The role of the inferior parietal lobule in writer's cramp.

Humans have a distinguishing ability for fine motor control that is subserved by a highly evolved cortico-motor neuronal network. The acquisition of a particular motor skill involves a long series of practice movements, trial and error, adjustment and refinement. At the cortical level, this acquisition begins in the parieto-temporal sensory regions and is subsequently consolidated and stratified in the premotor-motor cortex. Task-specific dystonia can be viewed as a corruption or loss of motor control confined to a single motor skill. Using a multimodal experimental approach combining neuroimaging and non-invasive brain stimulation, we explored interactions between the principal nodes of the fine motor control network in patients with writer's cramp and healthy matched controls. Patients and healthy volunteers underwent clinical assessment, diffusion-weighted MRI for tractography, and functional MRI during a finger tapping task. Activation maps from the task-functional MRI scans were used for target selection and neuro-navigation of the transcranial magnetic stimulation. Single- and double-pulse TMS evaluation included measurement of the input-output recruitment curve, cortical silent period, and amplitude of the motor evoked potentials conditioned by cortico-cortical interactions between premotor ventral (PMv)-motor cortex (M1), anterior inferior parietal lobule (aIPL)-M1, and dorsal inferior parietal lobule (dIPL)-M1 before and after inducing a long term depression-like plastic change to dIPL node with continuous theta-burst transcranial magnetic stimulation in a randomized, sham-controlled design. Baseline dIPL-M1 and aIPL-M1 cortico-cortical interactions were facilitatory and inhibitory, respectively, in healthy volunteers, whereas the interactions were converse and significantly different in writer's cramp. Baseline PMv-M1 interactions were inhibitory and similar between the groups. The dIPL-PMv resting state functional connectivity was increased in patients compared to controls, but no differences in structural connectivity between the nodes were observed. Cortical silent period was significantly prolonged in writer's cramp. Making a long term depression-like plastic change to dIPL node transformed the aIPL-M1 interaction to inhibitory (similar to healthy volunteers) and cancelled the PMv-M1 inhibition only in the writer's cramp group. These findings suggest that the parietal multimodal sensory association region could have an aberrant downstream influence on the fine motor control network in writer's cramp, which could be artificially restored to its normal function.

Effect of environment on the long-term consequences of chronic pain.

Much evidence from pain patients and animal models shows that chronic pain does not exist in a vacuum but has varied comorbidities and far-reaching consequences. Patients with long-term pain often develop anxiety and depression and can manifest changes in cognitive functioning, particularly with working memory. Longitudinal studies in rodent models also show the development of anxiety-like behavior and cognitive changes weeks to months after an injury causing long-term pain. Brain imaging studies in pain patients and rodent models find that chronic pain is associated with anatomical and functional alterations in the brain. Nevertheless, studies in humans reveal that lifestyle choices, such as the practice of meditation or yoga, can reduce pain perception and have the opposite effect on the brain as does chronic pain. In rodent models, studies show that physical activity and a socially enriched environment reduce pain behavior and normalize brain function. Together, these studies suggest that the burden of chronic pain can be reduced by nonpharmacological interventions.

Increased gray matter density in young women with chronic vulvar pain.

Provoked vestibulodynia (PVD) is a common form of chronic vulvar pain with unknown aetiology. Central pain regulatory mechanisms have been suggested to be disrupted in PVD, and consequently, PVD may be associated with anatomical changes in pain modulatory brain areas. Here, we compared total gray matter volumes and regional gray matter densities between 14 medication-free young women with relatively short-standing PVD (1 to 9 yrs) and 14 control subjects using whole brain voxel-based morphometry (VBM). VBM revealed that PVD subjects had significantly higher gray matter densities in pain modulatory and stress-related areas, i.e. the parahippocampal gyrus/hippocampus and basal ganglia (globus pallidus, caudate nucleus, and substantia nigra). In several of these regions, gray matter was related to clinical symptoms, namely lowered pain thresholds and increased pain catastrophizing scores. No region showed decreased gray matter density in the PVD group. These results point at the morphological alterations in supra-spinal pain modulatory circuitry, which might contribute to the clinical symptoms of patients with PVD. Previous VBM studies in older subjects with a longstanding chronic pain condition have demonstrated gray matter decreases in similar areas. We therefore speculate that gray matter density might increase in young pain patients with short disease duration and decrease in older subjects with longstanding disease, similarly to some psychiatric conditions, in which bi-directional changes of gray matter have been observed.

Feelings of warmth correlate with neural activity in right anterior insular cortex.

The neural coding of perception can differ from that for the physical attributes of a stimulus. Recent studies suggest that activity in right anterior insular cortex may underlie thermal perception, particularly that of cold. We now examine whether this region is also important for the perception of warmth. We applied cutaneous warm stimuli on the left leg (warmth) in normal subjects (n = 7) during functional magnetic resonance imaging (fMRI). After each stimulus, subjects rated their subjective intensity of the stimulus using a visual analogue scale (VAS), and correlations were determined between the fMRI signal and the VAS ratings. We found that intensity ratings of warmth correlated with the fMRI signal in the right (contralateral to stimulation) anterior insular cortex. These results, in conjunction with previous reports, suggest that the right anterior insular cortex is important for different types of thermal perception.

Tactile functions after cerebral hemispherectomy.

Patients that were hemispherectomized due to brain lesions early in life sometimes have remarkably well-preserved tactile functions on their paretic body half. This has been attributed to developmental neuroplasticity. However, the tactile examinations generally have been fairly crude, and subtle deficits may not have been revealed. We investigated monofilament detection and three types of tactile directional sensibility in four hemispherectomized patients and six healthy controls. Patients were examined bilaterally on the face, forearm and lower leg. Normal subjects were examined unilaterally. Following each test of directional sensibility, subjects were asked to rate the intensity of the stimulation. On the nonparetic side, results were almost always in the normal range. On the paretic side, the patients' capacity for monofilament detection was less impaired than their directional sensibility. Despite the disturbed directional sensibility on their paretic side the patients rated tactile sensations evoked by the stimuli, on both their paretic and nonparetic body halves, as more intense than normals. Thus, mechanisms of plasticity seem adequate for tactile detection and intensity coding but not for more complex tactile functions such as directional sensibility. The reason for the high vulnerability of tactile directional sensibility may be that it depends on spatially and temporally precise afferent information processed in a distributed cortical network.

Unmyelinated tactile afferents signal touch and project to insular cortex.

There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.

Central pain in a hemispherectomized patient.

We have examined a hemispherectomized patient who complained of touch-evoked pricking and burning pain in her paretic hand, especially when the hand was cold. Psychophysical examination showed that for the paretic side she confused cool and warm temperatures, and confirmed that she had a robust allodynia to brush stroking that was enhanced at a cold ambient temperature. Functional magnetic resonance imaging (fMRI) showed that during brush-evoked allodynia, brain structures implicated in normal pain processing (viz. posterior part of the anterior cingulate cortex, secondary somatosensory cortex, and prefrontal cortices) were activated. The fMRI findings thus indicate that the central pain in this patient was served by brain structures implicated in normal pain processing. Possible pathophysiological mechanisms include plasticity as well as thalamic disinhibition.

Cortical representation of the sensory dimension of pain.

It is well accepted that pain is a multidimensional experience, but little is known of how the brain represents these dimensions. We used positron emission tomography (PET) to indirectly measure pain-evoked cerebral activity before and after hypnotic suggestions were given to modulate the perceived intensity of a painful stimulus. These techniques were similar to those of a previous study in which we gave suggestions to modulate the perceived unpleasantness of a noxious stimulus. Ten volunteers were scanned while tonic warm and noxious heat stimuli were presented to the hand during four experimental conditions: alert control, hypnosis control, hypnotic suggestions for increased-pain intensity and hypnotic suggestions for decreased-pain intensity. As shown in previous brain imaging studies, noxious thermal stimuli presented during the alert and hypnosis-control conditions reliably activated contralateral structures, including primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate cortex, and insular cortex. Hypnotic modulation of the intensity of the pain sensation led to significant changes in pain-evoked activity within S1 in contrast to our previous study in which specific modulation of pain unpleasantness (affect), independent of pain intensity, produced specific changes within the ACC. This double dissociation of cortical modulation indicates a relative specialization of the sensory and the classical limbic cortical areas in the processing of the sensory and affective dimensions of pain.

Cortical activation by tactile and painful stimuli in hemispherectomized patients.

Hemispherectomized patients are able to perceive tactile and painful stimuli on their nonparetic as well as paretic body halves. We have used functional MRI to study the cortical mechanisms underlying this preserved somatosensory capacity. Nonpainful brushing and painful heat were applied to the skin of the legs in four hemispherectomized patients and, for comparison, in four normal subjects. Cortical activation was studied with a 1.5 T scanner using a BOLD (blood oxygen level dependent) protocol. All patients rated both the brushing and the heat pain as almost equally intense on each leg and the ratings were similar to those in normals. Brushing on the nonparetic leg activated primary and secondary somatosensory cortices (S1 and S2) in all patients, similar to findings in normals. Brushing on the paretic leg activated S1 in two patients and S2 in one of these patients. Heat pain activated S2, insular cortex and anterior cingulate cortex to a similar degree for both legs, but the activation was weaker in the patients than in the normals. For the individual patient, there was generally no obvious correlation between cortical activation as studied with the BOLD technique and psychophysical performance. The findings from tactile stimulation of the nonparetic leg, that the activation was similar to the contralateral activation in normals, suggest that tactile information processing in the hemisphere contralateral to the stimulation is independent of the corpus callosum. In contrast, the pain activation for the nonparetic leg was weaker than in normals, suggesting that pain activation in the hemisphere contralateral to the stimulation is dependent on transcallosal information processing. The latter finding was corroborated by a subnormal capacity for pain localization on the nonparetic foot in two of the patients. The findings from stimulation of the paretic leg show that areas typically involved in the processing of tactile and painful stimuli can be activated by ipsilateral pathways directly from the periphery. The tactile-evoked ipsilateral S1 activation may be due to subcortical reorganization, since it was not observed in the normal subjects.

Propofol anesthesia and cerebral blood flow changes elicited by vibrotactile stimulation: a positron emission tomography study.

We investigated the effects of the general anesthetic agent propofol on cerebral structures involved in the processing of vibrotactile information. Using positron emission tomography (PET) and the H(2)(15)O bolus technique, we measured regional distribution of cerebral blood flow (CBF) in eight healthy human volunteers. They were scanned under five different levels of propofol anesthesia. Using a computer-controlled infusion, the following plasma levels of propofol were targeted: Level W (Waking, 0 microg/ml), Level 1 (0.5 microg/ml), Level 2 (1.5 microg/ml), Level 3 (3.5 microg/ml), and Level R (Recovery). At each level of anesthesia, two 3-min scans were acquired with vibrotactile stimulation of the right forearm either on or off. The level of consciousness was evaluated before each scan by the response of the subject to a verbal command. At Level W, all volunteers were fully awake. They reported being slightly drowsy at Level 1, they had a slurred speech and slow response at Level 2, and they were not responding at all at Level 3. The following variations in regional CBF (rCBF) were observed. During the waking state (Level W), vibrotactile stimulation induced a significant rCBF increase in the left thalamus and in several cortical regions, including the left primary somatosensory cortex and the left and right secondary somatosensory cortex. During anesthesia, propofol reduced in a dose-dependent manner rCBF in the thalamus as well as in a number of visual, parietal, and prefrontal cortical regions. At Level 1 through 3, propofol also suppressed vibration-induced increases in rCBF in the primary and secondary somatosensory cortex, whereas the thalamic rCBF response was abolished only at Level 3, when volunteers lost consciousness. We conclude that propofol interferes with the processing of vibrotactile information first at the level of the cortex before attenuating its transfer through the thalamus.

Representation of acute and persistent pain in the human CNS: potential implications for chemical intolerance.

The study of pain may be relevant to the study of chemical intolerance (CI) in many ways. Pain is often reported as a symptom of CI and it is defined as a subjective experience similar to many other symptoms of CI, making its objectification difficult. Furthermore, the CNS plastic changes that underlie the development of persistent pain states and abnormal pain responses may share some similarities with those involved in the sensitization to environmental chemicals. Functional brain imaging studies in humans demonstrate that acute pain evoked by nociceptive stimulation is accompanied by the activation of a widely distributed network of cerebral structures, including the thalamus and the somatosensory, insular, and anterior cingulate cortices. Abnormal activity within these regions has been associated with the experience of pain following damage to the peripheral or central nervous system (neuropathic pain) in a number of clinical populations. In normal individuals, activity within this network is correlated with subjective pain perception, is highly modifiable by cognitive interventions such as hypnosis and attention, and has been associated with emotions. Other cognitive mediators such as expectations can also produce robust changes in pain perception (e.g., in placebo analgesia). These effects likely depend on both higher-order cerebral structures and descending mechanisms modulating spinal nociceptive activity. These psychological processes can be solicited to reduce clinical pain and we speculate that they may further attenuate or promote central mechanisms involved in the transition from acute to persistent pain states. The investigation of central determinants of subjective experience is essential to assess the possibility that higher-order brain/psychological processes modulate and/or mediate the development of persistent pain states. These factors may contribute to the development of symptoms in CI.

Effect of ambient temperature on human pain and temperature perception.

BACKGROUND: Animal studies show reduced nociceptive responses to noxious heat stimuli and increases in endogenous beta-endorphin levels in cold environments, suggesting that human pain perception may be dependent on ambient temperature. However, studies of changes in local skin temperature on human pain perception have yielded variable results. This study examines the effect of both warm and cool ambient temperature on the perception of noxious and innocuous mechanical and thermal stimuli. METHODS: Ten subjects (7 men and 3 women, aged 20-23 yr) used visual analog scales to rate the stimulus intensity, pain intensity, and unpleasantness of thermal (0-50 degrees C) and mechanical (1.2-28.9 g) stimuli applied on the volar forearm with a 1-cm2 contact thermode and von Frey filaments, respectively. Mean skin temperatures were measured throughout the experiment by infrared pyrometer. Each subject was tested in ambient temperatures of 15 degrees C (cool), 25 degrees C (neutral), and 35 degrees C (warm) on separate days, after a 30-min acclimation to the environment. Studies began in the morning after an 8-h fast. RESULTS: Mean skin temperature was altered by ambient temperature (cool room: 30.1 degrees C; neutral room: 33.4 degrees C; warm room: 34.5 degrees C; P < 0.0001). Ambient temperature affected both heat (44-50 degrees C) and cold (25-0 degrees C) perception (P < 0.01). Stimulus intensity ratings tended to be lower in the cool than in the neutral environment (P < 0.07) but were not different between the neutral and warm environments. Unpleasantness ratings revealed that cold stimuli were more unpleasant than hot stimuli in the cool room and that noxious heat stimuli were more unpleasant in a warm environment. Environmental temperature did not alter ratings of warm (37 and 40 degrees C) or mechanical stimuli. CONCLUSIONS: These results indicate that, in humans, a decrease in skin temperature following exposure to cool environments reduces thermal pain. Suppression of Adelta primary afferent cold fiber activity has been shown to increase cold pain produced by skin cooling. Our current findings may represent the reverse phenomenon, i.e., a reduction in thermal nociceptive transmission by the activation of Adelta cutaneous cold fibers.

Pain perception: is there a role for primary somatosensory cortex?

Anatomical, physiological, and lesion data implicate multiple cortical regions in the complex experience of pain. These regions include primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and regions of the frontal cortex. Nevertheless, the role of different cortical areas in pain processing is controversial, particularly that of primary somatosensory cortex (S1). Human brain-imaging studies do not consistently reveal pain-related activation of S1, and older studies of cortical lesions and cortical stimulation in humans did not uncover a clear role of S1 in the pain experience. Whereas studies from a number of laboratories show that S1 is activated during the presentation of noxious stimuli as well as in association with some pathological pain states, others do not report such activation. Several factors may contribute to the different results among studies. First, we have evidence demonstrating that S1 activation is highly modulated by cognitive factors that alter pain perception, including attention and previous experience. Second, the precise somatotopic organization of S1 may lead to small focal activations, which are degraded by sulcal anatomical variability when averaging data across subjects. Third, the probable mixed excitatory and inhibitory effects of nociceptive input to S1 could be disparately represented in different experimental paradigms. Finally, statistical considerations are important in interpreting negative findings in S1. We conclude that, when these factors are taken into account, the bulk of the evidence now strongly supports a prominent and highly modulated role for S1 cortex in the sensory aspects of pain, including localization and discrimination of pain intensity.

Psychophysical study of noxious and innocuous cold discrimination in monkey.

Psychophysical evidence shows that humans are better able to distinguish differences in the intensity of cutaneous temperature in the cool range than in the noxious cold range. In order to compare these human perceptual findings with physiological data from non-human primates, we performed similar psychophysical experiments of cold perception in monkeys. Two adult male rhesus monkeys were trained to detect cooling shifts from baseline temperatures between 0 degrees and 22 degrees C applied to the face with a 1-cm2 contact thermode. Detection thresholds were determined using the method of constant stimuli for one monkey and an adaptive psychophysical algorithm which insured constant behavioral performance for the other monkey. Results showed that both monkeys detected significantly smaller temperature decreases from innocuous cool baselines (i.e., 22 degrees and 16 degrees C) than from noxious and near-noxious baselines (10 degrees, 6 degrees, 0 degrees C). Similarly, the latencies for detecting the cooling shifts were shorter and less variable in the innocuous cool range than in the noxious cold range. The observation of more precise discrimination of innocuous cool than noxious cold temperatures in monkeys is consistent with human psychophysical data. Thus, these data suggest that differential patterns of neuronal activity evoked by cool and noxious cold cutaneous stimuli, observed in peripheral afferents as well as in the central nervous system of monkey and cat, probably also exist in the human.

Cerebral mechanisms of hypnotic induction and suggestion.

The neural mechanisms underlying hypnotic states and responses to hypnotic suggestions remain largely unknown and, to date, have been studied only with indirect methods. Here, the effects of hypnosis and suggestions to alter pain perception were investigated in hypnotizable subjects by using positron emission tomography (PET) measures of regional cerebral blood flow (rCBF) and electroencephalographic (EEG) measures of brain electrical activity. The experimental conditions included a restful state (Baseline) followed by hypnotic relaxation alone (Hypnosis) and by hypnotic relaxation with suggestions for altered pain unpleasantness (Hypnosis-with-Suggestion). During each scan, the left hand was immersed in neutral (35 degree C) or painfully hot (47 degrees C) water in the first two conditions and in painfully hot water in the last condition. Hypnosis was accompanied by significant increases in both occipital rCBF and delta EEG activity, which were highly correlated with each other (r = 0.70, p < 0.0001). Peak increases in rCBF were also observed in the caudal part of the right anterior cingulate sulcus and bilaterally in the inferior frontal gyri. Hypnosis-related decreases in rCBF were found in the right inferior parietal lobule, the left precuneus, and the posterior cingulate gyrus. Hypnosis-with-suggestions produced additional widespread increases in rCBF in the frontal cortices predominantly on the left side. Moreover, the medial and lateral posterior parietal cortices showed suggestion-related increases overlapping partly with regions of hypnosis-related decreases. Results support a state theory of hypnosis in which occipital increases in rCBF and delta activity reflect the alteration of consciousness associated with decreased arousal and possible facilitation of visual imagery. Frontal increases in rCBF associated with suggestions for altered perception might reflect the verbal mediation of the suggestions, working memory, and top-down processes involved in the reinterpretation of the perceptual experience. These results provide a new description of the neurobiological basis of hypnosis, demonstrating specific patterns of cerebral activation associated with the hypnotic state and with the processing of hypnotic suggestions.

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography.

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.

Pain affect encoded in human anterior cingulate but not somatosensory cortex.

Recent evidence demonstrating multiple regions of human cerebral cortex activated by pain has prompted speculation about their individual contributions to this complex experience. To differentiate cortical areas involved in pain affect, hypnotic suggestions were used to alter selectively the unpleasantness of noxious stimuli, without changing the perceived intensity. Positron emission tomography revealed significant changes in pain-evoked activity within anterior cingulate cortex, consistent with the encoding of perceived unpleasantness, whereas primary somatosensory cortex activation was unaltered. These findings provide direct experimental evidence in humans linking frontal-lobe limbic activity with pain affect, as originally suggested by early clinical lesion studies.

A model of transient hyperalgesia in the behaving monkey induced by topical application of capsaicin.

The aim of this study was to develop a model of transient hyperalgesia in the awake monkey performing operant tasks. An adult male rhesus monkey was trained to press a lever to receive food reward for detecting a light or to escape mechanical or thermal stimuli applied in the maxillary region of the face. A small contact thermode was positioned on one side of the face and a mechanical stimulator was placed on the other side. Noxious and innocuous thermal (43, 47 and 51 degrees C) or mechanical (245, 490, 736 and 1472 mN) stimuli of 4.5-s duration were presented in a pseudo-random order. The animal was tested before, 1 h and 24 h after topical capsaicin application (0.3 ml; 0.004 M). At the site of capsaicin application, the monkey escaped more thermal and mechanical stimuli 1 h after than before capsaicin, suggestive of thermal and mechanical hyperalgesia. At 24 h post-capsaicin, mechanical escape behavior had returned to baseline, but thermal escapes were still slightly elevated. Capsaicin had no significant effect on either mechanical or thermal escape behavior for stimuli presented to the contralateral site. Seven human subjects tested with these procedures reported higher pain intensity for similar stimuli after capsaicin application, in accordance with the monkey escape behavior. It is concluded that topical application of capsaicin on the maxillary face of the awake behaving monkey produces a transient thermal and mechanical hyperalgesia. The procedure is repeatable and produces no overt signs of distress. Thus it could provide an important tool for studying neural mechanisms of hyperalgesia and for testing analgesic treatments in primates.

Functional imaging of an illusion of pain.

Touching warm and cool bars that are spatially interlaced produces a painful burning sensation resembling that caused by intense, noxious cold. We demonstrated previously that this thermal grill illusion can be explained as an unmasking phenomenon that reveals the central inhibition of pain by thermosensory integration. In order to localize this unmasking in the human brain, we have used positron emission tomography (PET) to compare the cortical activation patterns evoked by the thermal grill and by cool, warm, noxious cold and noxious heat stimuli. The thermal grill illusion produces activation in the anterior cingulate cortex, whereas its component warm and cool stimuli do not. This area is also activated by noxious heat or cold. Thus, increased activity in the anterior cingulate cortex appears to be selectively associated with the perception of thermal pain. Disruption of thermosensory and pain integration may account for the central pain syndrome that can occur after stroke damage.

Evaluation of pain perception after anterior capsulotomy: a case report.

The medial prefrontal cortex has been implicated in pain perception by recent anatomical, physiological, and functional imaging data demonstrating that frontal and anterior cingulate cortices receive inputs related to nociception; neurosurgical case reports suggest that lesions involving these areas may specifically reduce the affective or emotional component of chronic intractable pain. We examined this hypothesis more closely by assessing psychophysical ratings of (1) warmth, pain intensity, and unpleasantness evoked by phasic thermal stimuli, (2) tolerance to tonic cold stimuli, and (3) perceived intensity of visual stimuli, both before and after neurosurgical lesions of the fiber tracts connecting the frontal lobes to subcortical structures. A 22-year-old male, with no history of chronic pain, underwent psychophysical testing 3 days before, 5 days after, and 6 months after receiving bilateral lesions of the anterior internal capsule (aIC), performed as treatment for obsessive-compulsive disorder. In each session, the patient rated the intensity and unpleasantness of 5-sec cutaneous heat stimuli (39-47 degrees C); pain tolerance was measured by means of a cold-pressor test (hand immersion in 1 degrees C water). The patient was able to differentially rate the intensities of heat stimuli during both pre- and postsurgical testing sessions (p < 0.001). However, he rated heat stimuli as less intense 5 days after surgery than during presurgical testing (p < 0.001), with significant decreases in both pain intensity (p < 0.005) and unpleasantness (p < 0.05). Likewise, the patient described the cold-water immersion as less painful following surgery, although his tolerance times were substantially shorter than those of the presurgical evaluation. Ratings of visual stimulus intensity did not differ across the pre- and postsurgical testing periods, suggesting that changes in pain perception were not related to attentional or cognitive deficits. Magnetic resonance imaging 5 days following surgery revealed bilateral lesions and edema centered in the aIC, with some edema in the left frontal lobe. Those 6 months later showed substantially smaller lesions involving less than half of the aIC and no edema; pain ratings and cold-water tolerance measured at that time indicated a substantial return toward the patient's presurgical values. These data suggest that blocking subcortical input to the anterior cingulate and frontal cortices reduces both the perceived intensity and the unpleasantness of noxious stimuli; reduced cold tolerance times--in the face of decreased pain perception--may reflect a disinhibition of cortical control on spinal reflexes.(ABSTRACT TRUNCATED AT 400 WORDS)