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Biomedical subjects

Karen D Davis

Publications and source records attributed to Karen D Davis.

At least 19 recordsLinked to original sources

Interactions of pain intensity and cognitive load: the brain stays on task.

Pain naturally draws one's attention. However, humans are capable of engaging in cognitive tasks while in pain, although it is not known how the brain represents these processes concurrently. There is some evidence for a cortical interaction between pain- and cognitive-related brain activity, but the outcome of this interaction may depend on the relative load imposed by the pain versus the task. Therefore, we used 3 levels of cognitive load (multisource interference task) and 2 levels of pain intensity (median nerve stimulation) to examine how functional magnetic resonance imaging activity in regions identified as pain-related or cognitive-related responds to different combinations of pain intensity and cognitive load. Overall, most pain-related or cognitive-related brain areas showed robust responses with little modulation. However, during the more intense pain, activity in primary sensorimotor cortex, secondary somatosensory cortex/posterior insula, anterior insula, paracentral lobule, caudal anterior cingulate cortex, cerebellum, and supplementary motor area was modestly attenuated by the easy task and in some cases the difficult task. Conversely, cognitive-related activity was not modulated by pain, except when cognitive load was minimal during the control task. These findings support the notion that brain networks supporting pain perception and cognition can be simultaneously active.

Adult↗

Deep brain stimulation for chronic neuropathic pain: long-term outcome and the incidence of insertional effect.

We conducted a retrospective analysis of long-term results of deep brain stimulation (DBS) for the treatment of neuropathic pain. Twenty-one patients had electrodes implanted in the ventrocaudalis thalamic nucleus (Vc) (n=13) or in both Vc and periaqueductal/periventricular gray matter (PAG/PVG) (n=8). After insertion of the electrodes, 9 patients (43%) had a substantial reduction in pain scores in the absence of stimulation (insertional effect). The effects of stimulation were studied right after surgery or upon return of the patients' pain after electrode insertion (stimulation trials). Patients with a greater than 50% reduction in pain scores were implanted with a pulse generator (IPG). Of interest, patients who had an insertional effect had a trend towards a successful stimulation trial (p=0.08). Overall, 13 of the 21 patients operated (62%) had a successful stimulation trial and received an IPG (12 with electrodes in Vc and one in both Vc and PAG/PVG). Seven patients (33%) did not benefit from stimulation and had the electrodes removed. One patient experienced a prolonged insertional effect and has not required stimulation. Of the 13 patients that received an IPG, 8 discontinued stimulation during the first year of treatment. Only 5 patients maintained long-term benefit (4 with stimulation in Vc and one in both Vc and PAG/PVG). The relatively low efficacy of DBS for the treatment of neuropathic pain stresses the need for further investigation and the exploration of new surgical targets.

Adult↗

Cortical responses to pain in healthy individuals depends on pain catastrophizing.

The personal experience of pain is complex and depends on physiological and psychological factors. From this latter category, pain catastrophizing plays an important role in pain behavior and response. We aimed to determine the effect of pain catastrophizing on central nociceptive processing in healthy individuals. Functional MRI was performed during two pain intensity levels evoked by electrical median nerve stimulation in 22 healthy individuals. Pain catastrophizing scores were determined for all subjects. Pain catastrophizing was not related to activity in regions associated with sensory-discriminative aspects of pain, such as the primary or secondary somatosensory cortex. Instead, during mild pain, there was a relationship between catastrophizing and activity in cortical regions associated with affective, attention, and motor aspects of pain, including dorsolateral prefrontal, insula, rostral anterior cingulate, premotor, and parietal cortices. During more intense pain, prefrontal cortical regions implicated in the top-down modulation of pain were negatively correlated with catastrophizing. These findings can be viewed from the framework of an attention model of pain catastrophizing, whereby a cortical vigilance network is engaged during mild pain, but diminished prefrontal cortical modulation impedes disengaging from and suppressing pain during more intense pain. These findings may also implicate catastrophizing in the progression to or persistence of chronic pain.

Adult↗

Human anterior cingulate cortex neurons encode cognitive and emotional demands.

The cortical mechanisms and substrates of cognitive and emotional demands are poorly understood. Lesion studies and functional imaging implicate the anterior cingulate cortex (ACC). The caudal ACC (cACC) has been implicated in cognitive processes such as attention, salience, interference, and response competition, mostly on the basis of neuroimaging results. To test the hypothesis that individual cACC neurons subserve these functions, we monitored neuronal activity from single cells in the cACC while subjects were engaged in a mental arithmetic task, the cognitively demanding counting Stroop task, and/or the emotional Stroop interference task. We now report the first direct measures of single neurons in humans identifying a population of cACC neurons that respond differentially or in a graded manner to cognitively demanding high- and low-conflict Stroop tasks, including those with emotional valence. These data indicate that cACC neurons may be acting as salience detectors when faced with conflict and difficult or emotional stimuli, consistent with neuroimaging results of cACC responses to abrupt sensory, novel, task-relevant, or painful stimuli.

Brain Mapping↗

Dissociation of phantom limb phenomena from stump tactile spatial acuity and sensory thresholds.

Most amputees experience phantom limb sensations and/or phantom limb pain as well as residual limb (stump) pain that are resistant to treatment. Phantom phenomena are not homogeneous; each patient presents with a unique combination of spontaneous or evoked sensations, pain, and/or awareness. In an effort to understand the underlying mechanisms, postamputation pain has been subclassified based on the perceived sensory qualities reported by the individual. However, little is known about the relationship between subjective phantom phenomena and sensory function of the residual stump. The aim of the present study was to determine if sensory processing, as measured psychophysically, reflected subjective reports of specific qualities of phantom and/or stump sensory phenomena. Twelve individuals who had recently (within 6 months) undergone traumatic unilateral upper extremity amputation participated in the study. Limb temperature, thermal thresholds, tactile sensory thresholds and tactile spatial acuity were compared between the residual limb and the intact limb, and related to patient reports of specific stump and phantom sensory phenomena. All but one subject reported phantom sensations and/or phantom pain. The remaining subject reported only stump pain. Mean skin temperature of the residual limb was significantly lower than that of the intact contralateral limb by approximately 0.9 degrees C in the proximal portion of the stump and 1.7 degrees C at the stump tip. However, the temperature of the stump (compared with the intact limb) did not reflect subjective reports of stump or phantom limb thermal characteristics. Thermal threshold abnormalities differed among patients, and did not suggest any pattern of small fibre loss of function or generalized hyperexcitability. Other than within grafted tissue or near the scar area, skin areas that the patient described as abnormally sensitive or tender to touch were not accompanied by corresponding abnormalities in static tactile thresholds or tactile spatial acuity. Tactile spatial acuity was heightened near the scar area only. The proportion of subjects who had decreased two-point discrimination thresholds at the stump did not differ significantly according to the reporting or non-reporting of dual percepts. Thus, despite a common injury, the sensory abnormalities varied within this cohort of subjects. In addition, psychophysical threshold measures of sensory function did not reflect, in any simple way, subjective phantom phenomena. Therefore, classification of phantom phenomena based on peripheral sensory function may be a misleading step in the search for specific mechanisms underlying postamputation sensory phenomena.

Adult↗

Cortical plasticity following upper extremity injury and reconstruction.

Today's view of the adult central nervous system is that of an adaptive and responsive system. Plastic surgeons, because of the motor and sensory reconstructions they perform, need to have an understanding of brain plasticity following upper extremity injury, reconstruction, and rehabilitation. Functional MRI and transcranial magnetic stimulation can identify cortical plasticity in humans. For instance, these techniques have identified changes in excitability and body site representation in the motor cortex in patients following motor reconstruction and motor relearning. Therefore, cortical plasticity and its manipulation may be an important contributor to functional outcome following reconstruction. In the future, cortical plasticity may have implications for reconstruction and rehabilitation.

Amputation, Traumatic↗

Characteristics of rectal perception are altered in irritable bowel syndrome.

A hallmark symptom of irritable bowel syndrome (IBS) is a lower pain threshold during rectal distension, but the mechanism underlying this disorder remains unclear. Examining the relationship between physiological and perceptual responses to rectal distension can provide insight into the underlying peripheral or central dysfunction in IBS. Therefore, we carried out a study of the rectal sensations of urge to defecate, pain and unpleasantness in relation to the varying states of the rectum. Ten IBS patients and 13 healthy controls underwent six sets of isobaric rectal distensions. The first set was ascending stepwise distensions terminating upon report of moderate pain where verbal ratings of urge, pain, and unpleasantness were acquired. The remaining sets were phasic or tonic distensions at a single pressure eliciting either moderate urge or moderate pain intensity where subjects gave continuous ratings of urge or pain percepts. The McGill Pain Questionnaire (MPQ) was used to assess different qualities of the pain experience during single pressure distensions. Abnormalities in IBS patients included: (1) higher incidence of distensions where unpleasantness is greater than pain intensity, (2) significantly longer persistence of ratings after stimulus termination during phasic distensions eliciting either moderate urge or moderate pain, (3) significantly smaller ratings fluctuations during tonic distensions, and (4) significantly higher MPQ scores for painful tonic distensions. Our study demonstrates that IBS patients have abnormal temporal and intensity properties of rectal sensation. These can be accounted for by either altered peripheral neuromuscular processing and/or processing of ascending rectal input in the central nervous system.

Humans↗

Very fast oscillations evoked by median nerve stimulation in the human thalamus and subthalamic nucleus.

Very fast oscillations (VFOs; 500-1,500 Hz) are associated with sensory-evoked potentials (SEPs), but their origin is unknown. To characterize the origins of VFOs, we studied 35 patients with deep brain stimulation (DBS) electrodes [15 with thalamic and 20 with the subthalamic nucleus (STN) electrodes]. We recorded median nerve stimulation-evoked SEPs from the thalamus and STN with microelectrodes during stereotactic surgery and from the contacts of the DBS electrodes postoperatively. We also examined the firing of individual neurons in thalamus in relation to the VFOs. In the thalamus, VFOs with frequencies around 1,000 Hz were superimposed on slow potentials. Both slow and fast SEP components showed phase reversals in the somatosensory thalamus [ventralis caudalis (Vc)]. Median nerve poststimulus time histograms showed that single thalamic neurons fired at preferred times at intervals between 0.8 to 1.2 ms that were synchronous with the VFOs, although the neurons fired only once or a few times per trial. In the STN, low-amplitude SEPs with VFOs were observed at a latency similar to the thalamic SEPs. The VFOs from STN probably represent volume conduction, possibly from the medial lemniscus. We conclude that the thalamic VFOs are generated within Vc and that they induce time-locked firing in a network of neurons.

Adult↗

Somatosensory evoked potentials (SEPs) recorded from deep brain stimulation (DBS) electrodes in the thalamus and subthalamic nucleus (STN).

OBJECTIVE: To examine the location of deep brain stimulation (DBS) electrode somatosensory evoked potentials (SEPs) and determine the generators of the median nerve SEPs recorded in thalamus and subthalamic nucleus (STN). METHODS: SEPs were recorded from contacts of DBS electrodes and microelectrodes in thalamus and STN to establish the latencies of N13, N18 and N20 in 24 patients (8 tremor, 4 chronic pain, 12 Parkinson disease) undergoing chronic DBS. RESULTS: A large SEP with a mean latency of 17.9+/-1.7 ms was recorded from thalamic contacts. Phase reversal occurred at the horizontal level of the anterior commissure-posterior commissure line. Smaller potentials with similar latency but no reversal could be recorded from STN electrodes. CONCLUSIONS: We propose that the thalamic SEP is generated by excitatory post-synaptic potentials in sensory relay neurons in nucleus ventrocaudalis. A small potential in STN at a similar latency, may be due to volume conduction from thalamus. Intraoperative and postoperative SEP recordings from DBS electrodes could be used to determine the optimal position of the contacts relative to the sensory pathways and the choice of contacts for chronic stimulation.

Adult↗

Cingulotomy for psychiatric disease: microelectrode guidance, a callosal reference system for documenting lesion location, and clinical results.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI)- and microelectrode recording-guided cingulotomy for patients with psychiatric disorders and to develop a new method of mapping lesion location in anterior cingulate cortex that takes into account the significant interindividual variability in callosal morphometry. METHODS: MRI and microelectrode recording were used to guide placement of radiofrequency lesions in patients with obsessive-compulsive disorder (n = 21) or affective disorders (n = 5). Postoperative improvement was evaluated with the Yale-Brown Obsessive-Compulsive Scale in 15 of the 21 obsessive-compulsive disorder patients studied. From the postoperative MRI scans, we developed a coordinate system for position in the anterior cingulate cortex. The callosal line passes from the most anterior point of the corpus callosum (c = 0) to the most posterior (c = 100). We reconstructed the lesions onto a sagittal map from the Talairach and Tournoux atlas using the distance along the callosal line and the distance above the upper surface of the corpus callosum. RESULTS: The location of neuronal activity distinguished gray and white matter and was useful in delineating the upper and lower cortical banks of the cingulate gyrus, the cingulate bundle, and the corpus callosum. This information was used to place the lesions. Lesions typically were 6 to 8 mm in diameter on T2-weighted MRI scans. The inferior margins were along the corpus callosum from c = 16 to c = 38. Four of 15 patients with obsessive-compulsive disorder had a documented decrease of more than 35% on the Yale-Brown Obsessive-Compulsive Scale, but only one patient had a sustained benefit for more than 1 year. CONCLUSION: Microelectrode recording is useful for lesion placement. Our system for reporting location in anterior cingulate cortex normalizes for differences in callosal morphometry. These techniques may aid future study.

Adult↗

Neural correlates of the prolonged salience of painful stimulation.

Pain is a unique class of sensory experience from the perspective of salience. Nonpainful somatosensory stimuli usually require behavioral relevance or voluntary attention to maintain salience. In contrast, painful stimuli tend to have sustained salience even without explicit behavioral relevance or voluntary attention. We have previously identified a frontal-parietal-cingulate network of regions responding transiently to nonpainful sensory events. This network is sensitive to the task relevance and novelty of sensory events and likely represents the salience of events in the sensory environment. Since pain can remain salient for a prolonged period, we hypothesized that this network should show transient responses to the onset or offset of a nonpainful stimulus, but sustained responses throughout the duration of a painful stimulus. To test this hypothesis, we used functional MRI to examine the response of these regions to sustained (60-s) periods of painful and nonpainful transcutaneous electrical nerve stimulation. As predicted, the temporoparietal, inferior frontal, and anterior cingulate cortex showed only transient responses to the onset or offset of nonpainful stimulation, but a sustained response throughout the duration of painful stimulation. These regions therefore show tonic responses to stimuli with tonic salience, supporting a general role for these areas in representing stimulus salience. The thalamus and putamen also responded tonically throughout painful but not nonpainful stimulation. Previous studies have implicated the basal ganglia in supporting voluntary sustained attention. Our findings suggest that the basal ganglia may play a more general role in supporting sustained salience, whether through voluntary or involuntary mechanisms.

Adult↗

The effect of tactile and visual sensory inputs on phantom limb awareness.

Multiple sensory stimuli contribute to the conscious awareness of the body. It is well known that limb amputation can result in abnormal body awareness, but the manner in which the CNS constructs and updates a body schema after injury is largely unknown. The purpose of the present study was to systematically evaluate the effects of sensory inputs on phantom limb awareness (PLA) shortly after unilateral upper extremity amputation. The location, quality and intensity of spontaneous and tactile-evoked phantom sensations and awareness were assessed in 13 amputees who were referred sequentially for their initial post-operative rehabilitation. Subjects were tested in three visual conditions: (i) with their eyes open; (ii) with their eyes closed; and (iii) while they viewed their intact hand in a mirror, which created an illusion of their amputated hand (i.e. mirror visual illusion). The mirror illusion was also used to test the effect of combined visual and movement-related stimuli during active voluntary movement. Spontaneous PLA was reported by 12 of the 13 amputees and was not affected by normal visual inputs. Tactile stimulation of the residual limb or face evoked dual percepts in six amputees; i.e. these amputees perceived these touch stimuli as if they were being applied both to the stimulus site and also to a location on the missing limb. This mislocalization phenomenon was most prevalent in the eyes-closed condition. Thus, normal vision can strongly override the phantom component of touch-evoked dual percepts. In eight cases, the visual illusion of the missing limb transiently enhanced the spontaneous conscious awareness of the phantom limb. However, the visual illusion did not change the capacity of a tactile stimulus to induce dual percepts. These findings demonstrate that (i) phantom awareness of an amputated body part is common within the 14 months after traumatic upper extremity amputation, (ii) evoked dual percepts are less common than spontaneous PLA, (iii) visual, tactile and sensorimotor systems contribute to PLA, (iv) subtle changes in congruence of sensory information affects both evoked dual percepts and spontaneous PLA, however, (v) sensorimotor information pertaining to the state of the motor system can strongly influence spontaneous PLA, whereas the visual system can predominantly influence evoked PLA.

Adult↗

The relationship between rectal pain, unpleasantness, and urge to defecate in normal subjects.

Rectal stimulation under normal or pathological conditions evokes numerous sensations. Previous studies have examined rectal stimulation-evoked pain and urge to defecate, but discrepancies in the findings remain because of the different methodologies used in each study and the reporting of sensations only at the end of or after the applied stimuli. Therefore, we conducted a psychophysical study of various aspects of rectal sensation in normal subjects using a variety of distension stimuli and continuous on-line rating of sensation. Ten normal healthy subjects (eight female and two male) were given rectal distension stimuli delivered by a computer-driven barostat. For some experiments, sensation was continuously monitored and rated on a visual analog scale. Subjects first underwent an ascending series of phasic (30 s) distensions to determine how urge, unpleasantness, and pain intensity varied and interrelated as rectal volume and pressure changed. A second series of distensions examined rectal physiology and perception during short phasic (30 s) or long (300 s) distensions at pressures that elicit either moderate urge or moderate pain and while continuously rating these sensations. The McGill Pain Questionnaire was used to assess the multidimensional aspects of rectal pain with each type of distension. The results of the ascending series revealed significant relationships between sensations as pressure and volume increased. The ratings of urge were double that of pain and unpleasantness, whereas unpleasantness and pain ratings were comparable. Isobaric phasic and tonic distensions were associated with an increase in volume (i.e. accommodation) with time. The magnitude of urge with repetitive short isobaric (30 s) distensions was overall not related to the slight increase in rectal volume, while phasic distensions at moderate pain intensity revealed a significant overall relationship between rectal volume and both unpleasantness and pain intensity. Long isobaric distensions evoked sensations that varied over time despite progressive increases in volume, but less variation in sensation was observed during short phasic distensions which also demonstrated a similar increase in rectal volume. Differences in temporal characteristics of sensations evoked by low-pressure distensions eliciting moderate urge versus high-pressure distensions eliciting moderate pain were illustrated by a significantly longer delay to the diminution of non-painful urge versus pain. Therefore, we conclude (1) Differences in the discrimination and the temporal characteristics of urge at subpainful rectal pressures and of pain at noxious pressures suggest that noxious and non-noxious stimuli are processed differently. (2) The overall unpleasantness and pain correlate with rectal volume during accommodation. However, instantaneous evoked sensations can vary independent of volume changes during constant pressure distension. (3) The reported sensation-related responses to tension and stretch will likely be different depending on the degree of accommodation that is occurring. Moreover, the peripheral receptor mechanisms which contribute to controlling this accommodation will also affect the perception of rectal stimuli. (4) Continuous ratings of rectal sensations are valuable in investigating rectal physiology and the multidimensional nature of rectal symptoms.

Adult↗

Noxious cold evokes multiple sensations with distinct time courses.

A noxious cold stimulus can evoke multiple sensations each occurring with a different time course. We have performed psychophysical studies to identify the time course of five sensations evoked by a noxious cold stimulus applied to the hand. Subjects continuously rated either pain, ache, cold, heat or prickle sensations throughout repeated presentations of a noxious cold stimulus (3 degrees C) from a neutral (32 degrees C) baseline. Separate runs were used to assess each of the five types of sensation. Cold was reported throughout the period of cooling. The time course of pain and ache sensations were similar. However, prickle and heat sensations had time courses that could be distinguished from each other, and from ache and pain. Identification of these temporal profiles could provide clues to their underlying mechanisms. The temporal dissociation of these sensations will also enable neuroimaging studies of the cortical mechanisms associated with these sensations. Thus our results constitute a first step toward identifying the distinct modes of neural activity associated with different types of pain sensation.

Adult↗

A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities.

Stimulus salience depends both on behavioral context and on other factors such as novelty and frequency of occurrence. The temporo-parietal junction (TPJ) responds preferentially to behaviorally relevant stimuli and is thought to play a general role in detecting salient stimuli. If so, it should respond preferentially to novel or infrequent events, even in a neutral behavioral context. To test this hypothesis, we used event-related functional magnetic resonance imaging (fMRI) to identify brain regions sensitive to the novelty of visual, auditory, and tactile stimuli during passive observation. Cortical regions with a greater response to novel than familiar stimuli across all modalities were identified at two sites in the TPJ region: the supramarginal gyrus (SMG) and superior temporal gyrus. The right inferior frontal gyrus (IFG), right anterior insula, left anterior cingulate cortex (ACC), and left inferior temporal gyrus also showed sensitivity to novelty. The novelty-sensitive TPJ activation in SMG overlaps a region previously identified as sensitive behavioral context. This region may play a general role in identifying salient stimuli, whether the salience is due to the current behavioral context or not. The IFG activation overlaps regions previously identified as responsive to nonnovel sensory events regardless of behavioral context. The IFG may therefore play a general role in stimulus evaluation rather than a specific role in identifying novel stimuli. The ACC activation lies in a region active during complex response-selection tasks, suggesting a general role in detecting and/or planning responses to salient events. A frontal-parietal-cingulate network may serve to identify and evaluate salient sensory stimuli in general.

Acoustic Stimulation↗

An fMRI study of the anterior cingulate cortex and surrounding medial wall activations evoked by noxious cutaneous heat and cold stimuli.

The anterior cingulate cortex (ACC) and adjacent regions in the medial wall have been implicated in sensory, motor and cognitive processes, including pain. Our previous functional magnetic resonance imaging (fMRI) studies have demonstrated pain-related activation of the posterior portion of the ACC during transcutaneous electrical nerve stimulation (TENS) and variable patterns of cortical activation with innocuous and noxious thermal stimuli in individual subjects. The present study represents the companion paper to our recent study of pain- and thermal-related cortical activations with the aim to use fMRI to delineate the activations in the ACC and surrounding regions of the medial wall during application of innocuous and noxious thermal stimuli as well as during performance of a motor task in individual subjects. Ten normal subjects were imaged on a conventional 1.5 T GE 'echospeed' system. Functional images were obtained from sagittal sections through each hemisphere centered at approximately 3-5 and 7-9 mm from midline. Each subject was imaged during innocuous (cool, warm) and noxious thermal (cold, hot) stimulation of the thenar eminence, and execution of a motor (sequential finger-thumb opposition) task. Task-related activations were mostly confined to contralateral and medial ipsilateral images. Although the present results demonstrate intersubject variability in the task-related activations, some general modality-specific patterns were apparent: (i) innocuous thermal-related activations were located mainly in the anterior ACC; (ii) noxious thermal-related activations were primarily located in the anterior ACC, the ventral portion of the posterior ACC, and the supplementary motor area (SMA); (iii) motor-related activations were primarily located in the SMA and dorsal portion of the posterior ACC. These results indicate that specific spatial patterns of activation exist within the ACC and surrounding regions of the medial wall for innocuous and noxious thermal stimuli, and that noxious thermal- and motor-related activations appear to be segregated within the ACC. Therefore, we propose a segregation of the ACC into an anterior non-specific attention/arousal system and a posterior pain system.

Adult↗