlation between LE and RE stimuli in the Alzheimer group, suggesting that a strong right-sided bias to the RE was associated with reduced attention to the LE. The relationship between the two ears was much lower in the control subjects. In contrast, a highly positive relation rather than a negative relation was observed in the monaural task. These findings offer support for Kinsbourne’s attentional model that, at least under dichotic stimulation, the two hemispheres are in a reciprocally inhibitory relationship to each other. Focused-attention task: random-ordered versus blocked instructions Irrespective of type of instructions, both Alzheimer patients and controls showed a strong REA in the FR condition. However, Alzheimer patients showed a REA when asked to focus attention on the LE, but controls showed a LEA. This indicates that Alzheimer patients were unable to attend selectively to the LE when they were required to report these stimuli first. As Fig. 3 shows, for both groups, a differential effect of blocked and random-ordered instructions was only observed in the FL condition. Remarkably, the instruction effect was comparable in the Alzheimer group and controls, that is, LE scores increased, but RE scores decreased in the blocked as compared to the random-ordered FL condition. These findings suggest that ear asymmetry shifted to a stronger involvement of the right hemisphere when expectancy to attend to the LE was maximal, as is the case in the blocked FL condition. Interestingly, in Alzheimer patients RE recall was extremely negatively correlated to LE recall in both the random-ordered and blocked task (see Table 1), indicating that the increased RE attentional bias is strongly related to decrease in performance of LE stimuli. Negative correlations were also obtained in controls, but not as strong as in Alzheimer patients. These results suggest that Alzheimer patients showed increased bottom-up processes in dichotic listening, which is reflected by a strong attentional bias to the RE. This effect is most likely due to severe deficits in top-down, executive control of attention, specifically when attention had to be focused on the LE. Alzheimer patients were able to activate the right hemisphere more strongly when they were required to consistently focus their attention on the LE (blocked attention) compared to the randomized condition. According to Kinsbourne’s view, we suggest that executive control functions rather than structural brain dysfunctions observed in AD

Fig. 3. Mean percentage correct responses per group in (a) the monaural task, (b) the free-attention task, and (c) the random-ordered and blocked attention condition of the focused-attention task (LE = left ear; RE = right ear). (Adapted and extended data from Bouma, 1998).

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Table 1 Correlations between the left and right ear for the different dichotic listening tasks. Dichotic listening task

*

Alzheimer group

Control group

Monaural task Free-attention task

0.89*** 0.82***

0.81*** 0.36*

Random-ordered attention task Focused left attention Focused right attention

0.91*** 0.96***

0.63** 0.53**

Blocked attention task Focused left attention Focused right attention

0.91*** 0.89***

0.58** 0.29ns

p < .05. p < .01. p < .001. ns p = not significant.

**

***

may be responsible for these findings. Nevertheless, Alzheimer patients were unable to switch their attention to the LE when conditions to focus attention on the LE were maximal. The increased negative relationship between LE and RE recall in the Alzheimer group compared to controls is in line with Kinsbourne’s idea that a stronger left hemisphere activation is coupled with decreased right hemisphere activation, and vice versa. We suggest that AD is associated with severe disruption of the attentional cortical network mediated by the frontal and parietal brain regions. AD is also characterized by memory disorders related to medial-temporal lobe lesions. In another study, we found that in Alzheimer patients digit span (forward and backward) measuring attention and mental control was specifically related to recall of the attended RE digits, but in healthy controls to recall of the attended LE digits. We did not find any relationship between ear performance and verbal memory as measured by the Dutch version of the Rey Auditory Verbal Learning Test in which subjects had to learn 15 one-syllable words in five successive trials (Bouma, 1997). On the basis of these findings, we suggest that a breakdown of attentional mechanisms rather than memory problems might play a crucial role in dichotic listening performance in AD. Remarkably, Alzheimer patients obtained a normal or slightly better RE performance in dichotic listening when order of report was free or when attention had to be focused on the RE. These results cannot easily be explained by intrahemispheric lesions. Rather, one could argue that these findings may be attributed to disturbances of the CC in AD, which is in agreement with other studies that found increased RE scores but normal or reduced LE scores in patients with callosal pathology (Westerhausen & Hugdahl, 2008). This implies that also interhemispheric disconnectivity contributes to decreased LE performance in AD.

4.1.2. The role of corpus callosum in dichotic listening in Alzheimer patients Since different cortical areas are involved in dichotic listening, one could expect that regional subareas of the CC are differentially involved as well. Namely, anterior callosal regions, connecting frontal cortical areas, may be more involved in controlling auditory attention, while posterior callosal regions, connecting posterior cortical areas, may be more strongly involved in transfer of auditory information (Westerhausen & Hugdahl, 2008). It is hypothesized that ear asymmetry is most strongly related to regional atrophy of the posterior callosal area, the isthmus, that is reported to transmit auditory information. In this study, 25 patients with the clinical diagnosis of probable AD to NINCDS-ADRDA criteria (McKhann et al., 1984), and 20 healthy controls with subjective memory complaints (HC-Mem), but no objective cognitive symptoms were selected. In addition,

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20 healthy controls (HC) without subjective memory complaints participated. Dichotic listening performance was measured by the blocked focused-attention task. Both control groups and the Alzheimer group showed superior recall for the attended RE compared to the unattended LE (for Alzheimer patients: M unattended LE = 11.3, M attended RE = 23.3; for HC-Mem: M unattended LE = 15.3, M attended RE = 27.8; for HC: M unattended LE = 13.5, M attended RE = 26.3. In the FL condition, the control groups showed clearly a LEA (for HC-Mem: M attended LE = 25.6, M unattended RE = 18.5; for HC: M attended LE = 24.4, M unattended RE = 15.6), while the Alzheimer group revealed negligible differences between both ears (M attended LE = 17.7, M unattended RE = 16.8). Alzheimer patients showed reduced recall performance of particularly the attended LE in the FL condition compared to the controls. Also, for each participant, an absolute laterality quotient (|LQ|) was calculated according the following formula: |LQ| = |(RE LE)/(RE + LE)|. The analyses showed that |LQ| was higher in the Alzheimer group compared to the control groups, which was attributed to increased inability to attend to the LE. These results support the earlier described findings that executive inhibitory functioning may be declined in AD. No significant differences in dichotic listening performance were obtained between the HC-Mem group and the HC-group. Thus, the presence of subjective memory complaints did not have declining effects on dichotic listening. Total callosal area (TCA) and areas of subcallosal areas were determined according to the method developed by Hampel et al. (1998). The CC was divided into five subregions (labeled C1, C2, C3, C4, and C5 in rostral-occipital direction, see Fig. 4). In the Alzheimer group, TCA was smaller compared to both control groups, and although callosal atrophy seemed to be strongest in C1 and C5, no significant group differences were found in callosal subareas (see Fig. 4). Decreased CC in AD is in line with earlier findings, and it might be that regional differences in callosal atrophy are too mild at early stages of dementia to become significant. As expected, |LQ| scores correlated negatively with TCA and with posterior callosal subarea C5, that represents the isthmus and splenium, in both control groups. However, in the Alzheimer group, no association was found between callosal size and |LQ| scores. It is

Fig. 4. (a) MRI scan, showing midsagittal section of the brain zoomed in at the corpus callosum indicating callosal subareas, and (b) Mean areas of callosal subregions per group. (Adapted from Gootjes, Bouma, et al., 2006; Gootjes, Bouma, Van Strien, et al., 2006).

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possible that heterogeneity in neuropathological processes, involving white and/or grey matter, masks possible associations in AD. Interestingly, callosal subarea C1, thought to connect frontal cortical areas, correlated with |LQ| specifically in the HC-Mem group, which suggests increased involvement of frontal functions like attention and executive functions in this group. Indeed, the task might be more demanding for the HC-Mem group compared to the HC-group, and increased frontal involvement might play a compensatory role. 5. Summary and conclusions The present results support Kimura’s dichotic digits paradigm as a valid measure for left hemispheric predominance for processing language stimuli. In addition to structural brain mechanism, we have clearly demonstrated that, in line with Kinsbourne’s view, attention modulates the direction and degree of ear asymmetry in dichotic listening. Since these findings are in agreement with other dichotic listening studies employing different types of stimuli (e.g., words, consonant-vocal stimulus pairs) or response procedures (e.g., recall of one ear only, ordered recall of attended and unattended ear), the dichotic listening procedure appears to be a strong paradigm to investigate these laterality effects. Age-related reduced performance has been observed particularly for digits of the unattended ear, which put higher demands on working memory processes than digits of the attended ear. Elderly have increasingly more difficulties focusing attention on the LE with advancing age. Dichotic listening performance in Alzheimer patients did not differ from that in healthy elderly when attention was focused on the RE; however, Alzheimer patients showed severe deficits to allocate attention to the LE, which could result in a REA, even when attention was focused on the LE across trials. Several processing mechanisms may contribute to these findings. First, reduced LE performance observed in elderly and Alzheimer patients may be attributed to decreased inhibitory control of attention. That is, dichotic listening performance may be increasingly determined by automatic, bottom-up processes rather than by intentional, top-down executive control. These attentional problems are thought to be subserved by the frontal lobe system. Second, parietal lobe dysfunctions to switch attention from one to the other ear (‘disengagement processes’) may contribute to the increased difficulties that elderly people and Alzheimer patients have in reporting the digits of the unattended ear. Third, disruption of the cortical attentional network may, at least in part, be caused by subcortical white matter lesions that play an important mediating factor in dichotic listening performance. Fourth, recall of LE rather than RE digits, and localization of RE rather than LE digits, appears to be vulnerable to reduced callosal size. Our conclusion is that intrahemispheric disconnectivity as well as interhemispheric disconnectivity contributes to deficient ear asymmetries in elderly and Alzheimer patients. These deficits appear to be more pronounced in the Alzheimer’s group, however, longitudinal studies are needed to get more insight into the question whether the pattern of dichotic listening performance and cerebral functioning in Alzheimer patients develop differentially from normal healthy aging. References Alden, J. D., Harrison, D. W., Snyder, K. A., & Everhart, D. E. (1997). Age differences in intention to left and right hemispace using a dichotic listening paradigm. Neuropsychiatry, Neuropsychology and Behavioral Neurology, 10, 239–242. Andersson, M., Reinvang, I., Wehling, E., Hugdahl, K., & Lundervold, A. J. (2008). A dichotic listening study of attention control in older adults. Scandinavian Journal of Psychology, 49, 299–304. Andersson, M., Ystad, M., Lundervold, A., & Lundervold, A. J. (2009). Correlations between measures of executive attention and cortical thickness of left posterior middle frontal gyrus – A dichotic listening study. Behavioral and Brain Functions, 5. Article Number: 4.

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