Attempts to control pain prioritize attention to signals of pain: an experimental study

Clinical evidence suggests that a persistent search for solutions for chronic pain may bring along costs at the cognitive, affective, and behavioral level. Specifically, attempts to control pain may fuel hypervigilance and prioritize attention towards pain-related information. This hypothesis was investigated in an experiment with 41 healthy volunteers. Prioritization of attention towards a signal for pain was measured using an adaptation of a visual search paradigm in which participants had to search for a target presented in a varying number of colored circles. One of these colors (Conditioned Stimulus) became a signal for pain (Unconditioned Stimulus: electrocutaneous stimulus at tolerance level) using a classical conditioning procedure. Intermixed with the visual search task, participants also performed another task. In the pain-control group, participants were informed that correct and fast responses on trials of this second task would result in an avoidance of the Unconditioned Stimulus. In the comparison group, performance on the second task was not instrumental in controlling pain. Results showed that in the pain-control group, attention was more prioritized towards the Conditioned Stimulus than in the comparison group. The theoretical and clinical implications of these results are discussed.

The effect of Parkinson's disease on time estimation as a function of stimulus duration range and modality

The present research sought to investigate the role of the basal ganglia in timing of sub- and supra-second intervals via an examination of the ability of people with Parkinson's disease (PD) to make temporal judgments in two ranges, 100-500 ms, and 1-5 s. Eighteen nondemented medicated patients with PD were compared with 14 matched controls on a duration-bisection task in which participants were required to discriminate auditory and visual signal durations within each time range. Results showed that patients with PD exhibited more variable duration judgments across both signal modality and duration range than controls, although closer analyses confirmed a timing deficit in the longer duration range only. The findings presented here suggest the bisection procedure may be a useful tool in identifying timing impairments in PD and, more generally, reaffirm the hypothesised role of the basal ganglia in temporal perception at the level of the attentionally mediated internal clock as well as memory retrieval and/or decision-making processes. (c) 2007 Elsevier Inc. All rights reserved.

Stimulus-driven selection of routes to imitation

Several models have proposed that an action can be imitated via one of two routes: a direct visuospatial route, which can in principle mediate imitation of both meaningful (MF) and meaningless (ML) actions, and an indirect semantic route, which can be used only for MF actions. The present study investigated whether selection between the direct and indirect routes is strategic or stimulus driven. Tessari and Rumiati (J Exp Psychol Hum Percept Perform 30:1107–1116, 2004) have previously shown, using accuracy measures, that imitation of MF actions is superior to imitation of ML actions when the two action types are presented in separate blocks, and that the advantage of MF over ML items is smaller or absent when they are presented in mixed blocks. We first replicated this finding using an automated reaction time (RT), as well as accuracy, measure. We then examined imitation of MF and ML actions in the mixed condition as a function of the action type presented in the previous trial and in relation to the number of previous test trials. These analyses showed that (1) for both action types, performance was worse immediately after ML than MF trials, and (2) even at the beginning of the mixed condition, responding to MF actions was no better than responding to ML items. These results suggest that the properties of the action stimulus play a substantial role in determining whether imitation is mediated by the direct or the indirect route, and that effects of block composition on imitation need not be generated through strategic switching between routes.

Minimum recovery time between reactive hyperemia stimulus in the repeated measurement of brachial flow-mediated dilatation.

The ability to undertake repeat measurements of flow-mediated dilatation (FMD) within a short time of a previous measurement would be useful to improve accuracy or to repeat a failed initial procedure. Although standard methods report that a minimum of 10 min is required between measurements, there is no published data to support this. Thirty healthy volunteers had five FMD measurements performed within a 2-h period, separated by various time intervals (5, 15 and 30 min). In 19 volunteers, FMD was also performed as soon as the vessel had returned to its baseline diameter. There was no significant difference between any of the FMD measurements or parameters across the visits indicating that repeat measurements may be taken after a minimum of 5 min or as soon as the vessel has returned to its baseline diameter, which in some subjects may be less than 5 min.

Measuring the effects of manipulating stimulus presentation time on sensorimotor alpha and low beta reactivity during hand movement observation

The present study addresses three methodological questions that have been ignored in previous research on EEG indices of the human mirror neuron system (hMNS), particularly in regard to autistic individuals. The first question regards how to elicit the EEG indexed hMNS during movement observation: Is hMNS activation best elicited using long stimulus presentations or multiple short repetitions? The second question regards what EEG sensorimotor frequency bands reflect sensorimotor reactivity during hand movement observation? The third question regards how widespread is the EEG reactivity over the sensorimotor cortex during movement observation? The present study explored sensorimotor alpha and low beta reactivity during hand movement versus static hand or bouncing balls observation and compared two experimental protocols (long exposure vs. multiple repetitions) in the same participants. Results using the multiple repetitions protocol indicated a greater low beta desynchronisation over the sensorimotor cortex during hand movement compared to static hand and bouncing balls observation. This result was not achieved using the long exposure protocol. Therefore, the present study suggests that the multiple repetitions protocol is a more robust protocol to use when exploring the sensorimotor reactivity induced by hand action observation. In addition, sensorimotor low beta desynchronisation was differently modulated during hand movement, static hand and bouncing balls observation (non-biological motion) while it was not the case for sensorimotor alpha and that suggest that low beta may be a more sensitive index of hMNS activation during biological motion observation. In conclusion the present study indicates that sensorimotor reactivity of low beta during hand movement observation was found to be more widespread over the sensorimotor cortex than previously thought.

The potential for skill across the range of the seamless weather-climate prediction problem: a stimulus for our science

Predictability is considered in the context of the seamless weather-climate prediction problem, and the notion is developed that there can be predictive power on all time-scales. On all scales there are phenomena that occur as well as longer time-scales and external conditions that should combine to give some predictability. To what extent this theoretical predictability may actually be realised and, further, to what extent it may be useful is not clear. However the potential should provide a stimulus to, and high profile for, our science and its application for many years.

Poverty-of-the-stimulus and SLA epistemology: considering L2 knowledge of aspectual phrasal semantics

Coupling a review of previous studies on the acquisition of grammatical aspects undertaken from contrasting paradigmatic views of second language acquisition (SLA) with new experimental data from L2 Portuguese, the present study contributes to this specific literature as well as general debates in L2 epistemology. We tested 31 adult English learners of L2 Portuguese across three experiments, examining the extent to which they had acquired the syntax and (subtle) semantics of grammatical aspect. Demonstrating that many individuals acquired target knowledge of what we contend is a poverty-of-the-stimulus semantic entailment related to the checking of aspectual features encoded in Portuguese preterit and imperfect morphology, namely, a [±accidental] distinction that obtains in a restricted subset of contexts, we conclude that UG-based approaches to SLA are in a better position to tap and gauge underlying morphosyntactic competence, since based on independent theoretical linguistic descriptions, they make falsifiable predictions that are amenable to empirical scrutiny, seek to describe and explain beyond performance, and can account for L2 convergence on poverty-of-the-stimulus knowledge as well as L2 variability/optionality.

Early and late stimulus-evoked cortical hemodynamic responses provide insight into the neurogenic nature of neurovascular coupling

Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained from modern neuroimaging techniques. This study investigated the hemodynamic and neural responses in rat somatosensory cortex elicited by 16 seconds electrical whisker stimuli. Hemodynamics were measured by optical imaging spectroscopy and neural activity by multichannel electrophysiology. Previous studies have suggested that the whisker-evoked hemodynamic response contains two mechanisms, a transient ‘backwards’ dilation of the middle cerebral artery, followed by an increase in blood volume localized to the site of neural activity. To distinguish between the mechanisms responsible for these aspects of the response, we presented whisker stimuli during normocapnia (‘control’), and during a high level of hypercapnia. Hypercapnia was used to ‘predilate’ arteries and thus possibly ‘inhibit’ aspects of the response related to the ‘early’ mechanism. Indeed, hemodynamic data suggested that the transient stimulus-evoked response was absent under hypercapnia. However, evoked neural responses were also altered during hypercapnia and convolution of the neural responses from both the normocapnic and hypercapnic conditions with a canonical impulse response function, suggested that neurovascular coupling was similar in both conditions. Although data did not clearly dissociate early and late vascular responses, they suggest that the neurovascular coupling relationship is neurogenic in origin.

Temporal coupling between stimulus-evoked neural activity and hemodynamic responses from individual cortical columns

Using previously published data from the whisker barrel cortex of anesthetized rodents (Berwick et al 2008 J. Neurophysiol. 99 787–98) we investigated whether highly spatially localized stimulus-evoked cortical hemodynamics responses displayed a linear time-invariant (LTI) relationship with neural activity. Presentation of stimuli to individual whiskers of 2 s and 16 s durations produced hemodynamics and neural activity spatially localized to individual cortical columns. Two-dimensional optical imaging spectroscopy (2D-OIS) measured hemoglobin responses, while multi-laminar electrophysiology recorded neural activity. Hemoglobin responses to 2 s stimuli were deconvolved with underlying evoked neural activity to estimate impulse response functions which were then convolved with neural activity evoked by 16 s stimuli to generate predictions of hemodynamic responses. An LTI system more adequately described the temporal neuro-hemodynamics coupling relationship for these spatially localized sensory stimuli than in previous studies that activated the entire whisker cortex. An inability to predict the magnitude of an initial 'peak' in the total and oxy- hemoglobin responses was alleviated when excluding responses influenced by overlying arterial components. However, this did not improve estimation of the hemodynamic responses return to baseline post-stimulus cessation.

The resting-state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus-evoked haemodynamics

Although promise exists for patterns of resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi-laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two-dimensional optical imaging spectroscopy measurements of resting-state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting-state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus-evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting-state haemodynamic fluctuations resembling the temporal profile of stimulus-evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting-state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus-evoked neurovascular responses.

Real-Time software control of neural stimulation in a closed loop Animat system

A recent area for investigation into the development of adaptable robot control is the use of living neuronal networks to control a mobile robot. The so-called Animat paradigm comprises a neuronal network (the ‘brain’) connected to an external embodiment (in this case a mobile robot), facilitating potentially robust, adaptable robot control and increased understanding of neural processes. Sensory input from the robot is provided to the neuronal network via stimulation on a number of electrodes embedded in a specialist Petri dish (Multi Electrode Array (MEA)); accurate control of this stimulation is vital. We present software tools allowing precise, near real-time control of electrical stimulation on MEAs, with fast switching between electrodes and the application of custom stimulus waveforms. These Linux-based tools are compatible with the widely used MEABench data acquisition system. Benefits include rapid stimulus modulation in response to neuronal activity (closed loop) and batch processing of stimulation protocols.

Further characterization of muscarinic agonist-induced epileptiform bursting activity in immature rat piriform cortex, in vitro

The characteristics of muscarinic acetylcholine receptor agonist-induced epileptiform bursting seen in immature rat piriform cortex slices in vitro were further investigated using intracellular recording, with particular focus on its postnatal age-dependence (P+14-P+30), pharmacology, site(s) of origin and the likely contribution of the muscarinic acetylcholine receptor agonist-induced post-stimulus slow afterdepolarization and gap junction functionality toward its generation. The muscarinic agonist, oxotremorine-M (10 microM), induced rhythmic bursting only in immature piriform cortex slices; however, paroxysmal depolarizing shift amplitude, burst duration and burst incidence were inversely related to postnatal age. No significant age-dependent changes in neuronal membrane properties or postsynaptic muscarinic responsiveness accounted for this decline. Burst incidence was higher when recorded in anterior and posterior regions of the immature piriform cortex. In adult and immature neurones, oxotremorine-M effects were abolished by M1-, but not M2-muscarinic acetylcholine receptor-selective antagonists. Rostrocaudal lesions, between piriform cortex layers I and II, or layer III and endopiriform nucleus in adult or immature slices did not influence oxotremorine-M effects; however, the slow afterdepolarization in adult (but not immature) lesioned slices was abolished. Gap junction blockers (carbenoxolone or octanol) disrupted muscarinic bursting and diminished the slow afterdepolarization in immature slices, suggesting that gap junction connectivity was important for bursting. Our data show that neural networks within layers II-III function as primary oscillatory circuits for burst initiation in immature rat piriform cortex during persistent muscarinic receptor activation. Furthermore, we propose that muscarinic slow afterdepolarization induction and gap junction communication could contribute towards the increased epileptiform susceptibility of this brain area.

Perceived controllability modulates the neural response to pain

The response to painful stimulation depends not only on peripheral nociceptive input but also on the cognitive and affective context in which pain occurs. One contextual variable that affects the neural and behavioral response to nociceptive stimulation is the degree to which pain is perceived to be controllable. Previous studies indicate that perceived controllability affects pain tolerance, learning and motivation, and the ability to cope with intractable pain, suggesting that it has profound effects on neural pain processing. To date, however, no neuroimaging studies have assessed these effects. We manipulated the subjects' belief that they had control over a nociceptive stimulus, while the stimulus itself was held constant. Using functional magnetic resonance imaging, we found that pain that was perceived to be controllable resulted in attenuated activation in the three neural areas most consistently linked with pain processing: the anterior cingulate, insular, and secondary somatosensory cortices. This suggests that activation at these sites is modulated by cognitive variables, such as perceived controllability, and that pain imaging studies may therefore overestimate the degree to which these responses are stimulus driven and generalizable across cognitive contexts. [References: 28]

A management architecture for active networks

In this paper we present an architecture for network and applications management, which is based on the Active Networks paradigm and shows the advantages of network programmability. The stimulus to develop this architecture arises from an actual need to manage a cluster of active nodes, where it is often required to redeploy network assets and modify nodes connectivity. In our architecture, a remote front-end of the managing entity allows the operator to design new network topologies, to check the status of the nodes and to configure them. Moreover, the proposed framework allows to explore an active network, to monitor the active applications, to query each node and to install programmable traps. In order to take advantage of the Active Networks technology, we introduce active SNMP-like MIBs and agents, which are dynamic and programmable. The programmable management agents make tracing distributed applications a feasible task. We propose a general framework that can inter-operate with any active execution environment. In this framework, both the manager and the monitor front-ends communicate with an active node (the Active Network Access Point) through the XML language. A gateway service performs the translation of the queries from XML to an active packet language and injects the code in the network. We demonstrate the implementation of an active network gateway for PLAN (Packet Language for Active Networks) in a forty active nodes testbed. Finally, we discuss an application of the active management architecture to detect the causes of network failures by tracing network events in time.