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Biomedical subjects

Dante R Chialvo

Publications and source records attributed to Dante R Chialvo.

16 recordsLinked to original sources
PubMed2006

Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain.

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n = 13 and n = 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n = 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self.

Atrophy↗
PubMed2006

Expression of IL-1beta in supraspinal brain regions in rats with neuropathic pain.

We examined mRNA expression of the pro-inflammatory cytokine IL-1beta in the brainstem, thalamus, and prefrontal cortex in two rat models of neuropathic pain. Rats received a neuropathic injury: spared nerve injury (SNI) or chronic constriction injury (CCI), sham injury, or were minimally handled (control). Neuropathic pain-like behavior was monitored by tracking tactile thresholds. SNI-injured animals showed a robust decrease in tactile thresholds of the injured foot, while CCI-injured animals did not show tactile threshold changes. Ten or 24 days after nerve injury, IL-1beta gene expression in the brain was determined by RT-PCR. IL-1beta expression changes were observed mainly at 10 days after injury in the SNI animals, contralateral to the injury side, with increased expression in the brainstem and prefrontal cortex. The results indicate that neuro-immune activation in neuropathic pain conditions includes supraspinal brain regions, suggesting cytokine modulation of supraspinal circuitry of pain in neuropathic conditions.

Animals↗
PubMed2006

Ghost stochastic resonance with distributed inputs in pulse-coupled electronic neurons.

We study experimentally the phenomenon of ghost stochastic resonance in pulse-coupled excitable systems, for input signals distributed among different elements. Specifically, two excitable electronic circuits are driven by different sinusoidal signals that produce periodic spikes at distinct frequencies. Their outputs are sent to a third circuit that processes these spiking signals and is additionally perturbed by noise. When the input signals are harmonics of a certain fundamental (that is not present in the inputs) the processing circuit exhibits, for an optimal amount of noise, a resonant response at the frequency of the missing fundamental (ghost frequency). In contrast with the standard case in which the signals being directly integrated are sinusoidal, this behavior relies here on a coincidence-detection mechanism. When the input signals are homogeneously shifted in frequency, the processing circuit responds with pulse packages composed of spikes at a frequency that depends linearly on the frequency shift. Expressions for the dependence of the package period and duration on the frequency shift and spike width, respectively, are obtained. These results provide an experimental verification of a recently proposed mechanism of binaural pitch perception.

Journal Article↗
PubMed2006

Inflammatory and neuropathic pain animals exhibit distinct responses to innocuous thermal and motoric challenges.

Most current methods for assessing pain in animals are based on reflexive measures and require constant interaction between the observer and the animal. Here we explore two new fully automated methods to quantify the impact of pain on the overall behavior of the organism. Both methods take advantage of the animals' natural preference for a dark environment. We used a box divided into two compartments: dark and bright. In the motoric operant task, "AngleTrack", one end of the box was raised so that the animals had to climb uphill to go from the light to the dark compartment. In the thermal operant task, "ThermalTrack", the floor of the dark compartment was heated to a given temperature, while the light compartment remained at 25 degrees C. Rats were individually placed in the light box and their crossing between chambers monitored automatically for 30 minutes. The angle of the box, or the temperature of the dark compartment, was altered to challenge the animals' natural preference. We test the hypothesis that different models of pain (inflammatory or neuropathic) can be differentiated based on performance on these devices. Three groups of rats were tested at five different challenge levels on both tasks: 1) normal, 2) neuropathic injury pain (Spared Nerve Injury), and 3) inflammatory pain (intraplantar injection of Carrageenan). We monitored the position of the animals as well as their rate of switching between compartments. We find significant differences between the three groups and between the challenge levels both in their average position with respect to time, and in their switching rates. This suggests that the angle-track and thermal-track may be useful in assessing automatically the global impact of different types of pain on behavior.

Animals↗
PubMed2005

Dynamics of pain: fractal dimension of temporal variability of spontaneous pain differentiates between pain States.

Spontaneous pain is a common complaint in chronic pain conditions. However, its properties have not been explored. Here we study temporal properties of spontaneous pain. We examine time variability of fluctuations of spontaneous pain in patients suffering from chronic back pain and chronic postherpetic neuropathy and contrast properties of these ratings to normal subjects' ratings of either acute thermal painful stimuli or of imagined back pain. Subjects are instructed to continuously rate their subjective assessment of the intensity of pain over a 6- to 12-min period. We observe that the fluctuations of spontaneous pain do not possess stable mean or variance, implying that these time series can be better characterized by fractal analysis. To this end, we apply time and frequency domain techniques to characterize variability of pain ratings with a single parameter: fractal dimension, D. We demonstrate that the majority of ratings of spontaneous pain by the patients have fractal properties, namely they show a power law relationship between variability and time-scale length; D is distinct between types of chronic pain, and from ratings of thermal stimulation or of imagined pain; and there is a correspondence between D for pain ratings and D for brain activity, in chronic back pain patients using fMRI. These results show that measures of variability of spontaneous pain differentiate between chronic pain conditions, and thus may have mechanistic and clinical utility.

Adult↗
PubMed2005

Spared nerve injury rats exhibit thermal hyperalgesia on an automated operant dynamic thermal escape task.

Well-established methods are available to measure thermal and mechanical sensitivity in awake behaving rats. However, they require experimenter manipulations and tend to emphasize reflexive behaviors. Here we introduce a new behavioral test, with which we examine thermal sensitivity of rats with neuropathic injury. We contrast thermal hyperalgesia between spared nerve injury and chronic constriction injury rats. This device is a fully automated thermal sensitivity assessment tool designed to emphasize integrated learned responses to thermal painful and non-painful stimuli that are applied dynamically to a surface on which the animal is standing. It documents escape behavior in awake, unrestrained animals to innocuous and noxious heating of the floor where the animal is located. Animals learn to minimize pain by escaping to the opposite non-heated side; escape latency is recorded. On this device, thermal stimulus-response curves showed > 6 degrees C leftward shift in both groups of neuropathic rats. In contrast, when these animals were tested on hotplate the stimulus-response shift was < 2 degrees C. Spared nerve injury rats showed even less evidence for thermal hyperalgesia when thermal sensitivity was tested by measuring paw withdrawal to infrared heating, plantar test. The implications of test dependent magnitude of thermal hyperalgesia are discussed from the viewpoint of the tests used, as well as the animal models studied. It is argued that the dynamic thermal operant task reveals the relevance of the neuropathic injury associated pain-like behavior in relation to the whole organism.

Animals↗
PubMed2005

Scale-free brain functional networks.

Functional magnetic resonance imaging is used to extract functional networks connecting correlated human brain sites. Analysis of the resulting networks in different tasks shows that (a) the distribution of functional connections, and the probability of finding a link versus distance are both scale-free, (b) the characteristic path length is small and comparable with those of equivalent random networks, and (c) the clustering coefficient is orders of magnitude larger than those of equivalent random networks. All these properties, typical of scale-free small-world networks, reflect important functional information about brain states.

Brain Mapping↗
PubMed2005

Low-dose cholinesterase inhibitors do not induce delayed effects on cerebral blood flow and metabolism.

The acetylcholinesterase (AChE) inhibitors sarin and pyridostigmine bromide (PB) have been proposed as causes of neurobehavioral dysfunction in Persian Gulf War veterans. To test possible delayed effects of these agents, we exposed rats to low (subsymptomatic) levels of sarin (0.5 LD50 s.c. 3 times weekly) and/or PB (80 mg/L in drinking water) for 3 weeks. Controls received saline s.c. and tap water. At 2, 4 and 16 weeks after exposure, regional cerebral blood flow (rCBF) and glucose utilization (rCGU) were measured in conscious animals with the Iodo-14C-antipyrine and 14C-2 deoxyglucose methods, respectively. Two weeks after exposure, PB+sarin caused significant rCBF elevations, but no changes in rCGU, in neocortex, with lesser effects on allocortex. Four weeks after exposure, the same general pattern was found with sarin. Only a few changes were found at 16 weeks post-treatment. The predominant effects of sarin or PB+sarin on rCBF at earlier times after treatment are consistent with the well known direct cerebral vascular effect of cholinergic agonists. The lack of changes in rCBF and rCGU observed at 16 weeks after treatment does not support the hypothesis that repeat exposure to low-dose cholinesterase inhibitors can generate permanent alterations in cerebral activity.

Animals↗
PubMed2004

Chronic pain patients are impaired on an emotional decision-making task.

Chronic pain can result in anxiety, depression and reduced quality of life. However, its effects on cognitive abilities have remained unclear although many studies attempted to psychologically profile chronic pain. We hypothesized that performance on an emotional decision-making task may be impaired in chronic pain since human brain imaging studies show that brain regions critical for this ability are also involved in chronic pain. Chronic back pain (CBP) patients, chronic complex regional pain syndrome (CRPS) patients, and normal volunteers (matched for age, sex, and education) were studied on the Iowa Gambling Task, a card game developed to study emotional decision-making. Outcomes on the gambling task were contrasted to performance on other cognitive tasks. The net number of choices made from advantageous decks after subtracting choices made from disadvantageous decks on average was 22.6 in normal subjects (n = 26), 13.4 in CBP patients (n = 26), and -9.5 in CRPS patients (n = 12), indicating poor performance in the patient groups as compared to the normal controls (P < 0.004). Only pain intensity assessed during the gambling task was correlated with task outcome and only in CBP patients (r = -0.75, P < 0.003). Other cognitive abilities, such as attention, short-term memory, and general intelligence tested normal in the chronic pain patients. Our evidence indicates that chronic pain is associated with a specific cognitive deficit, which may impact everyday behavior especially in risky, emotionally laden, situations.

Adult↗
PubMed2004

Organization, development and function of complex brain networks.

Recent research has revealed general principles in the structural and functional organization of complex networks which are shared by various natural, social and technological systems. This review examines these principles as applied to the organization, development and function of complex brain networks. Specifically, we examine the structural properties of large-scale anatomical and functional brain networks and discuss how they might arise in the course of network growth and rewiring. Moreover, we examine the relationship between the structural substrate of neuroanatomy and more dynamic functional and effective connectivity patterns that underlie human cognition. We suggest that network analysis offers new fundamental insights into global and integrative aspects of brain function, including the origin of flexible and coherent cognitive states within the neural architecture.

Brain↗
PubMed2004

Anticipated synchronization: a metaphorical linear view.

We study the regime of anticipated synchronization recently described on a number of dynamical systems including chaotic ones. We use simple linear caricatures to show the minimal setups able to reproduce the basic facts described.

Adaptation, Physiological↗
PubMed2003

How we hear what is not there: a neural mechanism for the missing fundamental illusion.

How the brain estimates the pitch of a complex sound remains unsolved. Complex sounds are composed of more than one tone. When two tones occur together, a third lower pitched tone is often heard. This is referred to as the "missing fundamental illusion" because the perceived pitch is a frequency (fundamental) for which there is no actual source vibration. This phenomenon exemplifies a larger variety of problems related to how pitch is extracted from complex tones, music and speech, and thus has been extensively used to test theories of pitch perception. A noisy nonlinear process is presented here as a candidate neural mechanism to explain the majority of reported phenomenology and provide specific quantitative predictions. The two basic premises of this model are as follows: (I) The individual tones composing the complex tones add linearly producing peaks of constructive interference whose amplitude is always insufficient to fire the neuron (II): The spike threshold is reached only with noise, which naturally selects the maximum constructive interferences. The spacing of these maxima, and consequently the spikes, occurs at a rate identical to the perceived pitch for the complex tone. Comparison with psychophysical and physiological data reveals a remarkable quantitative agreement not dependent on adjustable parameters. In addition, results from numerical simulations across different models are consistent, suggesting relevance to other sensory modalities.

Action Potentials↗
PubMed2002

Subharmonic stochastic synchronization and resonance in neuronal systems.

We study the response of a model neuron, driven simultaneously by noise and at least two weak periodic signals. We focus on signals with frequencies components kf(0),(k+1)f(0),...(k+n)f(0) with k>1. The neuron's output is a sequence of pulses spaced at random interpulse intervals. We find an optimum input noise intensity for which the output pulses are spaced approximately 1/f(0), i.e., there is a stochastic resonance (SR) at a frequency missing in the input. Even higher noise intensities uncover additional, but weaker, resonances at frequencies present in the input. This is a different form of SR whereby the most robust resonance is the one enhancing a frequency, which is absent in the input, and which is not possible to recover via any linear processing. This can be important in understanding sensory systems including the neuronal mechanism for perception of complex tones.

Algorithms↗
PubMedDate not supplied

Circadian rhythms of heart rate and locomotion after treatment with low-dose acetylcholinesterase inhibitors.

This study tested the hypothesis that repeated exposure to low levels of sarin, pyridostigmine bromide (PB) or their combination, at doses equivalent to those possibly experienced by veterans of the 1991 Persian Gulf War, could lead to persistent or delayed autonomic effects and thus help to explain the cause of clinical findings in this population. Male Sprague-Dawley rats were treated for 3 weeks with: saline injection (0.5 ml kg(-1), s.c., 3 times weekly) with tap drinking water (control); saline injection with PB (80 mg l(-1) in drinking water); sarin injection (62.5 microg kg(-1), s.c., 0.5 x LD(50), 3 times weekly) with tap drinking water (sarin); or sarin injection with PB in drinking water (sarin + PB). At 2, 4 or 16 weeks post-treatment, heart rate (HR) and locomotor activity (LA) were studied by radiotelemetry. Two weeks posttreatment, HR in drug-treated animals was significantly lower than in controls. A decrease in low-frequency HR power spectrum (PS) was found at 00:00 h and 08:00 h with sarin + PB and at 00:00 h with sarin, while total power was enhanced with sarin + PB at 22:00 h. Minimal effects of drug treatments on HR and HR PS were detected at 4 and 16 weeks post-treatment. No significant differences in LA between control and other groups were found. Since no consistent long-term effects were found in any of the variables studied, these experiments do not support the hypothesis that repeated administration of low doses of PB and the nerve agent sarin can induce persistent or delayed alterations in autonomic function.

Animals↗