1 Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Sunshine Hospital, 176 Furlong Road, St Albans, Victoria 3021, Australia, 2 Department of Psychology, School of Behavioural Science, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Melbourne, Victoria, 3010 Australia, 3 Applied Schizophrenia Division, Mental Health Research Institute, Victoria, Parkville, Victoria, 3052 Australia, 4 ORYGEN Research Centre, 35 Poplar Road (Locked Bag 10), Parkville, Victoria, 3052 Australia
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Abstract |
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Key Words: executive function, frontal lobe, MRI, sulcus, verbal fluency, working memory
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Introduction |
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Human anterior cingulate (AC) cortex is well suited for investigating such brainbehaviour relationships, specifically with respect to the incidence and extent of the paracingulate sulcus (PCS). The PCS is a tertiary sulcus present in only 3060% of cases (Paus et al., 1996b; Yücel et al., 2001
), and (when present) runs dorsal and parallel to the cingulate sulcus (CS), forming the superior border of the paracingulate gyrus. Converging evidence from in vivo Magnetic Resonance Imaging (MRI) (Paus et al., 1996a
) and post-mortem (Vogt et al., 1995
) investigations indicates that this produces a relative expansion of paralimbic AC cortex (corresponding to Brodmann Areas 24c and 32), such that it becomes located on the surface of the paracingulate gyrus, in contrast to occupying the dorsal bank of the CS when the PCS is absent (see Fig. 1). The paralimbic belt of the AC is also termed the paracingulate cortex, and represents a cingulo-frontal transition area, given its reciprocal connections with pre-frontal regions (Vogt et al., 1995
; Mega and Cummings, 1997
).
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In this study, we sought to investigate the neuropsychological consequences of variations in AC/paracingulate morphology in a healthy sample. Consistent with previous studies (Paus et al., 1996a,b; Yücel et al., 2001
), we used a categorical method for classifying PCS variability that is sensitive to variations in both the incidence and extent of the PCS across the two cerebral hemispheres, and examined their performance on a series of verbal and non-verbal neuropsychological tasks. Participants were classified as displaying either a leftward asymmetric, rightward asymmetric, or symmetric pattern of AC/paracingulate cortical folding, and their performance on a verbal and non-verbal test of executive cognition typically associated with frontal lobe function was compared. The former was assessed with a verbal fluency task (Spreen and Strauss, 1998
) and the latter with a test of SWM (Owen et al., 1990
). Both tasks have been shown to depend on executive cognitive processes that are impaired by lesions to the frontal lobes (Owen et al., 1990
, 1996b; Stuss et al., 1998
). Furthermore, previous functional imaging studies have demonstrated left paracingulate activation during verb generation (Herholz et al., 1996
; Crosson et al., 1999
), and right paracingulate activation during the SWM task (Owen et al., 1996a
). Consequently, comparing performance across verbal and spatial domains of executive functioning enabled us to determine whether the influence of PCS asymmetry on task performance was related to task parameters common to both tests, or whether it varied as a function of task modality. Consistent with the latter view, we expected that individuals possessing a leftward PCS asymmetry would demonstrate better performance on the Controlled Oral Word Association Task (COWAT), whereas a rightward PCS asymmetry would be associated with better performance on the SWM task. To examine the specificity of our findings, we also report data from performance on tests placing minimal demands on executive cognitive processes. Thus, we expected AC/paracingulate morphology to be associated with performance on tasks requiring executive cognitive processes associated with frontal lobe function, but not those tapping other processes likely to be mediated primarily by non-frontal brain regions.
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Materials and Methods |
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The data used in this study was obtained from a larger database comprising several ongoing research studies being conducted at the Mental Health Research Institute (MHRI), Victoria. Only participants with the relevant MRI and neuropsychological test data were included in the study. All data were collected following approval from appropriate ethics committees and informed consent was obtained from all participants prior to MRI scanning and neuropsychological testing. The sample comprised 30 right-handed males with no personal or family history of psychiatric illness or neurological complications. Only right-handed males were included since sex differences have been reported with respect to AC morphological asymmetries, and the effects of handedness are as yet unclear (Paus et al., 1996b; Yücel et al., 2001
). Handedness was assessed using the Edinburgh Handedness Inventory (Oldfield, 1971
). All but two participants had completed high school education. These remaining two had completed a minimum of 10 years of schooling.
MRI Protocol
Participants were scanned using a GE Signa 1.5 T scanner at the Royal Melbourne Hospital, Victoria, Australia. A three-dimensional volumetric SPGR sequence generated 124 contiguous, 1.5 mm coronal slices. Imaging parameters were: time-to-echo, 3.3 ms; time-to-repetition, 14.3 ms; flip angle, 30_; matrix size, 256 x 256; field of view, 24 x 24 cm; voxel dimensions, 0.938 x 0.938 x 1.5 mm. MRI data were transferred from DAT tape to an SGI-02 workstation and coded to ensure participants confidentiality and blinded rating. Classification of AC morphology was performed using MEDx 3.0 (Sensor Systems).
Classification of Anterior Cingulate Morphology
Within each hemisphere, the PCS was classified according to its presence/absence and rostro-caudal extent using a reliable method (see Yücel et al., 2001). Briefly, if there was a clearly observable horizontal sulcus running dorsal and parallel to the CS for >40 mm, with no more than 20 mm of interruptions in total between its anterior origin and an arbitrary vertical line passing through the anterior commissure, the PCS was considered prominent. If these interruptions were >20 mm, but there was still a clearly identifiable horizontal element running parallel to the CS for >20 mm, a classification of present was made. If there were no clearly identifiable horizontal sulci running dorsal and parallel to the CS for >20 mm, the PCS was considered absent. An asymmetry occurred if the PCS classification made in one hemisphere indicated a larger PCS than in the other. For example, a participant with a prominent right PCS and a present or absent left PCS would be classified as rightward asymmetric. Similarly, someone with a present left PCS and an absent right PCS would be classified as leftward asymmetric, and so on. A symmetric pattern occurred if the PCS classification was equivalent for both hemispheres. All classifications were made blind to cognitive performance. Examples of each PCS type and asymmetry category are presented in Figure 1.
In addition to facilitating comparisons with previous anatomical investigations of this region (Paus et al., 1996b; Yücel et al., 2001
), the advantage of this categorical method is that it allows consideration of all cases, irrespective of whether the PCS is present or absent. Other approaches, such as measuring the volume of intrasulcal grey matter (Paus et al., 1996a
), are limited to the extent that they are only applicable to individuals that actually have a PCS. Furthermore, the approach of pairing left and right hemisphere classifications to define a measure of asymmetry is more amenable to analysis of variance (ANOVA) models, since these analyses assume independence between categories and analysing the effects of morphology in both hemispheres separately for each individual does not yield independent observations.
Hemispheric Gyrification Index (HGI)
To determine the specificity of results regarding AC folding, we also used a previously validated and semi-automated method (see Yücel et al., 2001) to derive a hemispheric gyrification index (HGI) for each hemisphere of each participant. Briefly, surface-to-volume ratios were calculated separately for each hemisphere, expressed as the total number of surface voxels divided by the total number of volume voxels. As such, higher ratios indicate greater complexity of cortical folding. We derived an asymmetry score by subtracting the HGI for the right hemisphere from that of the left. Thus, negative values represent an overall rightward asymmetry and positive values a leftward asymmetry.
Neuropsychological Measures
Participants completed a number of cognitive tasks as part of ongoing research protocols conducted within our unit. Selection of specific tasks for this study was based on previous evidence indicating that the task tapped processes associated with dorsal AC function, and the practical constraint that performance data on all the tasks was available for all participants in the sample.
Verbal Fluency
Verbal fluency was assessed using the COWAT administered according to standard procedures (Spreen and Strauss, 1998). It comprises three 60 s trials and requires participants to generate as many words as possible beginning with a particular letter within the allotted time. Participants were instructed to avoid using proper nouns or numbers, repeating words, or adding suffixes to previously generated words (e.g. shoot, shooting, shot). Performance was assessed by summing the number of words produced across the three 60 s trials. As a corollary analysis, we divided the task into 30 s epochs to examine whether the influence of PCS variability varies with the working memory demands of the task. This follows recent evidence that these demands, and associated neural activity, vary as a function of time spent performing the task (Wood et al., 2001
). That is, while the first 30 s requires active search and retrieval of words from the lexical store, the latter 30 s places an increased demand on participants manipulation and inhibitory processes, as they must remember which words they have previously produced while trying to generate new ones. This, in turn, coincides with changes in regions of frontal cortex activated during task performance (Wood et al., 2001
).
SWM
SWM was assessed with the SWM subtest of the Cambridge Neuropsychological Test Automated Battery (CANTAB), and a detailed description has been provided elsewhere (Owen et al., 1996b). Briefly, participants had to perform a self-ordered search through an array of boxes in order to find a token hidden inside one of them (see Fig. 2). Once found, the boxes went blank again so that another search could be initiated, with the key instruction being that a token would never appear in a box in which it had already been found. The test comprised five levels of increasing difficulty, corresponding to two-, three-, four-, six-, and eight-box stages. Performance was assessed by recording the number of errors committed at each of the five stages. These occurred when, during the same search sequence, participants erroneously searched a box in which a token had already been found.
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We controlled for differences in SWM capacity using the Spatial Span subtest of the CANTAB (Owen et al., 1996b), which is a computerized version of the Corsi block tapping task (Milner, 1971
). Participants were presented with a series of white squares that changed colour and were required to remember the location and sequential order of the colour changes. The test began at a two square level, and increased by one following each successful trial until a maximum of nine squares. The spatial span was defined as the highest level at which participants remembered at least one sequence of colour changes correctly. While there is some evidence to suggest that intact spatial span performance relies on storage processes mediated by the parietal lobes, patients with frontal lobe lesions are unimpaired on this task (Owen et al., 1990
, 1996b; D'Esposito and Postle, 1999
). Consequently, this task served as a spatial control task deemed to be less dependent on the integrity of executive cognitive functions associated with the frontal lobes.
Verbal Paired Associate Learning (VPAL)
In the Verbal Paired Associate Learning (VPAL) task, participants must remember eight word pairs read to them by the experimenter. Four of these are easy pairs, based on their obvious semantic relation (e.g. baby-cries), and four are hard pairs that are made more difficult by their apparently arbitrary pairings (e.g. cabbage-pen). Performance on the easy pairs was at ceiling, so we only report that for the hard pairs, which was measured by summing the number of correctly recalled pairs across three learning trials (a maximum of 12 pairs). Performance on this task requires the ability to form arbitrary associations, and appears to be critically dependent on the integrity of medial temporal lobe structures (Saling et al., 1993; Weintrob et al., 2002
). Thus, it was employed here as a verbal control task that places less demand on executive cognitive processes traditionally associated with frontal lobe function.
National Adult Reading Test Estimated Intelligence Quotient (NART-estimated IQ)
Wechsler Adult Intelligence Scale Revised Full Scale IQ (Wechsler, 1981) was estimated from performance on the NART using re-standardization tables (Nelson and Willison, 1991
). Additionally, because the NART tests participants ability to read irregular words (e.g. KNIFE), performance depends on both IQ and vocabulary size. As such, this measure served as an appropriate control for both intellectual ability and individual differences in overall vocabulary size (an important consideration with respect to verbal fluency performance).
Data Processing and Analysis
Total verbal fluency performance was assessed using between-groups analysis of covariance (ANCOVA), while performance across the two 30 s COWAT epochs was analysed with repeated measures ANCOVA, using SPSS for Windows version 10.0. SWM performance at the two-, three- and four-box levels was at ceiling and produced insufficient variance for statistical analysis (see Fig. 4), so our analysis was restricted to the six- and eight-box levels. Initial inspection of these variables indicated gross departures from normality, meaning that traditional ANOVA was inappropriate.
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Results |
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Age and HGI asymmetry were not significant predictors of verbal fluency performance. As such, the results reported here are derived from models that do not covary for these measures. Covarying for NART-estimated IQ, there was a significant effect of PCS asymmetry on total verbal fluency performance [F(2,26) = 3.84, P = 0.035]. Simple planned contrasts revealed that individuals with either a symmetric or rightward pattern generated significantly fewer words than those with a leftward asymmetry [t(20) = 2.16, P = 0.021 and t(19) = 2.46, P = 0.041, respectively]. There was no difference between the rightward and symmetric groups [t(15) = 1.29, p = 0.723]. The effect of PCS asymmetry on total COWAT performance was no longer significant when NART-estimated IQ was omitted as a covariate [F(2,27) = 1.031, p = 0.370]. One possibility may have been that entry of NART-estimated IQ as a covariate lead to a significant difference because it suppressed the influence of outliers. To examine this further, we computed Cooks distance for all points in the data set. None of these values were >1 (range: 0.000.27), suggesting our results are not due to covariate suppression of outlier effects.
All groups produced significantly fewer words in the latter 30 s when controlling for NART-estimated IQ [F(1,26) = 4.30, P = 0.048]. However, there was no interaction between PCS asymmetry and epoch [F(2,26) = 0.46, P = 0.635], suggesting that the effect of PCS asymmetry was constant across COWAT epochs. This effect is illustrated in Figure 3.
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Given the non-normal distribution of the SWM variables, means and standard deviations are not the appropriate descriptive statistics. Rather, we present box and whisker plots of the number of errors committed by each group at each stage of the SWM task in Figure 4 to illustrate relative group differences as a function of working memory load. NART-estimated IQ, age, and HGI asymmetry were not significant predictors of SWM performance. Consequently, the results reported here are derived from models that do not covary for these measures. There were significant main effects of working memory load (z = 6.22, P < 0.001) and PCS asymmetry (z = 2.35, P = 0.019), but no interaction (z = 0.34, P = 0.732). Despite this, pairwise comparisons indicated that although there were no group differences at the six-box level, the leftward asymmetric group committed significantly fewer errors than either the symmetric or rightward asymmetric groups at the eight-box level (z = 2.08, P = 0.037 and z = 2.36, P = 0.018, respectively).
Spatial Span
Group means for spatial span performance are presented in Table 1. There were no significant group differences [F(2,26) = 0.301, P = 0.742]. NART-estimated IQ, age, and HGI asymmetry did not contribute to the model.
VPAL
The mean total VPAL (hard pairs) performance of each group is presented in Table 1. There were no significant group differences in VPAL performance [F(2,27) = 0.25, P = 0.78]. NART-estimated IQ, age, and HGI asymmetry did not contribute to the model.
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Discussion |
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Why Is a Leftward Asymmetry Associated with Better Task Performance?
Leftward PCS asymmetry is the most common pattern of AC/paracingulate folding seen in healthy populations (Paus et al., 1996b; Yücel et al., 2001
). That this asymmetry was associated with a performance advantage on both a verbal and non-verbal task goes against the view that the functional significance of such a population bias is restricted to the domain of language, as suggested by Paus et al. (1996a
,b). Moreover, the results contradict our expectations that the relationship between PCS asymmetry and task performance would vary as a function of task modality (i.e. that a leftward asymmetry would be associated with better verbal fluency performance, and a rightward asymmetry with better SWM performance). Rather, our findings indicate that a leftward PCS asymmetry is associated with an advantage for broader cognitive processes common to performance on both tasks (discussed below).
As a consequence, the precise reason for the existence of a leftward population bias, and why this may confer a processing advantage over a symmetric or rightward asymmetric pattern, remains unclear. Regarding why healthy individuals are more likely to manifest a leftward PCS asymmetry, the fact that sulcal/gyral patterns are principally formed perinatally (Armstrong et al., 1995; Chi et al., 1977
) suggests that certain aspects of the intrauterine environment bias the mechanisms responsible for gyral development (Welker, 1990
; Van Essen, 1997
) in such a manner that the incidence of the PCS will be greater in the left hemisphere for most people (Paus et al., 1996b
; Yücel et al., 2001
). Interestingly, Paus et al. (1996a
) have found that PCS grey matter volume negatively correlates with that of the anterior portion of the CS, leading them to suggest that the tendency towards a leftward PCS asymmetry is secondary to increased grey matter volume in the right anterior CS, since the latter is a primary sulcus whose emergence precedes that of the PCS. Given that the absence of a PCS is associated with enlarged limbic AC cortex and reduced paracingulate cortex (Vogt et al., 1995
; Paus et al., 1996a
), it is unclear whether the performance advantage of individuals with a leftward PCS asymmetry in our study was due to such an asymmetry leading to increased paracingulate volume in the left hemisphere, or increased limbic AC cortex in the right hemisphere. Considering the reported connections between paracingulate cortex and lateral PFC (Vogt et al., 1995
; Mega and Cummings, 1997
), and the fact that the dorsal, cognitive portion of the AC (of which the paracingulate forms a large part) is the specific region most often co-activated with lateral PFC during functional imaging studies of cognitive performance (Passingham, 1998
; Carter et al., 2000
; Duncan and Owen, 2000
; Koski and Paus, 2000
), we expect that the former is more likely.
Investigation of the nature of functional lateralization within AC and paracingulate cortex and how this is related to morphological variations of this region is needed to clarify such issues, and to begin to parse structurefunction relationships within the more broadly defined cognitive AC region (Bush et al., 2000). Indeed, our results suggest that a leftward PCS asymmetry represents a particularly efficient configuration, either within dorsal AC or between this region and other parts of the cerebrum, that facilitates its role within a neural network subserving performance on tests engaging executive cognitive processes.
How Might Variations in AC/Paracingulate Morphology Affect Task Performance?
The finding that AC/paracingulate morphology affected performance only on tasks engaging executive cognitive processes suggests that anatomical variations of this region have implications for frontal lobe function. Further, the performance advantage of leftward asymmetric individuals on both the verbal fluency and SWM task suggests that this influence does not vary as a function of task modality, but that it is related to cognitive processes common to both tasks. Recently, researchers have begun to emphasize the working memory component associated with COWAT performance, with patterns of neural activity varying in a predictable manner in accordance with the tests working memory demands (Wood et al., 2001). This would implicate the engagement of working memory processes as the common thread associated with a performance advantage for leftward asymmetric individuals across the verbal fluency and SWM tasks.
Broadly, working memory may be defined as the ability to retrieve and maintain information on-line, and to manipulate and use this information to guide behaviour (Baddeley, 1996). Although working memory processes are typically associated with lateral PFC (D'Esposito et al., 1998
; Goldman-Rakic, 1998
; Owen et al., 1999
), a role for AC cortex during performance on these tasks is suggested by converging evidence that it serves to detect non-routine situations and signal lateral PFC to engage working memory and other top-down cognitive processes that optimize task performance (Carter et al., 2000
; MacDonald et al., 2000
; Bunge et al., 2001
; Miller and Cohen, 2001
). Thus, one possibility is that the influence of PCS variability on task performance observed in our results reflects an alteration in the efficiency of functional interactions between dorsal AC and prefrontal regions. This view is supported by the fact that the effect of PCS variability on verbal fluency was significant only when controlling for differences in vocabulary size (using NART-estimated IQ), suggesting it was related to the on-line aspects of working memory performance, rather than differences in information (e.g. vocabulary) likely to be stored in posterior association areas (Jonides et al., 1998
). A similar pattern of performance was evident in the spatial domain to the extent that we found no group differences for the spatial span task. Performance on this task depends on integrity of posterior, but not frontal, cortical regions (Owen et al., 1990
; D'Esposito and Postle, 1999
), suggesting the additional working memory processes engaged by the SWM task appear to be those that were affected by PCS variability. Moreover, while a recent functional MRI study conducted by Wood et al. (2001
) has reported activation of both AC cortex and lateral PFC on the COWAT, only activation of the latter predicted task performance. Thus, the effect of PCS variability observed in our study may not be on the efficiency with which relevant functions are mediated by dorsal AC cortex per se, but may instead reflect differences in the efficiency of functional interactions between dorsal AC and prefrontal regions.
A final, unresolved issue is whether the influence of AC/paracingulate morphology on performance varies as a function of working memory load. Although co-activation of AC/paracingulate cortex and PFC in response to increasing load has been a common finding (Barch et al., 1997; Seidman et al., 1998
; Koski and Paus, 2000
) our results remain inconclusive on this issue. That is, although there was no interaction between PCS asymmetry and working memory load on the SWM task, simple comparisons revealed that significant differences only emerged at the most difficult eight-box level (see Fig. 4). Thus, the absence of an interaction in our results is likely to reflect the fact that we could only reliably analyse one increment in working memory load, which provided a relatively insensitive measure of performance as a function of increasing cognitive demands. A similar limitation applies to the verbal fluency task, limiting the conclusions that can be drawn on this issue. Alternatively, the lack of relationship in our results may reflect the fact that dorsal AC activity is associated with processes other than working memory during performance under conditions of increasing difficulty (Barch et al., 1997
).
Limitations and Conclusions
We attempted to minimize confounds by limiting our sample to right-handed males, following evidence that PCS asymmetries are not as pronounced in females, and that the influence of handedness is unclear (Paus et al., 1996b; Yücel et al., 2001
). As such, our findings are not generalizable outside this population until these effects are elucidated.
One of the problems in conducting an investigation of the type reported here in a prospective manner is that it requires large numbers, since it cannot be known a priori which PCS category an individual will fall into and previous evidence suggests an asymmetric distribution of group membership (Paus et al., 1996b; Yücel et al., 2001
). However, our retrospective analysis suggests that structurefunction relationships in AC/paracingulate cortex warrant further study. To this end, further testing of larger samples with a variety of neuropsychological tasks aimed at identifying the specific cognitive processes influenced by variations in AC/paracingulate morphology would assist in clarifying the nature of such relationships.
Despite these limitations, our results provide preliminary support for the notion that inter-individual variations in the convolutional patterns of the AC/paracingulate region, which reflect differences in its underlying structural and functional properties (Welker, 1990; Rademacher et al., 1993
; Vogt et al., 1995
; Paus et al., 1996a
; Scannell, 1997
; Van Essen, 1997
), are related to differential performance on tests of related cognitive functions. That is, our results suggest that the population bias for a leftward PCS asymmetry may represent a more efficient configuration of dorsal AC cortex that facilitates functional interactions between this region and lateral PFC. These findings carry implications not only for understanding the relationship between variations in brain morphology and individual differences in cognitive abilities, but also for functional imaging research that employs group averaging procedures. Indeed, our results suggest that the use of such methods reduces potentially important information regarding the influence of brain structure and function on cognitive performance.
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Notes |
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Address correspondence to Alexander Fornito, Cognitive Neuropsychiatry Research and Academic Unit, Sunshine Hospital, PO Box 294, St Albans, Victoria, 3021 Australia. Email: alexander.fornito{at}wh.org.au
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References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Armstrong E, Schleicher A, Omran H, Curtis M, Zilles K (1995) The ontogeny of human gyrification. Cereb Cortex 1:5663.
Baddeley A (1996) The fractionation of working memory. Proc Natl Acad Sci USA 93:1346813472.
Baker SC, Rogers RD, Owen AM, Frith CD, Dolan RJ, Frackowiak RSJ, Robbins TW (1996) Neural systems engaged by planning: a PET study of the Tower of London task. Neuropsychologia 34:515526.[CrossRef][ISI][Medline]
Barch DM, Braver TS, Nystrom LE, Forman SD, Noll DC, Cohen JD (1997) Dissociating working memory from task difficulty in human prefrontal cortex. Neuropsychologia 35:13731380.[CrossRef][ISI][Medline]
Bunge JA, Ochsner KN, Desmond JE, Glover GH, Gabrieli JDE (2001) Prefrontal regions involved in keeping information in and out of mind. Brain 124:20742086.
Bush G, Luu P, Posner MI (2000) Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 4:215222.[CrossRef][ISI][Medline]
Carter CS, Braver TS, Barch DM, Botvinick MM, Noll D, Cohen JD (1998) Anterior cingulate cortex, error detection, and the online monitoring of performance. Science 280:747749.
Carter CS, MacDonald AM, Botvinick M, Ross LL, Stenger VA, Noll D, Cohen JD (2000) Parsing executive processes: strategic vs evaluative functions of the anterior cingulate cortex. Proc Natl Acad Sci USA 97:19441948.
Chi JG, Dooling EC, Gilles FH (1977) Gyral development in the human brain. Ann Neurol 1:8693.[ISI][Medline]
Crosson B, Sadek JR, Bobholz JA, Gökçay D, Mohr CM, Leonard CM, Maron L, Auerbach EJ, Browd SR, Freeman AJ, Briggs RW (1999) Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy. Cereb Cortex 9:307316.
Dagher A, Owen AM, Boecker H, Brooks DJ (1999) Mapping the network for planning: a correlational PET activation study with the TOL task. Brain 122:19731987.
DEsposito M, Postle BR (1999) The dependence of span and delayed-response performance on prefrontal cortex. Neuropsychologia 37:13031315.[CrossRef][ISI][Medline]
DEsposito M, Aguirre GK, Zarahn E, Ballard D, Shin RK, Lease J (1998) Functional MRI studies of spatial and nonspatial working memory. Cogn Brain Res 7:113.[ISI][Medline]
Devinsky O, Morrell MJ, Vogt BA (1995) Contributions of anterior cingulate cortex to behaviour. Brain 118:279306.[Abstract]
Diggle P, Liang K-Y, Zeger S (1994) Analysis of longitudinal data. Oxford: Oxford Science.
Duncan J, Owen AM (2000) Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci 23:475483.[CrossRef][ISI][Medline]
Gardner W, Mulvey EP, Shaw EC (1995) Regression analyses of counts and rates: poisson, overdispersed poisson, and negative binomial models. Psychol Bull 118:392404.[CrossRef][ISI][Medline]
Goldman-Rakic PS (1998) The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive. In: The prefrontal cortex: executive and cognitive functions (Roberts AC, Robbins TW, Weiskrantz L, eds), pp 87102. New York: Oxford University Press.
Herholz K, Thiel A, Wienhard K, Pietrzyk U, von Stockhausen H-M, Karbe H, Kessler J, Bruckbauer T, Halber M, Heiss W-D (1996) Individual functional anatomy of verb generation. Neuroimage 3:185194.[CrossRef][ISI][Medline]
Jonides J, Schumacher EH, Smith EE, Koeppe RA, Awh E, Reuter-Lorenz PA, Marshuetz C, Willis CR (1998) The role of parietal cortex in verbal working memory. J Neurosci 18:50265034.
Koski L, Paus T (2000) Functional connectivity of the anterior cingulate cortex within the human frontal lobe: a brain-mapping meta-analysis. Exp Brain Res 133:5565.[CrossRef][ISI][Medline]
Liang K-Y, Zeger S (1986) Longitudinal data analysis using generalized linear models. Biometrika 73:1322.[ISI]
MacDonald AM, Cohen JD, Stenger VA, Carter CS (2000) Dissociating the role of the dorsolateral prefrontal cortex and anterior cingulate cortex in cognitive control. Science 288:18351838.
Mega MS, Cummings JL (1997) The cingulate and cingulate syndromes. In: Contemporary behavioural neurology (Trimble MR, Cummings JL, eds), pp. 189213. Boston, MA: Butterworth-Heinemann.
Mega MS, Thompson PM, Cummings JL, Back CL, Xu ML, Zohoori S, Goldkorn A, Moussai J, Fairbanks L, Small GW, Toga AW (1998) Sulcal variability in the Alzheimers brain: correlations with cognition. Neurology 50:145151.[Abstract]
Miller EK, Cohen JD (2001) An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24:167202.[CrossRef][ISI][Medline]
Milner B (1971) Interhemispheric differences in the localization of psychological processes in man. Br Med Bull 27:272277.[ISI][Medline]
Nelson HE, Willison J (1991) National Adult Reading Test: Test manual. Windsor: NFER Nelson.
Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh handedness inventory. Neuropsychologia 9:97114.[CrossRef][ISI][Medline]
Ono M, Kubik S, Abernathy CD (1990) Atlas of the cerebral sulci. New York: Thieme.
Owen AM, Downes JJ, Sahakian BJ, Polkey CE, Robbins TW (1990) Planning and spatial working memory following frontal lobes lesions in man. Neuropsychologia 28:10211034.[CrossRef][ISI][Medline]
Owen AM, Evans AC, Petrides M (1996a) Evidence for a two-stage model of spatial working memory processing within lateral frontal cortex: a positron emission tomography study. Cereb Cortex 6:3138.[Abstract]
Owen AM, Morris RG, Sahakian BJ, Polkey CE, Robbins TW (1996b) Double dissociations of memory and executive functions in working memory tasks following frontal lobes excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Brain 119:15971615.[Abstract]
Owen AM, Herrod NJ, Menon DK, Clark JC, Downey SPMJ, Carpenter TA, Minhas PS, Turkheimer FE, Williams EJ, Robbins TW, Sahakian BJ, Petrides M, Pickard JD (1999) Redefining the functional organization of working memory processes within human lateral prefrontal cortex. Eur J Neurosci 11:567574.[CrossRef][ISI][Medline]
Passingham RE (1998) Attention to action. In: The prefrontal cortex: executive and cognitive functions (Roberts AC, Robbins TW, Weiskrantz L, eds), pp. 131143. New York: Oxford University Press.
Paus T, Otkay N, Caramanos Z, MacDonald D, Zijdenbos A, DAvirro D, Gutmans D, Holmes C, Tomaiuolo F, Evans AC (1996a) In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior rostral sulci: hemispheric asymmetries, gender differences and probability maps. J Comp Neurol 376:664673.[CrossRef][ISI][Medline]
Paus T, Tomaiuolo F, Otkay N, MacDonald D, Petrides M, Atlas J, Morris R, Evans AC (1996b) Human cingulate and paracingulate sulci: pattern, variability, asymmetry, and probabilistic map. Cereb Cortex 6:207214.[Abstract]
Rademacher J, Caviness Jr VS, Steinmetz H, Galaburda AM (1993) Topographical variation of the human primary cortices: implications for neuroimaging, brain mapping, and neurobiology. Cereb Cortex 3:313329.[Abstract]
Saling MM, Berkovic SF, OShea MF, Kalnins RM, Darby DG, Bladin PF (1993) Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects. J Clin Exp Neuropsychol 15:608618.[ISI][Medline]
Scannell JW (1997) Determining cortical landscapes. Nature 386:452.[CrossRef][ISI][Medline]
Seidman LJ, Breiter HC, Goodman JM, Goldstein JM, Woodruff PWR, OCraven K, Savoy R, Tsuang MT, Rosen BR (1998) A functional magnetic resonance imaging study of auditory vigilance with low and high information processing demands. Neuropsychology 12:505518.[CrossRef][ISI][Medline]
Spreen O, Strauss E (1998) A compendium of neuropsychological tests: administration, norms and commentary. New York: Oxford University Press.
Stuss DT, Alexander MP, Hamer L, Palumbo C, Dempster R, Binns M, Levine B, Izukawa D (1998) The effects of focal anterior and posterior brain lesions on verbal fluency. J Intl Neuropsychol Soc 4:265278.
Thompson PM, Schwartz C, Lin RT, Khan AA, Toga AW (1996) Three-dimensional statistical analysis of sulcal variability in the human brain. J Neurosci 16:42614274.
Van Essen DC (1997) A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 385:313318.[CrossRef][ISI][Medline]
Vogt BA, Nimchinsky EA, Vogt LJ, Hof PR (1995) Human cingulate cortex: surface features, flat maps, and cytoarchitecture. J Comp Neurol 359:490506.[ISI][Medline]
Wechsler D (1981) The Wechsler Adult Intelligence Scale Revised. New York: The Psychological Corporation.
Weintrob WL, Saling MM, Berkovic SF, Berlangieri SU, Reutens DC (2002) Verbal memory in left temporal lobe epilepsy: evidence for task related localization. Ann Neurol 51:442447.[CrossRef][ISI][Medline]
Welker W (1990) Why does cerebral cortex fissure and fold? A review of determinants of sulci an gyri. In: Cerebral cortex (Jones EG, Peters A, eds), pp. 3136. New York: Plenum.
Wood AG, Saling MM, Abbott DF, Jackson GD (2001) A neurocognitive account of frontal lobe involvement in orthographic lexical retrieval: an fMRI study. Neuroimage 14:162169.[CrossRef][ISI][Medline]
Yücel M, Stuart GW, Maruff P, Velakoulis D, Crowe SF, Savage G, Pantelis C (2001) Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study. Cereb Cortex 11:1725.
Zeger S, Liang K-Y (1986) Longitudinal data analysis for discrete and continuous outcomes. Biometrics 42:121130.[ISI][Medline]