Exploiting semantic information in a spiking neural SLAM system.

To navigate in new environments, an animal must be able to keep track of its position while simultaneously creating and updating an internal map of features in the environment, a problem formulated as simultaneous localization and mapping (SLAM) in the field of robotics. This requires integrating information from different domains, including self-motion cues, sensory, and semantic information. Several specialized neuron classes have been identified in the mammalian brain as being involved in solving SLAM. While biology has inspired a whole class of SLAM algorithms, the use of semantic information has not been explored in such work. We present a novel, biologically plausible SLAM model called SSP-SLAM-a spiking neural network designed using tools for large scale cognitive modeling. Our model uses a vector representation of continuous spatial maps, which can be encoded via spiking neural activity and bound with other features (continuous and discrete) to create compressed structures containing semantic information from multiple domains (e.g., spatial, temporal, visual, conceptual). We demonstrate that the dynamics of these representations can be implemented with a hybrid oscillatory-interference and continuous attractor network of head direction cells. The estimated self-position from this network is used to learn an associative memory between semantically encoded landmarks and their positions, i.e., an environment map, which is used for loop closure. Our experiments demonstrate that environment maps can be learned accurately and their use greatly improves self-position estimation. Furthermore, grid cells, place cells, and object vector cells are observed by this model. We also run our path integrator network on the NengoLoihi neuromorphic emulator to demonstrate feasibility for a full neuromorphic implementation for energy efficient SLAM.

Biologically-Based Computation: How Neural Details and Dynamics Are Suited for Implementing a Variety of Algorithms.

The Neural Engineering Framework (Eliasmith & Anderson, 2003) is a long-standing method for implementing high-level algorithms constrained by low-level neurobiological details. In recent years, this method has been expanded to incorporate more biological details and applied to new tasks. This paper brings together these ongoing research strands, presenting them in a common framework. We expand on the NEF's core principles of (a) specifying the desired tuning curves of neurons in different parts of the model, (b) defining the computational relationships between the values represented by the neurons in different parts of the model, and (c) finding the synaptic connection weights that will cause those computations and tuning curves. In particular, we show how to extend this to include complex spatiotemporal tuning curves, and then apply this approach to produce functional computational models of grid cells, time cells, path integration, sparse representations, probabilistic representations, and symbolic representations in the brain.

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient.

A vascularized composite tissue allotransplantation (VCA) was performed at the Children's Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at "hand areas", reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip's somatosensory response.

Brain activity modifications following spinal cord stimulation for chronic neuropathic pain: A systematic review.

BACKGROUND AND OBJECTIVE: Spinal cord stimulation (SCS) is believed to exert supraspinal effects; however, these mechanisms are still far from fully elucidated. This systematic review aims to assess existing neurophysiological and functional neuroimaging literature to reveal current knowledge regarding the effects of SCS for chronic neuropathic pain on brain activity, to identify gaps in knowledge, and to suggest directions for future research. DATABASES AND DATA TREATMENT: Electronic databases and hand-search of reference lists were employed to identify publications investigating brain activity associated with SCS in patients with chronic neuropathic pain, using neurophysiological and functional neuroimaging techniques (fMRI, PET, MEG, EEG). Studies investigating patients with SCS for chronic neuropathic pain and studying brain activity related to SCS were included. Demographic data (age, gender), study factors (imaging modality, patient diagnoses, pain area, duration of SCS at recording, stimulus used) and brain areas activated were extracted from the included studies. RESULTS: Twenty-four studies were included. Thirteen studies used neuroelectrical imaging techniques, eight studies used haemodynamic imaging techniques, two studies employed both neuroelectrical and haemodynamic techniques separately, and one study investigated cerebral neurobiology. CONCLUSIONS: The limited available evidence regarding supraspinal mechanisms of SCS does not allow us to develop any conclusive theories. However, the studies included appear to show an inhibitory effect of SCS on somatosensory evoked potentials, as well as identifying the thalamus and anterior cingulate cortex as potential mediators of the pain experience. The lack of substantial evidence in this area highlights the need for large-scale controlled studies of this kind.

Dissociable contributions of ventromedial prefrontal and posterior parietal cortex to value-guided choice.

Two long-standing traditions have highlighted cortical decision mechanisms in the parietal and prefrontal cortices of primates, but it has not been clear how these processes differ, or when each cortical region may influence behaviour. Recent data from ventromedial prefrontal cortex (vmPFC) and posterior parietal cortex (PPC) have suggested one possible axis on which the two decision processes might be delineated. Fast decisions may be resolved primarily by parietal mechanisms, whereas decisions made without time pressure may rely on prefrontal mechanisms. Here, we report direct evidence for such dissociation. During decisions under time pressure, a value comparison process was evident in PPC, but not in vmPFC. Value-related activity was still found in vmPFC under time pressure. However, vmPFC represented overall input value rather than compared output value. In contrast, when decisions were made without time pressure, vmPFC transitioned to encode a value comparison while value-related parameters were entirely absent from PPC. Furthermore, under time pressure, decision performance was primarily governed by PPC, while it was dominated by vmPFC at longer decision times. These data demonstrate that parallel cortical mechanisms may resolve the same choices in differing circumstances, and offer an explanation of the diverse neural signals reported in vmPFC and PPC during value-guided choice.

Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters.

BACKGROUND: Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. METHODS: 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. KEY RESULTS: Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p < 0.005). Patients tolerated less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p < 0.001). At baseline, patients had a higher sympathetic tone (p = 0.04), whereas in response to pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). CONCLUSIONS & INFERENCES: In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling.

Psychological traits influence autonomic nervous system recovery following esophageal intubation in health and functional chest pain.

BACKGROUND: Esophageal intubation is a widely utilized technique for a diverse array of physiological studies, activating a complex physiological response mediated, in part, by the autonomic nervous system (ANS). In order to determine the optimal time period after intubation when physiological observations should be recorded, it is important to know the duration of, and factors that influence, this ANS response, in both health and disease. METHODS: Fifty healthy subjects (27 males, median age 31.9 years, range 20-53 years) and 20 patients with Rome III defined functional chest pain (nine male, median age of 38.7 years, range 28-59 years) had personality traits and anxiety measured. Subjects had heart rate (HR), blood pressure (BP), sympathetic (cardiac sympathetic index, CSI), and parasympathetic nervous system (cardiac vagal tone, CVT) parameters measured at baseline and in response to per nasum intubation with an esophageal catheter. CSI/CVT recovery was measured following esophageal intubation. KEY RESULTS: In all subjects, esophageal intubation caused an elevation in HR, BP, CSI, and skin conductance response (SCR; all p < 0.0001) but concomitant CVT and cardiac sensitivity to the baroreflex (CSB) withdrawal (all p < 0.04). Multiple linear regression analysis demonstrated that longer CVT recovery times were independently associated with higher neuroticism (p < 0.001). Patients had prolonged CSI and CVT recovery times in comparison to healthy subjects (112.5 s vs 46.5 s, p = 0.0001 and 549 s vs 223.5 s, p = 0.0001, respectively). CONCLUSIONS & INFERENCES: Esophageal intubation activates a flight/flight ANS response. Future studies should allow for at least 10 min of recovery time. Consideration should be given to psychological traits and disease status as these can influence recovery.

Gamma oscillatory amplitude encodes stimulus intensity in primary somatosensory cortex.

Gamma oscillations have previously been linked to pain perception and it has been hypothesized that they may have a potential role in encoding pain intensity. Stimulus response experiments have reported an increase in activity in the primary somatosensory cortex (SI) with increasing stimulus intensity, but the specific role of oscillatory dynamics in this change in activation remains unclear. In this study, Magnetoencephalography (MEG) was used to investigate the changes in cortical oscillations during four different intensities of a train of electrical stimuli to the right index finger, ranging from low sensation to strong pain. In those participants showing changes in evoked oscillatory gamma in SI during stimulation, the strength of the gamma power was found to increase with increasing stimulus intensity at both pain and sub-pain thresholds. These results suggest that evoked gamma oscillations in SI are not specific to pain but may have a role in encoding somatosensory stimulus intensity.

Cocaine induces a reversible stomatocytosis of red blood cells and increases blood viscosity.

Severe side effects of cocaine consumption are vasoocclusive events such as myocardial infarction and stroke. We have hypothesized that cocaine could affect red blood cells (RBCs) and alter the rheological behaviour of blood. Heparinized blood from healthy volunteers was incubated with a final hematocrit of 45% with increasing cocaine concentrations: 0, 10, 100, 1000, and 10'000 µmol/L plasma. Time dependence of the shape change was tested in phosphate buffered saline containing cocaine. RBCs were fixed in 1% glutaraldehyde for morphological analysis. Blood viscosity was measured with a Couette Viscometer (Contraves LS 30) at 37°C and a shear rate of 69.5 s⁻¹. RBC aggregation was assessed with a Myrenne aggregometer. Cocaine induced a dose-dependent stomatocytic shape transformation of RBCs, which was more pronounced in buffer than in plasma (plasma protein binding of the drug). Stomatocytosis occurs when a drug intercalates preferentially in the inner half of the membrane lipid bilayer. It was a time-dependent process with two components, an almost instant shape change occurring within 1 s, followed by a gradual further shape change during 10 min. Stomatocytosis was reversible by resuspension of the RBCs in cocaine-free buffer. This stomatocytic shape change increased whole blood viscosity at high shear rate from 5.69±0.31 mPa.s to 6.39±0.34 mPa.s for control and 10'000 µmol/L cocaine, respectively (p<0.01). RBC aggregation was not affected by the shape change. These effects occurred at a cocaine concentration, which is several-fold above those measured in vivo. Therefore, it is unlikely that hemorheological factors are involved in vascular events after cocaine consumption.

Sensory thresholds obtained from MEG data: cortical psychometric functions.

Sensory sensitivity is typically measured using behavioural techniques (psychophysics), which rely on observers responding to very large numbers of stimulus presentations. Psychophysics can be problematic when working with special populations, such as children or clinical patients who may lack the compliance or cognitive skills to perform the behavioural tasks. We used an auditory gap-detection paradigm to develop an accurate measure of sensory threshold derived from passively-recorded magnetoencephalographic (MEG) data. Auditory evoked responses were elicited by silent gaps of varying durations in an on-going noise stimulus. Source modelling was used to spatially filter the MEG data and sigmoidal 'cortical psychometric functions' relating response amplitude to gap duration were obtained for each individual participant. Fitting the functions with a curve and estimating the gap duration at which the amplitude of the evoked response exceeded one standard deviation of the prestimulus brain activity provided an excellent prediction of psychophysical threshold. Accurate sensory thresholds can therefore be reliably extracted from MEG data recorded while participants listen passively to a stimulus. Because our paradigm required no behavioural task, the method is suitable for studies of populations where variations in cognitive skills or vigilance make traditional psychophysics unsuitable.

The role of GABAergic modulation in motor function related neuronal network activity.

At rest, the primary motor cortex (M1) exhibits spontaneous neuronal network oscillations in the beta (15-30 Hz) frequency range, mediated by inhibitory interneuron drive via GABA-A receptors. However, questions remain regarding the neuropharmacological basis of movement related oscillatory phenomena, such as movement related beta desynchronisation (MRBD), post-movement beta rebound (PMBR) and movement related gamma synchronisation (MRGS). To address this, we used magnetoencephalography (MEG) to study the movement related oscillatory changes in M1 cortex of eight healthy participants, following administration of the GABA-A modulator diazepam. Results demonstrate that, contrary to initial hypotheses, neither MRGS nor PMBR appear to be GABA-A dependent, whilst the MRBD is facilitated by increased GABAergic drive. These data demonstrate that while movement-related beta changes appear to be dependent upon spontaneous beta oscillations, they occur independently of one other. Crucially, MRBD is a GABA-A mediated process, offering a possible mechanism by which motor function may be modulated. However, in contrast, the transient increase in synchronous power observed in PMBR and MRGS appears to be generated by a non-GABA-A receptor mediated process; the elucidation of which may offer important insights into motor processes.

Effective electromagnetic noise cancellation with beamformers and synthetic gradiometry in shielded and partly shielded environments.

The major challenge of MEG, the inverse problem, is to estimate the very weak primary neuronal currents from the measurements of extracranial magnetic fields. The non-uniqueness of this inverse solution is compounded by the fact that MEG signals contain large environmental and physiological noise that further complicates the problem. In this paper, we evaluate the effectiveness of magnetic noise cancellation by synthetic gradiometers and the beamformer analysis method of synthetic aperture magnetometry (SAM) for source localisation in the presence of large stimulus-generated noise. We demonstrate that activation of primary somatosensory cortex can be accurately identified using SAM despite the presence of significant stimulus-related magnetic interference. This interference was generated by a contact heat evoked potential stimulator (CHEPS), recently developed for thermal pain research, but which to date has not been used in a MEG environment. We also show that in a reduced shielding environment the use of higher order synthetic gradiometry is sufficient to obtain signal-to-noise ratios (SNRs) that allow for accurate localisation of cortical sensory function.

Oesophageal afferent pathway sensitivity in non-erosive reflux disease.

Patients with non-erosive reflux disease (NERD) report symptoms which commonly fail to improve on conventional antireflux therapies. Oesophageal visceral hyperalgaesia may contribute to symptom generation in NERD and we explore this hypothesis using oesophageal evoked potentials. Fifteen endoscopically confirmed NERD patients (four female, 29-56 years) plus 15 matched healthy volunteers (four female, 23-56 years) were studied. All patients had oesophageal manometry/24-h pH monitoring and all subjects underwent evoked potential and sensory testing, using electrical stimulation of the distal oesophagus. Cumulatively, NERD patients had higher sensory thresholds and increased evoked potential latencies when compared to controls (P = 0.01). In NERD patients, there was a correlation between pain threshold and acid exposure as determined by DeMeester score (r = 0.63, P = 0.02), with increased oesophageal sensitivity being associated with lower DeMeester score. Reflux negative patients had lower pain thresholds when compared to both reflux positive patients and controls. Evoked potentials were normal in reflux negative patients but significantly delayed in the reflux positive group (P = 0.01). We demonstrate that NERD patients form a continuum of oesophageal afferent sensitivity with a correlation between the degree of acid exposure and oesophageal pain thresholds. We provide objective evidence that increased oesophageal pain sensitivity in reflux negative NERD is associated with heightened afferent sensitivity as normal latency evoked potential responses could be elicited with reduced afferent input. Increased oesophageal afferent pain sensitivity may play an important role in a subset of NERD and could offer an alternate therapeutic target.

A comparison of non-radioactive methods for assessing viability in ex vivo cultured cancellous bone: technical note.

Biocompatibility studies are carried out either in two dimensional monolayer culture or in animal studies. Bone organ cultures are therefore required in order to reduce the number of animal studies performed, while at the same time ensuring a more natural environment than that provided by monolayer culture of isolated cells. Due to the three dimensional nature of bone explants, assays that determine the distribution of viable cells are required, however dense mineralised bone is not easily penetrated by soluble factors. We sought to compare a number of non-radioactive viability methods in order to assess their suitability for use with cancellous bone. Fluorescent live/dead staining, MTT activity and lactate dehydrogenase detection were all investigated on either whole bone explants (9.5 mm in diameter, 5 mm high) or on sections of explants. All these assays are routinely used in 2 dimensional cell culture systems, yet each required modifications to be suitable for use with cancellous bone. Factors such as penetration of reagent, incubation time, assay temperature and ease of determining viable cells were all compared. It was demonstrated that penetration of the reagents into whole cores was a major problem which easily led to artefacts that could be overcome by preparing 250 mum unfixed sections. Fluorescent live/dead staining had extra complications caused by the autofluorescence of the bone generating a high signal to noise ratio, making assessment of osteocyte viability impossible. MTT staining was difficult to interpret due to the punctate nature of the stain. We found that lactate dehydrogenase staining of 250 mum thick unfixed sections led to excellent viability determination of osteocytes within the mineralised matrix. It also maintained marrow structure and enabled marrow viability to be assessed as a factor of volume occupied by viable marrow. Decreasing the viscosity of the LDH assay solution used in published methods led to a greatly improved penetration into the calcified matrix. Quantification of thick sections is aided by using the autofluorescence of the bone to highlight the darkly stained osteocytes against the fluorescing bone.

Dissociating the spatio-temporal characteristics of cortical neuronal activity associated with human volitional swallowing in the healthy adult brain.

Human swallowing represents a complex highly coordinated sensorimotor function whose functional neuroanatomy remains incompletely understood. Specifically, previous studies have failed to delineate the temporo-spatial sequence of those cerebral loci active during the differing phases of swallowing. We therefore sought to define the temporal characteristics of cortical activity associated with human swallowing behaviour using a novel application of magnetoencephalography (MEG). In healthy volunteers (n = 8, aged 28-45), 151-channel whole cortex MEG was recorded during the conditions of oral water infusion, volitional wet swallowing (5 ml bolus), tongue thrust or rest. Each condition lasted for 5 s and was repeated 20 times. Synthetic aperture magnetometry (SAM) analysis was performed on each active epoch and compared to rest. Temporal sequencing of brain activations utilised time-frequency wavelet plots of regions selected using virtual electrodes. Following SAM analysis, water infusion preferentially activated the caudolateral sensorimotor cortex, whereas during volitional swallowing and tongue movement, the superior sensorimotor cortex was more strongly active. Time-frequency wavelet analysis indicated that sensory input from the tongue simultaneously activated caudolateral sensorimotor and primary gustatory cortex, which appeared to prime the superior sensory and motor cortical areas, involved in the volitional phase of swallowing. Our data support the existence of a temporal synchrony across the whole cortical swallowing network, with sensory input from the tongue being critical. Thus, the ability to non-invasively image this network, with intra-individual and high temporal resolution, provides new insights into the brain processing of human swallowing.

Co-registration of magnetoencephalography with magnetic resonance imaging using bite-bar-based fiducials and surface-matching.

OBJECTIVE: To introduce a new technique for co-registration of Magnetoencephalography (MEG) with magnetic resonance imaging (MRI). We compare the accuracy of a new bite-bar with fixed fiducials to a previous technique whereby fiducial coils were attached proximal to landmarks on the skull. METHODS: A bite-bar with fixed fiducial coils is used to determine the position of the head in the MEG co-ordinate system. Co-registration is performed by a surface-matching technique. The advantage of fixing the coils is that the co-ordinate system is not based upon arbitrary and operator dependent fiducial points that are attached to landmarks (e.g. nasion and the preauricular points), but rather on those that are permanently fixed in relation to the skull. RESULTS: As a consequence of minimizing coil movement during digitization, errors in localization of the coils are significantly reduced, as shown by a randomization test. Displacement of the bite-bar caused by removal and repositioning between MEG recordings is minimal ( approximately 0.5 mm), and dipole localization accuracy of a somatosensory mapping paradigm shows a repeatability of approximately 5 mm. The overall accuracy of the new procedure is greatly improved compared to the previous technique. CONCLUSIONS: The test-retest reliability and accuracy of target localization with the new design is superior to techniques that incorporate anatomical-based fiducial points or coils placed on the circumference of the head.

Central neural mechanisms mediating human visceral hypersensitivity.

Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 +/- 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 +/- 2.3 and 15.8 +/- 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity.

Comparison of cortical potentials evoked by mechanical and electrical stimulation of the rectum.

Patients with irritable bowel syndrome have heightened perception of gut sensation. The mechanisms responsible for this remain unknown, due to current poor knowledge of the central processing of gut sensation. Cortical evoked potentials (CEPs) have been recorded following both electrical rectal stimulation (ERS) and mechanical rectal stimulation (MRS). Because of the lack of a direct comparison of these two methods, their robustness for future clinical use remains unknown. The aim of our study was to compare the characteristics of CEPs following ERS and MRS. CEPs were recorded from the vertex in 14 healthy volunteers following ERS with bipolar ring electrodes, and MRS by repeated rectal distension. CEPs were recorded in all subjects following electrical stimulation, but only in 11 subjects following mechanical stimulation. In comparison with electrical stimulation, mechanical stimulation produced CEPs with a smaller amplitude and longer latency. However, the morphology of CEPs following electrical and mechanical rectal stimulation was similar, with no difference in the interpeak latencies. In conclusion, we have demonstrated that electrical rectal stimulation is a more reliable stimulus for recording CEPs. The similarity of the morphology and interpeak latencies of the CEPs suggests that both stimuli are activating a similar network of cortical neurones.

A cortical evoked potential study of afferents mediating human esophageal sensation.

The aim of this study was to compare the characteristics of esophageal cortical evoked potentials (CEP) following electrical and mechanical stimulation in healthy subjects to evaluate the afferents involved in mediating esophageal sensation. Similarities in morphology and interpeak latencies of the CEP to electrical and mechanical stimulation suggest that they are mediated via similar pathways. Conduction velocity of CEP to either electrical or mechanical stimulation was 7.9-8.6 m/s, suggesting mediation via thinly myelinated Adelta-fibers. Amplitudes of CEP components to mechanical stimulation were significantly smaller than to electrical stimulation at the same levels of perception, implying that electrical stimulation activates a larger number of afferents. The latency delay of approximately 50 ms for each mechanical CEP component compared with the corresponding electrical CEP component is consistent with the time delay for the mechanical stimulus to distend the esophageal wall sufficiently to trigger the afferent volley. In conclusion, because the mechanical and electrical stimulation intensities needed to obtain esophageal CEP are similar and clearly perceived, it is likely that both spinal and vagal pathways mediate esophageal CEP. Esophageal CEP to both modalities of stimulation are mediated by myelinated Adelta-fibers and produce equally robust CEP responses. Both techniques may have important roles in the assessment of esophageal sensory processing in health and disease.

Identification of the optimal parameters for recording cortical potentials evoked by mechanical stimulation of the human oesophagus.

Cortical evoked potentials (CEP) have been recorded in response to both electrical stimulation (ES) and mechanical stimulation (MS) of the oesophagus. While the optimal parameters for recording reproducible oesophageal CEP to ES have recently been established, they have not yet been determined for MS, and reported CEP to MS show considerable variability. This study aimed to identify the optimal parameters required to record reproducible MS induced CEP. CEP were recorded from the vertex (Cz) in six subjects (one female; age range 23-47 years). MS was performed 5 cm above the lower oesophageal sphincter by rapidly inflating a 2-cm long silicone balloon at a frequency of 0.2 Hz. The rise time to maximum inflation was 165 ms. In order to determine the minimum number of stimuli required to produce optimal signal-to-noise quality, we acquired data in runs of 25, 50, 100 and 300 stimuli and to determine the stimulation intensity that produced the shortest latency and the largest amplitude CEP, we averaged four runs of 50 stimuli at five different intensities ranging from sensory threshold to pain. CEP reproducibility was then assessed in three subjects on three separate occasions using parameters determined from these measurements. We found that optimal signal-to-noise quality was achieved by averaging four runs of 50 stimuli; that P1 latency was shortest and P1-N1 amplitude largest at intensities of 75% and pain threshold and that highly reproducible CEP were obtained in all individuals. We conclude that it is possible to obtain highly reproducible oesophageal CEP to MS which can now be compared to those obtained by ES in order to identify which is most suitable for clinical studies.