A connectionist modeling study of the neural mechanisms underlying pain's ability to reorient attention.

Connectionist modeling was used to investigate the brain mechanisms responsible for pain's ability to shift attention away from another stimulus modality and toward itself. Different connectionist model architectures were used to simulate the different possible brain mechanisms underlying this attentional bias, where nodes in the model simulated the brain areas thought to mediate the attentional bias, and the connections between the nodes simulated the interactions between the brain areas. Mathematical optimization techniques were used to find the model parameters, such as connection strengths, that produced the best quantitative fits of reaction time and event-related potential data obtained in our previous work.

Neural mechanisms underlying pain's ability to reorient attention: evidence for sensitization of somatic threat detectors.

Pain typically signals damage to the body, and as such can be perceived as threatening and can elicit a strong emotional response. This ecological significance undoubtedly underlies pain's well-known ability to demand attention. However, the neural mechanisms underlying this ability are poorly understood.

The role of somatic threat feature detectors in the attentional bias toward pain: effects of spatial attention.

Our previous work suggests that somatic threat feature detectors indexed by a pain-evoked midlatency negative scalp potential play an important role in the attentional bias toward pain. In these studies the somatic threat feature detectors facilitated the shift in attention to a somatic threat when attention was focused on another stimulus modality but not when it was focused on another spatial location. This experiment used the Posner cuing paradigm to investigate possible explanations for this discrepancy.

EEG indices of tonic pain-related activity in the somatosensory cortices.

Objective: To identify EEG features that index pain-related cortical activity, and to identify factors that can mask the pain-related EEG features and/or produce features that can be misinterpreted as pain-specific.

Methods: The EEG was recorded during three conditions presented in counterbalanced order: a tonic cold pain condition, and pain anticipation and arithmetic control conditions. The EEG was also recorded while the subjects made a wincing facial expression to estimate the contribution of scalp EMG artifacts to the pain-related EEG features.

An artificial neural network model of orienting attention toward threatening somatosensory stimuli.

An artificial neural network model was designed to test the threat detection hypothesis developed in our experimental studies, where threat detector activity in the somatosensory association areas is monitored by the medial prefrontal cortex, which signals the lateral prefrontal cortex to redirect attention to the threat. As in our experimental studies, simulated threat-evoked activations of all three brain areas were larger when the somatosensory target stimulus was unattended than attended, and the increase in behavioral reaction times when the target stimulus was unattended was smaller for threatening than nonthreatening stimuli. The model also generated a number of novel predictions, for example, the effect of threat on reaction time only occurs when the target stimulus is unattended, and the P3a indexes prefrontal cortex activity involved in redirecting attention toward response processes on that trial and sensory processes on subsequent trials.

Neural mechanisms of detecting and orienting attention toward unattended threatening somatosensory target stimuli. II. Intensity effects.

Negative potentials evoked by painful electrical stimulation of the sural nerve that occur at 100-180 ms poststimulus over the contralateral temporal scalp (CTN100-180) and at 130-200 ms over the fronto-central scalp (FCN130-200) exhibit unusual attention effects. That is, their amplitudes are larger when the painful evoking stimulus is unattended than when it is attended. In this experiment, I show that attention has no effect on the CTN100-180 evoked by a weak, nonthreatening sural nerve electrical stimulus.

Neural mechanisms of detecting and orienting attention toward unattended threatening somatosensory targets. I. Intermodal effects.

Our previous work has identified four components of the somatosensory-evoked potential elicited by painful electrical stimulation of the sural nerve that might index an involuntary process that detects and orients attention toward threatening somatosensory stimuli. These components include a negativity over the central scalp at 70-110 ms poststimulus (CN70-110), a contralateral temporal negativity at 100-180 ms (CTN100-180), a frontocentral negativity at 130-200 ms, and a positive potential at 270-340 ms (the pain-related P2). The results of the endogenous cuing experiment used here suggest that the CN70-110 and CTN100-180 index somatosensory cortex activity that detects a threatening somatosensory stimulus when the subject's attention is focused on another stimulus modality but not another location.

Effects of response conflict on pain-evoked medial prefrontal cortex activity.

Experimental studies of pain may introduce a response conflict, where the subject must inhibit an escape response and make a pain-rating response. Several lines of evidence have shown that the medial prefrontal cortex is activated by painful stimuli and by response conflict. It is not clear, however, to what extent pain-evoked medial prefrontal cortex activation reflects response conflict.

The pain-evoked P2 is not a P3a event-related potential.

The topographic pattern and latency of the P2 component of the somatosensory evoked potential elicited by painful electrical stimulation of the sural nerve was compared to the P3a event-related potential evoked by an infrequent task-irrelevant (deviant) innocuous sural nerve stimulus presented as part of the deviant-odd ball paradigm. Conditions typically used to record the sural nerve pain-evoked P2 (multiple stimulus levels, short fixed inter-stimulus intervals, and the subjects engaged in a pain rating task) did not elicit a P3a. The P3a was elicited when the painful stimuli were presented at a long and variable inter-stimulus interval.

The role of the pain-evoked negative difference potential in dual-task response conflict.

The possible role of the generators of the sural nerve pain-evoked negative difference potential (NDP), the anterior cingulate cortex and supplementary somatosensory area, in monitoring response conflict was investigated in 19 healthy adults. Each trial consisted of a visual arrow stimulus and a painful electrical stimulus applied to the sural nerve. The subjects determined whether their left or right sural nerve had been stimulated and whether the arrow was pointing to the left or to the right.

Electrophysiological indices of orienting attention toward pain.

This study examined the effects of orienting on two pain-related components of the sural nerve-evoked somatosensory evoked potential: the NDP (80-230 ms), which is generated in part by the anterior cingulate cortex (ACCc), and SP6 (280-340 ms). NDP and SP6 amplitudes were larger when subjects oriented their attention away from an invalidly cued location and toward the sural nerve pain than when their attention remained focused on the pain. These results and our earlier studies suggest that the ACCc activity generating the NDP is involved in detecting transient painful stimuli.

Distraction produces an increase in pain-evoked anterior cingulate activity.

This study examined the effects of distraction on pain-evoked activity in the anterior cingulate cortex (ACC). Twenty-eight healthy adults were given painful electrical stimulation of the sural nerve during an attend condition, where they rated the subjective magnitude of each electrical stimulus, and during a distraction condition, where they performed an arithmetic distraction task. The magnitude of the pain-evoked ACC activity was estimated from the dipole source localization analysis of the somatosensory evoked potential.

Topographic analysis of painful laser and sural nerve electrical evoked potentials.

A quantitative scalp topographic pattern analysis was used to compare evoked potentials elicited by painful laser (LEP) and electrical stimulation of the sural nerve (snSEP) in 22 healthy adults. The snSEP and LEP were separated into stable periods (consecutive time points having the same topographic pattern). The topographic pattern is dependent upon the number, location, orientation and relative magnitudes of the brain areas active at that time (source configuration).

Pain-evoked anterior cingulate activity generating the negative difference potential may reflect response selection processes.

The effects of a heterotopic cold pain stimulus applied to the hand on the scalp-recorded negative difference potential (NDP) and subjective pain ratings elicited by electrical stimulation of the sural nerve were examined in 24 participants. Our previous work strongly suggests that the NDP is generated in part by the cognitive division of the anterior cingulate cortex (ACCcd). The latency and magnitude of the ACCcd activity were estimated from the NDP and from the dipole source localization analysis of the NDP.

Possible startle response contamination of the spinal nociceptive withdrawal reflex.

The objective of this study was to examine the possibility that the spinal nociceptive withdrawal reflex, otherwise known as the RIII reflex, is contaminated by the startle response, which is a non-pain-related supraspinal response. Startle response contamination of the RIII reflex would seriously compromise the RIIIs ability to measure spinal nociceptive processes in man, since a change in the startle response affecting EMG amplitude in the RIII latency range would be erroneously interpreted as a change in a spinal nociceptive process. EMG responses evoked by electrical stimulation of the sural nerve were recorded from the orbicularis oculi, neck, biceps, and biceps femoris muscles in 31 healthy human volunteers.

Spinal and supraspinal correlates of nociception in man.

The objective of this work was to simultaneously measure pain-related spinal and supraspinal physiological responses in humans. The sural nerve compound action potential (CAP), the spinal withdrawal reflex (RIII), the somatosensory evoked potential (SEP) and subjective magnitude ratings were elicited by electrical stimulation of the sural nerve in 10 healthy subjects. The sural nerve CAP was used to normalize the evoking stimulus current and to help identify the peripheral nerve afferent types contributing to the physiological and psychophysical responses.