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.