Original ContributionsInfluence of attention focus on neural activity in the human spinal cord during thermal sensory stimulation
Introduction
Understanding how normal perceptions of sensation or pain are produced is a prerequisite for understanding how these functions are altered by trauma or disease. After a spinal cord injury 60% to 80% of patients suffer chronic pain [1], so understanding the genesis and propagation of this pain is of great importance [2]. However, pain and sensation are difficult to quantify because they are subjective perceptions of sensory inputs, and not the inputs themselves [3], [4]. In healthy people, these perceptions are the result of a network integrating the sensory spino-thalamo-cortical pathway and the descending pain modulatory system that arises in the frontal cortex, anterior cingulate cortex, amygdala and hypothalamus, which connects via the periaqueductal gray matter (PAG), dorsolateral pontine tegmentum (DLPT) and rostral ventromedial medulla (RVM) to control spinal pain transmission neurons directly [5], [6], [7]. This descending modulation and the consequent perception of pain or sensation have been shown to be influenced strongly by factors such as attention, anticipation and emotion [8], [9], [10].
Functional magnetic resonance imaging (fMRI) of the spinal cord (spinal fMRI) is currently the only noninvasive means of mapping neural function and the effects of the descending control in the human spinal cord. This method has the potential to be an extremely important clinical tool because it has been shown to be sensitive to differences in neural function between painful and nonpainful sensory stimuli [11], [12], [13] and has demonstrated spinal cord activity involved with sexual function [14], differences in pain responses in patients with carpal tunnel syndrome compared to healthy controls [15], the effects of multiple-sclerosis on spinal cord function [16], [17], and also sensory and motor functions caudal to sites of spinal cord trauma [18], [19]. The effects of the descending control from the brainstem and higher cortical structures are as important to the overall spinal cord function and determination of the effects of injury, as are the ascending neural inputs from the periphery. The importance of understanding both the ascending and descending inputs to the cord is demonstrated by the fact that one likely mechanism for the chronic pain experienced after spinal cord injury is the result of a change or imbalance of the descending modulation relative to the ascending signals [20], [21], [22].
An important missing link in our understanding, however, arises from the fact that normal sensory and pain processing have rarely been studied in the intact human spinal cord. The spinal cord inputs from the brainstem have only been inferred from detailed animal studies [20], [23] and from observing the effects of injury and of therapy [24], [25]. The areas of the brain and rostral portions of the brainstem that play a key role in pain/sensation perception and descending modulation have been observed in humans by means of fMRI and positron emission tomography and by microstimulation during surgical procedures [8], [9], [26], [27], [28], [29]. Spinal cord neural responses to descending modulation have only been observed in healthy humans in a single previous study as a result of changes in emotional status, alertness, or attention across repeated spinal fMRI studies [11].
Here, we investigate how, or if, activity in the human cervical spinal cord is modulated by changing the focus of the person's attention (i.e., their “attention state”) at the same time that a sensory stimulus is applied. We hypothesize that activity in the cervical spinal cord during thermal stimulation of the hand, is influenced by the attention state, as it is in the cortex and brainstem [8], [9].
Section snippets
FMRI data acquisition
This study consisted of three protocols which were carried out with separate groups of healthy adult volunteers with no previous history of neurological trauma or disease. Three different protocols were employed in order to determine the influence of the “attention state” on the activity elicited by cooling the hand, distinct from other task-related effects such as motor and visual responses, as described below. For the purposes of this study, we use the term attention state to mean the state
Ratings of sensations and question responses during fMRI experiments
The subjective ratings obtained during “Rating” tasks, and the responses provided during “Movie,” “Detect,” or “Challenge” tasks indicate that the participants performed the tasks correctly, and that their attention states and experiences of the thermal stimuli were successfully altered by the tasks. These results are summarized in Table 2.
In Protocol 1 (Fig. 1A, Table 2A), during the experiments with “Rating” conditions, the correlation between the subjects' responses and the stimulation
Discussion
The key finding of this study is that activity in the human cervical spinal cord in response to a thermal sensory stimulus, as detected by spinal fMRI, depended on the participant's attention state. Contrasted results between task conditions (Fig. 3) demonstrated significantly lower signal in the ipsilateral dGM of the spinal cord in response to thermal stimulation while “Rating” conditions were applied, as compared to during any of the cognitive tasks (i.e. “Movie,” “Detect,” or “Challenge”).
Conclusions
Here, we demonstrate that the attention state can modulate neural function in the human spinal cord during thermal sensory stimulation, as detected by spinal fMRI. The results support our hypothesis that activity in the cervical spinal cord during thermal stimulation of the hand was influenced by what the participant was thinking about while the stimulus was applied. This means that, in healthy humans, the ability to play through the pain in sports or to focus on responding to danger in spite
Acknowledgments
We gratefully acknowledge the technical assistance of Sharon David, helpful input from Dr. Irene Armstrong and grant support from the International Spinal Research Trust, the Canada Research Chairs Program, and the Harry Botterell Foundation.
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2011, Magnetic Resonance ImagingCitation Excerpt :The consistent activity across the group was represented by the number of participants that exceeded a significance level (T-value) of 2.5 in the individual (first-level) analysis at each voxel, as described previously [9,20]. The group activity expressed in the manner is similar to that produced by a random-effects analysis, but makes more allowance for the fact that not all variation between studies can be considered to be errors, but can reflect true physiological variation because the neural activity in the spinal cord and brain stem can depend on emotional factors such as anticipation, anxiety and attention [17,21]. While we tried to control these variables by providing complete information prior to the study and verbal reassurance between periods of fMRI data acquisition, complete control is not possible.