Chemo-somatosensory evoked potentials: A sensitive tool to assess conditioned pain modulation?

Background: Chemo-somatosensory evoked potentials (CSSEPs) elicited by chemical stimulation (CO₂ gas) of the nasal mucosa have been shown to be sensitive enough to pick up even weak analgesic effects. With the present study we wanted to investigate whether CSSEPs are also a sensitive tool to capture endogenous pain inhibitory mechanisms elicited by conditioned pain modulation (CPM; where a first conditioning stimulus reduces the sensitivity for a second test stimulus) with a conditioning stimulus of rather low noxious load.

Methods: Seventeen healthy participants were tested for CPM effects (conditioning stimulus: tonic heat pain with intensities around the pain threshold induced via a thermode; test stimulus: chemonasal stimulation (73% and 78% CO₂)) on CSSEPs and on self-report ratings.

Results: We found significant CPM effects in the CSSEPS, with reduced amplitudes and prolonged latencies at several electroencephalogram (EEG) recording positions when using the lower CO₂ concentration (73% CO₂). In contrast to the visible inhibitory effects on the CSSEPs, subjective ratings of the test stimulus did not reflect CPM action.

Discussion: The experimental pain model using CO₂ stimuli to elicit CSSEPs proved to be sensitive enough to capture weak CPM effects elicited by a conditioning stimulus of rather low noxious load. The usage of such mild noxious conditioning stimuli—in contrast to stimuli of higher noxious load (e.g., cold pressor test)—has the advantage that the activation of other types of pain inhibitory mechanisms in parallel (like attentional distraction, stress-induced analgesia) can be avoided.     

Theory and practice of a posteriori “Wiener” filtering of average evoked potentials

In this study a theoretical and practical analysis of the technique of a posteriori Wiener filtering of averaged evoked potentials is presented. It is shown that spectral smoothing plays a central role in obtaining a reliable estimate. Attention is paid to some practical problems that arise when the method is applied in discrete time. In an illustrative case study results are compared to theoretical Wiener filtering, while the influence of slow amplitude modulation has also been investigated. Some of the conflicting results regarding the method that have been reported in several recent papers are discussed. It is concluded, that when the method is applied with prudence, it may lead to an improved estimation of those evoked potentials that can be assumed to be approximately stationary. If the latter assumption is not valid, application of a time-varying filter technique is recommended instead.     

Accumulation of aluminum in rat brain: does it lead to behavioral and electrophysiological changes?

The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each of the groups consisted of 10 animals. Aluminum chloride (AlCl₃) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 μg/g (wet weight), 0.963±0.491 μg/g (wet weight) and 1.816±1.157 μg/g (wet weight), respectively.     

Body odor evoked potentials: a new method to study the chemosensory perception of self and non‐self in humans

A new method will be presented which allows the perception of body odors in humans to be studied objectively. The analysis of body odor‐evoked potentials was used to investigate if and how the human brain is able to differentiate self from non‐self body odor for the first time. Six subjects (three females) participated in two experimental sessions. In each session, two body odors (axillary hair) were presented within an olfactory oddball paradigm. One of the odors was collected from the subject and the other from an odor donor of the same sex. In the first session the subjects' attention was distracted to a secondary task (passive paradigm), in the second session the subjects were asked to actively differentiate the odors (active paradigm). For the EEG recordings the odors were presented within a constantly flowing airstream. The results show that the subjects could hardly differentiate the body odors subjectively. However, it could be demonstrated that the central nervous processing of one's own odor was faster than the processing of the chemosensory non‐self signal. Moreover, in the active paradigm, the potentials appeared to be larger when the subjects perceived their own body odor. The conclusion is reached that the measurement of chemosensory event‐related potentials (CSERP) is the method of choice for the investigation of HLA‐associated body odors. This revised version was published online in July 2006 with corrections to the Cover Date.     

Separate generators with distinct orientations for N20 and P22 somatosensory evoked potentials to finger stimulation?

Sequential spatial maps of scalp potentials, obtained with a 16-channel montage, were used in 12 healthy subjects in order to assess the temporal and spatial distribution of early cortical SEPs to single finger stimulation. It was found that when the contralateral parietal N20 negativity peaks there is a synchronous frontal P20 positivity, supporting the view of a tangentially orientated dipolar generator for this couple of scalp SEPs components. It was not possible to show a distribution of N20 peak on the scalp that would parallel the somatotopic finger representations in area S1; however, the orientation of the putative dipolar source of the N20/P20 complex was found to change according to the finger stimulated. A central P22 component was also constantly obtained without any synchronous negativity on the scalp surface corresponding to the electrode array; a clear somatotopic organisation was found for P22. These features favour the hypothesis that this latter component has a radially orientated generator situated in the prerolandic motor cortex, close to the scalp surface. Because of overlapping between the P20 and P22 components, the determination of P22 onset latency was hazardous in some cases, and spatial mapping was then essential to identify this component. The conclusion that the contralateral parietal N20 and central P22 could be generated by separate dipolar generators with distinct orientations is supported by recent data from combined electrical and magnetic field recording.     

Scalp potentials following sudden coherence and discoherence of binaural noise and change in the inter-aural time difference: a specific binaural evoked potential or a “mismatch” response?

When uncorrelated random noise signals presented to the two ears suddenly become identical (coherent), a centrally located sound image is abruptly perceived and long latency scalp potentials are evoked. When the same signals are presented monaurally there is no perceived change and no potentials are evoked: hence the response must be purely a function of the binaural interaction.P70, N130 and P220 components were consistently recorded to both coherence and discoherence. N130 was usually largest at Fz and P220 at Cz. No potentials of shorter latency were identified, even after averaging 5000 or more sweeps. When the noise became coherent with an inter-aural time difference (δT) of ±0.5 msec (giving rise to an off-centre sound image), the responses were of slightly longer latency and showed no significant asymmetries between C3 and C4. In binaurally coherent noise, δT changes of ±0.5 or ±1.0 msec evoked similar responses which showed no significant asymmetries on the scalp. N130 was of longer latency when δT was changed from ±0.5 msec to zero, as compared with the converse change.In view of the similarity of all these responses it is considered unlikely that they were due to specific populations of binaurally responsive cortical neurones. The N130 and P220 components are thought to be non-specific potentials which are elicited by amy perceptible change in steady auditory stimulus conditions, due to a “mismatch” between the stimulus and the contents of a short-term auditory memory.     

Genomics and policymaking: from static models to complex systems?

In the 20 years following the launching of the Human Genome Project, socio-ethical and legal responses to the policy issues raised have varied across jurisdictions. There seems, however, to be a move away from the more static, classical responses that characterized the first decade to a more epigenetic and complex one. The latter policy approach better reflects the dynamic nature of the science itself.     

Auditory pathways: are 'what' and 'where' appropriate?

New evidence confirms that the auditory system encompasses temporal, parietal and frontal brain regions, some of which partly overlap with the visual system. But common assumptions about the functional homologies between sensory systems may be misleading.     

Stimulus–response characteristics of motor evoked potentials and silent periods in proximal and distal upper-extremity muscles

ObjectiveTo compare stimulus–response characteristics of both motor evoked potentials (MEP) and silent periods (SP) induced by transcranial magnetic stimulation (TMS) in proximal and distal upper-extremity muscles.MethodsStimulus–response curves of MEPs and SPs were obtained from the biceps brachii (BB) and abductor digiti minimi (ADM) muscles in 15 healthy participants. A nonlinear mixed model was used to fit the stimulus–response curves to a sigmoid Boltzmann function.ResultsSmall residuals of the function were found for MEPs and SPs in both muscles. Higher maximal MEP amplitudes were found for the BB compared to the ADM (p < 0.01). The active motor threshold to obtain a SP was less for the ADM compared to the BB (p < 0.01). The slope parameter of the function of the SP duration was steeper and more variable in the ADM than in the BB (p < 0.01). For the MEP amplitude no difference in active motor threshold and slope of the function was found between both muscles.ConclusionsExcitatory (MEP) and inhibitory (SP) effects of TMS differ between proximal arm and distal hand muscles in healthy participants. The adequate fit of our model suggests that this model can be used to study between and within subject changes in future studies.     

Optimal (‘Wiener’) digital filtering of auditory evoked potentials: use of coherence estimates

Auditory evoked potentials (AEPs) to 40 Hz clicks and amplitude-modulated 500 Hz tones in human subjects were digitally filtered using an optimal (‘Wiener’) filter uniquely determined for each AEP. Use of coherence functions to compute coefficients appropriate for filtering grand average AEPs or subsets such as split-half averages is described. Wiener-filtered AEPs correlated better than unfiltered AEPs with split-half replicates and with references AEPs (obtained with long data collection periods). Visual detection thresholds were lower (more sensitive) for the Wiener-filtered AEPs, but not as low as objectively determined thresholds using coherence values.     

Is there evidence for a shift in fish growth and recruitment success linked to climate change?

This study investigated whether a putative shift in climate regime in the North Atlantic in the 1990s coincided with changes in the growth and recruitment of roach Rutilus rutilus in the north-east of England. The relationships between R. rutilus growth and recruitment and the environment were significantly different before and after the putative shift in climate regime. Water temperature, river discharge, growth, recruitment success and the Gulf Stream Index co-varied until the late 1990s, indicating a gradual progression between periods of warm-and-dry and cold-and-wet summers. Since the late 1990s, there has been an increased prevalence of warm-and-wet summers, and recruitment success has oscillated between extremes on an almost annual basis. The north wall (northern boundary) of the Gulf Stream has been undergoing a displacement south since the late 1990s, and the speed and amplitude of the change appears to support the hypothesis that there was a regime shift in the climate of the North Atlantic Ocean. It is possible that a continued displacement south of the north wall of the Gulf Stream will lead to further increases in river discharge, reductions in water temperature and reduced fish growth and recruitment success in the long term.     

The genetics of speciation: are complex incompatibilities easier to evolve?

Reproductive isolation can evolve readily when genotypes containing incompatible alleles are connected by chains of fit intermediates. Experimental crosses show that such Dobzhansky–Muller incompatibilities (DMIs) are often complex (involving alleles at three or more loci) and asymmetrical (such that reciprocal introgressions have very different effects on fitness). One possible explanation is that asymmetrical and complex DMIs are ‘easier to evolve’, because they block fewer of the possible evolutionary paths between the parental genotypes. To assess this argument, we model evolutionary divergence in allopatry and calculate the delays to divergence caused by DMIs of different kinds. We find that the number of paths is sometimes, though not always, a reliable predictor of the time to divergence. In particular, we find limited support for the idea that symmetrical DMIs take longer to evolve, but this applies largely to two‐locus symmetrical DMIs (which leave no path of fit intermediates). Symmetrical complex DMIs can also delay divergence, but only in a limited region of parameter space. In most other cases, the presence and form of DMIs have little influence on times to divergence, and so we argue that ease of evolution is unlikely to be important in explaining the experimental data.     

Mercury and autism: accelerating evidence?

The causes of autism and neurodevelopmental disorders are unknown. Genetic and environmental risk factors seem to be involved. Because of an observed increase in autism in the last decades, which parallels cumulative mercury exposure, it was proposed that autism may be in part caused by mercury. We review the evidence for this proposal. Several epidemiological studies failed to find a correlation between mercury exposure through thimerosal, a preservative used in vaccines, and the risk of autism. Recently, it was found that autistic children had a higher mercury exposure during pregnancy due to maternal dental amalgam and thimerosal-containing immunoglobulin shots. It was hypothesized that children with autism have a decreased detoxification capacity due to genetic polymorphism. In vitro, mercury and thimerosal in levels found several days after vaccination inhibit methionine synthetase (MS) by 50%. Normal function of MS is crucial in biochemical steps necessary for brain development, attention and production of glutathione, an important antioxidative and detoxifying agent. Repetitive doses of thimerosal leads to neurobehavioral deteriorations in autoimmune susceptible mice, increased oxidative stress and decreased intracellular levels of glutathione in vitro. Subsequently, autistic children have significantly decreased level of reduced glutathione. Promising treatments of autism involve detoxification of mercury, and supplementation of deficient metabolites.     

Evaluation of genetic tests for susceptibility to common complex diseases: why, when and how?

Recent research into the human genome has generated a wealth of scientific knowledge and increased both public and professional interest in the concept of personalised medicine. Somewhat unexpectedly, in addition to increasing our understanding about the genetic basis for numerous diseases, these new discoveries have also spawned a burgeoning new industry of ‘consumer genetic testing’. In this paper, we present the principles learnt though the evaluation of tests for single gene disorders and suggest a comparable framework for the evaluation of genetic tests for susceptibility to common complex diseases. Both physicians and the general public will need to be able to assess the claims made by providers of genetic testing services, and ultimately policy-makers will need to decide if and when such tests should be offered through state funded healthcare systems.     

Developmental programming of reproduction and fertility: what is the evidence?

The concept of the foetal/developmental origins of adult disease has been around for ~20 years and from the original epidemiological studies in human populations much more evidence has accumulated from the many studies in animal models. The majority of these have focused upon the role of early dietary intake before conception, through gestation and/or lactation and subsequent interactions with the postnatal environment, e.g. dietary and physical activity exposures. Whilst a number of theoretical models have been proposed to place the experimental data into a biological context, the underlying phenomena remain the same; developmental deficits (of single (micro) nutrients) during critical or sensitive periods of tissue growth alter the developmental pathway to ultimately constrain later functional capacity when the individual is adult. Ageing, without exception, exacerbates any programmed sequelae. Thus, adult phenotypes that have been relatively easy to characterise (e.g. blood pressure, insulin sensitivity, body fat mass) have received most attention in the literature. To date, relatively few studies have considered the effect of differential early environmental exposures on reproductive function and fecundity in predominantly mono-ovular species such as the sheep, cow and human. The available evidence suggests that prenatal insults, undernutrition for example, have little effect on lifetime reproductive capacity despite subtle effects on the hypothalamic-pituitary-gonadal axis and gonadal progenitor cell complement. The postnatal environment is clearly important, however, since neonatal/adolescent growth acceleration (itself not independent from prenatal experience) has been shown to significantly influence fecundity in farm animals. The present paper will expand these interesting areas of investigation and review the available evidence regarding developmental programming of reproduction and fertility. However, it appears there is little strong evidence to indicate that offspring fertility and reproductive senescence in the human and in farm animal species are overtly affected by prenatal nutrient exposure. Nevertheless, it is clear that the developing gonad is sensitive to its immediate environment but more detailed investigation is required to specifically test the long-term consequences of nutritional perturbations during pregnancy on adult reproductive well-being.     

Metapopulation shift and survival of woodland birds under climate change: will species be able to track?

Climate change has been widely recognized as a key factor driving changes in species distributions. In this study we use a metapopulation model, with a window of suitable climate moving polewards, to explore population shifts and survival of woodland birds under different climate change scenarios and landscape configurations. Extinction vulnerability and expansion ability are predicted for the middle spotted woodpecker Dendrocopus medius and two alternative r‐K strategies under west European climate change scenarios of 1, 2 and 4°C temperature increase per century, corresponding to isotemperature velocities of ca 2, 4 and 8 km yr^?1. The simulated northward expansion of the bird's distribution is typically in the range of only 0–3 km yr^?1, in spite of 10–20 times larger maximum dispersal distances. This is too slow to track the climate change‐driven range contraction of 4 or 8 km yr^?1 in the south resulting in metapopulation extinction. Especially K‐selected (large‐bodied) species are vulnerable in the simulations. With a temperature increase of 4°C per century bird species go extinct within 104–178 yr. We present a simple approximation formula to predict the mean time to metapopulation extinction using 1) the rate of climate change, which determines the speed of range contraction in the south, 2) the size of the distribution range, which serves as a buffer against extinction, and 3) the northward expansion velocity, determined by species traits and landscape properties. Finally, our results indicate that the northward expansion rate is not constant. It will be initially lagged suggesting that recently observed expansion rates might be underestimations of future northward expansion rates.     

The Late Palaeozoic phytoplankton blackout — Artefact or evidence of global change?

The fossil record of the Palaeozoic documents one of the most dramatic changes in Phanerozoic marine primary production, although causes and effects of these changes have been the subject of rather controversial discussions. During the early Palaeozoic the marine phytoplankton experienced an enormous radiation and diversification of taxa especially among acritarchs, which was punctuated by a few extinction events possibly associated with climate changes. Phytoplankton diversity was drastically reduced at the Devonian/Carboniferous boundary, a phenomenon here designated as the “Phytoplankton Blackout”.After a lapse of about 130 million years phytoplankton diversity was gradually restored during the Late Triassic with the appearance of dinoflagellates and somewhat later of coccolithophorids and diatoms. Evidence from recent phytoplankton suggests that the dominant groups of phytoplankton differ from those of the Palaeozoic in their nutritional requirements and that fundamental changes in ocean chemistry have played an important role.The remarkable temporal coincidence of the Phytoplankton Blackout with plate tectonic processes during the assembly and breakup of Pangaea and the concomitant rise of land plants towards the end of the Devonian provide arguments that nutrient depletion in the ocean may have played a decisive role in controlling the phytoplankton blackout. Contrary arguments in favour of oceanic eutrophication, changes in life cycles of dominant phytoplankton groups or selective preservation are discussed and weighed against the scenario presented here. Metazoan evolution seems only loosely linked with the phytoplankton blackout. However, there is good agreement between phytoplankton and reef evolution throughout the Phanerozoic.