Saturday, August 4, 2007

Behavioural improvements with thalamic stimulation

N. D. Schiff, J. T. Giacino, K. Kalmar, J. D. Victor, K. Baker, M. Gerber, B. Fritz, B. Eisenberg, J. O’Connor, E. J. Kobylarz, S. Farris, A. Machado, C. McCagg, F. Plum, J. J. Fins, A. R. Rezai
Nature 448, 600-603(2 August 2007) doi:10.1038/nature06041

Widespread loss of cerebral connectivity is assumed to underlie
the failure of brain mechanisms that support communication and
goal-directed behaviour following severe traumatic brain injury.
Disorders of consciousness that persist for longer than 12 months
after severe traumatic brain injury are generally considered to be
immutable; no treatment has been shown to accelerate recovery or
improve functional outcome in such cases1,2. Recent studies have
shown unexpected preservation of large-scale cerebral networks in
patients in the minimally conscious state (MCS)3,4, a condition
that is characterized by intermittent evidence of awareness of self
or the environment5. These findings indicate that there might be
residual functional capacity in some patients that could be supported
by therapeutic interventions. We hypothesize that further
recovery in some patients in the MCS is limited by chronic underactivation
of potentially recruitable large-scale networks. Here, in
a 6-month double-blind alternating crossover study, we show that
bilateral deep brain electrical stimulation (DBS) of the central
thalamus modulates behavioural responsiveness in a patient
who remained in MCS for 6 yr following traumatic brain injury
before the intervention. The frequency of specific cognitively
mediated behaviours (primary outcome measures) and functional
limb control and oral feeding (secondary outcome measures)
increased during periods in which DBS was on as compared with
periods in which it was off. Logistic regression modelling shows a
statistical linkage between the observed functional improvements
and recent stimulation history. We interpret the DBS effects as
compensating for a loss of arousal regulation that is normally
controlled by the frontal lobe in the intact brain. These findings
provide evidence that DBS can promote significant late functional
recovery from severe traumatic brain injury. Our observations,
years after the injury occurred, challenge the existing practice of
early treatment discontinuation for patients with only inconsistent
interactive behaviours and motivate further research to
develop therapeutic interventions.

PMID: 17671503

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