Brain (2002), 125, 1782±1792
The functional signi®cance of perinatal corpus
callosum damage: an fMRI study in young adults
A. M. Santhouse,1 D. H. ffytche,1 R. J. Howard,1 S. C. R. Williams,1 A. L. Stewart,2 M. Rooney,1
J. S. Wyatt,2 L. Rifkin1 and R. M. Murray1
1Instituteof Psychiatry, King's College and 2Perinatal Correspondence to: A. M. Santhouse, Institute of
Brain Research Group, Department of Paediatrics, Psychiatry, De Crespigny Park, London SE5 8AF, UK
University College London Medical School, London, UK E-mail: email@example.com
We used functional MRI (fMRI) to establish the func- with damaged corpora callosa had signi®cantly different
tional signi®cance of corpus callosum damage in young activation patterns compared with the two control
adults who had been born very preterm. Seven subjects groups. In the visual task, additional activity was seen
from a cohort of individuals who had been born at <33 in the right dorsolateral prefrontal cortex of the dam-
weeks gestation and who had sustained callosal damage aged callosum group, possibly because the task was
visualized on structural MRI were compared while they accomplished by storing information in working mem-
carried out auditory and visual tasks requiring callosal ory. On the auditory task, a de®cit of activity was seen
transfer with nine very preterm subjects with corpora in the right temporal lobe of the callosum group. The
callosa of normal appearance on structural MRI, and ®ndings reveal a plasticity of function compensating for
with seven full-term controls. The very preterm subjects early damage to the corpus callosum.
Keywords: corpus callosum; cerebral plasticity; periventricular haemorrhage; preterm birth; fMRI
Although the mortality rate among preterm and low birth performance subscale of the WISC-R (Wechsler, 1974) at
weight infants has fallen sharply since the introduction of age eight (Roth et al., 1993). In adolescence, preterm
neonatal intensive care (Nishida, 1993; Battin et al., 1998; individuals have more neurological, adjustment and reading
Richardson et al., 1998), little is known about the effects of impairments than controls born at term (Stewart et al., 1999)
preterm birth for long-term neuropsychological function. and have poorer educational outcome (Botting et al., 1998).
We previously have reported the results of structural MRI In order to investigate the functional consequences of the
examination of the brains of 72 adolescents who had been corpus callosum abnormalities, we examined the perform-
born before 33 weeks of gestation (Stewart et al., 1999). The ance of preterm-born young adult males with corpus callosal
most common focal structural abnormality in these individ- damage, preterm-born young adult males without corpus
uals was thinning/atrophy of the corpus callosum, particularly callosum damage and term-born controls on visual and
posteriorly, which was noted in 43% of preterm individuals auditory tasks requiring callosal transfer during functional
but in only 14% of age- and sex-matched controls who had MRI (fMRI). The two sensory modalities allowed us to
been born at full term. The corpus callosum is known to be examine different portions of the corpus callosum. Visual
especially vulnerable to adverse consequences of premature ®bres are carried in the splenium of the corpus callosum, and
birth such as ischaemia, haemorrhage and sepsis, because of auditory ®bres in the posterior third of the body of the corpus
its longer myelogenetic cycle (Valk and Njiokiktjien, 1991) callosum (Berlucchi and Aglioti, 1999). Our strategy was to
and also because of its position adjacent to the periventricular compare brain activity during the performance of two tasks
region, one of the most common sites for haemorrhage in the within each sensory modality, one of which required the
preterm infant (Thorburn et al., 1981; Fawer et al., 1984). callosal transfer of information and the other of which did not,
These abnormalities of the corpus callosum may have and to examine differences in the pattern of activation
functional signi®cance. For example, follow-up studies of between the three participant groups. While the tasks
preterm infants have indicated that callosal abnormalities themselves may have non-callosal components, their design
underlie poor performance on the Kaufman Assessment ensured that callosal transfer facilitated successful comple-
Battery for Children (K-ABC) (Kaufman and Kaufman, tion of the task. In the visual domain, we compared the
1983), and on the simultaneous processing scale and activity related to a bilateral task in which stimuli were
ã Guarantors of Brain 2002
Corpus callosum function 1783
1980. These individuals became part of a longitudinal study
of development, and underwent structural MRI scanning at
age 14 or 15 years (Stewart et al., 1999) and the scans were
rated independently by two neuroradiologists. From the
radiologists' reports, those scans showing thinning or atrophy
of the corpus callosum and no other focal brain abnormalities
were identi®ed (i.e. no severe generalized or lobar atrophy,
Fig. 1 Positioning of the simple shapes with respect to the central CSF shunts or other focal damage). From these subjects,
crosswire. `x' is 4° of visual angle lateral to the crosswire; `y' and seven male right-handed individuals between the ages of 18
`z' are 1° above and below the crosswire. Shapes appear for `a' in and 20 years were invited to take part in the study. A further
position x,x; for `b' in position x (left),z; and for `c' in position group of nine right-handed individuals from the cohort whose
MRI scan was reported normal and without callosal thinning
at age 14 or 15 years were also recruited, together with a
presented across the vertical meridian with a unilateral task in group of seven right-handed age-matched subjects who had
which stimuli were presented in one hemi®eld. In the bilateral been born at full term.
task, each shape is presented to a different hemisphere, the Handedness was assessed according to the Edinburgh
one in the right visual ®eld to the left hemisphere and the one Handedness Inventory (Old®eld, 1971). Subjects also com-
in the left visual ®eld to the right hemisphere. Agenesis of the pleted a National Adult Reading Test (NART) (Nelson,
corpus callosum leads to a performance de®cit in this task, 1982). Handedness data for one of the subjects in the preterm
suggesting that its normal completion requires a callosal control group, and NART data for one of the subjects in the
transfer (Karnath et al, 1991). For the unilateral task, visual term controls were not available. All subjects included had:
callosal transfer is not required since both shapes are (i) no contraindications to MRI; (ii) vision unimpaired
presented to a single hemisphere. without glasses; (iii) no dif®culties in hearing; (iv) no
In the auditory domain, we compared the activity related to neurological illness; or (v) no history of substance misuse. All
a timbre discrimination task presented to the left or right ear. subjects gave written informed consent and the study was
The rationale for this approach relates to the ®ndings that (i) approved by the ethical committee of The Bethlem and
monaural stimulation activates predominantly the contral- Maudsley Hospital.
ateral hemisphere through subcortical pathways (Woldorff
et al., 1999) and (ii) timbre discrimination is processed in the
right hemisphere (Sidtis, 1980; Samson and Zatorre, 1994;
Platel et al., 1997). We hypothesized that auditory stimuli Experiment 1: visual paradigm
presented to the left ear would cross subcortically to the right Subjects were instructed to focus on a central crosswire on a
hemisphere and undergo timbre discrimination processing projection screen throughout the experiment. Stimuli were
without callosal transfer. In contrast, auditory stimuli pre- black outlines of geometric shapes (square, rectangle, rhom-
sented to the right ear cross subcortically to the left boid) projected tachistoscopically onto a screen with an
hemisphere, and then require a callosal transfer back to the exposure time of 150 ms and subtending a visual angle of 1°.
right hemisphere for timbre discrimination processing. Subjects were instructed to respond as to whether pairs of
We predicted that the group with callosal thinning would shapes were the `same' or `different', using a button press
have poorer performance on the bilateral visual task and the with their right hand.
right ear auditory task, compared with the unilateral visual Pairs of shapes were presented in blocks of six in 30 s
and left ear auditory tasks, and that this would be re¯ected in a scanning epochs under the following conditions: (i) bilat-
different cortical activation pattern compared with the erally, 4° to either side of the central crosswire; (ii)
preterm controls with normal callosal appearance and term- unilaterally, one located centrally 1° below the crosswire
born controls. We also predicted that we would not ®nd any and the other 4° to the left of the central crosswire; and (iii)
differences between the group of term-born controls and the centrally, 1° above and 1° below the crosswire (Fig. 1). The
preterm normal callosum group. The pattern of group-speci®c central stimulus was included as part of a separate study to
differences would help elucidate the neurobiological mech- investigate the bilateral ®eld advantage and will not be
anisms compensating for perinatal damage to the corpus discussed further here (Santhouse et al., 2002).
callosum. Each block was presented four times in a pseudorandom
order during the 6 min fMRI experiment so that a total of 72
pairs of stimuli were seen altogether in the 12 blocks.
Methods Response times were measured from the onset of presentation
Subjects were recruited from a cohort of infants who had been of the stimuli, and a log was kept of response accuracy.
born before 33 weeks gestation and admitted to University Subjects practised the paradigm for 6 min before they entered
College Hospital London Neonatal Unit between 1979 and the scanner.
1784 A. M. Santhouse et al.
Fig. 2 The sound stimuli consisted of the fundamental frequency of 440 Hz plus the ®rst two harmonics (top); the fundamental frequency
and three harmonics (middle); or the fundamental frequency and four harmonics (bottom).
Experiment 2: auditory paradigm presented to the right ear; and (ii) presented to the left
Subjects were asked to close their eyes and judge as to ear. Each block was presented alternately ®ve times
whether pairs of sounds were the `same' or `different'. throughout the 5 min experiment, a total of 50 compari-
Stimuli were notes at 440 Hz, generated using Cool Edit 96 sons over the course of 5 min. Response times were
(Syntrillium Software Corporation, Ariz., USA) which measured from the onset of presentation of the stimuli,
differed only in their timbre (Fig. 2). Each sound lasted for and response accuracy was measured. Subjects performed
750 ms and was separated from its paired sound by a gap of the experiment (i) with the button press in their left hand
1000 ms. and (ii) with the button press in their right hand. Subjects
The stimuli were presented in blocks of ®ve in 30 s practised the paradigm for 5 min before entering the
scanning epochs under the following conditions: (i) scanner.
Corpus callosum function 1785
Fig. 3 Structural differences between callosum and control groups. To the left of the ®gure are the areas of signi®cant differences (in red)
in white matter between callosum and control groups superimposed on a mean structural image. To the right is shown the grey matter and
CSF differences between the callosum and control groups. The graphs show the voxel intensity values in the anterior callosum (left panel)
and left superior temporal gyrus (right panel) for each subject in each of the three groups.
Analyses between-subject factor, group, with three levels. Multivariate
Behavioural data statistics were used to test signi®cance.
The data were analysed by means of SPSS for Windows
(version 8.0.2). For accuracy data, a single score of the
percentage of correct responses was included for each Imaging
subject. Separate analyses were conducted on accuracy and Scan parameters
response times. For visual experiments, a two-way repeated Functional images were acquired on a 1.5 Ta GE Neuro-
measures analysis of variance (ANOVA) was carried out with optimized Signa LX Horizon System (General Electric,
®eld (bilateral and unilateral) as a within-subject factor and Milwaukee, Wisc., USA), using a gradient echo planar
group as a between-subject factor, with three levels (term sequence sensitive to blood oxygenation level-dependent
controls, preterm controls and damaged corpus callosum). (BOLD) contrast (TR, repetition time = 3 s; TE, echo
For auditory experiments, three-way repeated measures time = 40 ms; ¯ip angle 90°; 64 Q 64 matrix; in-plane voxel
ANOVAs were performed, with two within-subject factors size 3.75 Q 3.75 mm) and 20 axial slices, 7 mm thick with a
(ear and hand) each with two levels (left or right); and one 0.7 mm interslice gap
1786 A. M. Santhouse et al.
Fig. 4 Bar chart showing response accuracy in both visual (A) and auditory (B) tasks. For visual tasks, the response accuracy is for
bilateral and unilateral tasks; for auditory accuracy, the response is for all tasks. The error bars show the standard error of the mean.
Image analysis preterm controls; and damaged callosum group versus
Structural images. High resolution sagittal images were preterm controls. Within-group comparisons were made for
acquired for all of the term control group, ®ve of the preterm the visual and auditory tasks for each of the subject groups
control group and ®ve of the damaged corpus callosum group. using a ®xed effects model, to show activations in the groups
Data for the other subjects were unavailable. For each separately.
group, the images were normalized using SPM99 (http:// For the structural comparisons, separate ANOVAs were
www.®l.ion.ucl.ac.uk/spm) and a mean image generated, to generated for white matter, grey matter and CSF images. All
help localization of activation maxima. The normalized random effects structural and functional statistical parametric
structural image from each subject was segmented into white maps were thresholded at P < 0.01, corrected for multiple
matter, grey matter and CSF images. comparisons at the cluster level. Within-group ®xed effects
Functional images. Auditory and visual experiments were models were thresholded at P < 0.001, corrected for multiple
analysed separately. For each subject, the time series was comparisons at the cluster level.
motion corrected (Friston et al., 1996), transformed into
standard stereotaxic space (Talairach and Tournoux, 1988)
smoothed with a 10 mm FWHM (full width half maximum) Results
Gaussian ®lter and high pass ®ltered using SPM99. There was no signi®cant difference in handedness between
Covariates were modelled with a boxcar convolved with the the full-term controls, preterm controls and damaged
haemodynamic response function. callosum group. Mean laterality quotient scores on the
Edinburgh Handedness Scale were, respectively, 89.7 (SD
12.2), 89.1 (SD 13.8) and 76.3 (SD 28.7) [F(2,19) = 1.08,
Statistical inferences P = 0.358]. There were no signi®cance differences in
In order to compare the generic activations associated with intelligence in the three groups, as measured by the NART.
each of the three groups, a two-stage random effects analysis Mean IQ scores for the three groups were, respectively, for
was used for each hypothesis tested (Friston et al., 1999). The the full-term controls, preterm controls and damaged
®rst stage generated subject-speci®c contrast images from the callosum group 114 (SD 4), 109 (SD 9.5) and 104 (SD
weighted linear sum of covariate parameter estimates. For the 10.7) [F(2,19) = 2.16, P = 0.14)].
visual task, the contrast images were for bilateral versus the
unilateral stimulation, while for the auditory task the contrast
images were for left ear versus right ear stimulation. The Structural image comparisons
second stage assessed the differences in generic activations Statistical comparison of the white matter images in the
for each group with pairwise t test comparisons: term controls damaged callosum group and control groups showed a
versus damaged callosum group; term controls versus signi®cant loss of callosal ®bres in the splenium, anterior
Corpus callosum function 1787
for one of the subjects in the preterm control group. For visual
response times, the two-way ANOVA showed a signi®cant
main effect of group [F(2,539) = 12.6, P < 0.001], with the
damaged callosum group signi®cantly slower on both tasks.
Although not reaching signi®cance, Fig. 5A shows a pattern
of response times in the damaged callosum group different
from that of the control groups. Both preterm and term
controls show a bilateral ®eld advantage, with the bilateral
comparison performed faster than the unilateral one. In
contrast, the damaged callosum group shows a bilateral ®eld
disadvantage, with the response time to the bilateral stimulus
being slower than that to the unilateral stimulus
[F(2,529) = 1.2, Hotelling's trace = 0.004, P = 0.3] (Fig. 5A).
The auditory task accuracy data showed a signi®cant group
effect. The damaged callosum group were least accurate, with
mean and SDs for the damaged callosum group, preterm
controls and normal controls, respectively, being 17.8 (3.9),
19.3 (3.8) and 20.6 (1.7) [F(2, 19) = 3.85, P = 0.039] (Fig. 4B).
Data were not available for one of the damaged callosum
As in the visual data, we found a signi®cant group effect in
the response time data, with the damaged callosum group
signi®cantly slower than the term and preterm controls
[F(2,542) = 80, P < 0.001]. There was a signi®cant ear by
group interaction, with the right ear response times slower
than the left ear response times in the damaged callosum
group, but no left ear±right ear differences in the control
groups [F(2,542) = 3.02, Hotelling's trace = 0.011, P = 0.05)
There was also a signi®cant effect of hand, independent of
group or ear. The direction of the effect (right hand 100 ms
faster than left) was in the opposite direction to the expected
superiority of left hand over right for the right hemisphere
timbre discrimination task. It was also much longer than
previous estimates of callosal transfer time (i.e. Clarke and
Zaidel, 1989). We therefore concluded that the hand effect
identi®ed was not due to callosal transfer but seemed instead
to relate to hand dominance or task practice, as all subjects
Fig. 5 Bar charts showing mean reaction times for bilateral and performed the left hand response experiments before the right
unilateral tasks in each of the three groups (A) and mean reaction hand response experiments. We therefore ignored the hand
times for right and left ears in the auditory task (B).
effect and pooled left hand and right hand experimental data
in our fMRI analysis.
corpus callosum, genu, forceps major and forceps minor (see
Fig. 3). We also found signi®cant atrophy of the superior
temporal gyrus in both hemispheres in the callosal group, as Differences in BOLD activation pattern between
evidenced by a loss of grey matter on the left and increase of groups
CSF on the right. There were no signi®cant increases in white
Visual task (bilateral presentation >unilateral
matter or grey matter in the damaged callosum group
compared with the controls. presentation)
Bilateral stimuli did not lead to signi®cantly more activation
than unilateral stimuli in either of the control groups. In
contrast, the same comparison led to a signi®cant difference
Performance data in activity in the right dorsolateral prefrontal cortex (BA 9/10)
There were no signi®cant differences in accuracy between the of the damaged callosum group (Fig. 6). This difference
three subject groups in the visual tasks [F(2,19) = 0.032, between the groups was signi®cant when we compared the
P = 0.96] (Fig. 4A). For technical reasons, data were missing damaged callosum group and term controls (Z = 3.9; P = 0.04)
1788 A. M. Santhouse et al.
showed activation of the right superior temporal gyrus (BA
22). The activation in the damaged callosum group was
signi®cantly greater than in either the term or preterm control
groups (Z = 3.83; P = 0.05 full-term control; Z = 4.65; P = 0.04
preterm control) (Fig. 7).
Signi®cantly more activity was also seen in the right
precentral gyrus (Z = 4.32, P < 0.01) and left precentral gyrus
(Z = 3.92; P = 0.04) of the damaged callosum group compared
with the term control group. The same regions were active in
the comparison of the preterm control group and the damaged
callosum group using an a priori region of interest approach
(search volume 0.5 cm sphere at x, y, z coordinates 44, ±14,
58, Z = 4.24, P < 0.01 for right precentral gyrus; left
precentral gyrus search volume 0.5 cm sphere at x, y, z
coordinates ±32, ±12, 66, Z = 2.44, P = 0.04) (Table 2). No
signi®cant differences were seen between the full-term and
preterm control groups, and no brain regions were signi®-
cantly more active in the two controls groups than in the
damaged callosum group.
Our results show that preterm callosal damage affects
behavioural performance and functional cerebral anatomy
in early adulthood. The damaged callosum patients in our
study could complete timbre and bilateral ®eld comparison
tasks, although at a reduced level of performance. One
interpretation of the residual ability is that their callosal
damage was insuf®cient to cause a performance de®cit and
that tasks were completed using the same neural mechanisms
as found in normal subjects. However, the fact that we found
Fig. 6 Changes in BOLD contrast in comparison of `bilateral' signi®cant differences in the task-related pattern of activity
versus `unilateral'. One pair of `glass brain' views (from the side for the damaged callosum and control groups suggests that
and from above) is shown for each patient group. All the images this was not the case. An alternative interpretation of the
have been thresholded at P < 0.001, corrected for multiple ®ndings is that compromised callosal function has led to
comparisons at the cluster level. Only the damaged corpus
alternative neural strategies to compensate for the perinatal
callosum group shows a difference between the two conditions,
with an area of signi®cant activation in the right dorsolateral injury. In what follows, we examine the neural basis of this
prefrontal cortex. The difference between activation patterns in the functional plasticity.
damaged callosum group and term controls is signi®cant and is
shown rendered onto a single brain.
Callosal-speci®c performance de®cits
In the visual task, the two control groups showed the normal
(Fig. 6). The same region was also signi®cant in the damaged pattern of behavioural responses, with reaction times for
callosum±preterm control comparison using an a priori bilateral comparisons being faster than those for unilateral
region of interest approach (search volume 0.5 cm sphere at comparisons (i.e. Davis and Schmit, 1971; Dimond and
x, y, z coordinates 38, 54, 24; Z = 2.8; P = 0.03) (Table 1). No Beaumont, 1971; Merola and Liederman, 1990; Norman
regions were signi®cantly more active in the control groups et al., 1992). In contrast, the damaged callosum group showed
than the damaged callosum group, and there were no the opposite pattern, with reaction times for unilateral
signi®cant differences between the control groups. comparisons being faster than those for bilateral ones. Our
previous study of the cerebral activity underlying the bilateral
®eld advantage suggested that bilateral and unilateral com-
Auditory task (left ear presentation > right ear parisons were carried out by different processing mechan-
presentation) isms, the bilateral comparison requiring a callosal transfer
There were no signi®cant activations for the left ear > right and the unilateral comparison requiring working memory
ear comparison in the term control group. In contrast, the resources. The results presented above support this hypoth-
preterm control group and the damaged callosum group esis by revealing a bilateral disadvantage in subjects with a
Corpus callosum function 1789
Table 1 The regions of differential group activation for the comparison bilateral > unilateral for the visual callosal
Areas activated x y z Cluster size Z score P (corr) BA
Callosum group > term controls
Right dorsolateral prefrontal cortex 38 54 26 626 3.9 0.04 9/10
Callosum group > preterm controls
Right dorsolateral prefrontal cortex* 38 54 24 31 2.8 0.03 9/10
The table shows x,y,z coordinates, cluster size and Brodmann area (BA) of the most signi®cant voxel in each cluster. Also shown are the
Z values and corrected P values. *Region examined with a priori hypothesis. For term and preterm control groups > callosum group and
term > preterm control, preterm > term control, there were no differences in activation.
Fig. 7 BOLD contrast in the comparison of the left versus right ear. One pair of `glass brain' views (from the side and from above) is
shown for each patient group for the left ear greater than right ear comparison (thresholding as for Fig. 6). The damaged callosum group
shows a signi®cant area of activation in the right superior temporal gyrus. This is signi®cantly different from the term control group (left
panel) and preterm control group (right panel), shown rendered onto an individual brain.
damaged corpus callosum. Our fMRI results reveal how the cortex in an area that previously has been associated with
damaged callosum group accomplishes the task. While working memory (Braver et al., 1997; Cohen et al., 1997;
normal subjects show no activity for the bilateral > unilateral Nystrom et al., 2000; Stern et al., 2000). One possible
comparison (Fig. 6) (Santhouse et al., 2002), the damaged explanation for the delay in reaction time for the bilateral
corpus callosum group activates the dorsolateral prefrontal comparison in the damaged callosum group is that shapes
1790 A. M. Santhouse et al.
Table 2 Regions of differential group activation for the timbre comparison of left ear versus right ear
Area activated x y z Cluster size Z score P (corr) BA
Callosum group > term controls
Right superior temporal gyrus 60 ±32 16 618 3.83 0.05 22
Right precentral gyrus 44 ±16 56 973 4.32 <0.01 4
Left precentral gyrus ±34 ±8 68 644 3.92 0.04 4/6
Callosum group > preterm controls
Right superior temporalgyrus 64 ±32 22 646 4.65 0.04 22
Right precentral gyrus* 44 ±14 58 80 4.24 <0.01
Left precentral gyrus* ±32 ±12 66 24 2.44 0.04
The table shows x,y,z coordinates, cluster size and Brodmann area (BA) of the most signi®cant voxel in each cluster. Also shown are the
Z values and corrected P values. *Region examined with a priori hypothesis. For preterm controls > term, term controls > preterm,
preterm controls > callosum and term controls > callosum, there were no differences in activation.
presented for comparison across a damaged corpus callosum the right ear task, even though their performance is impaired.
are held `on line' in working memory, to compensate for the One possibility is that they use the left hemisphere, and partial
impaired callosal transfer. support for this comes from the fact that we found, using an a
In normal individuals, the discrimination of timbre takes priori region of interest approach, signi®cantly greater
place largely in the right hemisphere (Sidtis, 1980; Samson activation of the left superior temporal gyrus of the damaged
and Zatorre, 1994; Platel et al., 1997). The speci®c areas corpus callosum group than the term control group for the
identi®ed in previous imaging studies include the superior right ear greater than left ear comparison (search volume
and posterior temporal regions (Mazziotta et al., 1982) and 0.5 cm sphere at x, y, z coordinates ±60, ±32, 16; BA 22;
the superior, middle frontal and precentral gyri (Platel et al., Z = 3.0; P = 0.02).
1997). In theory, the right ear response time should be a few
milliseconds slower than the left ear response times, as the
right ear presentation requires a callosal transfer of signals for Non-speci®c performance de®cits
timbre discrimination (right ear®left hemisphere®right We found the damaged callosum group to be slower on both
hemisphere). We did not ®nd a signi®cant difference in left the visual and auditory tasks, regardless of whether they
and right ear reaction times in our two control groups as the involved a callosal transfer. For the visual data, the longer
number of trials presented in an fMRI experiment are response times enabled the callosal group to perform with
insuf®cient to show such a small effect. In contrast, the accuracy equivalent to the two control groups. For the
damaged callosum group did show a signi®cant difference in auditory data, the damaged callosum group were signi®cantly
response times to left and right ear stimuli, with the right ear less accurate [F(2,19) = 3.85, P = 0.039] despite the delay in
response, which in normal subjects requires a callosal response. The ®ndings suggest that the callosal damage on
transfer, being signi®cantly slower than the left ear response. MRI scans at age 14±15 years is associated with other more
The pattern of brain activity elicited by the auditory stimuli subtle brain abnormalities not apparent on the structural
provides an explanation for the behavioural effect. In control images. Another possibility is that the atrophy found in the
subjects, the right superior temporal gyrus would process anterior corpus callosum compromised the transfer of motor
timbre stimuli regardless of the ear of presentation, either by signals, introducing a delay in response time. We also found
direct stimulation (left ear to right hemisphere) or through a atrophy of the superior temporal gyrus bilaterally in the
callosal transfer (right ear®left hemisphere®corpus callo- damaged callosum group. While this could have led to a non-
sum®right hemisphere). The result is that there is no speci®c de®cit in the auditory task, it could not explain the
signi®cant difference in activation of the region between non-speci®c de®cit found in the visual task. It is unclear why
left ear and right ear stimulation. In contrast, the damaged this particular region is vulnerable; however, damage here
callosum group would be unable to perform an adequate raises an interesting possibility that it underlies language
callosal transfer from left hemisphere to the right, leading to impairments found in preterm individuals during adolescence
an activation of the right superior temporal gyrus for left ear (Stewart et al., 1999)
stimulation, but not for right ear stimulation (Fig. 7). We
hypothesize that it is the inability to access the timbre
discrimination area which underlies the slowing in reaction Methodological issues
time for right ear stimulation. We also found additional left Our structural comparisons of grey matter, white matter and
and right precentral gyrus activity in the damaged callosum CSF images required normalization of each individual's brain
group compared with the term controls. The right precentral to a standard template. The procedure will therefore correct
gyrus has been associated with timbre processing in previous any overall differences in brain size between subject groups.
studies (Platel et al., 1997). An interesting question arises as However, the warping procedure does not attempt to match
to how the damaged callosum group are still able to perform individual anatomical structures (the ventricles or speci®c
Corpus callosum function 1791
gyri, for example), with the result that group differences at callosum necessitates adoption of a different neural strategy
this anatomical level remain. for forced callosal transfer tasks. The exact nature of the
The overall performance de®cit in the damaged callosum change is dependent on the modality of the pathways
group confounds the interpretation of the fMRI data. An affected.
alternative interpretation of the activations is that they relate
to task dif®culty and not to differences in functional anatomy.
To protect against this possibility, our analytical strategy was
to compare differences between pairs of stimuli (e.g. bilateral Acknowledgements
versus unilateral) across groups rather than single stimuli. We wish to thank the subjects and the controls for giving their
The fMRI environment is uncomfortable, has distracting time to the study, Jan Townsend at University College
sounds and subjects are required to lie horizontally with their London Department of Paediatrics for coordinating follow-up
movements restricted. These stimulus conditions are different of these subjects, and Chris Andrew for technical assistance
from those of the psychophysical laboratories in which with computer programming. This work was supported by the
reaction time experiments would normally take place. Medical Research Council G9821480. D.H.ff. is a Wellcome
However, we do not think that the fMRI environment Trust Clinician Scientist Fellow.
explains the non-speci®c de®cits in the damaged callosum
group, as the other two control groups were subject to the
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