- Email: [email protected]
Domain-specific distribution of working memory processes along human prefrontal and parietal cortices: a functional magnetic resonance imaging study
Neuroscience Letters 297 (2001) 29±32
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Domain-speci®c distribution of working memory processes along human prefrontal and parietal cortices: a functional magnetic resonance imaging study O. Gruber*, D.Y. von Cramon Max Planck Institute of Cognitive Neuroscience, P.O. Box 500 355, D-04303 Leipzig, Germany Received 20 September 2000; received in revised form 2 November 2000; accepted 2 November 2000
Abstract This study reinvestigated the functional neuroanatomy of phonological and visual working memory in humans. Articulatory suppression was used to deprive the human subjects of species-speci®c verbal strategies in order to make the functional magnetic resonance imaging results more comparable to ®ndings in non-human primates. Both phonological and visual working memory processes activated similar prefronto-parietal networks but were found to be differentially distributed along several cortical structures, in particular along the anterior and posterior parts of the intermediate frontal sulcus. These results suggest that a domain-speci®c topographical organization of neural working memory mechanisms in the primate brain is conserved in evolution. However, the ®ndings also underline the critical dynamic in¯uence that the additional availability of language may have on working memory processes and their functional implementation in the human brain. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Phonological loop; Rehearsal; Functional homology; Principal sulcus
The prefrontal cortex (PFC) has been recognized for a long time as a structure supporting many higher cognitive functions such as problem-solving, planning and reasoning. However, its functional organization even at the macroscopic level is still a matter of current debate [5,17]. Based on studies of non-human primates using single-cell recordings, anatomical tract-tracing and other invasive techniques, it has been proposed that the PFC may be parcellated into subregions that process mnemonic representations of different kinds of information, in particular spatial or object information [6]. While some functional neuroimaging studies of working memory in human subjects produced results consistent with the ®ndings in non-human primates [3,4,9], others failed to con®rm the suggested organizational principle [13,15]. One possible explanation for such discrepancies between results in human and in non-human primates are species-speci®c differences in brain function caused by evolutionary pressure [5]. One of the most obvious differences between the cognitive capacities of humans and non-human primates is the special endowment with language. While it has been recog* Corresponding author. Tel.: 149-341-9940-158; fax: 149-3419940-204. E-mail address: [email protected] (O. Gruber).
nized recently that the emergence of language may have led to an anatomical displacement of brain areas subserving spatial and object-related cognitive processes [3,19], the additional dynamic in¯uence that the availability of language may have on working memory processes and their functional implementation in the human brain has been neglected so far. The probably best way to make working memory task performance of human subjects more comparable to that of non-human primates is to use articulatory suppression in order to deprive subjects of strategies which presumably are speci®c to the human species. The articulatory suppression effect refers to the observation that verbal short-term memory is reduced when one has to perform other concurrent articulations, and presumably is caused by a disruption of the rehearsal mechanism. Thus, memory performance under articulatory suppression would have to rely on alternative phonological and/or visual storage mechanisms that could be similar to working memory mechanisms in non-human primates. In a recent functional magnetic resonance imaging (fMRI) study, silent articulatory suppression eliminated memory-related activity in classical verbal working memory areas and, most importantly, led to the occurrence of other memory-related activations in prefrontal and parietal cortices. Consequently, the
0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 0 0) 01 66 5- 7
30
O. Gruber, D.Y. von Cramon / Neuroscience Letters 297 (2001) 29±32
coexistence of a second, fronto-parietal brain system subserving the short-term maintenance of simple phonological information apart from the rehearsal mechanism was postulated [7]. The present study was set in to investigate in more detail how this brain system may be related to visual working memory and, in particular, whether it could be anatomically differentiated from frontal and parietal areas that are known to underlie visual working memory processes. Five right-handed subjects (three men and two women; mean age: 23.8 ^ 3.6 years) participated in this study. A 3.0 Tesla magnetic resonance imaging (MRI) scanner (Bruker Medspec 30/100) with a circularly polarized head coil was used to obtain a high-resolution structural scan for each subject followed by two runs of 688 gradient echoplanar image (EPI) volumes each (TR 2 s, TE 40 ms, ¯ip angle 908; number of slices 16, voxel size 3 £ 3 £ 5 mm 3, distance factor 0.2) that were synchronized with stimulus presentation. Subjects were pretrained, and they performed different item-recognition tasks (letter, colour, or form recognition) in a counterbalanced order. Each of these tasks was presented in blockwise alternation with a letter case judgement task that was matched for sensory, motor and unspeci®c cognitive processing in the corresponding memory condition. The stimulus material consisted of coloured letters in different fonts. Trials began with a 1-s presentation of four letters, which were randomly assigned four different colours and fonts. This presentation was followed by a 4-s ®xation delay which was ®lled with 4000 Hz-tones (SOA 300 ms) that paced silent counting repeatedly from 1 to 4, i.e. silent articulatory suppression. A cue instructed the subjects if and which of the features of the four target letters were to be memorized and to be maintained during the delay. Afterwards they had to decide by button press whether a probe letter matched one of the memorized items with respect to the relevant feature. Alternatively, the subjects had to read the letters without memorizing, and to
judge whether the single presented letter was uppercase or lowercase. In the visual memory conditions (and the corresponding letter case judgement tasks) articulatory suppression already began during the target presentation, in order to prevent subjects from verbally encoding colours and forms. In addition, a fourth experimental condition was employed which consisted of the phonological letter-recognition task (alternating with letter case judgement), however, each performed without articulatory suppression. Using SPM99 the functional images were realigned, corrected for motion, global signal intensity variation and low frequency ¯uctuations, co-registered, normalized into standard stereotactic space (MNI template) and spatially smoothed with an 12 mm full-width-half-maximum Gaussian kernel. Statistical tests were based on a ®xed effects model and performed for the different memory conditions by contrasting them with the corresponding control conditions. Subsequently, these memory-speci®c effects were directly compared to each other using interaction contrasts in order to reveal domain-speci®c effects of memory task performance. Results are reported for brain activations that reached a voxelwise signi®cance level of P , 0:05, corrected. To allow comparison, ®ndings in those areas are also listed for the other statistical contrasts, provided these foci passed a signi®cance level of P , 0:001, uncorrected. The behavioural data obtained during scanning excluded any signi®cant differences between visual and phonological memory task performance under articulatory suppression (mean reaction time/accuracy in the phonological task: 1032 ms/76.1%; in the visual tasks: 971 ms/77.5%; P 0:35/P 0:82). Overall, when comparing the memory conditions with their respective matched control conditions memory-related brain activity was observed in widely distributed networks comprising multiple frontal, parietal, temporal, cerebellar and subcortical regions which, for reasons of space, can only partly be reported here (Table 1).
Table 1 Brain regions showing signi®cant activity related to phonological and visual working memory under conditions of articulatory suppression a Region
(A) L/R anterior intermediate frontal sulcus L/R inferior parietal lobule (B) L/R posterior intermediate frontal sulcus L/R posterior superior frontal sulcus L/R superior parietal lobule
Talairach co-ordinates
Statistical effects (T-value) Phonological memory
Visual form Visual colour Phonological Visual vs. memory memory vs. visual phonological
232 48 28, 28 52 20
11.34/12.82
3.60*/8.36
260 244 28, 56 244 24 252 28 40, 48 20 44
4.41/3.41* 11.52/13.73
236 24 56, 32 24 60 240 268 60, 32 268 60
n.s./3.20*
6.66/5.75
n.s./n.s.
n.s./n.s. 23.88/23.14
n.s./n.s. 17.41/13.67
8.87/7.09 n.s./n.s.
n.s./n.s. 7.45/3.81*
n.s./3.24*
11.81/13.86
6.56/6.34
n.s./n.s.
6.97/5.60
6.89/10.27
19.90/22.82
12.96/16.53
n.s./n.s.
7.78/7.67
a The T-values given in the table correspond to a signi®cance threshold of P , 0:05, corrected, (i.e. T . 4.39), except the ones marked by an asterix that correspond to a signi®cance threshold of P , 0:001, uncorrected, (i.e. T . 3.09). (A) Areas preferentially activated by phonological memory task performance; (B) areas preferentially activated by visual memory task performance; L, left; n.s., not signi®cant (P . 0.962, corrected); R, right. For a complete list of activations please contact the author.
O. Gruber, D.Y. von Cramon / Neuroscience Letters 297 (2001) 29±32
While at ®rst sight the activity patterns elicited by the different memory tasks may appear quite similar (Fig. 1A±C), direct comparisons revealed clear domain-speci®c effects of memory task performance, i.e. the activity in most of these brain areas signi®cantly depended on the type of memory representation that had to be held in mind (Table 1 and Fig. 1D,E). Most interestingly, the phonological task variant elicited strong activations along the anterior intermediate frontal sulcus (Fig. 1A and Table 1A), whereas working memory for both visual letter forms and colours predominantly activated other, more posterior prefrontal regions along the intermediate and superior frontal sulci
Fig. 1. Activations associated with phonological and visual working memory in a representative subject. (A) Phonological memory for letter names, (B) visual memory for letter forms and (C) visual memory for letter colours, each under conditions of articulatory suppression. (D) Signi®cant domain-speci®c differences between the memory-related activation patterns as shown in (A±C), and (E) as rendered onto the surface of the individual brain and viewed from top-right. Enhanced brain activity during the phonological memory task is indicated in yellow/red, whereas increased brain activity during the visual memory tasks is shown in blue/green. (F) Activations related to phonological memory for letter names, i.e. the same task as in (A), however, when the subject was allowed and explicitly instructed to rehearse. All statistical parametric maps were thresholded at P , 0:05, corrected, except those shown in (D,E) which were thresholded at P , 0:001, uncorrected, to delineate spatial extent.
31
(Fig. 1B,C and Table 1B; see Fig. 1D,E for direct statistical comparisons). At a signi®cance level of P , 0:001, uncorrected, these effects were present in every single subject. These results are consistent with ®ndings from previous functional neuroimaging studies that showed activation of the cortex along the posterior superior frontal sulcus during the maintenance of visual, in particular visuospatial information [3,4,9,19]. Furthermore, they suggest that the human PFC along the intermediate frontal sulcus may be parcellated into anterior and posterior subdivisions that are differentially involved in phonological and visual working memory processes, respectively. Thus, our ®ndings demonstrate a similar anterior-posterior segregation of domainspeci®c working memory processes as it appears to exist in the PFC of non-human primates where recent studies indicate a possible role of the posterior principal sulcus in visuospatial and possibly also in auditory-spatial processing, whereas the anterior part of the principal sulcus may subserve non-spatial auditory and probably also some aspects of phonetic processing [8,14,16]. In addition, our ®ndings receive support from recent neuroimaging studies in human subjects that showed similar anterior prefrontal activations during non-verbal auditory and phonological working memory tasks [10,18]. While from the former study it cannot be excluded that the anterior prefrontal area may also subserve memory for simple phonemes when they will not or even cannot be rehearsed, the second study revealed activation of the anterior PFC when it was explicitly tested for phonological storage [10]. Most remarkably, not only this anterior prefrontal focus, but actually the complete pattern of brain activity that was associated with phonological storage in this study is strikingly similar to the activations that were related to verbal memory under articulatory suppression in the present study. Thus, although we cannot exclude from the present experiment alone that some of these activations may represent executive processes evoked by conditions of interference, taken together these neuroimaging studies provide converging evidence that a network of anterior prefrontal and inferior parietal brain areas may subserve a mechanism by which not only auditory, but also simple phonological information can be maintained over brief periods of time. Furthermore, the results of the present study indicate that phonological and visual working memory processes under articulatory suppression go along with very similar activations in frontal and parietal brain areas (Fig. 1A±C), but are differentially distributed along these cortical structures (Fig. 1D,E and Table 1). With respect to parietal areas our data are consistent with recent ®ndings of a domain-speci®c, preferential involvement of the inferior parietal lobule in auditory, and of the superior parietal lobule in visual localisation tasks [1]. Overall, these data provide some support for the existence of domain-speci®c parallel networks as proposed by Goldman-Rakic [6]. However, the speci®city observed in the present study is related to the domains of phonological and visual information, whereas we cannot make predictions on a
32
O. Gruber, D.Y. von Cramon / Neuroscience Letters 297 (2001) 29±32
possible neuroanatomical differentiation of spatial and object domains in the human PFC. Furthermore, it is important to note that we did not ®nd a strict segregation between phonological and visual memory processes, but rather overlapping networks with a domainspeci®c differential activation of their single components. This observation is consistent with a recent study that indicated that different processes or domains in visual working memory are not exactly attributable to speci®c modules in the frontal lobe, but are related to varying degrees of participation of different frontal regions in the task [9]. Given some methodological differences between the studies it is probably also compatible with previous reports which had emphasized such an overlap of activation in working memory tasks regardless of the modality of information that had to be remembered [11,12]. Recently it has been proposed that common activations produced by different working memory tasks may result from an automatic encoding of multiple dimensions into working memory [13]. The relative, domain-speci®c differences found in the present and in other working memory studies may then be regarded as effects of selective attention to a certain informational domain in working memory as previous neuroimaging studies have repeatedly demonstrated an enhancement of mapping contrast in brain areas that process the attended information [2]. To conclude, phonological and visual working memory processes were found to be differentially distributed along several identical anatomical structures, in particular along the intermediate frontal sulcus. In close analogy to the well-established functional neuroanatomy of working memory in non-human primates [6], we assume that these brain structures represent a multimodal working memory system whose subdivisions deal with different informational domains. Thus, the present study may also provide new evidence for a functional homology between the intermediate frontal sulcus in humans and the principal sulcus in monkeys. So far, support for this homology was only indirectly derived from structural, particularly cytoarchitectonic investigations [14], and not based on the functional relevance of these structures. Finally, the neural correlates of the rehearsal mechanism have been shown to be clearly distinct from the brain regions presumed to underlie this putative multimodal working memory system in humans [7] (cf. Fig. 1A±C,F). In addition, no homologous mechanism has been found so far for rehearsal in non-human primates. Therefore, it appears plausible to postulate a fundamental difference between the rehearsal mechanism and a multimodal working memory system in terms of their different evolutionary origin as it has been done in the evolutionary-based model of human working memory [7]. [1] Bushara, K.O., Weeks, R.A., Ishii, K., Catalan, M.-J., Tian, B., Rauschecker, J.P. and Hallett, M., Modality-speci®c frontal and parietal areas for auditory and visual spatial localization in humans, Nat. Neurosci., 2 (1999) 759±766.
[2] Coull, J.T., Neural correlates of attention and arousal: insights from electrophysiology, functional neuroimaging and psychopharmacology, Prog. Neurobiol., 55 (1998) 343± 361. [3] Courtney, S.M., Petit, L., Maisog, J.M., Ungerleider, L.G. and Haxby, J.V., An area specialized for spatial working memory in human frontal cortex, Science, 279 (1998) 1347±1351. [4] Courtney, S.M., Ungerleider, L.G., Keil, K. and Haxby, J.V., Object and spatial working memory activate separate neural systems in human cortex, Cereb. Cortex, 6 (1996) 39±49. [5] Goldman-Rakic, P.S., Localization of function all over again, Neuroimage, 11 (2000) 451±457. [6] Goldman-Rakic, P.S., The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive, Philos. Trans. R. Soc. Lond. B, 351 (1996) 1445±1453. [7] Gruber, O., Two different brain systems underlie phonological short-term memory in humans, Neuroimage, 11 (2000) S407. [8] Hackett, T.A., Stepniewska, I. and Kaas, J.H., Prefrontal connections of the parabelt auditory cortex in macaque monkeys, Brain Res., 817 (1999) 45±58. [9] Haxby, J.V., Petit, L., Ungerleider, L.G. and Courtney, S.M., Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory, Neuroimage, 11 (2000) 380±391. [10] Henson, R.N.A., Burgess, N. and Frith, C.D., Recoding, storage, rehearsal and grouping in verbal short-term memory: an fMRI study, Neuropsychologia, 38 (2000) 426±440. [11] Klingberg, T., Concurrent performance of two working memory tasks: potential mechanisms of interference, Cereb. Cortex, 8 (1998) 593±601. [12] Klingberg, T., Kawashima, R. and Roland, P.E., Activation of multi-modal cortical areas underlies short-term memory, Eur. J. Neurosci., 8 (1996) 1965±1971. [13] Nystrom, L.E., Braver, T.S., Sabb, F.W., Delgado, M.R., Noll, D.C. and Cohen, J.D., Working memory for letters, shapes, and locations: fMRI evidence against stimulus-based regional organization in human prefrontal cortex, Neuroimage, 11 (2000) 424±446. [14] Petrides, M. and Pandya, D.N., Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns, Eur. J. Neurosci., 11 (1999) 1011±1036. [15] Postle, B.R., Stern, C.E., Rosen, B.R. and Corkin, S., An fMRI investigation of cortical contributions to spatial and nonspatial visual working memory, Neuroimage, 11 (2000) 409±423. [16] Romanski, L.M., Tian, B., Fritz, J., Mishkin, M., GoldmanRakic, P.S. and Rauschecker, J.P., Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex, Nat. Neurosci., 2 (1999) 1131±1136. [17] Rushworth, M.F.S. and Owen, A.M., The functional organization of the lateral frontal cortex: conjecture or conjuncture in the electrophysiological literature? Trends Cogn. Sci., 2 (1998) 46±53. [18] Stevens, A.A., Goldman-Rakic, P.S., Gore, J.C., Fulbright, R.K. and Wexler, B.E., Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging, Arch. Gen. Psychiatry, 55 (1998) 1097±1103. [19] Ungerleider, L.E., Courtney, S.M. and Haxby, J.V., A neural system for human visual working memory, Proc. Natl. Acad. Sci. USA, 95 (1998) 883±890.
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Domain-speci®c distribution of working memory processes along human prefrontal and parietal cortices: a functional magnetic resonance imaging study O. Gruber*, D.Y. von Cramon Max Planck Institute of Cognitive Neuroscience, P.O. Box 500 355, D-04303 Leipzig, Germany Received 20 September 2000; received in revised form 2 November 2000; accepted 2 November 2000
Abstract This study reinvestigated the functional neuroanatomy of phonological and visual working memory in humans. Articulatory suppression was used to deprive the human subjects of species-speci®c verbal strategies in order to make the functional magnetic resonance imaging results more comparable to ®ndings in non-human primates. Both phonological and visual working memory processes activated similar prefronto-parietal networks but were found to be differentially distributed along several cortical structures, in particular along the anterior and posterior parts of the intermediate frontal sulcus. These results suggest that a domain-speci®c topographical organization of neural working memory mechanisms in the primate brain is conserved in evolution. However, the ®ndings also underline the critical dynamic in¯uence that the additional availability of language may have on working memory processes and their functional implementation in the human brain. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Phonological loop; Rehearsal; Functional homology; Principal sulcus
The prefrontal cortex (PFC) has been recognized for a long time as a structure supporting many higher cognitive functions such as problem-solving, planning and reasoning. However, its functional organization even at the macroscopic level is still a matter of current debate [5,17]. Based on studies of non-human primates using single-cell recordings, anatomical tract-tracing and other invasive techniques, it has been proposed that the PFC may be parcellated into subregions that process mnemonic representations of different kinds of information, in particular spatial or object information [6]. While some functional neuroimaging studies of working memory in human subjects produced results consistent with the ®ndings in non-human primates [3,4,9], others failed to con®rm the suggested organizational principle [13,15]. One possible explanation for such discrepancies between results in human and in non-human primates are species-speci®c differences in brain function caused by evolutionary pressure [5]. One of the most obvious differences between the cognitive capacities of humans and non-human primates is the special endowment with language. While it has been recog* Corresponding author. Tel.: 149-341-9940-158; fax: 149-3419940-204. E-mail address: [email protected] (O. Gruber).
nized recently that the emergence of language may have led to an anatomical displacement of brain areas subserving spatial and object-related cognitive processes [3,19], the additional dynamic in¯uence that the availability of language may have on working memory processes and their functional implementation in the human brain has been neglected so far. The probably best way to make working memory task performance of human subjects more comparable to that of non-human primates is to use articulatory suppression in order to deprive subjects of strategies which presumably are speci®c to the human species. The articulatory suppression effect refers to the observation that verbal short-term memory is reduced when one has to perform other concurrent articulations, and presumably is caused by a disruption of the rehearsal mechanism. Thus, memory performance under articulatory suppression would have to rely on alternative phonological and/or visual storage mechanisms that could be similar to working memory mechanisms in non-human primates. In a recent functional magnetic resonance imaging (fMRI) study, silent articulatory suppression eliminated memory-related activity in classical verbal working memory areas and, most importantly, led to the occurrence of other memory-related activations in prefrontal and parietal cortices. Consequently, the
0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 0 0) 01 66 5- 7
30
O. Gruber, D.Y. von Cramon / Neuroscience Letters 297 (2001) 29±32
coexistence of a second, fronto-parietal brain system subserving the short-term maintenance of simple phonological information apart from the rehearsal mechanism was postulated [7]. The present study was set in to investigate in more detail how this brain system may be related to visual working memory and, in particular, whether it could be anatomically differentiated from frontal and parietal areas that are known to underlie visual working memory processes. Five right-handed subjects (three men and two women; mean age: 23.8 ^ 3.6 years) participated in this study. A 3.0 Tesla magnetic resonance imaging (MRI) scanner (Bruker Medspec 30/100) with a circularly polarized head coil was used to obtain a high-resolution structural scan for each subject followed by two runs of 688 gradient echoplanar image (EPI) volumes each (TR 2 s, TE 40 ms, ¯ip angle 908; number of slices 16, voxel size 3 £ 3 £ 5 mm 3, distance factor 0.2) that were synchronized with stimulus presentation. Subjects were pretrained, and they performed different item-recognition tasks (letter, colour, or form recognition) in a counterbalanced order. Each of these tasks was presented in blockwise alternation with a letter case judgement task that was matched for sensory, motor and unspeci®c cognitive processing in the corresponding memory condition. The stimulus material consisted of coloured letters in different fonts. Trials began with a 1-s presentation of four letters, which were randomly assigned four different colours and fonts. This presentation was followed by a 4-s ®xation delay which was ®lled with 4000 Hz-tones (SOA 300 ms) that paced silent counting repeatedly from 1 to 4, i.e. silent articulatory suppression. A cue instructed the subjects if and which of the features of the four target letters were to be memorized and to be maintained during the delay. Afterwards they had to decide by button press whether a probe letter matched one of the memorized items with respect to the relevant feature. Alternatively, the subjects had to read the letters without memorizing, and to
judge whether the single presented letter was uppercase or lowercase. In the visual memory conditions (and the corresponding letter case judgement tasks) articulatory suppression already began during the target presentation, in order to prevent subjects from verbally encoding colours and forms. In addition, a fourth experimental condition was employed which consisted of the phonological letter-recognition task (alternating with letter case judgement), however, each performed without articulatory suppression. Using SPM99 the functional images were realigned, corrected for motion, global signal intensity variation and low frequency ¯uctuations, co-registered, normalized into standard stereotactic space (MNI template) and spatially smoothed with an 12 mm full-width-half-maximum Gaussian kernel. Statistical tests were based on a ®xed effects model and performed for the different memory conditions by contrasting them with the corresponding control conditions. Subsequently, these memory-speci®c effects were directly compared to each other using interaction contrasts in order to reveal domain-speci®c effects of memory task performance. Results are reported for brain activations that reached a voxelwise signi®cance level of P , 0:05, corrected. To allow comparison, ®ndings in those areas are also listed for the other statistical contrasts, provided these foci passed a signi®cance level of P , 0:001, uncorrected. The behavioural data obtained during scanning excluded any signi®cant differences between visual and phonological memory task performance under articulatory suppression (mean reaction time/accuracy in the phonological task: 1032 ms/76.1%; in the visual tasks: 971 ms/77.5%; P 0:35/P 0:82). Overall, when comparing the memory conditions with their respective matched control conditions memory-related brain activity was observed in widely distributed networks comprising multiple frontal, parietal, temporal, cerebellar and subcortical regions which, for reasons of space, can only partly be reported here (Table 1).
Table 1 Brain regions showing signi®cant activity related to phonological and visual working memory under conditions of articulatory suppression a Region
(A) L/R anterior intermediate frontal sulcus L/R inferior parietal lobule (B) L/R posterior intermediate frontal sulcus L/R posterior superior frontal sulcus L/R superior parietal lobule
Talairach co-ordinates
Statistical effects (T-value) Phonological memory
Visual form Visual colour Phonological Visual vs. memory memory vs. visual phonological
232 48 28, 28 52 20
11.34/12.82
3.60*/8.36
260 244 28, 56 244 24 252 28 40, 48 20 44
4.41/3.41* 11.52/13.73
236 24 56, 32 24 60 240 268 60, 32 268 60
n.s./3.20*
6.66/5.75
n.s./n.s.
n.s./n.s. 23.88/23.14
n.s./n.s. 17.41/13.67
8.87/7.09 n.s./n.s.
n.s./n.s. 7.45/3.81*
n.s./3.24*
11.81/13.86
6.56/6.34
n.s./n.s.
6.97/5.60
6.89/10.27
19.90/22.82
12.96/16.53
n.s./n.s.
7.78/7.67
a The T-values given in the table correspond to a signi®cance threshold of P , 0:05, corrected, (i.e. T . 4.39), except the ones marked by an asterix that correspond to a signi®cance threshold of P , 0:001, uncorrected, (i.e. T . 3.09). (A) Areas preferentially activated by phonological memory task performance; (B) areas preferentially activated by visual memory task performance; L, left; n.s., not signi®cant (P . 0.962, corrected); R, right. For a complete list of activations please contact the author.
O. Gruber, D.Y. von Cramon / Neuroscience Letters 297 (2001) 29±32
While at ®rst sight the activity patterns elicited by the different memory tasks may appear quite similar (Fig. 1A±C), direct comparisons revealed clear domain-speci®c effects of memory task performance, i.e. the activity in most of these brain areas signi®cantly depended on the type of memory representation that had to be held in mind (Table 1 and Fig. 1D,E). Most interestingly, the phonological task variant elicited strong activations along the anterior intermediate frontal sulcus (Fig. 1A and Table 1A), whereas working memory for both visual letter forms and colours predominantly activated other, more posterior prefrontal regions along the intermediate and superior frontal sulci
Fig. 1. Activations associated with phonological and visual working memory in a representative subject. (A) Phonological memory for letter names, (B) visual memory for letter forms and (C) visual memory for letter colours, each under conditions of articulatory suppression. (D) Signi®cant domain-speci®c differences between the memory-related activation patterns as shown in (A±C), and (E) as rendered onto the surface of the individual brain and viewed from top-right. Enhanced brain activity during the phonological memory task is indicated in yellow/red, whereas increased brain activity during the visual memory tasks is shown in blue/green. (F) Activations related to phonological memory for letter names, i.e. the same task as in (A), however, when the subject was allowed and explicitly instructed to rehearse. All statistical parametric maps were thresholded at P , 0:05, corrected, except those shown in (D,E) which were thresholded at P , 0:001, uncorrected, to delineate spatial extent.
31
(Fig. 1B,C and Table 1B; see Fig. 1D,E for direct statistical comparisons). At a signi®cance level of P , 0:001, uncorrected, these effects were present in every single subject. These results are consistent with ®ndings from previous functional neuroimaging studies that showed activation of the cortex along the posterior superior frontal sulcus during the maintenance of visual, in particular visuospatial information [3,4,9,19]. Furthermore, they suggest that the human PFC along the intermediate frontal sulcus may be parcellated into anterior and posterior subdivisions that are differentially involved in phonological and visual working memory processes, respectively. Thus, our ®ndings demonstrate a similar anterior-posterior segregation of domainspeci®c working memory processes as it appears to exist in the PFC of non-human primates where recent studies indicate a possible role of the posterior principal sulcus in visuospatial and possibly also in auditory-spatial processing, whereas the anterior part of the principal sulcus may subserve non-spatial auditory and probably also some aspects of phonetic processing [8,14,16]. In addition, our ®ndings receive support from recent neuroimaging studies in human subjects that showed similar anterior prefrontal activations during non-verbal auditory and phonological working memory tasks [10,18]. While from the former study it cannot be excluded that the anterior prefrontal area may also subserve memory for simple phonemes when they will not or even cannot be rehearsed, the second study revealed activation of the anterior PFC when it was explicitly tested for phonological storage [10]. Most remarkably, not only this anterior prefrontal focus, but actually the complete pattern of brain activity that was associated with phonological storage in this study is strikingly similar to the activations that were related to verbal memory under articulatory suppression in the present study. Thus, although we cannot exclude from the present experiment alone that some of these activations may represent executive processes evoked by conditions of interference, taken together these neuroimaging studies provide converging evidence that a network of anterior prefrontal and inferior parietal brain areas may subserve a mechanism by which not only auditory, but also simple phonological information can be maintained over brief periods of time. Furthermore, the results of the present study indicate that phonological and visual working memory processes under articulatory suppression go along with very similar activations in frontal and parietal brain areas (Fig. 1A±C), but are differentially distributed along these cortical structures (Fig. 1D,E and Table 1). With respect to parietal areas our data are consistent with recent ®ndings of a domain-speci®c, preferential involvement of the inferior parietal lobule in auditory, and of the superior parietal lobule in visual localisation tasks [1]. Overall, these data provide some support for the existence of domain-speci®c parallel networks as proposed by Goldman-Rakic [6]. However, the speci®city observed in the present study is related to the domains of phonological and visual information, whereas we cannot make predictions on a
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possible neuroanatomical differentiation of spatial and object domains in the human PFC. Furthermore, it is important to note that we did not ®nd a strict segregation between phonological and visual memory processes, but rather overlapping networks with a domainspeci®c differential activation of their single components. This observation is consistent with a recent study that indicated that different processes or domains in visual working memory are not exactly attributable to speci®c modules in the frontal lobe, but are related to varying degrees of participation of different frontal regions in the task [9]. Given some methodological differences between the studies it is probably also compatible with previous reports which had emphasized such an overlap of activation in working memory tasks regardless of the modality of information that had to be remembered [11,12]. Recently it has been proposed that common activations produced by different working memory tasks may result from an automatic encoding of multiple dimensions into working memory [13]. The relative, domain-speci®c differences found in the present and in other working memory studies may then be regarded as effects of selective attention to a certain informational domain in working memory as previous neuroimaging studies have repeatedly demonstrated an enhancement of mapping contrast in brain areas that process the attended information [2]. To conclude, phonological and visual working memory processes were found to be differentially distributed along several identical anatomical structures, in particular along the intermediate frontal sulcus. In close analogy to the well-established functional neuroanatomy of working memory in non-human primates [6], we assume that these brain structures represent a multimodal working memory system whose subdivisions deal with different informational domains. Thus, the present study may also provide new evidence for a functional homology between the intermediate frontal sulcus in humans and the principal sulcus in monkeys. So far, support for this homology was only indirectly derived from structural, particularly cytoarchitectonic investigations [14], and not based on the functional relevance of these structures. Finally, the neural correlates of the rehearsal mechanism have been shown to be clearly distinct from the brain regions presumed to underlie this putative multimodal working memory system in humans [7] (cf. Fig. 1A±C,F). In addition, no homologous mechanism has been found so far for rehearsal in non-human primates. Therefore, it appears plausible to postulate a fundamental difference between the rehearsal mechanism and a multimodal working memory system in terms of their different evolutionary origin as it has been done in the evolutionary-based model of human working memory [7]. [1] Bushara, K.O., Weeks, R.A., Ishii, K., Catalan, M.-J., Tian, B., Rauschecker, J.P. and Hallett, M., Modality-speci®c frontal and parietal areas for auditory and visual spatial localization in humans, Nat. Neurosci., 2 (1999) 759±766.
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