Akaysha C. Tang

Validation of SOBI components from high density EEG

Second-order blind identification (SOBI) is a blind source separation (BSS) algorithm that can be used to decompose mixtures of signals into a set of components or putative recovered sources. Previously, SOBI, as well as other BSS algorithms, has been applied to magnetoencephalography (MEG) and electroencephalography (EEG) data. These BSS algorithms have been shown to recover components that appear to be physiologically and neuroanatomically interpretable. While some proponents of these algorithms suggest that fundamental discoveries about the human brain might be made through the application of these techniques, validation of BSS components has not yet received sufficient attention. Here we present two experiments for validating SOBI-recovered components. The first takes advantage of the fact that noise sources associated with individual sensors can be objectively validated independently from the SOBI process. The second utilizes the fact that the time course and location of primary somatosensory (SI) cortex activation by median nerve stimulation have been extensively characterized using converging imaging methods. In this paper, using both known noise sources and highly constrained and well-characterized neuronal sources, we provide validation for SOBI decomposition of high-density EEG data. We show that SOBI is able to (1) recover known noise sources that were either spontaneously occurring or artificially induced; (2) recover neuronal sources activated by median nerve stimulation that were spatially and temporally consistent with estimates obtained from previous EEG, MEG, and fMRI studies; (3) improve the signal-to-noise ratio (SNR) of somatosensory-evoked potentials (SEPs); and (4) reduce the level of subjectivity involved in the source localization process.

Reliable detection of bilateral activation in human primary somatosensory cortex by unilateral median nerve stimulation

In non-human primates, a bilateral representation of unilaterally presented somatosensory information can be found at the lowest level of cortical processing as indicated by the presence of neurons with bilateral receptive fields in the hand region of primary somatosensory (SI) cortex. In humans, such bilateral activation of SI is considered controversial due to highly variable detection rates for the much weaker ipsilateral response across different studies (ranging from 3% to 100%). Second-order blind identification (SOBI) is a blind source separation algorithm that has been successfully used to isolate neuronal signals from functionally distinct brain regions, including the left- and right-SI. SOBI-aided extraction of left- and right-SI responses to median nerve stimulation from high-density EEG has been previously validated against the fMRI and MEG literature. Here, we applied SOBI to EEG data and examined whether relatively weaker ipsilateral activations could be reliably detected across subjects. In single subject analysis, statistically significant somatosensory evoked potentials (SEPs) in response to unilateral stimulation were detected from both SI contralateral to and SI ipsilateral to the side of stimulation. Furthermore, these ipsilateral responses were observed in both the left and right hemispheres of all 10 subjects studied. Together these results demonstrate that unilateral stimulation of the median nerve, whether applied to the left or right wrist, can activate both the left- and right-SI, raising the possibility that in humans, unilateral sensory input may be bilaterally represented at the lowest level of cortical processing.

Recovery of correlated neuronal sources from EEG: The good and bad ways of using SOBI

Second-order blind identification (SOBI) is a blind source separation (BSS) algorithm that has been applied to MEG and EEG data collected during a range of sensory, motor, and cognitive tasks. SOBI can decompose mixtures of electric or magnetic signals by utilizing detailed temporal structures present in the continuously recorded signals. Successful decomposition critically depends on the choice of temporal delay parameters used for computing multiple covariance matrices. Here, we present empirical findings from high-density EEG data (128 channels) to show that SOBIs ability to recover correlated neuronal sources critically depends on the appropriate use of these temporal delay parameters. Specifically, we applied SOBI to EEG data collected during correlated activation of the left and right primary somatosensory cortices (SI). We show that separation of signals originating from the left and right SI is better achieved by using a large number and a wide range of temporal delays between a few and several hundred milliseconds when compared to results using various subsets of these delays. The paper also offers non-mathematician/engineer users a gentle introduction to the inner workings of SOBI.

Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat

Early life environmental manipulations have been shown to affect hippocampal-dependent learning, hippocampal volume and cerebral lateralization. In this study, we investigated the effects of neonatal stimulation on hippocampal volumetric asymmetry. Long-Evans hooded rats were exposed to a novel non-home environment 3 min daily for the first 3 weeks of life. Histological measures of the left and right hippocampus were made at 8 months of age. We found that neonatal novelty exposure resulted in a long-lasting change in hippocampal volumetric asymmetry. Specifically, this brief and transient early life stimulation increased the right hippocampal volumetric dominance at mid-adulthood.

Effects of Long-Term Estrogen Replacement on Social Investigation and Social Memory in Ovariectomized C57BL/6 Mice

Estrogen has been shown to play a role in modulating social recognition memory. However, the literature regarding the influence of estrogen on social memory is sparse and only covers two experimental manipulations: acute injections and receptor knockout. Long-term effects of estrogen replacement on social investigation and social recognition are unknown. Furthermore, existing social recognition protocols focus on memory of very short durations (<2 h). In the present study, we examined long-term effects of estrogen replacement on both short- (<30 min) and long-term (24 h) social recognition in ovariectomized female C57BL/6 mice by implanting 60-day time-release pellets containing physiological doses of estradiol (0, 0.18, or 0.72 mg of 17beta-estradiol). After 55 days of treatment, evidence of social recognition memory, measured by 24-h habituation, was found only in mice receiving the 0.72-mg pellet. This result is remarkable as previous reports indicate that individually-housed untreated rats and mice do not show habituation beyond 2 h. Our study further revealed that estrogen also increased frequencies of baseline social investigation without affecting general activity levels and decreased delayed post-swim-stress serum corticosterone concentration. Thus, these results suggest that long-term estrogen replacement increased the interest in social interaction as well as decreased stress responses. It is likely that the 24-h habituation observed in the estrogen replacement group is mediated jointly by the non-mnemonic effects of estrogen on the behavior displayed during the stage of memory encoding as well as mnemonic effects during the stage of memory consolidation.

Independent components of magnetoencephalography: Single-trial response onset times

Werecently demonstrated that second-order blind identification (SOBI), an independent component analysis (ICA) method, can separate the mixture of neuronal and noise signals in magnetoencephalographic (MEG) data into neuroanatomically and neurophysiologically meaningful components. When the neuronal signals had relatively higher trial-to-trial variability, SOBI offered a particular advantage in identifying and localizing neuronal source activations with increased source detectability (A. C. Tang et al., 2002, Neural Comput. 14, 1827-1858). Here, we explore the utility of SOBI in the analysis of temporal aspects of neuromagnetic signals from MEG data. From SOBI components, we were able to measure single-trial response onset times of neuronal populations in visual, auditory, and somatosensory modalities during cognitive and sensory activation tasks, with a detection rate as high as 96% under optimal conditions. Comparing the SOBI-aided detection results with those obtained directly from the sensors, we found that with SOBI preprocessing, we were able to measure, among a greater proportion of trials, single-trial response onset times that are above background neuronal activity. We suggest that SOBI ICA can improve our current capability in measuring single-trial responses from human subjects using the noninvasive brain imaging method MEG.

Early life modulators and predictors of adult synaptic plasticity.

Early life experience can induce long‐lasting changes in brain and behaviour that are opposite in direction, such as enhancement or impairment in regulation of stress response, structural and functional integrity of the hippocampus, and learning and memory. To explore how multiple early life events jointly determine developmental outcome, we investigated the combined effects of neonatal trauma (anoxia on postnatal day 1, P1) and neonatal novelty exposure (P2–21) on adult social recognition memory (3 months of age) and synaptic plasticity in the CA1 of the rat hippocampus (4.5–8 months of age). While neonatal anoxia selectively reduced post‐tetanic potentiation (PTP), neonatal novel exposure selectively increased long‐term potentiation (LTP). No interaction between anoxia and novelty exposure was found on either PTP or LTP. These findings suggest that the two contrasting neonatal events have selective and distinct effects on two different forms of synaptic plasticity. At the level of behaviour, the effect of novelty exposure on LTP was associated with increased social memory, and the effect of anoxia on PTP was not accompanied by changes in social memory. Such a finding suggests a bias toward the involvement of LTP over PTP in social memory. Finally, we report a surprising finding that an early behavioural measure of emotional response to a novel environment obtained at 25 days of age can predict adult LTP measured several months later. Therefore, individual differences in emotional responses present during the juvenile stage may contribute to adult individual differences in cellular mechanisms that underlie learning and memory.

On the causes of early life experience effects: Evaluating the role of mom

Early life experiences are thought to have long-lasting effects on cognitive, emotional, and social function during adulthood. Changes in neuroendocrine function, particularly the hypothalamic-pituitary-adrenal (HPA) axis, contribute to these systems-level behavioral effects. In searching for causal mechanisms underlying these early experience effects, pioneering research has demonstrated an important role for maternal care in offspring development, and this has led to two persistent ideas that permeate current research and thinking: first, environmental impact on the developing infant is mediated through maternal care behavior; second, the more care that a mother provides, the better off her offspring. While a good beginning, the reality is likely more complex. In this review, we critically examine these ideas and propose a computationally-motivated theoretical framework, and within this framework, we consider evidence supporting a hypothesis of maternal modulation. These findings may inform policy decisions in the context of child health and development.

Single-trial detection in EEG and MEG: Keeping it linear

Conventional electroencephalography (EEG) and magnetoencephalography (MEG) analysis often rely on averaging over multiple trials to extract statistically relevant di7erences between two or more experimental conditions. We demonstrate that by linearly integrating information over multiple spatially distributed sensors within a prede9ned time window, one can discriminate conditions on a trial-by-trial basis with high accuracy. We restrict ourselves to a linear integration as it allows the computation of a spatial distribution of the discriminating source activity. In the present set of experiments the resulting source activity distributions correspond to functional neuroanatomy consistent with the task (e.g. contralateral sensory-motor cortex and anterior cingulate). c � 2003 Elsevier Science B.V. All rights reserved.

Neonatal Novelty-Induced Persistent Enhancement in Offspring Spatial Memory and the Modulatory Role of Maternal Self-Stress Regulation

Development of spatial memory in the rat is influenced by both maternal and nonmaternal aspects of the postnatal environment. Yet it remains poorly understood how these two aspects of the postnatal environment interact to program offspring cognitive development. By considering the joint influence of neonatal environmental novelty and maternal self-stress regulation on the development of spatial memory function in Long–Evans hooded rats, we show a persistent neonatal novelty-induced enhancement in spatial reference and working memory functions among the same individual offspring from juvenility to adulthood and a contrasting transient maternal modulatory influence on this novelty-related enhancement present during only juvenility. Specifically, at and only at juvenility, for mothers with good self-stress regulation as indexed by a low circulating basal corticosterone level, offspring showed a novelty-induced enhancement in spatial memory function, whereas for mothers with poor self-stress regulation, indexed by a high basal corticosterone level, offspring showed little enhancement or even small impairments. These findings indicate that maternal and nonmaternal postnatal environments exert separate but interacting influences on offspring cognitive development and support a maternal modulation model of cognitive development that considers maternal self-stress regulation as an important factor among the multitude of maternal influences.