Andrew C. N. Chen

Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study.

Two- or 100-Hz electrical acupoint stimulation (EAS) can induce analgesia via distinct central mechanisms. It has long been known that the extent of EAS analgesia showed tremendous difference among subjects. Functional MRI (fMRI) studies were performed to allocate the possible mechanisms underlying the frequency specificity as well as individual variability of EAS analgesia. In either frequencies, the averaged fMRI activation levels of bilateral secondary somatosensory area and insula, contralateral anterior cingulate cortex and thalamus were positively correlated with the EAS-induced analgesic effect across the subjects. In 2-Hz EAS group, positive correlations were observed in contralateral primary motor area, supplementary motor area, and ipsilateral superior temporal gyrus, while negative correlations were found in bilateral hippocampus. In 100-Hz EAS group, positive correlations were observed in contralateral inferior parietal lobule, ipsilateral anterior cingulate cortex, nucleus accumbens, and pons, while negative correlation was detected in contralateral amygdala. These results suggest that functional activities of certain brain areas might be correlated with the effect of EAS-induced analgesia, in a frequency-dependent dynamic. EAS-induced analgesia with low and high frequencies seems to be mediated by different, though overlapped, brain networks. The differential activations/de-activations in brain networks across subjects may provide a neurobiological explanation for the mechanisms of the induction and the individual variability of analgesic effect induced by EAS, or that of manual acupuncture as well.

Automatic recognition of alertness and drowsiness from EEG by an artificial neural network

We present a novel method for classifying alert vs drowsy states from 1 s long sequences of full spectrum EEG recordings in an arbitrary subject. This novel method uses time series of interhemispheric and intrahemispheric cross spectral densities of full spectrum EEG as the input to an artificial neural network (ANN) with two discrete outputs: drowsy and alert. The experimental data were collected from 17 subjects. Two experts in EEG interpretation visually inspected the data and provided the necessary expertise for the training of an ANN. We selected the following three ANNs as potential candidates: (1) the linear network with Widrow-Hoff (WH) algorithm; (2) the non-linear ANN with the Levenberg-Marquardt (LM) rule; and (3) the Learning Vector Quantization (LVQ) neural network. We showed that the LVQ neural network gives the best classification compared with the linear network that uses WH algorithm (the worst), and the non-linear network trained with the LM rule. Classification properties of LVQ were validated using the data recorded in 12 healthy volunteer subjects, yet whose EEG recordings have not been used for the training of the ANN. The statistics were used as a measure of potential applicability of the LVQ: the t-distribution showed that matching between the human assessment and the network output was 94.37+/-1.95%. This result suggests that the automatic recognition algorithm is applicable for distinguishing between alert and drowsy state in recordings that have not been used for the training.

EEG default mode network in the human brain: spectral regional field powers.

Eyes-closed (EC) and eyes-open (EO) are essential behaviors in mammalians, including man. At resting EC-EO state, brain activity in the default mode devoid of task-demand has recently been established in fMRI. However, the corresponding comprehensive electrophysiological conditions are little known even though EEG has been recorded in humans for nearly 80 years. In this study, we examined the spatial characteristics of spectral distribution in EEG field powers, i.e., sitting quietly with an EC and EO resting state of 3 min each, measured with high-density 128-ch EEG recording and FFT signal analyses in 15 right-handed healthy college females. Region of interest was set at a threshold at 90% of the spectral effective value to delimit the dominant spatial field power of effective energy in brain activity. Low-frequency delta (0.5-3.5 Hz) EEG field power was distributed at the prefrontal area with great expansion of spatial field and enhancement of field power (t=-2.72, p<0.02) from the EC to the EO state. Theta (4-7 Hz) EEG field power was distributed over the fronto-central area and leaned forward from EC to the EO state but with drastic reduction in field power (t=4.04, p<0.01). The middle-frequency alpha-1 (7.5-9.5 Hz) and alpha-2 (10-12 Hz) EEG powers exhibited bilateral distribution over the posterior areas with an anterior field in lower alpha-1. Both showed significantly reduction of field powers (respectively, W=120, p<0.001 for alpha-1; t=4.12, p<0.001 for alpha-2) from EC to the EO state. Beta-1 (13-23 Hz) exhibited a similar spatial region over the posterior area as in alpha-2 and showed reduction of field power (t=4.42, p<0.001) from EC to the EO state. In contrast, high-frequency beta-2 and gamma band exhibited similar, mainly prefrontal distribution in field power, and exhibited no change from EC to the EO state. Corresponding correlation analyses indicated significant group association between EC and EO only in the field powers of delta (r=0.95, p<0.001) and theta (r=0.77, p<0.001) band. In addition, the great inter-individual variability (90 folds in alpha-1, 62 folds in alpha-2) in regional field power was largely observed in the EC state (10 folds) than the EO state in subjects. To summarize, our study depicts a network of spectral EEG activities simultaneously operative at well defined regional fields in the EC state, varying specifically between EC and EO states. In contrast to transient EEG spectral rhythmic dynamics, current study of long-lasting (e.g. 3 min) spectral field powers can characterize state features in EEG. The EEG default mode network (EEG-DMN) of spectral field powers at rest in the respective EC or EO state is valued to serve as the basal electrophysiological condition in human brain. In health, this EEG-DMN is deemed essential for evaluation of brain functions without task demands for gender difference, developmental change in age span, and brain response to task activation. It is expected to define brain dysfunction in disease at resting state and with consequences for sensory, affective and cognitive alteration in the human brain.

Contact heat evoked potentials as a valid means to study nociceptive pathways in human subjects

Contact heat evoked potentials (CHEPs) have been difficult to elicit due to slow temperature rise times. A recently developed heat-foil technology was used to elicit pain and CHEPs. Two groups of subjects were separately stimulated at the left arm with contact heat via one fast-acting (70 degrees C/s) heat-foil thermode. A set of CHEPs was recorded, each at three subjective intensities: warm; slight; and moderate pain. In CHEPs, the 3D topography exhibited four components: T3-T4/N450; Cz/N550; Cz/P750; and Pz/P1000. A vertex topography map was observed in the late Cz/N550-Cz/P750 and parietal topography in the very-late Pz/P1000 components. Consistent statistical values in the peak latencies and amplitudes were noted between consecutive investigations. The correlation between the pain intensity ratings and the major Cz/P750 amplitudes was highly significant in each study. Our validity tests suggested CHEPs to be useful for research and clinical applications in studying human pain activation related to thermal and nociceptive pathways.

New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain.

With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the 1990s, greater understanding of pain processing in the brain now elucidates and may even challenge the classical theory of pain mechanisms. This review scans across the cultural diversity of pain expression and modulation in man. It outlines the difficulties in defining and studying human pain. It then focuses on methods of studying the brain in experimental and clinical pain, the cohesive results of brain mapping and neuroimaging of noxious perception, the implication of pain research in understanding human consciousness and the relevance to clinical care as well as to the basic science of human psychophysiology. Non-invasive brain studies in man start to unveil the age-old puzzles of pain-illusion, hypnosis and placebo in pain modulation. The neurophysiological and neurohemodynamic brain measures of experimental pain can now largely satisfy the psychophysiologists dream, unimaginable only a few years ago, of modelling the body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad: physics (stimulus energy); physiology (brain activities); and psyche (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to integrate a cohesive theory of human pain in the brain; (b) what levels of analyses are necessary and sufficient; (c) what constitutes the structural organisation of the pain matrix; (d) what are the modes of processing among and across the sites of these structures; and (e) how can neural computation of these processes in the brain be carried out? We may envision that modular identification and delineation of the arousal-attention, emotion-motivation and perception-cognition neural networks of pain processing in the brain will also lead to deeper understanding of the human mind. Two foreseeable impacts on clinical sciences and basic theories from brain mapping/neuroimaging are the plausible central origin in persistent pain and integration of sensory-motor function in pain perception.

Dynamic changes and spatial correlation of EEG activities during cold pressor test in man.

To explore the effects of tonic cold pain in man, the pain rating (intensity and distress), skin temperature, and continuous EEG recording were conducted before, during, and after cold pressor test (CPT) in 15 young healthy males. The acquired electroencephalogram (EEG) data was analysed in four ways: (1) comparison of EEG topographic patterns and power spectra across baseline, CPT, and post-CPT; (2) dynamic EEG changes during CPT; (3) correlation of EEG activities at the isolated focal maxima across the three experimental stages; and (4) spatial correlation of EEG powers among the focal sites during CPT. Compared to baseline, CPT induced significant differences in EEG topographic patterns and power spectra, which showed the following characteristics. (A) The delta and theta activities increased in frontal areas with maxima at F8. (B) The alpha activities decreased in the posterior part of the head with maxima at POz

Event-related functional MRI study on central representation of acute muscle pain induced by electrical stimulation.

Although pathological muscle pain involves a significantly larger population than any other pain condition, the central mechanisms are less explored than those of cutaneous pain. The aims of the study were to establish the pain matrix for muscle pain in the full head volume and, further, to explore the possibility of a functional segregation to nonpainful and painful stimuli within the area of the parasylvian cortex corresponding to the secondary somatosensory area. Additionally, we speculate that a randomization of nonpainful and painful stimuli may target specific structures related to stimulus salience. We used event-related functional magnetic resonance imaging (MRI) and the high sensitivity of the 3-T MRI scanner to study the central processing of acute muscle pain induced by intramuscular electrostimulation. Brief nonpainful and painful stimuli (1-ms duration, interstimulus interval = 12 s) were randomly applied to the left abductor pollicis brevis of 10 subjects. The data disclose a pain matrix for muscle pain similar to that for cutaneous pain. Individual analysis suggests separate representations within the area bounded by the upper bank of the Sylvian fissure (SF) and the circular sulcus of insula (CSI). Nonpainful stimulation activated the superficial parietal operculum adjoining the SF, while the painful condition additionally targeted the deeper parietal operculum bordering the CSI. Randomization of stimuli of different intensities likely introduces cognitive components that engage neural substrates servicing the appreciation of stimulus salience in the context of affect-laden pain imposition.

Dipolar modelling of the scalp evoked potentials to painful contact heat stimulation of the human skin

Contact heat evoked potentials (CHEPs) were collected in 12 healthy subjects by stimulating the forearm skin with a couple of thermodes at a painful intensity. The stimulated area was 628 mm(2) and the repetition rate was 0.1 Hz. The electroencephalogram was recorded by 31 electrodes placed on the scalp according to an extended 10-20 System. A dipolar model explaining the scalp CHEP distribution was built by using the brain electrical source analysis. The model includes two dipoles located bilaterally in the perisylvian region, one dipole in the deep midline region and two dipoles located bilaterally in the deep temporal lobe. This dipolar model is very similar to that previously described to explain the topography of evoked potentials to radiant heat stimulation by laser pulses. Since laser stimuli activate the nociceptive fibres, the strong similarity of the cerebral dipoles activated by contact heat stimuli and by laser pulses suggests that only nociceptive inputs are involved in the scalp painful CHEP building. Therefore, CHEP recording can be useful for clinical examination of the nociceptive system.

Anticipatory cortical responses during the expectancy of a predictable painful stimulation. A high-resolution electroencephalography study.

In the present study, high‐resolution electroencephalography techniques modelled the spatiotemporal pattern of human anticipatory cortical responses preceding expected galvanic painful stimuli (non‐painful stimuli as a control). Do these responses reflect the activation of associative other than somatosensory systems? Anticipatory processes were probed by alpha oscillations (6–12 Hz) for the evaluation of thalamocortical channels and by negative event‐related potentials for the evaluation of cortical excitability. Compared with the control condition, a progressive reduction of the alpha power was recognized over the primary somatosensory cortex from 2 s before the painful stimulation. In contrast, the anticipatory event‐related potentials were negligible during the expectancy period. The results on the alpha power suggest that the expectancy of the painful stimulation specifically facilitated the somatosensory thalamocortical channel. Remarkably, the associative frontal‐parietal areas were not involved, possibly due to the predictable and repetitive features of the painful stimulus. The present results also suggest that negative event‐related potentials are modest preceding warned stimuli (even if painful) with a simple information content.

Human brain oscillatory activity phase-locked to painful electrical stimulations: a multi-channel EEG study

The main aims of this study were 1) a fine spatial analysis of electroencephalographic (EEG) oscillations after galvanic painful stimulation (nonpainful stimulation as a reference) and 2) a comparative evaluation of phase‐ and nonphase‐locked component of these EEG oscillations. Preliminary surface Laplacian transformation of EEG data (31 channels) reduced head volume conductor effects. EEG phase values were computed by FFT analysis and the statistical evaluation of these values was performed by Rayleigh test (P < 0.05). About 50% of the EEG single trials presented statistically the same FFT phase value of the evoked EEG oscillations (phase‐locked single trials), indicating a preponderant phase‐locked compared to nonphase‐locked component. The remaining single trials showed random FFT phase values (nonphase‐locked single trials), indicating a preponderant nonphase‐locked compared to phase‐locked component. Compared to nonpainful stimulation, painful stimulation increased phase‐locked theta to gamma band responses in the contralateral hemisphere and decreased the phase‐locked beta band response in the ipsilateral hemisphere. Furthermore, nonphase‐locked alpha band response decreased in the ipsilateral fronto‐central area. In conclusion, both decreased and increased EEG oscillatory responses to galvanic painful stimulation would occur in parallel in different cortical regions and in the phase‐ and nonphase‐locked EEG data sets. This enriches the actual debate on the mapping of event‐related oscillatory activity of human brain. Hum. Brain Mapping 15:112–123, 2002.