Elsevier

NeuroImage

Volume 36, Issue 3, 1 July 2007, Pages 979-992
NeuroImage

When thoughts become action: An fMRI paradigm to study volitional brain activity in non-communicative brain injured patients

https://doi.org/10.1016/j.neuroimage.2007.02.047Get rights and content

Abstract

The assessment of voluntary behavior in non-communicative brain injured patients is often challenging due to the existence of profound motor impairment. In the absence of a full understanding of the neural correlates of consciousness, even a normal activation in response to passive sensory stimulation cannot be considered as proof of the presence of awareness in these patients. In contrast, predicted activation in response to the instruction to perform a mental imagery task would provide evidence of voluntary task-dependent brain activity, and hence of consciousness, in non-communicative patients. However, no data yet exist to indicate which imagery instructions would yield reliable single subject activation. The aim of the present study was to establish such a paradigm in healthy volunteers. Two exploratory experiments evaluated the reproducibility of individual brain activation elicited by four distinct mental imagery tasks. The two most robust mental imagery tasks were found to be spatial navigation and motor imagery. In a third experiment, where these two tasks were directly compared, differentiation of each task from one another and from rest periods was assessed blindly using a priori criteria and was correct for every volunteer. The spatial navigation and motor imagery tasks described here permit the identification of volitional brain activation at the single subject level, without a motor response. Volunteer as well as patient data [Owen, A.M., Coleman, M.R., Boly, M., Davis, M.H., Laureys, S., Pickard J.D., 2006. Detecting awareness in the vegetative state. Science 313, 1402] strongly suggest that this paradigm may provide a method for assessing the presence of volitional brain activity, and thus of consciousness, in non-communicative brain-injured patients.

Introduction

Improvements in medical practice have led to an increasing number of patients surviving acute brain injury. Survivors of severe traumatic or hypoxic–ischemic brain damage classically go through distinct clinical stages before partially or fully recovering consciousness. Coma is defined as ‘unarousable unresponsiveness’. After some days or weeks comatose patients may eventually open their eyes. When this return to ‘wakefulness’ is accompanied by reflexive motor activity only, devoid of any voluntary interaction with the environment, the condition is called a vegetative state (The Multi-Society Task Force on PVS, 1994). The vegetative state may be a transition to further recovery. Limited but reproducible signs of self- or environment-awareness characterize the minimally conscious state (MCS) (Giacino et al., 2002). Functional communication indicates the next boundary – emergence from MCS – in the course of recovery (Laureys et al., 2005).

There currently exists no method for acquiring an objective physical measure of conscious awareness in either a patient or a healthy volunteer. Its estimation in patients requires expert clinical interpretation of voluntary versus reflexive behaviors, necessarily relying on ‘motor responsiveness’ (Majerus et al., 2005). Indeed, the only method that any of us can use to demonstrate our awareness to others is through some form of motor activity—speech, facial expression, eye-tracking, limb movement, shrugging shoulders, nodding-shaking the head, etc. (Majerus et al., 2005). Therefore, clinical assessment is limited in the extent to which ‘internal awareness’ can be established in a patient who lacks the motor function to demonstrate this awareness (Giacino and Zasler, 1995). These difficulties may partly explain the high frequency of misdiagnosis (up to 43%) among non-communicative brain injured patients (Tresch et al., 1991, Childs et al., 1993, Andrews et al., 1996). A recent study of 42 locked-in syndrome patients (fully conscious but completely paralyzed) found a mean diagnosis delay of 2.5 months (78.1 days) from the time the patient suffered the stroke or traumatic brain injury (Leon-Carrion et al., 2002). Some fully aware but non-communicative patients sometimes even stay misdiagnosed (as being in a vegetative state) for periods as long as 4 years (Leon-Carrion et al., 2002).

Several brain imaging studies have shown relatively normal patterns of brain activation in response to complex sensory stimulation in some non-communicative patients, mainly responding to the clinical criteria of minimally conscious state (Bekinschtein et al., 2004, Boly et al., 2004, Laureys et al., 2004, Owen et al., 2005, Schiff et al., 2005). However, in the absence of a full understanding of the neural correlates of consciousness, even a near-to-normal activation in response to passive sensory stimulation cannot be considered as a proof of the presence of awareness in these patients. Instead, all that can be inferred is that a specific brain region is, to some degree, still able to process the relevant sensory stimuli. Our hypothesis is that functional imaging could be a tool for assessing certain forms of volitional brain activity without requiring any motor output from the volunteers. Our reasoning was that a predictable activation in response to the instruction to perform a mental imagery task would provide evidence of consciousness in non-communicative patients. However, no data yet exist to indicate which imagery tasks would be most suitable in this context, and in addition, which tasks are likely to yield reliable results in individual subjects. Indeed, the reliability of the results obtained in individual volunteers rather than across a group is crucial for any clinical application where interpretation will take place on a single subject basis. The aim of the present study was to validate this approach in healthy volunteers.

The experimental procedure took place in three steps. Two exploratory experiments searched for appropriate mental imagery tasks that elicited in individual healthy volunteers robust brain activation in task-specific areas (as previously reported in the neuroimaging literature). A third experiment compared the two most reproducible tasks to one another and tested whether a blind analysis could differentiate each task from one another and from rest periods in each volunteer.

Section snippets

Volunteers

The two exploratory experiments were performed at the Wolfson Brain Imaging Centre (WBIC), Addenbrookes Hospital, University of Cambridge, UK. The third experiment was performed at the Cyclotron Research Center (CRC), University of Liège, Belgium. Twelve volunteers participated in each experiment (whole group mean age 24 ± 4, 12 males). Volunteers gave their written informed consent to participate in the study. None of the volunteers declared any history of neurological or psychiatric disease.

Experiment 1

Spatial navigation (imagine moving around the rooms of your home) activated the bilateral precuneus/parieto-occipital junction and retrosplenial cortex in all volunteers, and parahippocampal cortex in 11/12 volunteers, both compared to rest and to sub-vocal rehearsal.

Sub-vocal rehearsal (imagine singing jingle bells) produced activation of the left superior temporal gyrus only in 3/12 volunteers.

Group activations for each task compared to rest are shown in Table 2. Individual results for each

Modality-specific activations

A number of studies have suggested that mental imagery engages many of the same cognitive and neural mechanisms that are involved in perception (Kosslyn et al., 1995, O'Craven and Kanwisher, 2000a) or action (Jeannerod and Frak, 1999). In the visual domain, O’Craven et al. (O’Craven and Kanwisher, 2000a) have shown that context-specific neural activity in extrastriate visual cortex can be created by voluntary imagination even when no visual stimulus is presented at all. Studies using binocular

Acknowledgments

An MRC programme grant (number G9439390 ID 56833) and the Belgian National Fund for Scientific Research (FNRS) funded this work. MB, SL and PM are respectively Research Fellow, Qualified Researcher and Research Director at FNRS.

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