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PubMed2005

Multimodal pain stimulations in patients with grade B oesophagitis.

AIM: To obtain a better understanding of nociceptive processing in patients with oesophagitis. PATIENTS AND METHODS: Eleven patients with grade B oesophagitis were compared with an age and sex matched group of 16 healthy subjects. A probe was positioned in the lower part of the oesophagus. After preconditioning of the tissue, painful mechanical stimuli were applied as distensions with a bag using an impedance planimetric method. Distensions were done before and after pharmacological impairment of distension induced smooth muscle contractions. Thermal stimulation was performed by recirculating water at 1 and 60 degrees C in the bag. The area under the temperature curve (AUC) represented caloric load. The referred pain area (being a proxy for the central pain mechanisms) to the mechanical stimuli was drawn at maximum pain intensities. RESULTS: Patients were hyposensitive to mechanical stimuli, as assessed by the distending volume (F=8.1, p=0.005). After relaxation of smooth muscle with butylscopolamine, the difference between the two groups was more evident (F=27.4, p<0.001). AUC for cold stimulation was 1048.6 (242.7) degrees Cxs in controls and 889.8 (202.6) degrees Cxs in patients (p=0.5). For heat stimuli, AUC values were 323.3 (104.1) and 81.3 (32.3) degrees Cxs in controls and patients, respectively (p=0.04). The referred pain area to the mechanical stimulations was larger and more widespread in patients (49.3 (6.2) cm2 compared with controls 23.9 (7) cm2; p=0.02). CONCLUSIONS: The data indicate that peripheral sensitisation of heat sensitive receptors and pathways combined with facilitation of central pain mechanisms may explain the symptoms in patients with oesophagitis.

Adult↗

PubMed1992

Infants' responsiveness to the auditory and visual attributes of a sounding/moving stimulus.

Responses to unimodal and multimodal attributes of a compound auditory/visual stimulus were investigated in 4-, 6-, 8-, and 10-month-old infants. First, infants were habituated to a compound stimulus consisting of a visual stimulus that moved up and down on a video monitor and a sound that occurred each time the visual stimulus reversed direction at the bottom. Once each infant met a habituation criterion, a series of test trials was administered to assess responsiveness to the components of the compound stimulus. Response was defined as the total duration of visual fixation in each trial. In the two unimodal test trials, the rate at which the component was presented was changed while the rate of the other component remained the same, whereas in the bimodal test trial the rate of both components was changed simultaneously. Results indicated that infants at each age successfully discriminated the bimodal and the two unimodal changes and that regression to the mean did not account for the results. Results also showed that disruption of the temporal relationship that accompanied the change in rate in the two unimodal test trials was also discriminable, but rate changes appeared to play a greater role in responsiveness than did synchrony changes. Considered together with results from similar prior studies, the current results are consistent with the modality appropriateness hypothesis in showing that discrimination of temporal changes in the auditory and visual modalities is dependent on the specialization of the sensory modalities.

Arousal↗

PubMed1998

Gustatory and multimodal neuronal responses in the amygdala during licking and discrimination of sensory stimuli in awake rats.

The amygdala (AM) receives information from various sensory modalities via the neocortex and directly from the thalamus and brain stem and plays an important role in ingestive behaviors. In the present study, neuronal activity was recorded in the AM and amygdalostriatal transition area of rats during discrimination of conditioned sensory stimuli and ingestion of sapid solutions. Of the 420 responsive neurons, 227 responded exclusively to one sensory modality, 120 responded to two or more modalities, and the remaining 73 could not be classified. Among the responsive neurons, 108 responded to oral-sensory stimulation (oral-sensory neurons). In detailed analyses of 84 of these oral-sensory neurons, 24 were classified as taste responsive and were located mainly in the central nucleus of the AM. The other 60 oral-sensory neurons were classified as nontaste oral-sensory neurons and were distributed widely throughout the AM. Both the taste and nontaste oral-sensory neurons also responded to other sensory stimuli. Of the 24 taste neurons, 21 were tested at least with four standard taste solutions. On the basis of the magnitudes of their responses to these sapid stimuli, the taste neurons were classified as follows: seven sucrose-best, four NaCl-best, three citric acid-best, and six quinine HCl-best. The remaining cell responded significantly only to lysine HCl and monosodium glutamate. Multivariate analyses of these 21 taste neurons suggested that, in the AM, taste quality was processed based on palatability. Taken with previous lesion studies, the present results suggest that the AM plays a role in the evaluation of taste palatability and in the association of taste stimuli with other sensory stimuli.

Acoustic Stimulation↗

PubMed2002

Communicating about sexuality: an initiative across the core clerkships.

OBJECTIVES: Recently there has been a renewed interest in teaching communication skills in U.S. medical schools. Yet a large number of physicians and medical students may be uncomfortable discussing matters of sexuality with their patients. We have developed a comprehensive, cross-clerkship curriculum for third-year medical students that strives to fill the educational gap concerning a variety of topics in sexuality. The objectives of this project are (1) to increase awareness among medical students that communication about sexuality is central to comprehensive health care; (2) to train faculty to teach students the knowledge, skills and attitudes necessary for communicating effectively with patients about issues of sexuality; and (3) to improve the level of student comfort in discussing sexual issues. DESCRIPTION: With support from the Josiah Macy, Jr. Foundation (part of the UMass Macy Initiative in Health Communication), and in consultation with clerkship directors, specific topics in sexuality were chosen for inclusion in four clerkships: internal medicine, family medicine, pediatrics, and psychiatry. The family medicine clerkship incorporated a fictional female adolescent into their case-based "standardized family." Faculty were trained to lead their small groups in a discussion of the potentially wide range of sexual behavior in this case study. Supplemental readings were provided and a PDA application is being developed. During the internal medicine clerkship a "difficult interview" session was held. Student volunteers interviewed three standardized patients with sexual issues: a sexually active young woman desiring contraception, a homosexual young man at risk for HIV, and a heterosexual male noncompliant with blood pressure medication due to sexual dysfunction. An HIV counselor was brought in as a discussant. The pediatric clerkship utilized a multimodal format to cover topics pertaining to gay and lesbian youth. Included were a didactic presentation, a videotaped panel discussion featuring two youths and a parent, and a modeled patient interview. The psychiatry clerkship included three relevant interventions: a didactic session around the topic of medication-related sexual dysfunction; a videotaped modeled interview of a sexually traumatized woman; and a session involving a standardized patient-a lesbian whose sexual orientation was not part of her psychopathology. Adjunct activities included a cross-clerkship faculty development session, evaluation components, and a module designed for the staff of a private office. The latter was piloted in the office of a community pediatrician. DISCUSSION: Medical students who experienced the curriculum found it valuable. Student self-evaluations, done at the end of each clerkship, indicate increased comfort in dealing with issues of sexuality. During the pediatric clerkships only, half the students received the curriculum while the other half served as a comparison group. The intervention group showed a slight decrease in homophobic attitudes; the lack of a larger effect is likely due to a high level of baseline acceptance and comfort around issues of sexual orientation in this particular medical school class. The pediatric segment will be modified to take this into account and present more advanced topics around sexual orientation and interviewing. The entire curriculum is being incorporated into ongoing clerkships using existing resources at the medical school.

Clinical Clerkship↗

PubMed1995

Failure to update the egocentric representation of the visual space through labyrinthine signal.

The present study evaluated the capacity to compare retinal and vestibular signals in a heterosensorial matching task. In the first experiment, subjects evaluated the magnitude of passive whole-body rotations in relation to the eccentricity of a visual target briefly presented before rotation. Such a task elicits multimodal sensory stimulations experienced by a subject during normal goal-oriented head movements, i.e., retinal and vestibular stimulations. A good capacity to evaluate vestibular signals in relation with retinal inputs might suggest that the labyrinthine output is part of a cognitive feedback-loop controlling active head movements oriented toward a visual target and/or that the labyrinthine signal might make a major contribution to judging the position of the target in space after goal-directed head movements. Results showed that body rotation magnitudes had to exceed the amplitude of the visual target by about 120 and 89% to be perceived as having a similar magnitude to a 10 degree and an 18 degree visual target, respectively. A second experiment was designed to test whether this major discrepancy originated either from (a) an overestimation of the peripheral visual target locations, (b) an underestimation of the labyrinthine signal, (c) a deficiency in matching sensory signals from different modalities, or (d) any combination of (a), (b), and (c). In the second experiment, the actual perception of retinal and labyrinthine signals, as indicated by verbal responses, was quantified. Results from this experiment showed that most of the large underestimation of the vestibular stimulation found in Experiment I ought to emerge from a poor capacity to integrate heterogeneous sensory signals by the perceptual system rather than from pure misperception of the retinal and/or labyrinthine signals. Overall, results from Experiments I and II argue for a deficiency of the CNS to integrate labyrinthine signals for updating the egocentric representation of the peripheral visual target during passive body (head) rotations.

Adult↗

PubMed1993

Thalamic VPM nucleus in the behaving monkey. II. Response to air-puff stimulation during discrimination and attention tasks.

1. Single-unit activity was recorded in the ventral posterior medial (VPM) thalamic nucleus of awake monkeys while they performed detection and discrimination tasks involving tactile air-puff stimuli presented to the face. Neuronal responsiveness was compared directly with the monkey's discriminative performance. In addition, neuronal activity was compared when the monkey's attention was directed to the air-puff stimulus and when it was directed to a concurrent visual stimulus. 2. Neurons responding to the air-puff stimuli were classified as slowly adapting (SA), rapidly adapting (RA), inhibitory (IN), or multimodal (MM), according to their responses to manual and thermal stimulation, as well as their adaption rates to the air puff. Of 47 neurons responsive to air-puff stimulation and studied extensively in the behavioral task, 14 were classified as RA, 15 as SA, 6 as IN, and 12 as MM. The 12 MM neurons were so classified because, in addition to air puff, they responded to noxious heat, innocuous cooling, or noxious pinch. 3. Neurons from each class had restricted contralateral receptive fields localized within one division of the trigeminal nerve. There was no systematic difference in receptive-field size among groups. 4. A prominent difference in tactile responsiveness of MM neurons was response latency. Although the mean latency for RA, SA, and IN neurons was not significantly different (6.1, 9.1, and 12.2 ms, respectively), the mean latency for MM neurons was significantly longer than that for each of the other neuronal categories (28.8 ms; Ps < 0.001). These data suggest that the excitatory tactile afferent input to MM neurons is different from that to low-threshold neurons. 5. For RA, SA, and MM neurons the frequency of the neuronal discharge evoked by the air-puff stimulation was proportional to the intensity of the air puff. Thus responses of each neuronal class coded air-puff stimulus intensity. 6. The monkeys' ability to detect air-puff stimuli of various intensities was compared with the frequency of neuronal responses to those stimuli. Both the percent success in detecting differences in air-puff intensity and the detection latency were highly correlated with neuronal response frequency. The responses of all three excitatory neuronal categories corresponded well with the monkey's performance. Thus any or all of RA, SA, and MM neurons could play a role in the discrimination of air-puff intensities.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1993

Thalamic VPM nucleus in the behaving monkey. I. Multimodal and discriminative properties of thermosensitive neurons.

1. The role of the thalamic ventroposterior medial (VPM) nucleus in the discriminative aspects of nociception and thermoreception was evaluated in alert, trained rhesus monkeys. Single-unit responses were recorded from VPM while the monkeys performed a battery of tasks involving noxious heat, innocuous cool, and air-puff stimuli presented to the face. The discriminative ability of the monkey was compared directly with the responses of single neurons, to determine whether the neuronal response could subserve the monkey's discriminative behavior. 2. Most thermally sensitive neurons exhibited multimodal properties. Only 18% responded exclusively to heat (HT-Heat neurons), whereas 27% responded to innocuous mechanical, as well as noxious mechanical and heat stimuli (WDR-Heat). Twenty-three percent responded to innocuous mechanical stimuli and innocuous skin cooling (Mechano-Cool), and 32% responded to mechanical, innocuous cool, and noxious heat stimuli (WDR-Heat-Cool). 3. Almost all mechanical receptive fields were confined to one division of the trigeminal nerve. This was true for all of the above categories of VPM neurons, even those showing highly convergent properties (WDR-Heat-Cool). 4. Heat-activated neurons produced graded responses to noxious skin heating in the 46 to 49 degrees C range. Stimulus-response functions of neurons that responded to both heat and cool did not differ from those of neurons that responded exclusively to skin heating. 5. When the monkeys were detecting small changes in the intensity of a noxious heat stimulus (e.g., from 47 to 47.1-47.8 degrees C), heat-activated neurons responded to the smallest temperature changes that could be detected by the monkeys. Further, there was a high correlation between the monkey's success in detecting the stimulus changes and the magnitude of the neuronal responses to those changes. 6. Although the responsiveness of VPM cool-activated neurons was not compared with the monkeys' threshold for detecting cooling changes, larger stimulus changes (2 degrees C) that the monkey reliably detected produced significant neuronal responses. Further studies are needed to determine whether VPM neurons respond to the smallest detectable changes in skin cooling. 7. Several thermally sensitive VPM neurons were tested under two attentional conditions: 1) while the monkey was required to attend to a visual stimulus, and 2) while it was required to attend to the thermal stimulus to obtain reward. None showed a significant difference in heat- or cool-evoked activity in the two attentional states.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed2003

A multivariate, spatiotemporal analysis of electromagnetic time-frequency data of recognition memory.

Electromagnetic indices of "fast" (above 12 Hz) oscillating brain activity are much more likely to be considerably attenuated by time-averaging across multiple trials than "slow" (below 12 Hz) oscillating brain activity. To the extent that both types of oscillations represent the activity of temporally and topographically separable neural populations, time averaging can cause a loss of brain activity information that is important both conceptually and for multimodal integration with hemodynamic techniques. To address this issue for recognition memory, simultaneous electroencephalography (EEG) and whole-head magnetoencephalography (MEG) recordings of explicit word recognition from 11 healthy subjects were analyzed in two different ways. First, the time course of neural oscillations ranging from theta (4.5 Hz) to gamma (42 Hz) frequencies were identified using single-trial continuous wavelet transforms. Second, traditional analyses of amplitude variations of time-averaged EEG and MEG signals, event-related potentials (ERPs), and fields (ERFs) were performed and submitted to distributed source analyses. To identify data patterns that covaried with the difference between correctly recognized studied (old) words and correctly rejected nonstudied (new) words, a multivariate statistical tool, partial least squares (PLS), was applied to both types of analyses. The results show that ERPs and ERFs are mainly displaying those neural indices of recognition memory that oscillate in the theta (4.5-7.5 Hz), alpha (8-11.5), and to some extent in the beta1 (12-19.5 Hz) frequency range. The sources of the ERPs/ERFs were in good agreement with the topography of theta/alpha/beta 1 oscillations in being confined to the anterior temporal lobe at 400 ms and being distributed across temporal, parietal, and occipital areas between 500 and 700 ms. Gamma oscillations covaried either positively or negatively with theta/alpha/beta1 oscillations. A positive covariance, for instance, was detected over left anterior temporal sensors as early as 200-350 ms and is compatible with studies in rodents showing that gamma and theta oscillations emerge together out of the interaction of the hippocampus and the entorhinal and perirhinal cortices. Fast beta oscillations (20-29.5 Hz), on the other hand, did not strongly covary with slow oscillations and were likely to arise from neural populations not adequately represented in ERPs/ERFs. In summary, by providing a more comprehensive description of electromagnetic signals, time-frequency data are of potential benefit for integrating electrophysiological and hemodynamic indices of brain activity and also for integrating human and animal electrophysiology.

Adolescent↗

PubMed2000

Functional role of the limbic system and basal ganglia in motivated behaviors.

It has been suggested that the cortico- and limbic-striatal systems are important in various motor functions such as motivated behaviors. In this paper we review our previous studies to investigate neuronal mechanisms of feeding behaviors. We recorded neuronal activity from the amygdala, caudate nucleus, globus pallidus, and substantia nigra during feeding behavior in monkeys, and compared neuronal responses recorded from these brain areas. First, of 710 amygdalar neurons tested, 129 (18.2%) responded to single sensory stimulation (48 to vision, 32 to audition, 49 to ingestion), 142 (20%) to multimodal stimulation, and 20 to only one item with affective significance. Eight food related amygdalar neurons were tested in reversal by salting food or introducing saline, and all responses were modulated by reversal. These results suggest that the amygdala might be important in ongoing recognition of the affective significance of complex stimuli (food-nonfood discrimination). Second, activity was recorded from 351 neurons in the head of the caudate nucleus of monkeys during an operant feeding task. The 16% of these neurons responded in the discrimination phase. Some of these neurons responded specifically to food. The magnitude of these food-specific neurons depended on the rewarding nature of the food (reward value), and was inversely related to the latency of the onset of bar press. Of the caudate neurons, 10% responded in the bar press phase. Activity of most neurons which responded in the bar press phase was not correlated to individual bar presses. Cooling of the dorsolateral prefrontal cortex abolished sustained responses during bar pressing, but did not abolish the feeding behavior. However, bar press speed tended to be delayed by prefrontal cooling. Third, activity of 358 neurons was recorded from the monkey globus pallidus, and 204 neurons responded during the feeding task. In the globus pallidus, few neurons responded to food in the discrimination phase. On the other hand, activity of most responsive neurons changed during bar press and/or ingestion phases. Activity of about half of these responsive neurons was directly related to specific feeding motor acts such as arm extension, flexion, bar pressing, grasping, chewing, etc. Some of these neurons showed motor-related responses with gradual and preparatory responses. These motor-related neurons were located mainly in the caudodorsal part of the globus pallidus. On the other hand, about one third, especially in the rostroventral part of the globus pallidus, showed dissociating responses in that they responded during bar pressing for food or during ingestion in an operant task, but not during bar pressing for nonfood or during forcible ingestion. The response magnitude of the neurons during arm extension and bar pressing depended on the nature of the food. Fourth, activity of 261 neurons was recorded from the substantia nigra pars reticulata. Most of responding neurons (more than two-thirds of the recorded neurons) responded during the bar press and/or ingestion phases. Activity of the one-third of neurons was related to specific motor execution such as arm extension, flexion and bar pressing, but not to motor preparation. These neurons were located mainly in the rostral part of the nucleus. More than one-third of the recorded neurons responded during feeding and/or drinking acts and intra- and perioral sensory stimuli, and were located mainly in the caudomedial part of the nucleus. Based upon these responses and known anatomical evidence, various information including that from the amygdala and prefrontal cortex is integrated in the basal ganglia, and converted to coordinated motivated behaviors such as feeding behavior.

Animals↗

PubMed2002

Radiosurgery for residual or recurrent nonfunctioning pituitary adenoma.

OBJECT: Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study is to evaluate the efficacy and role of gamma knife radiosurgery (GKS) in the management of residual or recurrent nonfunctioning pituitary adenomas. METHODS: A review was conducted of the data obtained in 42 patients who underwent adjuvant GKS at the University of Pittsburgh between 1987 and 2001. Prior treatments included transsphenoidal resection, craniotomy and resection, or conventional radiotherapy. Endocrinological, ophthalmological, and radiological responses were evaluated. The duration of follow-up review varied from 6 to 102 months (mean 31.2 months). Fifteen patients were observed for more than 40 months. The mean radiation dose to the tumor margin was 16 Gy. Conformal radiosurgery planning was used to restrict the dose to the optic nerve and chiasm. Tumor control after GKS was achieved in 100% of patients with microadenomas and 97% of patients with macroadenomas. Gamma knife radiosurgery was equally effective in controlling adenomas with cavernous sinus invasion and suprasellar extension. No patient developed a new endocrinological deficiency following GKS. One patient's tumor enlarged with an associated decline in visual function. Another patient experienced a deterioration of visual fields despite a decrease in tumor size. CONCLUSIONS: Gamma knife radiosurgery can achieve tumor control in virtually all residual or recurrent nonfunctioning pituitary adenomas. Dose sparing facilitates tumor management even when the adenoma is close to the optic apparatus or invades the cavernous sinus.

Adenoma↗