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Circumstances of witnessed drug overdose in New York City: implications for intervention.

Drug users frequently witness the nonfatal and fatal drug overdoses of their peers, but often fail to intervene effectively to reduce morbidity and mortality. We assessed the circumstances of witnessed heroin-related overdoses in New York City (NYC) among a predominantly minority population of drug users. Among 1184 heroin, crack, and cocaine users interviewed between November 2001 and February 2004, 672 (56.8%) had witnessed at least one nonfatal or fatal heroin-related overdose. Of those, 444 (67.7%) reported that they or someone else present called for medical help for the overdose victim at the last witnessed overdose. In multivariable models, the respondent never having had an overdose her/himself and the witnessed overdose occurring in a public place were associated with the likelihood of calling for medical help. Fear of police response was the most commonly cited reason for not calling or delaying before calling for help (52.2%). Attempts to revive the overdose victim through physical stimulation (e.g., applying ice, causing pain) were reported by 59.7% of respondents, while first aid measures were attempted in only 11.9% of events. Efforts to equip drug users to manage overdoses effectively, including training in first aid and the provision of naloxone, and the reduction of police involvement at overdose events may have a substantial impact on overdose-related morbidity and mortality.

Adolescent↗

Impaired disengagement from threatening cues of impending pain in a crossmodal cueing paradigm.

This paper reports an experimental investigation of attentional engagement to and disengagement from cues of impending pain. Pain-free volunteers performed a cueing task in which they were instructed to detect somatosensory and tone targets. Target stimuli were preceded by visual cues informing participants of the modality of the impending stimuli. Participants were randomly assigned to a pain group (n = 54) or to a control group (n = 53). Somatosensory targets consisted of painful electrocutaneous stimuli in the pain group and non-painful vibrotactile targets in the control group. Analyses revealed a similar amount of attentional engagement to both cues signalling somatosensory targets, irrespective of their threat value. However, participants had significantly more difficulty in disengaging attention from a threatening cue of impending pain compared to a cue signalling the non-painful vibrotactile target. Our findings provide further evidence that pain cues demand attention, particularly resulting in impaired disengagement.

Acoustic Stimulation↗

Lifetime egg maturation by host-deprived Venturia canescens.

The study investigated egg maturation and deposition by the endoparasitoid wasp Venturia canescens under conditions of host deprivation. Female V. canescens maintained without hosts began to deposit eggs onto the sides of the culture vessel on the day of eclosion. The maturation of additional eggs was not inhibited once the maximum oviduct egg load was reached but rather continued for the duration of the experiment (up to 39 days), at a rate of around 5.8% of the remaining unmatured eggs per day. Following host access, wasps matured additional eggs at an increased rate. Artificial damage to the ovipositor resulted in a reduced rate of egg maturation even though the oviducts were partly egg depleted, while damage to the auxiliary valvulae had no effect. These results suggest two conclusions. Under conditions of host deprivation, the rate at which eggs are matured is determined by the rate of synthesis of precursors by the fat body that in turn is modified by feedback from the ovipositor, induced by physical stimulation. Further, the discarding of eggs is due to the involuntary unidirectional movement of eggs down the oviduct, facilitated by the ongoing maturation of additional eggs.

Animals↗

A fiber optic-based system for behavioral eyeblink measurement in a MRI environment.

We previously described a reliable system to control the timing of multiple stimuli and to detect behavioral eyeblink responses in fMRI studies of learning in animals. Here, we report a significant advancement of the original system, which incorporates a fiber-optic probe in order to avoid the interference associated with the application of pulsed field gradients during MR imaging, particularly echo planar imaging. Eyeblink responses recorded with our fiber-optic probe and modified detection circuit demonstrate the ability of our new system to acquire behavioral data free of gradient-induced artifacts, thereby eliminating the need for low-pass filtering. This fiber optic-based system should be applicable to both animal and human imaging experiments.

Animals↗

Soman-induced convulsions in rats terminated with pharmacological agents after 45 min: neuropathology and cognitive performance.

It has been demonstrated that a triple regimen consisting of procyclidine (6 mg/kg), diazepam (10 mg/kg) and pentobarbital (30 mg/kg) can effectively terminate soman-induced (1 x LD50) seizures/convulsions in rats when administered 30-40 min following onset. However, convulsive activity lasting for only 45 min can result in marked neuronal pathology. The purpose of the present study was to examine potential cognitive impairments of such brain lesions. The results showed that the neuronal pathology (assessed with Fluoro-Jade B) varied from none at all to 30% damage in the index areas (hippocampus, amygdala, piriform cortex). Cognitive deficits were seen in a novelty test (11 days post-exposure) and retention of a brightness discrimination task (28 days post-exposure) among the rats with neuropathology. Furthermore, significant correlations between neuropathology scores and behavioral measures were found for the animals that convulsed. Among these rats, the mortality rate was relatively high (60%) compared with rats in a previous study that had undergone implantation of hippocampal electrodes (17%). Neither the soman poisoning in the absence of convulsions nor the triple regimen alone affected behavior. It is concluded that early management of soman-induced convulsions is of major importance in preventing neuropathology and accompanying cognitive impairments.

Animals↗

Comparison of hemodynamic response nonlinearity across primary cortical areas.

Hemodynamic responses to auditory and visual stimuli and motor tasks were assessed for the nonlinearity of response in each of the respective primary cortices. Five stimulus or task durations were used (1, 2, 4, 8, and 16 s), and five male subjects (aged 19 +/- 1.9 years) were imaged. Two tests of linearity were conducted. The first test consisted of using BOLD responses to short stimuli to predict responses to longer stimuli. The second test consisted of fitting ideal impulse response functions to the observed responses for each event duration. Both methods show that the extent of the nonlinearity varies across cortices. Results for the second method indicate that the hemodynamic response is nonlinear for stimuli less than 10 s in the primary auditory cortex, nonlinear for tasks less than 7 s in the primary motor cortex, and nonlinear for stimuli less than 3 s in the primary visual cortex. In addition, neural adaptation functions were characterized that could model the observed nonlinearities.

Acoustic Stimulation↗

Multisensory stimulation with or without saccades: fMRI evidence for crossmodal effects on sensory-specific cortices that reflect multisensory location-congruence rather than task-relevance.

During covert attention to peripheral visual targets, presenting a concurrent tactile stimulus at the same location as a visual target can boost neural responses to it, even in sensory-specific occipital areas. Here, we examined any such crossmodal spatial-congruence effects in the context of overt spatial orienting, when saccadic eye-movements were directed to each peripheral target or central fixation maintained. In addition, we tested whether crossmodal spatial-congruence effects depend on the task-relevance of visual or tactile stimuli. On each trial, subjects received spatially congruent (same location) or incongruent (opposite hemifields) visuo-tactile stimulation. In different blocks, they made saccades either to the location of each visual stimulus, or to the location of each tactile stimulus; or else passively received the multisensory stimulation. Activity in visual extrastriate areas and in somatosensory parietal operculum was modulated by spatial congruence of the multisensory stimulation, with stronger activations when concurrent visual and tactile stimuli were both delivered at the same contralateral location. Critically, lateral occipital cortex and parietal operculum showed such crossmodal spatial effects irrespective of which modality was task relevant; and also of whether the stimuli were used to guide eye-movements or were just passively received. These results reveal crossmodal spatial-congruence effects upon visual and somatosensory sensory-specific areas that are relatively 'automatic', determined by the spatial relation of multisensory input rather than by its task-relevance.

Adolescent↗

Oscillatory motor cortex-muscle coupling during painful laser and nonpainful tactile stimulation.

Noxious stimulation activates-in addition to the brain structures related to sensory, emotional, and cognitive components of pain-also the brain's motor system. Effect of noxious input on the primary motor (MI) cortex remains, however, poorly understood. To characterize this effect in more detail, we quantified the ongoing oscillatory communication between the MI cortex and hand muscles during selectively noxious laser stimulation. The subjects maintained an isometric contraction of finger muscles while receiving the laser stimuli to the dorsum of the hand. Tactile stimuli with well-known effects on the MI cortex reactivity served as control stimuli. Cortex-muscle coherence was computed between magnetoencephalographic (MEG) signals from the contralateral MI and electromyographic (EMG) signals from the hand muscles. Statistically significant coherence at approximately 20 Hz was found in 6 out of 7 subjects. The coherence increased phasically after both types of stimuli but significantly later after laser than tactile stimuli (mean +/- SEM peak latencies 1.05 +/- 0.12 s vs. 0.58 +/- 0.06 s; P < 0.05), and the coherence increase lasted longer after laser than tactile stimuli (0.87 +/- 0.09 s vs. 0.50 +/- 0.06 s, P < 0.05). The observed coherence increase could be related to stabilization of the motor-cortex control after sensory input. Our findings add to the clinically interesting evidence about the cortical pain-motor system interaction.

Adult↗

The fast optical signal--robust or elusive when non-invasively measured in the human adult?

Near infrared spectroscopy (NIRS) can detect vascular changes in cerebral cortical tissue elicited by functional stimulation. For some 10 years, another optical signal has been reported to be accessible by NIRS. This signal has been reported to correlate to the electrophysiological response rendering NIRS an exquisite non-invasive approach to investigate neurovascular coupling in the human adult. Due to their typical latency of up to hundreds of milliseconds, these signals have been termed "fast" optical signals and have been postulated to stem from scatter changes in neuronal tissue, as a fingerprint of the electrophysiological response. Here, we utter a less optimistic view on the non-invasive detectability of these changes in the human, motivated by an upper limit signal size estimation, predicting a signal size by orders of magnitude smaller than those previously reported. Also, we discuss the influence of small stimulus correlated movement artifacts potentially mimicking a fast optical signal. Based on invasive studies, we perform an upper limit estimation for changes in intensity and mean time of flight, which can be expected assuming a scatter change in the cerebral cortex while measuring on the surface of the head of an adult subject. Since the resulting numbers are far below those previously reported, we constructed a simple system, which minimizes technical noise. The system allows us to detect rather small intensity changes (2 x 10(-3)%) when averaging over approximately 3000 stimuli. Despite this outstandingly low noise level of the system, we find a reliable change in response to a sub-motor-threshold steady state median nerve stimulation in just one single subject (8 subjects examined, 4 subjects twice). Exceeding the motor threshold leads to large stimulus related artifacts, on a similar time scale and with comparable amplitude as previously reported signals. To check for potential modality specific problems, we next performed a visual stimulation study, avoiding potential motor artifacts. For the steady state visually evoked response, no subject yielded a reliable result (11 subjects examined, 4 subjects twice). The paper discusses these findings by a review of the literature on fast optical signals and their being accessible in the adult human.

Adult↗

Fooling your feelings: artificially induced referred sensations are linked to a modulation of the primary somatosensory cortex.

Recent studies demonstrated tactile illusions in healthy subjects by manipulating visual and tactile information. For example, a rubber hand, lying on a table in front of the subject and not connected with the body, can be felt by the subject as belonging to his or her own body by a simple visuotactile manipulation. Aim of the present study was to create an illusion in which the subject feels touch on a body site which is different from the actual touch, hence showing a referral of touch similar to those reported in phantom limb patients. Since it is known from animal studies that tactile illusions can alter early sensory processing, we were interested in the role of the primary somatosensory cortex (SI) during this kind of illusion. Thus, we manipulated the visual and tactile information in eight healthy subjects. The participants were stimulated on their fifth digit (D5) while watching a video, which showed a life-sized hand where the first digit (D1) was stimulated, hence inducing a conflict in feeling and seeing. The visual and tactile stimulation was in-phase in one condition and out-of-phase in a control condition. The video was presented in the peripersonal space of the subject at the distance where the real hand would be expected. Subjects reported a referred sensation of feeling the stimulation on D1 instead of D5 when the stimulation was in-phase with the video. Neuromagnetic source imaging of the topography of the functional organization of SI related to tactile stimulation of D1 and D5 showed that the source extent of the cortical representation of D5 increased during the illusion. The results suggest that a simple manipulation of visual and tactile information can induce referred sensations in healthy subjects in a very fast manner. Since the amount of the referred sensation was significantly correlated with the modulation in SI, we argue that SI is involved in this kind of artificially induced referred sensation.

Adult↗

Dynamic modulation of the primary somatosensory cortex during seeing and feeling a touched hand.

Previous work has demonstrated cross-modal links between vision and somatosensation at an early stage of sensory processing. Furthermore, recent behavioral studies have shown that viewing the stimulated body part can enhance tactile discrimination ability at the stimulated site. This study aims to investigate the role of the primary somatosensory cortex (SI) during visuotactile integration processes. Subjects looked at a hand in a video being touched on the first digit (D1) in synchrony with felt touches on their real hidden hand as compared with watching a video with asynchronous touches. During synchronous stimulation, subjects reported to feel the tactile sensation on the video hand, thus indicating that in this condition the subjects regarded the video hand as their own touched hand. This feeling disappeared in the asynchronous condition. Using neuromagnetic source imaging, we assessed the topography of the functional organization of SI related to tactile stimulation of D1. The cortical representation of D1 moved to a more inferior location during synchronous in comparison to asynchronous stimulation and rest. This modulation of the map in SI was significantly positively correlated with the feeling that the seen touch in the video represented the touch on the real hand. Thus, only if the seen touch is attributed to the own body, SI seems to be modulated.

Adolescent↗

Towards natural stimulation in fMRI--issues of data analysis.

In search for suitable tools to study brain activation in natural environments, where the stimuli are multimodal, poorly predictable and irregularly varying, we collected functional magnetic resonance imaging data from 6 subjects during a continuous 8-min stimulus sequence that comprised auditory (speech or tone pips), visual (video clips dominated by faces, hands, or buildings), and tactile finger stimuli in blocks of 6-33 s. Results obtained by independent component analysis (ICA) and general-linear-model-based analysis (GLM) were compared. ICA separated in the superior temporal gyrus one independent component (IC) that reacted to all auditory stimuli and in the superior temporal sulcus another IC responding only to speech. Several distinct and rather symmetric vision-sensitive ICs were found in the posterior brain. An IC in the V5/MT region reacted to videos depicting faces or hands, whereas ICs in the V1/V2 region reacted to all video clips, including buildings. The corresponding GLM-derived activations in the auditory and early visual cortices comprised sub-areas of the ICA-revealed activations. ICA separated a prominent IC in the primary somatosensory cortex whereas the GLM-based analysis failed to show any touch-related activation. "Intrinsic" components, unrelated to the stimuli but spatially consistent across subjects, were discerned as well. The individual time courses were highly consistent in sensory projection cortices and more variable elsewhere. The ability to differentiate functionally meaningful composites of activated brain areas and to straightforwardly reveal their temporal dynamics renders ICA a sensitive tool to study brain responses to complex natural stimuli.

Acoustic Stimulation↗

Sequential neural processes of tactile-visual crossmodal working memory.

Working memory is essential to learning and performing sensory-motor behaviors that in many situations require the integration of stimuli of one modality with stimuli of another. In the present study, we focused on the neural mechanisms underlying crossmodal working memory. We hypothesized that in performance of the tactile crossmodal working memory task, there would be sequentially discrete task-correlated neural activities representing the processes of crossmodal working memory. Scalp-recorded event-related potentials were collected from 15 electrodes in humans performing each of four tasks: tactile-tactile unimodal delayed matching-to-sample task, tactile-visual crossmodal delayed matching-to-sample task, tactile unimodal control spatial task, and tactile crossmodal control spatial task. Two positive event-related potential peaks were observed during the delay of the task. One peak (late positive component-1) was at about 330 ms after the onset of the tactile stimulus, and the other (late positive component-2) was at about 600 ms. Late positive component-1 was observed in all four tasks. There was no significant difference in late positive component-1 either between the unimodal tasks, or between the crossmodal tasks, but late positive component-1 was significantly larger in the crossmodal tasks than that in the unimodal tasks, and showed a specific pattern of larger activity over parietal areas than activity over frontal areas. Late positive component-2 was not observed in the unimodal matching task but was observed in all other three tasks over parietal areas. During the late delay (1000 ms-1500 ms), significant differences in negative potentials (late negative component) were found between the tasks. The present study shows sequential changes in event-related potentials during the retention period of working memory tasks. It indicates that in performance of a crossmodal working memory task, there are sequentially discrete neural processes that may represent neural activities related to different cognitive functions, such as crossmodal transfer of information, and the working memory of the stimulus.

Adult↗

Neural correlates of spatial working memory in humans: a functional magnetic resonance imaging study comparing visual and tactile processes.

Recent studies of neural correlates of working memory components have identified both low-level perceptual processes and higher-order supramodal mechanisms through which sensory information can be integrated and manipulated. In addition to the primary sensory cortices, working memory relies on a widely distributed neural system of higher-order association areas that includes posterior parietal and occipital areas, and on prefrontal cortex for maintaining and manipulating information. The present study was designed to determine brain patterns of neural response to the same spatial working memory task presented either visually or in a tactile format, and to evaluate the relationship between spatial processing in the visual and tactile sensory modalities. Brain activity during visual and tactile spatial working memory tasks was measured in six young right-handed healthy male volunteers by using functional magnetic resonance imaging. Results indicated that similar fronto-parietal networks were recruited during spatial information processing across the two sensory modalities-specifically the posterior parietal cortex, the dorsolateral prefrontal cortex and the anterior cingulate cortex. These findings provide a neurobiological support to behavioral observations by indicating that common cerebral regions subserve generation of higher order mental representations involved in working memory independently from a specific sensory modality.

Adult↗

Modulation of somatosensory event-related potential components in a tactile-visual cross-modal task.

Human tactile discrimination studies have shown that visual stimuli enhance tactile performance. Other studies on event-related potentials showed that somatosensory N140 was enhanced when attention of human subjects was directed to tactile stimuli. Therefore, we hypothesized that N140 would be modulated when human subjects performed tactile cross-modal delay tasks. Scalp-event-related potentials were recorded from normal subjects performing either a tactile-tactile unimodal, or a tactile-visual cross-modal delayed matching-to-sample task. Identical tactile stimuli were used in both tasks. N140 component evoked by the tactile stimuli was enhanced in the cross-modal task. Enhancement of this component was also observed in control cross-modal tasks. The results suggest that tactile-visual cross-modal association affects tactile sensory-perceptual processes in humans.

Adult↗

Cardiovascular sensitivity to epinephrine in the trained and untrained states.

Heart rate (HR), blood pressure (BP) and inotropic responses to acute exercise are partially mediated by sympathetic stimulation. Physical conditioning reduces exercise HR and improves maximal stroke volume and cardiac output. Uncertainty exists regarding the role of altered catecholamine sensitivity in producing these changes in man. In 6 highly trained men, noninvasive methods were used to serially assess the effect of cessation of training on the resting HR, BP and left ventricular contractile function in response to constant epinephrine infusion. Plasma epinephrine concentration during infusion did not vary with inactivity and was similar to that attained with strenuous exercise. Two subjects showed an increase in chronotropic sensitivity to epinephrine and 4 showed no consistent change. Despite a significant decline in exercise capacity and no apparent change in cardiac loading conditions, there was no persistent effect of inactivity on BP or left ventricular function as assessed by echocardiography and systolic time intervals. Therefore, an alteration in sensitivity to epinephrine is unlikely to account for the hemodynamic adaptations to endurance exercise training in healthy men.

Adaptation, Physiological↗

Test-retest reliability of the sensory organization test in noninstitutionalized older adults.

The purpose of this study was to determine the 1-week test-retest reliability of the Sensory Organization Test (SOT), using computer-generated scores and loss of balance (LOB) episodes in noninstitutionalized older adults. The SOT was administered to each subject on two separate days 1 week apart in an out-patient clinic. A volunteer sample of 40 individuals who were at least 65 years of age participated in this study. The main outcome measures were computer-generated scores for the first trial and the average of the three trials in each of the six sensory conditions of the SOT; computer-generated composite score of the six conditions; LOB on the first trial and any of three trials in each condition. The intraclass correlation coefficients (ICC) for the SOT first trial data ranged from .15 in Condition 3 to 0.70 in Condition 5. The ICCs for the SOT average of three trials ranged from 0.26 in Condition 3 to 0.68 and 0.64 in Conditions 5 and 6. Percent agreement was 77% to 100% for LOB on the first trial, as well as LOB on any of three trials of Conditions 1 through 6. As the conditions became more difficult, an increasing number of subjects experienced LOB. Analysis revealed fair to good test-retest reliability for computer-generated scores and good reliability for LOB across some conditions of the SOT. A modification to the current scoring system is suggested which would improve the reliability of the computer-generated scores of the SOT.

Aged↗

Enriched environment delays the onset of hippocampal damage after global cerebral ischemia in rats.

An enriched environment has been shown to improve cognitive, behavioral and histopathological outcome after focal cerebral ischemia and head trauma. The purpose of this study was to determine the effect of an enriched environment on histopathology following global cerebral ischemia. Wistar rats (21 weeks of age) were placed in different environments [standard cages (SC) or enriched environment (EE) cages] for 2 months before and either 6 days or 2 months after ischemia. Rats underwent 10 min of global ischemia by bilateral carotid artery occlusions plus hypotension. Five groups (n=4-5 in each group) were studied: (1) rats kept in SC before and 2 months after ischemia; (2) rats kept in SC before ischemia but transferred to an EE for 2 months after ischemia; (3) rats kept in EE before and after ischemia for 2 months; (4) rats kept in SC before and 6 days after ischemia; (5) rats kept in EE before and 6 days after ischemia. At 7 days or 2 months after ischemia, brains were perfusion-fixed, and ischemic injury was assessed by counting numbers of normal neurons in the hippocampal CA1 sector. Physiological variables showed no inter-group differences. Rats housed in EE for 2 months before and for 6 days (but not 2 months) after global ischemia showed significantly better preservation of pyramidal neurons in the hippocampal CA1 area when compared to control animals (middle CA1, 20.5+/-5.4 vs. 2.8+/-0.6; lateral CA1, 31.5+/-7.2 vs. 2.6+/-0.6, respectively). The present data suggest that housing in EE for 2 months before and 6 days after ischemia can delay the onset of damage to hippocampal pyramidal neurons, which eventually occurs despite 2-month EE.

Animals↗