To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks (P<0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group (P<0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands (P<0.04) and for the warmth and TSL thresholds on the cheeks (P<0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.
Information about the future trajectory of a visual target is contained not only in the history of target motion but also in static visual cues, e.g., the street provides information about the car's future trajectory. For most natural moving targets, this information imposes strong constraints on the relation between velocity and acceleration which can be exploited by predictive smooth pursuit mechanisms. We questioned how cue-induced predictive changes in pursuit direction depend on target speed and how cue- and target-induced pursuit interact. Subjects pursued a target entering a +/-90 degrees curve and moving on either a homogeneous background or on a low contrast static band indicating the future trajectory. The cue induced a predictive change of pursuit direction, which occurred before curve onset of the target. The predictive velocity component orthogonal to the initial pursuit direction started later and became faster with increasing target velocity. The predictive eye acceleration increased quadratically with target velocity and was independent of the initial target direction. After curve onset, cue- and target-induced pursuit velocity components were not linearly superimposed. The quadratic increase of eye acceleration with target velocity is consistent with the natural velocity scaling implied by the two-thirds power law, which is a characteristic of biological controlled movements. Comparison with linear pursuit models reveals that the ratio between eye acceleration and actual or expected retinal slip cannot be considered a constant gain factor. To obey a natural velocity scaling, this acceleration gain must linearly increase with target or pursuit velocity. We suggest that gain control mechanisms, which affect target-induced changes of pursuit velocity, act similarly on predictive changes of pursuit induced by static visual cues.
To determine if patients with Parkinson's disease (PD) are able to use a visual contextual cue to induce a predictive change in smooth pursuit direction and if this ability depends on the state of the dopaminergic system, we measured predictive smooth pursuit in nine patients with mild to moderate PD during OFF and ON medication. These values were compared with those of nine age-matched and sex-matched healthy controls.Our focus was on the horizontal smooth pursuit when subjects pursued a downward moving target entering a+/-90 deg curve. The target moved on a homogeneous background or on a static "street" that indicated the future trajectory of the target. Our main result is that PD patients were impaired in eliciting predictive smooth pursuit using the context information of the street compared to healthy subjects. The control group elicited predictive pursuit 250 ms before target onset. In contrast, PD patients showed significantly longer latency (100-120 ms) and reduced maximal pursuit velocity. However, without the street guiding pursuit, a delay of about 250 ms was seen in both groups. There was no significant difference in the smooth pursuit performance between OFF and ON medication in the patient group.These results show that early stage PD patients are impaired in the use of static visual information as a cue for predictive pursuit compared to controls and that this deficit does not depend on dopaminergic medication. In the context of predictive eye movement, the involvement of the striatal-frontal pathway and the spatial working memory is discussed.
Stimulating the skin with intensities close to the sensory threshold causes erroneous localization of the site of stimulation. Previous studies using manual methods for applying faint tactile stimuli have shown that localization errors obey a somatotopic principle in which tactile stimuli are preferentially mislocalized to sites adjacent to the stimulated skin region. However, manual testing of mislocalization is time consuming and only partially objective because results depend on the skills of the tester. To improve the testing procedure, an automated apparatus was developed. The procedure adjusted stimulus intensity adaptively during testing to remain near the individual subject's sensory threshold, so that mislocalizations occurred often enough to assess somatotopic organization. The new method was applied to 12 healthy subjects. In each subject, the five digits of the right hand were stimulated singly in random order. Localization errors were distributed preferentially to fingers close to the stimulated finger rather than to distant fingers. The profile of mislocalization differed significantly from that expected on the basis of response bias or guessing behavior. The present results replicate previous findings obtained for manual testing with improved sensitivity and indicate that the new technique is a useful tool for the study of somatosensory processing on a perceptual level.
Anticipatory pursuit is not exclusively based on the recent history of target motion ("temporal anticipation"): it can also use static visual cues ("non-temporal anticipation"). Large non-temporal anticipatory changes of the direction of smooth pursuit are observed when the future trajectory of the target can be inferred from a visual "path cue" (Ladda et al. Exp Brain Res 182:343-356, 2007). It is not known whether these anticipatory responses can be considered an example of volitional pursuit or whether a more automatic, fast mechanism exists that associates the visual shape of the path cue with a future change of target motion. We therefore compared anticipatory direction changes induced by path cues with those induced by more symbolic visual cues. Further, we measured the processing time of path cues by keeping them ambiguous until 300 ms before the target entered the curve. The cues became unambiguous either when a missing part of the path cue suddenly appeared or when a misleading (invalid) path cue disappeared. Five main results suggest that the non-temporal smooth pursuit anticipation induced by path cues is due to a particular visual processing of the cue, rather than to a general volitional smooth pursuit component: (1) A curved static band providing detailed spatial information about the target's trajectory was much more efficient than more symbolic visual cues. (2) The latency for processing the path cue was less than 200 ms. (3) The effect of the path cue did not depend on a visual transient in the retinal periphery. (4) It critically depended on the spatial relation between path cue and target trajectory. (5) The anticipatory response decreased, but was still highly significant when the path cue was non-informative with respect to the future target trajectory. These findings indicate that anticipatory modifications of ongoing pursuit do not rely exclusively on the processing of motion signals, but can directly interact with low-level processes analyzing background structures.
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