Dr. Hurlemann was supported by a German Research Foun-
dation grant (HU-1302/2-2) and by a Starting Independent
Researcher Grant (Neuromodulation of Emotion) jointly
provided by the Ministry of Innovation, Science, Research,
and Technology of the German State of North Rhine-
Westphalia and the University of Bonn, Germany.
This letter (doi: 10.1176/appi.ajp.2012.12070905) was accepted
for publication in November 2012.
Altered Functional and Structural Connectivity
in a Schizophrenia Patient With Complete
Agenesis of the Corpus Callosum
To the Editor: We incidentally detected complete agenesis
of the corpus callosum (1, 2) in a 34-year-old married African
American man with schizophrenia who was referred for a
resting-state functional MRI (fMRI) and diffusion tensor im-
aging (DTI) research study. The patient had a 5-year history of
FIGURE 1. Brain Imaging From a Study of Complete Agenesis of the Corpus Callosuma
Agenesis of the Corpus Callosum
Agenesis of the
Default Mode Network Visual Network
DTI-Fractional Anisotropy FornixAnterior Commissure
aPanel A depicts the anatomical and DTI images from a healthy comparison subject (a–e) and the patient with agenesis of the corpus callosum
(CC) (f–j). The corpus callosum is completely absent in the patient, leading to enlarged ventricles (colcocephaly) and prominent Probst bundles
(green in panel h). In contrast, the fornix (d, i) is preserved, and the anterior commissure is prominent (e, j). Panel B depicts resting blood-
oxygen-level-dependent images (a, b, d, e, g, h, j, k) and DTI tractography images (c, f, i, l) from a healthy comparison subject (a–f) and the
patient with agenesis of the corpus callosum (g–l). Regions of interest were placed in the left and right lateral parietal and visual cortex to
study the default mode (a, b) and visual networks (d, e). Relative to the healthy comparison subject, default mode network (g, h) and visual
network (g, h) connectivity were markedly reduced in the patient (3,z,7). The callosal fibers connecting the parietal (c) and visual (f) cortex
region of interest in the healthy comparison subject are missing in the patient with agenesis of the corpus callosum (i, l).
ajp.psychiatryonline.org Am J Psychiatry 170:1, January 2013
LETTERS TO THE EDITOR
schizophrenia that was treated with risperidone, 4 mg/day,
and he was mildly ill at the time of the study (Positive and
Negative Syndrome Scale subscores of 7 [positive], 10 [nega-
tive], and 20 [general psychopathology]). We compared his
ethnicity-matched comparison subject.
The images in Figure 1A show the absent corpus callosum
in the patient and prominent Probst bundles running parallel
to the interhemispheric fissure. The fornix, although skewed
in orientation, was intact, and the anterior commissure was
moreprominentin ourpatientthanin thecomparisonsubject.
Figure 2A shows that the patient had slightly higher fractional
anisotropy values in the fornix and anterior commissure.
We used independent component analysis in FMRIB’s
Software Library to identify resting-state activity involving the
lateral parietal region in the default mode network and in-
volving the primary visual cortex in the visual network. These
functionally defined regions of interest in the lateral parietal
and primary visual cortex were then used for two-region DTI
tractography using MedINRIA (3) to evaluate interhemispheric
connections via the corpus callosum as well as noncallosal
connections via the cortico-spinal tract, fornix, and anterior
The patient showed dramatically reduced interhemispheric
but strong ipsilateral functional connectivity in the default
mode network and the primary visual cortex (Figure 1B). DTI
tractography showed that connections between the left and
right lateral parietal and primary visual cortex regions, me-
diated via the corpus callosum, were absent in the patient
(panels i and l of Figure 1B). We calculated correlation co-
efficients between the left and right brain regions (Figure 2B)
and found reduced temporal synchrony in the lateral parietal
butnormal synchronyin thehippocampus (connectedviathe
fornix and anterior commissure) and the caudate nuclei
(possibly from long-term compensatory or robustly devel-
oped indirect pathways).
Consistent with the view that functional connectivity
demonstrated by resting-state blood-oxygen-level-dependent
fMRIisrelated toanatomical connectivity, weobserved highly
lateralized and reduced interhemispheric connectivity in re-
gions dependent on an intact corpus callosum in our patient.
Nonetheless,functional andstructuralconnectivity acrossthe
two brain hemispheres via other interhemispheric fiber tracts
were preserved. This case report provides a broad under-
standing of the morphological and functional modifications
that occur in agenesis of the corpus callosum. Altered brain
function in a patient with complete agenesis of the corpus
callosum was successfully illustrated using fMRI. Further-
connectivity that was observed with DTI.
1. Lungu O, Stip E: Agenesis of corpus callosum and emotional infor-
mation processing in schizophrenia. Front Psychiatry 2012; 3:1–8
2. Johnston JM, Vaishnavi SN, Smyth MD, Zhang D, He BJ, Zempel
JM, Shimony JS, Snyder AZ, Raichle ME: Loss of resting
interhemispheric functional connectivity after complete section
of the corpus callosum. J Neurosci 2008; 28:6453–6458
3. Toussaint N, Souplet JC, Fillard P: MedINRIA: Medical Image
Navigation and Research Tool by INRIA, in Proceedings of MICCAI
Workshop on Interaction in Medical Image Analysis and Visuali-
zation. Brisbane, Australia, 2007. Available at http://www-sop.
SWATI RANE, PH.D.
SAMET KOSE, M.D., PH.D.
JOHN C. GORE, PH.D.
STEPHAN HECKERS, M.D.
From the Institute of Imaging Science, Department of Radiology
and Radiological Sciences, and the Department of Psychiatry,
Vanderbilt University, Nashville.
The authors report no financial relationships with commer-
This letter (doi: 10.1176/appi.ajp.2012.12060822) was accepted
for publication in October 2012.
FIGURE 2. Fractional Anisotropy Values and Bilateral Func-
tional Connectivity in a Study of Complete Agenesis of the
B. Functional Connectivity (Temporal Correlation Coefficient - r)
A. Fiber Tract Fractional Anisotropy
aPanel A shows that the fractional anisotropy values of interhe-
mispheric pathways (fornix and anterior commissure) and the
corticospinal tract are higher in the patient with agenesis of the
corpus callosum. In Panel B, correlation coefficients (r) for tem-
poral synchrony between left and right brain hemispheres were
reduced in cortical regions and the putamen but normal in the
hippocampus and caudate.
Am J Psychiatry 170:1, January 2013 ajp.psychiatryonline.org
LETTERS TO THE EDITOR