The effects of left and right monocular viewing on hemispheric activation.

BACKGROUND/OBJECTIVES: Prior research has revealed that whereas activation of the left hemisphere primarily increases the activity of the parasympathetic division of the autonomic nervous system, right-hemisphere activation increases the activity of the sympathetic division. In addition, each hemisphere primarily receives retinocollicular projections from the contralateral eye. A prior study reported that pupillary dilation was greater with left- than with right-eye monocular viewing. The goal of this study was to test the alternative hypotheses that this asymmetric pupil dilation with left-eye viewing was induced by activation of the right-hemispheric-mediated sympathetic activity, versus a reduction of left-hemisphere-mediated parasympathetic activity. Thus, this study was designed to learn whether there are changes in hemispheric activation, as measured by alteration of spontaneous alpha activity, during right versus left monocular viewing. METHOD: High-density electroencephalography (EEG) was recorded from healthy participants viewing a crosshair with their right, left, or both eyes. RESULTS: There was a significantly less alpha power over the right hemisphere's parietal-occipital area with left and binocular viewing than with right-eye monocular viewing. CONCLUSIONS: The greater relative reduction of right-hemisphere alpha activity during left than during right monocular viewing provides further evidence that left-eye viewing induces greater increase in right-hemisphere activation than does right-eye viewing.

The effects of constrained left versus right monocular viewing on the autonomic nervous system.

Asymmetrical activation of right and left hemispheres differentially influences the autonomic nervous system. Additionally, each hemisphere primarily receives retinocollicular projections from the contralateral eye. To learn if asymmetrical hemispheric activation induced by monocular viewing would influence relative pupillary size and respiratory hippus variability (RHV), a measure of parasympathetic activity, healthy participants had their left, right or neither eye patched. Pupillary sizes were then recorded with infrared pupillography. Pupillary dilation was significantly greater with left than right eye viewing. RHV, however, was not different between eye viewing conditions. These differences in pupil dilatation may have been caused by relatively greater activation of the right hemispheric-mediated sympathetic activity induced by left monocular viewing or relatively greater deactivation of the left hemispheric-mediated parasympathetic activity induced by right eye patching. The absence of an asymmetry in RHV, however, suggests that hemispheric asymmetry of sympathetic activation was primarily responsible for this ocular asymmetry of pupil dilation.

Does throbbing pain have a brain signature?

Pain sometimes has a throbbing, pulsating quality, particularly when it is severe and disabling. We recently challenged the presumption that this throbbing quality is a sensory experience of arterial pulsations, but were unable to offer an alternative explanation for its rhythmic character. Here we report a case study of a woman with a history of daily headache consistent with the diagnosis of chronic migraine, but whose throbbing quality persisted long after the resolution of the headache. This chronic, daily, and persistent throbbing sensation, in the absence of headache pain, prompted closer examination for its neurophysiological correlate. By simultaneously recording the subjective report of the throbbing rhythm, arterial pulse, and high-density electroencephalogram, we found that the subjective throbbing rate (48±1.7beats per minute) and heart rate (68±2beats per minute) were distinct, in accord with our previous observations that the 2 are unrelated. On spectral analysis of the electroencephalogram, we found that the overall amount of activity in the alpha range (8 to 12Hz), or alpha power, increased in association with greater throbbing intensity. In addition, we also found that the rhythmic oscillations of overall alpha power, the so-called modulations of alpha power, coincided with the timing of the throbbing rhythm, and that this synchrony, or coherence, was proportional to the subjective intensity of the throbbing quality. This index case will motivate further studies whose aim is to determine whether modulations of alpha power could more generally represent a neurophysiological correlate of the throbbing quality of pain.

Coupling between visual alpha oscillations and default mode activity.

Although, on average, the magnitude of alpha oscillations (8 to 12 Hz) is decreased in task-relevant cortices during externally oriented attention, its fluctuations have significant consequences, with increased level of alpha associated with decreased level of visual processing and poorer behavioral performance. Functional MRI signals exhibit similar fluctuations. The default mode network (DMN) is on average deactivated in cognitive tasks requiring externally oriented attention. Momentarily insufficient deactivation of DMN, however, is often accompanied by decreased efficiency in stimulus processing, leading to attentional lapses. These observations appear to suggest that visual alpha power and DMN activity may be positively correlated. To what extent such correlation is preserved in the resting state is unclear. We addressed this problem by recording simultaneous EEG-fMRI from healthy human participants under two resting-state conditions: eyes-closed and eyes-open. Short-time visual alpha power was extracted as time series, which was then convolved with a canonical hemodynamic response function (HRF), and correlated with blood-oxygen-level-dependent (BOLD) signals. It was found that visual alpha power was positively correlated with DMN BOLD activity only when the eyes were open; no such correlation existed when the eyes were closed. Functionally, this could be interpreted as indicating that (1) under the eyes-open condition, strong DMN activity is associated with reduced visual cortical excitability, which serves to block external visual input from interfering with introspective mental processing mediated by DMN, while weak DMN activity is associated with increased visual cortical excitability, which helps to facilitate stimulus processing, and (2) under the eyes-closed condition, the lack of external visual input renders such a gating mechanism unnecessary.

Classification of Alzheimer Diagnosis from ADNI Plasma Biomarker Data.

Research into modeling the progression of Alzheimer's disease (AD) has made recent progress in identifying plasma proteomic biomarkers to identify the disease at the pre-clinical stage. In contrast with cerebral spinal fluid (CSF) biomarkers and PET imaging, plasma biomarker diagnoses have the advantage of being cost-effective and minimally invasive, thereby improving our understanding of AD and hopefully leading to early interventions as research into this subject advances. The Alzheimer's Disease Neuroimaging Initiative* (ADNI) has collected data on 190 plasma analytes from individuals diagnosed with AD as well subjects with mild cognitive impairment and cognitively normal (CN) controls. We propose an approach to classify subjects as AD or CN via an ensemble of classifiers trained and validated on ADNI data. Classifier performance is enhanced by an augmentation of a selective biomarker feature space with principal components obtained from the entire set of biomarkers. This procedure yields accuracy of 89% and area under the ROC curve of 94%.

Is there a relationship between throbbing pain and arterial pulsations?

Pain can have a throbbing quality, especially when it is severe and disabling. It is widely held that this throbbing quality is a primary sensation of one's own arterial pulsations, arising directly from the activation of localized pain-sensory neurons by closely apposed blood vessels. We examined this presumption more closely by simultaneously recording the subjective report of the throbbing rhythm and the arterial pulse in human subjects of either sex with throbbing dental pain-a prevalent condition whose pulsatile quality is widely regarded a primary sensation. Contrary to the generally accepted view, which would predict a direct correspondence between the two, we found that the throbbing rate (44 bpm ± 3 SEM) was much slower than the arterial pulsation rate (73 bpm ± 2 SEM, p < 0.001), and that the two rhythms exhibited no underlying synchrony. Moreover, the beat-to-beat variation in arterial and throbbing events observed distinct fractal properties, indicating that the physiological mechanisms underlying these rhythmic events are distinct. Confirmation of the generality of this observation in other pain conditions would support an alternative hypothesis that the throbbing quality is not a primary sensation but rather an emergent property, or perception, whose "pacemaker" lies within the CNS. Future studies leading to an improved understanding of the neurobiological basis of clinically relevant pain qualities, such as throbbing, will also enhance our ability to measure and therapeutically target severe and disabling pain.

Exploring resting-state functional connectivity with total interdependence.

Resting-state fMRI has become a powerful tool for studying network mechanisms of normal brain functioning and its impairments by neurological and psychiatric disorders. Analytically, independent component analysis and seed-based cross correlation are the main methods for assessing the connectivity of resting-state fMRI time series. A feature common to both methods is that they exploit the covariation structures of contemporaneously (zero-lag) measured data but ignore temporal relations that extend beyond the zero-lag. To examine whether data covariations across different lags can contribute to our understanding of functional brain networks, a measure that can uncover the overall temporal relationship between two resting-state BOLD signals is needed. In this paper we propose such a measure referred as total interdependence (TI). Comparing TI with zero-lag cross correlation (CC) we report three results. First, when combined with a random permutation procedure, TI can reveal the amount of temporal relationship between two resting-state BOLD time series that is not captured by CC. Second, comparing resting-state data with task-state data recorded in the same scanning session, we demonstrate that the resting-state functional networks constructed with TI match more precisely the networks activated by the task. Third, TI is shown to be more statistically sensitive than CC and provides better feature vectors for network clustering analysis.

Neuronal mechanisms and attentional modulation of corticothalamic α oscillations.

Field potential oscillations in the ∼10 Hz range are known as the alpha rhythm. The genesis and function of alpha has been the subject of intense investigation for the past 80 years. Whereas early work focused on the thalamus as the pacemaker of alpha rhythm, subsequent slice studies revealed that pyramidal neurons in the deep layers of sensory cortices are capable of oscillating in the alpha frequency range independently. How thalamic and cortical generating mechanisms in the intact brain might interact to shape the organization and function of alpha oscillations remains unclear. We addressed this problem by analyzing laminar profiles of local field potential and multiunit activity (MUA) recorded with linear array multielectrodes from the striate cortex of two macaque monkeys performing an intermodal selective attention task. Current source density (CSD) analysis was combined with CSD-MUA coherence to identify intracortical alpha current generators and assess their potential for pacemaking. Coherence and Granger causality analysis was applied to delineate the patterns of interaction among different alpha current generators. We found that (1) separable alpha current generators are located in superficial, granular, and deep layers, with both layer 4C and deep layers containing primary local pacemaking generators, suggesting the involvement of the thalamocortical network, and (2) visual attention reduces the magnitude of alpha oscillations as well as the level of alpha interactions, consistent with numerous reports of occipital alpha reduction with visual attention in human EEG. There is also indication that alpha oscillations in the lateral geniculate cohere with those in V1.

Attentional modulation of alpha oscillations in macaque inferotemporal cortex.

Recent work reported the observation of alpha frequency oscillations (8-12 Hz) in several regions of macaque visual cortex, including V2, V4, and inferotemporal cortex (IT). While alpha-related physiology in V2 and V4 appears consistent with a role in attention-related suppression, in IT, alpha reactivity appears conflicted with such a role. We addressed this issue directly by analyzing laminar profiles of local field potentials and multiunit activities from the IT of macaque monkeys during performance of an intermodal selective attention task (visual versus auditory). We found that (1) before visual stimulus onset (-200 to 0 ms), attention to visual input increased ongoing alpha power in IT relative to attention to auditory input, and (2) in contrast to the prevailing view of alpha inhibition, the increased ongoing alpha activity is accompanied by increased concurrent multiunit firing and facilitates visual stimulus processing. These results suggest that ongoing alpha oscillations in IT play a different functional role than that in the occipital cortex and may be part of the neuronal mechanism representing task-relevant information.

Analyzing coherent brain networks with Granger causality.

Multielectrode neurophysiological recording and functional brain imaging produce massive quantities of data. Multivariate time series analysis provides the basic framework for analyzing the patterns of neural interactions in these data. Neural interactions are directional. Being able to assess the directionality of neuronal interactions is thus a highly desired capability for understanding the cooperative nature of neural computation. Research over the last few years has identified Granger causality as a promising technique to furnish this capability. In this paper, we first introduce the concept of Granger causality and then present results from the application of this technique to multichannel local field potential data from an awake-behaving monkey.