NeuroImage 20 (2003) 244 256

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Semantic and episodic memory of music are subserved by distinct neural networks
Herve Platel,a,* Jean-Claude Baron,b Be atrice Desgranges,a a Fre de ric Bernard, and Francis Eustachea,c
a

Inserm E.0218-Universite de Caen, Gip Cyceron, Laboratoire de Neuropsychologie, CHU Co te de Nacre, Caen, France b Department of Neurology, University of Cambridge, Cambridge UK c Ecole Pratique des Hautes Etudes, CNRS 8581, Universite Rene Descartes, Paris 5, France Received 26 September 2002; revised 14 February 2003; accepted 16 May 2003

Abstract Numerous functional imaging studies have shown that retrieval from semantic and episodic memory is subserved by distinct neural networks. However, these results were essentially obtained with verbal and visuospatial material. The aim of this work was to determine the neural substrates underlying the semantic and episodic components of music using familiar and nonfamiliar melodic tunes. To study musical semantic memory, we designed a task in which the instruction was to judge whether or not the musical extract was felt as familiar. To study musical episodic memory, we constructed two delayed recognition tasks, one containing only familiar and the other only nonfamiliar items. For each recognition task, half of the extracts (targets) were presented in the prior semantic task. The episodic and semantic tasks were to be contrasted by a comparison to two perceptive control tasks and to one another. Cerebral blood ow was assessed by means of the oxygen-15-labeled water injection method, using high-resolution PET. Distinct patterns of activations were found. First, regarding the episodic memory condition, bilateral activations of the middle and superior frontal gyri and precuneus (more prominent on the right side) were observed. Second, the semantic memory condition disclosed extensive activations in the medial and orbital frontal cortex bilaterally, the left angular gyrus, and predominantly the left anterior part of the middle temporal gyri. The ndings from this study are discussed in light of the available neuropsychological data obtained in brain-damaged subjects and functional neuroimaging studies. 2003 Elsevier Inc. All rights reserved.
Keywords: PET; Music; Semantic memory; Episodic memory; Frontal lobes; HERA model

Introduction Many moments of our life are associated with a song or a particular melody. However, the neural substrates of musical perception and musical memory processes are still little known. Although it is common belief that perception of music is a specic ability of the right hemisphere, studies in brain-damaged subjects demonstrate that musical capabilities are distributed in both hemispheres (Lechevalier et al., 1995; Peretz, 1994, 2001; Platel, 2002). Thus, in the

* Corresponding author. EMI-E.0218 Inserm-Universite de Caen, U.F.R. de Psychologie, Universite de Caen, Esplanade de la Paix, 14032 Caen Cedex, France. E-mail address: platel@scvie.unicaen.fr (H. Platel). 1053-8119/03/$ see front matter 2003 Elsevier Inc. All rights reserved. doi:10.1016/S1053-8119(03)00287-8

brain there is no center for music but a number of neural networks that deal with the different components of music perception (e.g., pitch, timber, rhythm, intensity); these neural networks are very sensitive to musical training and expertise and could differ from one subject to another (Altenmu ller, 2001; Schlaug, 2001). Over the past 10 years, the most relevant information relating to the musical processes have clearly emerged from functional neuroimaging studies, but most of these have addressed perceptual treatments (Zatorre et al., 1992; Sergent et al., 1992b; Platel et al., 1997; Grifths et al., 1999). So far, very few neuropsychological, psychophysical, or imaging studies have related to the mnemonic aspects of music, and the concept of a modular musical memory is little considered in the psychological and neuropsychological literatures.

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Experimental psychology and psychoacoustic investigations mainly relate to the elementary characteristics of musical perception and more rarely on the mnemonic processes as such, while the rare studies that did so focussed on working rather than long-term memory processes (Deutsch, 1970; Semal and Demany, 1991, 1993). Experimental investigations of the recall of well-known or new musical parts generally concurred in showing the importance of melodic relative to rhythmic information in both the encoding and the retrieval processes for musical material (Halpern, 1984; Dowling et al., 1995; He bert and Peretz, 1997). This supports the idea of a melodic advantage in the constitution of the musical lexicon. Findings in brain-damaged subjects suggest that musical memory could have a different cerebral organization from other kinds of memory, such as verbal and visual memory. Clinical reports show that although identication and recognition of a musical piece appears to involve both hemispheres, integrity of the left hemisphere is however critical (see review in Lechevalier et al., 1995), as illustrated by a left brain-damaged patient who exhibited impaired melodic identication despite intact melodic discrimination (Eustache et al., 1990). Interestingly, these disturbances in melodic identication were found to be dissociated from the language impairment observed following cerebral lesions involving specically the verbal semantic processes (Signoret et al., 1987). In addition, the studies carried out by Zatorre (1985) and Samson and Zatorre (1991) in patients with right or left temporal lobectomies revealed a major role of the right temporal areas in the recognition of unknown melodies, suggesting that such recognition, which is not based on a semantic strategy, is subtended by a perceptive analysis and a comparison of the melodies. The observation of patient C.N. (Peretz, 1996) is particularly relevant because, several years after having sustained bilateral temporal lesions, this patient was unable to memorize new musical tunes. Furthermore, there was a lack of priming effect for musical material in this patient, which suggested abolished access and encoding specic to music. For the author, this clinical case argues for the existence of a long-term memory subsystem specic to musical material. Another argument in favour of a possible separate longterm memory subsystem between language and music comes from event-related brain potentials studies (ERPs; Besson and Scho n, 2001), which show differential ERP effects for semantic processes when subjects focus their attention only to the lyrics or to the music of opera excerpts. The aim of this work was to determine the neural substrates underlying the semantic and episodic components of music memory. The distinction between episodic and semantic memory has become very popular since it was rst proposed by Tulving in 1972. Episodic memory is conceived as the memory of life events linked to their spatial and temporal context of acquisition, while semantic memory corresponds to the memory of concepts, transcending a particular context (Tulving, 1985, 2001). In this work, we dene musical seman-

tic memory as that referring to well-known excerpts of music stored in memory without it being possible to retrieve the temporal or spatial circumstances surrounding their encounter. Semantic memory allows us to identify or to have a strong feeling of knowing for familiar songs or melodies. We may name the tune (composer or performer) or just have the capacity to hum or whistle the subsequent notes of a melody. Musical semantic memory may represent a musical lexicon, separate of a verbal lexicon, even though strong links certainly exist between them. Our previous PET study, which dealt with the music components of music perception, did tackle the semantic processing of music (Platel et al., 1997). In this investigation, judging whether or not musical sequences were familiar induced specic activation of the left inferior frontal gyrus (area 47 of Brodmann) and anterior part of the left superior temporal gyrus relative to attention to the other musical components (i.e., rhythm, pitch, and timber). However, in their study of mental imagery for familiar melodies, Halpern and Zatorre (1999) claimed that musical semantic memory primarily engaged right-sided regions. These ndings however appear somewhat to conict with the large neuroimaging literature about recall of verbal or visual material from semantic memory (see Cabeza and Nyberg, 2000, for review), in which preferential implication of the left temporal and prefrontal regions is a regular feature. It may therefore be argued that the right-sided engagement reported by Halpern and Zatorre (1999) may reect the nonverbal nature of the musical material used by these authors. The neural substrates of musical semantic memory therefore remain uncertain. Episodic memory for musical information will be referred here as the capacity to recognize a musical excerpt (whether familiar or not) for which the spatiotemporal context surrounding its former encounter (i.e., when, where, and how) can be recalled. Neuroimaging studies have conrmed the importance of the medial temporal and frontal lobes in the encoding and retrieval of episodic information (Cabeza and Nyberg, 2000; Fletcher and Henson, 2001). Mayes and Montaldi (2001) however note that functional neuroimaging has been much less successful at conrming the roles of the midline diencephalon and basal forebrain structures in episodic memory tasks. Explanatory hypotheses stressed both technical and methodological limitations (Desgranges et al., 1998). Yet, other structures, such as the anterior cingulate and the precuneus, have been found to engage during episodic memory tasks (Sanders et al., 2000). Concerning the prefrontal lobes, the HERA model (Tulving et al., 1994) ascribes to the left prefrontal cortex a preferential role in the encoding process of episodic material and the recall of semantic information, while the right prefrontal cortex would preferentially operate in the recall of episodic information. Nyberg (1998) further proposed that the right anterior prefrontal cortex would be involved in all memory tasks, and the right posterior prefrontal cortex in the more difcult retrieval conditions. Other studies (Kelley et al., 1998) have suggested that lateralization of activations may depend not so much on whether encoding or retrieval are

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primarily being engaged, but on whether verbal or hard-toverbalize materials are being processed. So far, however, experimental data have almost exclusively concerned verbal or visual material, and practically nothing is known about the functional anatomy of episodic memory for music. Based on our previous PET study (Platel et al., 1997), as well as on the neuropsychological literature, we hypothesize that musical semantic processes will induce activation of the left inferior frontal and left anterior temporal areas, but could also produce right prefrontal activations (Halpern and Zatorre, 1999). Concerning musical episodic memory, we anticipate activation of the classic episodic memory network, namely involving the right prefrontal cortex, the anterior cingulate gyrus, the precuneus, and potentially also the hippocampal regions, while whether or not additional activation specically related to the use of musical material would occur cannot be rmly predicted.

tration, but with the same timber of instrument (ute). All were real melodies, extracted from the classic and modern repertoires, but excluding songs so as to limit verbal associations. We also excluded extracts which might spontaneously evoke autobiographical memories, such as the wedding march or melodies used in popular TV spots. The 128 tunes comprised 64 familiar and 64 nonfamiliar tunes. The familiar melodies were those judged very familiar by more than 70% of subjects in a pilot study of 150 subjects matched with the experimental sample,1 while the nonfamiliar melodies were those judged as unknown by more than 80% of the subjects from the same population. Both samples were extracted from a larger database of melodies that was used in this preexperimental study. Paradigm In the musical semantic memory task, the instruction was to classify the melody heard as familiar or nonfamiliar. Half of the stimuli were familiar based on the above criteria (target items), and half were nonfamiliar. According to our design (see below), this semantic judgment will involve incidental encoding of the stimuli, and the subjects will be asked to recall the latter in the subsequent episodic memory tasks. We deliberately eschewed explicit encoding in our paradigm so as to avoid the subjects from doing a double task, namely, memorizing the items while judging their familiarity. To highlight activations specic to musical semantic memory, a perceptive control condition was designed where decisional and motor processes were present. The instruction was to indicate if the last two notes of each sequence had the same pitch. Since by necessity the semantic task contained both familiar and nonfamiliar items, two distinct control tasks had to be constructed, one containing only familiar and the other only nonfamiliar melodies. None of the melodies used in these two perceptual control tasks were employed in the other conditions. So as to equalize attentional involvement, these control tasks were made to be difcult, with hit rates ranging from 60% to 70% in preexperimental studies. As already explained above, musical episodic memory was studied by asking the subjects to recognize, among distractors, melodies (either familiar or nonfamiliar) that

Materials and methods Subjects Nine young healthy men were selected from a population of university students. They were all right-handed and free of any psychiatric or organic pathology and had normal hearing. To avoid specic cognitive strategies related to musical expertise, these subjects were selected so as to belong to class I of Wertheim and Botez (1959), i.e., Musical people without theoretical musical studies and musical knowledge. We purposely studied nonmusical subjects so that our ndings would generalize to the largest population, whereas musicians have specic strategies for listening to music, which depend in particular on the played instrument. The subjects who participated in this research were selected on the basis of two principal criteria: rst, they were to be common listeners (i.e., not music lovers, who tend to listen to a specic type of music only), and second, they were to have normal performances in a test of pitch perception. The subjects selected for the PET study were very similar to the subjects who took part in the selection of the familiar and nonfamiliar melodies; thus, the general musical culture of these two groups was equivalent. They were told that the experiment in which they were to take part related to the perception of the music, but never informed that the experiment related to musical memory, so that they did not train themselves to memorize melodies before the experiment. All of them gave written informed consent prior to participation and the research protocol was approved by the regional ethics committee. The study was performed in line with the Declaration of Helsinki. Nature of the musical material Musical material was specially created for this study and comprised 128 short melodies (5 s) played without orches-

1 Some examples of selected familiar melodies: L. W. Beethoven, excerpts from Symphony Nos. 6 and 9; D. Brubeck, Take Five; M. Mussorgsky, Pictures at an exhibition; A. Vivaldi, excerpts from The Seasons; P.I. Tchaikovsky excerpts from Nutcracker Suite; J. Williams, Raiders March; S. Prokoev, excerpts from Peter and the Wolf; A. Dvorak, Symphony No. 9, from the New World; M. Ravel, Daphnis et Chloe ; W.A. Mozart, Eine Kleine Nachtmusik; Vangelis, Conquest of Paradise; E. Grieg, excerpts from Peer Gynt Suite. Some examples of selected nonfamiliar melodies: L. W. Beethoven, excerpts from Corolian overture, Piano sonata No. 14; W.A. Mozart, Salzburg symphony No. 1; R. Wagner Tannhausser Overture; C. Debussy, Syrinx; Vangelis, Antartica; P.I. Tchaikovsky, excerpts from Swan Lake; B. Smetana, The Moldau; F. Schubert, excerpts from Symphony No. 6 and 8.

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Fig. 1. Experimental paradigm.

they heard earlier, during the semantic task. Because, in contrast with the semantic task, there was no obligation for the episodic task to mix familiar and unfamiliar items and to be consistent with the control tasks, two episodic tasks were constructed (i.e., using nonfamiliar and familiar items, to be referred to as F and NF in what follows). In each, half of the items were targets (previously heard melodies), and half were distractors. Thus, both episodic tasks had to be given after the semantic task. Brain activations specically related to musical episodic retrieval were to be assessed by comparing the episodic tasks (NF F) to the control tasks (NF F), as for the semantic task. In addition, separating the familiar and nonfamiliar items was meant to enable us to assess the effect of familiarity, by comparing each episodic task (NF or F) to the corresponding control task (NF or F) and each episodic condition to one another (episodic NF vs. F, and F vs. NF). To highlight possible automatic semantic processes during the episodic and control tasks with familiar melodies (F), we contrasted these conditions with the nonfamiliar episodic or control conditions (NF). Moreover, we directly compared episodic (NF F) versus semantic and semantic versus episodic (NF F) conditions, and nally the pattern of activations for control tasks (NF F) was revealed by comparing these control conditions with rest measurements. Altogether therefore, ve tasks were constructed, i.e., one semantic, two episodic, and two control tasks, with, as stated above, the semantic task always coming before the episodic tasks. Because our preexperimental studies had shown that the recall performance for the familiar items was

signicantly better than that for nonfamiliar items, (80 and 70%, respectively), we partly counterbalanced this difference by giving the episodic task with nonfamiliar items before that with familiar items, so as to lengthen the retention interval for the familiar items. In addition, the items of the semantic tasks of each version were refreshed between the scans, before the episodic tasks (see Fig. 1). In all ve conditions, the subjects were instructed to respond by pressing with their right index nger the yes or no button of a computer mouse. Each task lasted 2 min and consisted of eight target and eight nontarget items. Each item was 5 s long, with an interstimulus interval of 3 s. Each subject carried out each task twice and thus two versions of each task, using different items, were constructed. The order of the two versions of each task was counterbalanced. Finally, two rest scans (eyes closed and without auditory stimulation) were acquired. Altogether, therefore, 12 PET scans were acquired per subject (i.e., 10 activation tasks and two rest measurements). With a total of nine subjects, we thus collected 18 scans per condition. The entire sequence of scans is illustrated in Fig. 1.

Data acquisition and analysis Data acquisition Measurements of regional distribution of radioactivity were performed with an ECAT HR (Siemens) PET camera with full-volume acquisition allowing the reconstruction

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of 63 planes. Transmission scans were obtained with a 68Ga source prior to emission scans. The duration of each scan was 90 s. About 7 mCi of H2O15 was administered as a slow bolus in the left antecubital vein by means of an automatic infusion pump. Each experimental condition was started 30 s before data acquisition and continued until scan completion. This process was repeated for each of the 12 scans, for a total injected dose of 80 mCi. The interval between injections was 6 min 40 s. Subjects were scanned while lying supine in a darkened and quiet room. The head was gently immobilized in a dedicated head rest. Head position was aligned transaxially to the orbitomeatal line with a laser beam. The position of the head was controlled with the laser beam prior to each injection. Data analysis All calculations and image transformation were performed on Unix System work stations. First, the 12 scans of each subject were realigned to each other, using the AIR3.0 software. For subsequent data analysis, the Statistical Parametric Mapping software (SPM99, Wellcome Department of Cognitive Neurology) implemented in the MATLAB environment was used. The images were nonlinearly transformed into standard space, MRI template of SMP99, which is in Talairach space. The images were smoothed using a 12-mm Gaussian lter. The images were scaled to an overall CBF grand mean of 50 ml/100 g/min; we therefore refer to adjusted rCBF in what follows. We used a gray matter threshold of 80% of the whole brain mean; and covariates were centered before inclusion in the design matrix. An ANCOVA (analysis of covariance), using global activity as a confounding covariate, was performed on a pixel-by-pixel basis. The results of t statistic (SPM {t}) were then transformed into a normal standard distribution (SPM {z}). The signicance cutoff was set at P 0.05, cluster-level-corrected for multiple comparisons. Anatomical/cytoarchitechtonic localization of the significant activations was based on the SPM99 MRI template and Talairachs coordinates, which were obtained using M. Bretts linear transforms (see http://www.mrc-cbu.cam.ac.uk/Imaging/mnispace.html). All the coordinates listed in the sections below are SPM99 coordinates.

melodies (P 0.001). However, this result is particularly related to the bad performance of one subject of the group who did not succeed in recognizing more than two nonfamiliar items, whereas his performance for the familiar items was accurate. If this subject is discarded, the average percentage of success becomes 73%, consistent with our standards. Mean false alarms was rather small for all target items of the semantic and episodic tasks (20%); as expected, false alarms on nontargets items were commoner (mean 31%) for episodic tasks with nonfamiliar melodies. At debrieng, no subject expressed to have been aware of the dichotomy of the tasks according to the material (i.e., familiar or not). More precisely, the subjects stated not to have clearly realized that there were only familiar or unknown melodies for the control as for the episodic tasks. They did not try to make particular effort to maintain in memory the material presented. There was no signicant improvement of the performance in the course of time. PET data Comparing the semantic with the control tasks (NF F) showed extensive activation of the medial frontal areas (BA 11 and 10) bilaterally, left middle temporal gyrus (extending into the inferior frontal gyrus), and left angular gyrus (Table 1 and Fig. 3). Activation of these areas was not observed in the right hemisphere. Comparing the episodic (NF F) with the control (NF F) tasks revealed bilateral activation of the precuneus (BA 7), the middle frontal gyri (BA 9 and 10), and the medial surface of the frontal lobe at the junction between BA9 and the anterior cingulate cortex. Although bilateral, these activations were stronger on the right hemisphere (Table 1 and Fig. 4). Comparing the episodic (NF F) with the semantic tasks revealed activation of the precuneus (BA 7; right side predominantly), right superior frontal gyrus (BA 11), and right middle frontal gyrus (BA 8 and 9). All of these activations were clearly right-sided (Table 1 and Fig. 5). Comparing the semantic with the episodic tasks (NF F) revealed activation of the bilateral medial frontal cortex (BA 11/10), left inferior and bilateral middle temporal gyrus (BA 20/21), and right cerebellum (Table 1 and Fig. 6). Comparing the two control tasks (NF F) with rest revealed extensive bilateral activation mainly of the lateral temporal areas (middle and superior temporal gyri), bilateral inferior frontal gyrus, and cerebellum (Table 1 and Fig. 7). The temporal activations included the primary and secondary auditory cortices and were particularly conspicuous on the right hemisphere. Activation of the cerebellum, on the other hand, was more pronounced on the left side. Comparing the control tasks (F) with control tasks (NF) revealed activations of left middle and inferior frontal gyrus (BA 11/47), left precentral gyrus (BA 6, including Broca), and left medial frontal cortex (BA 8) (Table 1 and Fig. 8). Comparing the episodic (F) with the control (F) tasks

Results Behavioral data The average performance across the nine subjects was consistent with that obtained in the preexperimental population, with nearly 70% hit rate in the control tasks, more than 80% in the semantic task, and 89% in the episodic task with familiar melodies (Fig. 2). As expected, the performance for the episodic task with nonfamiliar melodies (66% hit rate) was signicantly lower than that for the familiar

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Fig. 2. Hit rates for the memory tasks and the control tasks: Semantic, semantic tasks carried out during PET scans; Episodic NF, episodic tasks with non-familiar melodies; Episodic F, episodic tasks with familiar melodies; Control NF, perceptive/control tasks with nonfamiliar melodies; Control F, perceptive/control tasks with familiar melodies.

revealed activation of the right precuneus (BA 7) and right superior frontal gyrus (BA 10) only (Table 1 and Fig. 9). Comparing the episodic (NF) with the control (NF) tasks revealed bilateral activation of the superior and middle frontal gyri (BA 10) bilateraly and of the medial frontal cortex (BA 8 and 9) (Table 1 and Fig. 10). Finally, no signicant activation was found for the control (NF) versus control (F) contrast and for the two direct comparison between the episodic tasks (NF vs. F or F vs. NF).

Discussion The activation pattern of the control perceptive tasks (control NF F vs. rest) is an awaited result and consolidates the idea of a right temporal preferential contribution in the perception of melody and pitch judgment (Zatorre et al., 1994). In addition to temporal activations, bilateral activation of the intrasylvian (opercular) inferior frontal areas is observed. As shown in Fig. 7 (axial cuts), these frontal activations do not reach the outer surface of the cortex and are not observed in the comparisons relating to the memory tasks. These frontal activations could correspond to working memory processes or contribute to the perceptual analysis of the melodies (Fletcher and Henson, 2001). Activations of the cerebellum reect par-

ticularly the motor control, and these were more accentuated in the left hemisphere because the task response was carried out with the right-hand ngers. The performance for these control tasks indicates that these tasks were difcult. However, they could be performed, according to debrieng, without a feeling of failure, consistent with our goal. Accordingly, compared to the rest condition, the pattern of activation mainly reected an auditory perceptual activity. Consequently, we consider that our control tasks were appropriate perceptual control conditions to serve as reference for memory tasks. Compared to the control tasks, the activation patterns observed for the semantic and episodic tasks were clearly independent (Figs. 3 and 4). Only a very limited overlap of activation may be considered in the medial frontal regions. These distinct and new results, obtained here with musical material, conrm the signicant functional independence between semantic and episodic memory processes, already documented with verbal and visuospatial material (Cabeza and Nyberg, 2000; Mayes and Montaldi, 2001). Semantic memory During the semantic task, activation was found to be extensive in two distinct brain regions: rst, the medial frontal region (involving mainly BA 11 and 10) and, sec-

250 Table 1 Activation results

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t Semantic vs. control (NF F) Bilateral medial frontal cortex (BA 11/10) 7.03 6.14 6.00 6.14 5.43 5.54 4.93 5.96 5.67 4.97 5.23 4.17 3.99 4.57 4.50 4.80 4.35 6.32 5.39 4.59 4.54 3.84 3.79 12.37 9.6 7.54 6.73 7.11 6.90 6.09 6.76 5.75 5.48 4.91 4.36 4.82 4.74 5.52 4.00 4.84 4.33 4.37 5.45 4.58 5.18 4.37 5.08 4.26 4.95 4.34

(z) (6.29) (5.62) (5.51) (5.61) (5.05) (5.14) (4.63) (5.47) (5.24) (4.67) (4.89) (3.99) (3.83) (4.71) (4.27) (4.53) (4.14) (5.75) (5.02) (4.35) (4.31) (3.69) (3.65) (inf) (inf) (6.65) (6.06) (6.34) (6.19) (5.58) (6.09) (5.31) (5.09) (4.62) (4.15) (4.54) (4.48) (5.13) (3.83) (4.56) (4.12) (4.16) (5.07) (4.34) (4.85) (4.16) (4.77) (4.06) (4.65) (4.13)

Cluster size 6197

x, y, z 0, 59, 08 4, 17, 16 6, 15, 18 55, 9, 15 57, 27, 2 38, 13, 16 51, 59, 29 2, 62, 33 30, 58, 3 34, 62, 11 34, 56, 8 28, 62, 22 2, 36, 22 36, 66, 38 4, 56, 42 34, 52, 14 38, 12, 44 0, 60, 10 4, 18, 18 32, 84, 38 56, 4, 24 48, 26, 22 54, 2, 18 63, 21, 5 53, 10, 3 59, 17, 3 51, 2, 7 38, 67, 20 36, 60, 26 32, 73, 18 14, 17, 17 30, 25, 02 44, 3, 20 40, 22, 10 34, 20, 17 22, 56, 16 26, 49, 23 38, 50, 20 42, 24, 8 42, 0, 36 54, 12, 6 10, 36, 40 5, 67, 33 28, 57, 0 32, 59, 16 38, 57, 6 32, 54, 8 24, 57, 10 10, 33, 48 4, 33, 33

Left middle temporal gyrus (BA 21) Left inferior frontal gyrus (BA 47) Left angular gyrus (BA 39) Episodic (NF F) vs. control (NF F) Right precuneus (BA 7) Right middle frontal gyrus (BA 10) Left middle frontal gyrus (BA 10) Medial frontal cortex (BA 9) Episodic (NF F) vs. semantic Right precuneus (BA 7/BA 19) Precuneus (BA 7) Right superior frontal gyrus (BA 11) Right middle frontal gyrus (BA 8/9) Semantic vs. episodic (NF F) Bilateral medial frontal cortex (BA 11/10) Right cerebellum Right middle temporal gyrus (BA 21) Left inferior and middle temporal gyri (BA 20/21) Control (NF F) vs. rest Right superior temporal gyrus (BA 22) Left superior temporal gyrus (BA 22) Left cerebellum Right cerebellum Left thalamus Left caudate Left inferior frontal gyrus (BA 44) Right inferior frontal gyrus (BA 45) Right superior frontal gyrus (BA 11) Control (F) vs. control (NF) Left middle and inferior frontal gyrus (BA 11/47) Left precentral gyrus (BA 6, Broca area) Medial frontal cortex (BA 8) Episodic (F) vs. control (F) Right precuneus (BA 7) Right superior frontal gyrus (BA 10) Episodic (NF) vs. control (NF) Right superior and middle frontal gyri (BA 10) Left superior and middle frontal gyri (BA 10) Medial frontal cortex (BA 8/9)

2932

220 782 1825 964 439 637 373 558 450 3252 484 363 544

3922 2788 6688

3314

772 403

875 1157 403 551 270 1242 961 704

Note. Areas signicantly activated at P 0.001, but using the P 0.05 corrected for multiple comparisons (cluster level) cutoff. Anatomical localization of the signicant activations and approximate Brodmanns areas was as described under Materials and methods. Stereotaxic coordinates shown are those listed in SPM99.

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Fig. 3. Semantic tasks versus control tasks (NF F). Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons, displayed with surface rendering. Illustrated here is the relative contribution of the different conditions of our paradigm, according to the effects of interests for selected peaks. The contrast was centred around zero, and the ordinate of each plot is the mean size of the effect for each condition SEM, within the peak voxel. Fig. 4. Episodic tasks (NF F) versus control tasks (NF F). Same as Fig. 3.

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Fig. 5. Episodic tasks (NF F) versus semantic tasks. Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons, displayed with surface rendering. Fig. 6. Semantic tasks versus episodic tasks (NF F). Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons, displayed with surface rendering. Fig. 7. Control tasks (NF F) versus rest. Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons displayed with surface rendering (left) and illustrative cuts (right) of the SPM99 T1 weights MRI template. Fig. 8. Control tasks (F) versus control tasks (NF). Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons, displayed with surface rendering.

ond, the left hemisphere involving an extensive band of the middle temporal gyrus (BA 21) and extending into the inferior frontal gyrus (BA 47). Further to these two main activation foci, an isolated activation of the left angular gyrus was noted. The semantic versus episodic contrast (Fig. 6), however revealed an additional right middle temporal gyrus activation (BA 21), suggesting a contribution of these right-sided areas in semantic memory processes. This

activation prole, mainly lateralized to the left hemisphere, is entirely consistent with previous functional neuroimaging of semantic memory tasks (Cabeza and Nyberg, 2000; Fletcher and Henson, 2001) and also with the HERA model (Tulving et al., 1994). The diagrams showing the effects of interests (Fig. 3) clearly document no noticeable participation of the two control and episodic conditions in the nding of activation in these medial frontal and left middle tempo-

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Fig. 9. Episodic tasks (F) versus control tasks (F). Comparison for only familiar melodies. Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons, displayed in SPM99 standard cuts (sagittal, coronal, and transverse). Fig. 10. Episodic tasks. (NF) versus control tasks (NF). Comparison for only nonfamiliar melodies. Signicantly activated regions at the threshold of P 0.05 corrected for multiple comparisons, displayed in SPM99 standard cuts (sagittal, coronal, and transverse).

ral regions. On the other hand, there was a substantial level of activity of these regions during rest, suggesting a heterogeneous cognitive activity during this condition among the subjects and justifying the importance of designing control conditions that strongly engage attention, as purposely implemented for this paradigm. Taken together, these data conrm a functional asymmetry in favour of the left hemisphere for semantic memory tasks. Regarding the medial frontal activation, similar ndings have been reported occasionally with semantic tasks (Sergent et al., 1992a; Kapur et al., 1994; Vandenberghe et al., 1996). According to the review of Cabeza and Nyberg (2000), this activity would be specically linked to the process of categorization of semantic information. We therefore consider that in our study, the medial frontal activation would specically reect the categorization process (i.e., the decision on familiar vs. nonfamiliar melodies). For example, the results obtained by Tempini et al. (1998) are in close agreement with the present investigation. Their study, in which the association of names and familiar faces (famous people) was studied, revealed an activation of the medial frontal areas (BA 10 and 11), left anterior temporal areas (BA 21), and angular gyrus. The activation of the left angular gyrus may contribute to this categorization process and also possibly to attempts in verbal labeling of the heard melodies. An activation of the left angular gyrus has also been observed previously in tasks of verb or word generation (Frith et al., 1991; Warburton et al., 1996). Thus, activation of neither the medial frontal areas nor the left angular gyrus appears to be very specic to musical semantic memory. In contrast, could the activation of the left middle temporal and inferior frontal regions characterize the access to a musical semantic memory? This latter nding replicates that we obtained previously in a task of judgment of musical familiarity (Platel et al., 1997). Fur-

thermore, activation of the left inferior frontal gyrus, although less extensive than in our earlier study, was obtained here with a different musical material and experimental paradigm. Additional elements support the hypothesis that this activation points to cortical regions that underlie musical semantic memory. One meta-analysis of activation peaks from PET studies relating to the perception of language and music (data from Petersen et al., 1988, and Sergent et al., 1992b) revealed an absence of complete overlap of activations (Drury and Van Essen, 1997). Thus, the perception of simple sounds, melodies, or timber produces mainly temporal and prefrontal activations that only partially overlap those obtained for the perception of phonemes, logatoms, or real words (Petersen et al., 1988; Sergent et al., 1992b; De monet et al., 1994; Zatorre et al., 1992; Platel et al., 1997), and activation peaks obtained with musical material appeared more anteriorly located than for linguistic material. We suggest therefore that the left anterior temporal and inferior frontal regions subtend specic nonverbal auditory processing abilities and that they might underlie a musical lexicon. Why should there be a left hemisphere specialization for musical semantic memory? The prevalent idea that the right hemisphere preferentially underlies the perception of music arises primarily from experimental studies (in particular with the dichotic listening technique) using nonfamiliar melodies (Peretz, 1994). Meanwhile, the few neuropsychological case studies in which a specic impairment of musical identication was present (in the absence of perceptual decit) almost exclusively concerned left hemisphere lesions (Dupre and Nathan, 1911; Souques and Baruk, 1930; Eustache et al., 1990). The few functional neuroimaging studies that have focused on musical memory (Zatorre et al., 1994; Matteis et al., 1997; Holcomb et al., 1998; Halpern and Zatorre, 1999) showed mainly bilateral, but preferen-

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tially right-sided, frontal and anterior temporal activations. However, apart from the work of Halpern and Zatorre (1999), these studies did not address musical semantic memory, but rather recognition processes for nonfamiliar melodies. In the Halpern and Zatorre study (1999), the comparison of the second task (to imagine the continuation of familiar melodies) with the third task (mental repetition of new melodies) was designed to remove the functional activity related to auditory analysis, working memory, and mental imagery and to reveal only the recovery processes in semantic memory. This comparison revealed activation in the right inferior and middle frontal gyri, the right inferior and superior temporal gyri, the right anterior cingulate, and the parietal cortex. Activation of the left inferior and middle frontal gyri was also observed, though with less intensity than on the right side. According to Halpern and Zatorre, the observed asymmetry in favor of the right hemisphere would be related to the musical specicity of the cognitive processes. There might however be some difculty in the interpretation of this nding, given a contamination by episodic processes, acknowledged by the authors in their paradigm. Indeed, in contrast to our study, their subjects were selected initially so as to have a strong feeling of familiarity with the chosen musical extracts, and moreover, each subject was trained to imagine the continuation of these familiar melodies before the scan sessions. In contrast, our paradigm was specically designed for the study of musical semantic memory, and we believe that the preferential left-sided activation pattern obtained for the semantic tasks does not only reect verbal processing during performance of this task. Indeed, all the familiar melodies were selected so as not to be popular songs (see Materials and methods) and to be difcult to name for nonmusicians. For example, an extract like the Toccata and Fugue in D Minor from J.S. Bach would be easily judged as familiar by virtually all nonmusicians subjects, but only few of them would be able to produce the title and/or the composer of this musical piece. Thanks to dichotomizing the familiar and nonfamiliar material in our design, it was also possible, in addition to the semantic condition, to assess the brain activity involved in semantic memory during the control tasks with familiar melodies. In other words, contrasting the control tasks with familiar versus nonfamiliar melodies makes it possible to highlight the cerebral areas dedicated to the implicit access to musical semantic memory. This contrast (Fig. 8) revealed signicant differences in the left prefrontal areas (in particular BA 6), as well as the left middle, inferior, and medial frontal regions. Thus, a left dominance was again present for this contrast, strengthening the idea that mainly left cerebral areas support the access to musical semantic memory. However, activations observed in this comparison could also reect processes of humming, if subjects involuntarily sung (covertly) those melodies that were familiar to them. In agreement with Scott et al. (2000), we think that the

right posterior superior temporal regions play a specic part in the dynamic treatment of pitch variations (for music and language) and that the left hemisphere homologous areas are more particularly dedicated to the phonological treatment and the comprehension of language. However, based on the present work and our earlier study (Platel et al., 1997), we believe that the anterior part of the left temporal cortex is particularly involved in nonverbal semantic processes and could sustain musical semantic representations. Overall, therefore, the left middle temporal activations observed in our semantic task would mainly represent the access to musical semantic memory while the frontal activations would represent essentially the process of categorization of the presented melodies. Episodic memory Recognition of the familiar and nonfamiliar melodies heard at the time of the semantic task induced a prole of activation clearly different from that obtained for the semantic task. The observed activation of the rostral-most part of the middle frontal areas (BA 9 and 10) and the precuneus (BA 7), although bilateral, predominantly involved the right hemisphere (Fig. 4). Predominantly right-sided frontal and prefrontal activation has been frequently reported with retrieval of either verbal or nonverbal material (Cabeza and Nyberg, 2000). Comparing the episodic versus semantic tasks (Fig. 5) conrmed rst the right dominance for the retrieval processes and second that our musical semantic memory task mobilized no evident resource in the right hemisphere given that subtracting the semantic processes from the episodic tasks did not decrease or remove these activations of the right hemisphere. Regarding activation of the precuneus, although previous functional imaging studies on perception and processing of musical material have reported activation near this area (Sergent et al., 1992b; Platel et al., 1997), similar ndings have concerned nonmusical material, and thus this nding has been interpreted as reecting a process of mental imagery triggered by the particular task (Kosslyn et al., 1997). However, precuneus activation has also been observed in episodic memory tasks, regardless of whether or not the items possessed imageable characteristics (Krause et al., 1999). According to Kapur et al. (1995), this cerebral region would be particularly involved in episodic retrieval and more precisely in the success of episodic recall. This interpretation would t well with our results, as our musical material did not involve particularly imageable features. Further arguments in favor of this interpretation would be the lack of activation of the precuneus in our semantic task despite use of the same musical material as for the episodic task and the fact that, at debrieng, no subject mentioned having employed a specic mental representation strategy for episodic recall, whether the melodies were familiar or not. In addition, the separate comparisons between the episodic and the control tasks for familiar (Fig. 9) and nonfa-

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miliar melodies (Fig. 10) show that the recognition of the familiar melodies is associated with strictly right-lateralized activations (precuneus and superior frontal regions), whereas the recognition of nonfamiliar melodies produces bilateral activations of the frontal areas (medial, superior, and middle). Since our subjects could easily recognize the familiar melodies, these data would support the idea that the precuneus activation was linked with the success of episodic retrieval. On the other hand, the signicant engagement of the frontal regions during the recognition of the nonfamiliar melodies reects undoubtedly the difculties experienced by the subjects to achieve this task and suggests the occurrence of executive control processes (such as maintenance, planning, and inhibition). Nolde et al. (1998) also proposed that the extent of left prefrontal activations during retrieval probably increases as the executive demands of retrieval increase. Overall, the results of the present investigation would be in agreement with the HERA model proposed by Tulving and collaborators (1994), which is based on functional asymmetry in favor of the left hemisphere for semantic memory research and right hemisphere dominance for episodic retrieval. Despite the fact that the HERA model remains controversial owing to conicting results from some functional neuroimaging studies, the review of the literature carried out by Cabeza and Nyberg (2000) highlighted the fact that the majority of the published data reported such more or less marked asymmetry (Blanchet et al. 2001). The bilaterality of frontal activations observed in many studies using widely different paradigms does however mitigate the notion of a strict right-sided predominance for episodic retrieval. Some works suggest notably that lateralization of activations may not depend so much on whether encoding or retrieval are primarily being engaged, but more on whether verbal or hard-to-verbalize materials are being processed (Kelley et al., 1998; Mayes and Montaldi, 2001). This hypothesis ts poorly with our results, showing more left-sided engagement of frontal regions for episodic retrieval of hard-to-verbalize (nonfamiliar) melodies and clear right-sided activations with easier retrieval of familiar melodies. Our feeling, which concurs with that of Nolde et al. (1998), is that the extent of left prefrontal activations during retrieval probably reects the executive demands. To conclude, these new ndings from a study of semantic and episodic memory of musical material are altogether consistent with the results established earlier with verbal or visuospatial material. However, some functional specicity for musical memory does appear to exist. Based on our data, the left anterior temporal cortex would appear particularly involved in semantic memory for musical material.

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