doi:10.1093/brain/awv245
BRAIN 2016: 139; 1–2
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LETTER TO THE EDITOR
Reply: Strategy and suppression impairments after right lateral and
orbito-frontal lesions
Michael Hornberger and Maxime Bertoux
Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK
Correspondence to: Dr Michael Hornberger,
Department of Clinical Neuroscience,
University of Cambridge,
Cambridge, UK
E-mail: [email protected]
Sir,
We are delighted that Cipolotti and colleagues have
taken up our suggestion (Hornberger and Bertoux, 2015)
on their previous study (Robinson et al., 2015). Despite the
impressive findings of the Robinson study, which showed
that right lateral prefrontal cortex was involved in strategy
and suppression deficits, we suggested that an orbitofrontal
cortex lesion group would have been beneficial to contrast
against the right lateral group, due to the well-known role
of the orbitofrontal cortex in disinhibition. The current
letter by Cipolotti et al. (2015) addresses this gap by presenting data for five right lateral and six orbitofrontal
cortex lesion patients. As in their previous study,
Cipolotti and colleagues show that patients with right lateral lesion have deficits in suppressing responses as well as
in adopting appropriate task strategies. It is reassuring that
the authors confirm this finding in an independent sample,
though slightly weaker due to the smaller sample size compared to the previous study. More importantly, the authors
also show that orbitofrontal cortex lesion patients were not
significantly impaired compared to controls for the suppression and strategy deficit scores of the Hayling test and were
significantly different to right lateral patients.
These findings corroborate the crucial role the right lateral has in response suppression/inhibition as well as highlighting the specificity of strategy use in this region of the
prefrontal cortex. The result is also of great interest as it
contrasts with a large body of literature linking disinhibition to orbitofrontal cortex lesions in animals and humans
(Stalnaker et al., 2015), a result that has been consistently
observed in neurodegenerative conditions. The findings by
Cipolotti and colleagues show that the mapping of such
neurodegenerative lesions on disinhibition might not be as
straightforward as previously thought. For example, our
previous study (Hornberger et al., 2011) revealed a specific
covariation between orbitofrontal cortex grey matter decrease and Hayling suppression errors in patients with
frontotemporal dementia (FTD) with significant orbitofrontal cortex atrophy and disinhibition symptoms. At the time
we interpreted these findings as a general disinhibition deficit in the patients, which corroborated their clinical symptomology. However, in light of the current Cipolotti
findings, the results could be also interpreted in a way
that patients with FTD may have been insensitive to the
negative feedback following their error and, as a consequence, may have faced difficulty reversing the rule that
has been reinforced in the first part of the test. Thus, our
original findings might have been more akin to a reversal
learning deficits than ‘pure’ disinhibition.
The interesting question emerging from this contrast of
stroke and neurodegenerative lesion findings is in how far
do they inform each other? Most human lesion studies use
patients with localized stroke or tumour lesions that cause
grey and white matter damage either downstream of the
vascular regions where the stroke occurred or where the
tumour is co-localized or has been removed. By contrast,
neurodegenerative lesions are rarely regarded as ‘pure lesions’ despite the fact that they cause highly specific grey
and white matter changes and associated cognitive symptoms. Both lesion types have obviously fundamental differences in aetiology (stroke/tumour versus protein
accumulation) and progression (static versus progressive),
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| BRAIN 2016: 139; 1–2
however, it becomes clear that contrasting them might in
fact allow a new view on lesion mapping.
More specifically, the progressive nature of neurodegenerative lesions is usually seen as a disadvantage in lesioncognition mapping. However, since protein aggregation
(e.g. amyloid, tau, TDP-43) progresses in a very systematic
way, neurodegenerative conditions might allow a more network lesion approach, which can be complemented by a
region-specific stroke lesion approach. Current neuroimaging developments are strongly targeted towards brain network changes due to the fact that virtually all complex
behaviours, such as inhibition, involve different cognitive/
affective processes recruiting a variety of brain regions.
Thus, contrasting more network-based neurodegenerative
lesions versus more localized stroke lesions would allow a
complementary approach towards the study of complex
behaviours. Again, in this regard our previous findings
(Hornberger et al., 2011) were of interest, which not only
showed orbitofrontal cortex damage being related to
Hayling performance but also temporal pole atrophy. The
substantial temporal pole atrophy covariation highlighted
that patients require an intact semantic knowledge to perform a verbal inhibition task such as the Hayling. In addition, the white matter connectivity between orbitofrontal
cortex and temporal pole also was related to Hayling performance, demonstrating that the successful interaction of
Letter to the Editor
the frontotemporal network was necessary to perform correctly on this verbal inhibition task.
In summary, future investigations contrasting stroke
versus neurodegenerative lesions might allow a new way
of lesion mapping, combining a localized versus a network
approach, respectively. This will not only allow establishing
specificity of regional lesions but also how whole network
lesions impact on complex behaviours with implications for
future diagnostics and treatments of brain lesion patients.
References
Cipolotti L, Healy C, Spanò B, Lecce F, Robinson G, Chan E. et al.
Strategy and suppression impairments after right lateral and orbitofrontal lesions. Brain 2015; in press.
Hornberger M, Bertoux M. Right lateral prefrontal cortex–specificity
for inhibition or strategy use? Brain 2015; 138: 833–5.
Hornberger M, Geng J, Hodges JR. Convergent grey and white matter
evidence of orbitofrontal cortex changes related to disinhibition in
behavioural variant frontotemporal dementia. Brain 2011; 134:
2502–12.
Robinson GA, Cipolotti L, Walker DG, Biggs V, Bozzali M, Shallice
T. Verbal suppression and strategy use: a role for the right lateral
prefrontal cortex? Brain 2015; 138: 1084–96.
Stalnaker TA, Cooch NK, Schoenbaum G. What the orbitofrontal
cortex does not do. Nat. Neurosci 2015; 18: 620–627.