BRAIN

A JOURNAL OF NEUROLOGY
LETTER TOTHE EDITOR
Subcortical damage and white matter disconnection associated with non-fluent speech
Leonardo Bonilha and Julius Fridriksson
Department of Communication Sciences and Disorders, University of South Carolina, Columbia, SC, USA
Correspondence to: Leondardo Bonilha,
Department of Communication Sciences and Disorders,
Williams-Brice Building,
University of South Carolina,
Columbia, SC, USA
E-mail: bonilha@musc.edu
Sir, In a recent paper published in Brain, Dronkers and colleagues
(2007) re-examined the brain damage in two historic patients of
P. Paul Broca, Leborgne and Lelong, who had lost the ability to
speak following brain damage. The observation of these cases lead
Broca to suggest that the left inferior frontal lobe (later coined
Brocas area) is the crucial lesion location associated with acquired
motor speech impairment.
Utilizing high resolution MRI, Dronkers and colleagues observed
that the brain damage in both of Brocas cases extend further
subcortically than Broca could have observed, therefore, suggest-
ing that the critical lesion location for motor speech production
is not restricted to the inferior frontal gyrus. In particular, the
authors demonstrated that the superior longitudinal fasciculus
was damaged in both cases, arguing that this lesion may also
have affected Brocas patients speech production.
This timely examination by Dronkers et al. combines a historical
perspective and the current debate regarding the critical lesion
location associated with non-uent speech. In an earlier study
employing lesion mapping in chronic stroke patients, Dronkers
(1996) suggested that damage to the left anterior insula, but
not to Brocas area, is the crucial lesion location associated with
non-uent speech. Until then, Brocas initial ndings were largely
undisputed by tangible evidence. These observations, however,
were contrasted in a controlled study by Hillis and colleagues
(2004) which investigated acute patients and observed that,
indeed, Brocas area, as opposed to left anterior insular damage,
is strongly associated with non-uent speech. In support of these
ndings, numerous studies utilizing functional MRI in normal
participants have demonstrated a strong relationship between
Brocas area activity and speech production (Bonilha et al.,
2006; Ozdemir et al., 2006; Guenther et al., 2006). For example,
our group showed that the contrast between speech and non-
speech oral movements revealed Brocas area activity associated
with speech movements but left anterior insula activity related to
non-speech oral movements. Moreover, transcranial magnetic sti-
mulation of the posterior portion of Brocas area (i.e. pars oper-
cularis) reliably interrupts speech production (Devlin and Watkins,
2007). How can these seemingly paradoxical ndings be recon-
ciled? In our opinion, these ndings are not necessarily in conict
but, instead, provide complementary evidence regarding acquired
non-uent speech. In particular, these observations indicate that
the integrity of the connections between the primary language
areas are crucial for speech processing and production. Recently,
our group showed that severing of the arcuate fasciculus with
complete cortical sparing results in severe non-uent aphasia
(Fridriksson et al., 2007). We therefore suggest that subcortical
damage, in particular involving insular lesions, leads to essential
damage to bre pathways conveying information for speech
production (Ay et al., 2008). In order to examine this hypo-
thesis, we performed a probabilistic tractography analysis
of high-resolution diffusion tensor imaging (single shot EPI with
voxels of 223mm, employing 12 diffusion directions
with b-value of 1000 s/mm
2
, TR=6000ms, TE =90 ms, matris
size =128 128) from 51 normal participants. We assessed the
probabilistic pathway of the bres travelling from the left
Brodmann area (BA) 22 to left BA 45 on each individual using
FMRIBs Diffusion ToolboxFDT v2.0 (http://www.fmrib.ox.ac.
uk/fsl/fdt/index.html). The results were transformed into stereo-
taxic space and averaged onto a normal brain template. These
results are displayed in Fig. 1, where it is evident that these path-
ways funnel immediately below the gray matter surface of the
insula. Therefore, insular damage may lead to acquired non-
uent speech not because of gray matter damage but, instead,
because of disconnection between posterior and anterior speech
areas. In fact, Dronkers et al. in study in Brain demonstrate that
Leborgne brains showed cortical insular damage, while Lelongs
doi:10.1093/brain/awn200 Brain 2009: 132; 12 | e108
Received April 1, 2008. Revised June 10, 2008. Accepted July 31, 2008. Advance Access publication August 22, 2008
The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
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brain did not. Functionally, the feedback role of the posterior
language areas in speech production has been extensively demon-
strated by Guenther et al. (2006).
In conclusion, in accordance with Dronkers et al. ndings, we
suggest that Brocas area is crucial for speech production, while
its disconnection (e.g. at the level of the anterior insula) from
the posterior language areas may also result in non-uent
speech. The integrity of the insular white matter and of the con-
nections between the superior temporal cortex and the inferior
frontal area is crucial for speech production.
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Figure 1 This gure shows the anatomical location of reconstructed white matter pathways travelling from BA 22 to BA 45. The scale
bar represents the overlap among tracts among the subjects. Fibre pathways are overlaid onto multi slices as well as a transparent 3D
reconstruction of a normal brain template.
e108 | Brain 2009: 132; 12 Letter to the Editor