Brain Reactions to Opening and Closing the Eyes: Salivary Cortisol and Functional Connectivity.

This study empirically assessed the strength and duration of short-term effects induced by brain reactions to closing/opening the eyes on a few well-known resting-state networks. We also examined the association between these reactions and subjects' cortisol levels. A total of 55 young adults underwent 8-min resting-state fMRI (rs-fMRI) scans under 4-min eyes-closed and 4-min eyes-open conditions. Saliva samples were collected from 25 of the 55 subjects before and after the fMRI sessions and assayed for cortisol levels. Our empirical results indicate that when the subjects were relaxed with their eyes closed, the effect of opening the eyes on conventional resting-state networks (e.g., default-mode, frontal-parietal, and saliency networks) lasted for roughly 60-s, during which we observed a short-term increase in activity in rs-fMRI time courses. Moreover, brain reactions to opening the eyes had a pronounced effect on time courses in the temporo-parietal lobes and limbic structures, both of which presented a prolonged decrease in activity. After controlling for demographic factors, we observed a significantly positive correlation between pre-scan cortisol levels and connectivity in the limbic structures under both conditions. Under the eyes-closed condition, the temporo-parietal lobes presented significant connectivity to limbic structures and a significantly positive correlation with pre-scan cortisol levels. Future research on rs-fMRI could consider the eyes-closed condition when probing resting-state connectivity and its neuroendocrine correlates, such as cortisol levels. It also appears that abrupt instructions to open the eyes while the subject is resting quietly with eyes closed could be used to probe brain reactivity to aversive stimuli in the ventral hippocampus and other limbic structures.

A Wireless Magnetic Resonance Device for Optogenetic Applications in an Animal Model.

The currents of optical stimulation devices with tethered or untethered systems have various disadvantages, including optical fiber breakage, disrupted animal movements, heavy batteries carried on heads, and high-frequency electromagnetic impacts. Our novel wireless remote control was developed to address these issues. The novel wireless device uses a magnetic resonance technique to modify the deficits of the conventional magnetic induction or radio-frequency power sources. The present device emits a strong and steady electromagnetic power. It is cheaper than previous versions, and the receiver coil on its head is very light (≦ 1 g). For the present wireless remote-controlled device, the electromagnetic field's range (i.e., +5 cm and -5 cm of the outside coil) is larger than the range for the magnetic induction and radio-frequency power sources. The present device controls animals' behavior by the electromagnetic field's effective range via photostimulation. The novel wireless remote-controlled device with a magnetic resonance technique can be applied in many behavioral tasks in mice and rats. To avoid the adverse effects of high radio frequency and to extend the electromagnetic field's range, this novel technique serves as a helpful tool to modulate the neuronal activity of target neurons in specific brain areas for optogenetic experiments.

Cortical surface alignment in multi-subject spatiotemporal independent EEG source imaging.

Brain responses to stimulus presentations may vary widely across subjects in both time course and spatial origins. Multi-subject EEG source imaging studies that apply Independent Component Analysis (ICA) to data concatenated across subjects have overlooked the fact that projections to the scalp sensors from functionally equivalent cortical sources vary from subject to subject. This study demonstrates an approach to spatiotemporal independent component decomposition and alignment that spatially co-registers the MR-derived cortical topographies of individual subjects to a well-defined, shared spherical topology (Fischl et al., 1999). Its efficacy for identifying functionally equivalent EEG sources in multi-subject analysis is demonstrated by analyzing EEG and behavioral data from a stop-signal paradigm using two source-imaging approaches, both based on individual subject independent source decompositions. The first, two-stage approach uses temporal infomax ICA to separate each subject's data into temporally independent components (ICs), then estimates the source density distribution of each IC process from its scalp map and clusters similar sources across subjects (Makeig et al., 2002). The second approach, Electromagnetic Spatiotemporal Independent Component Analysis (EMSICA), combines ICA decomposition and source current density estimation of the artifact-rejected data into a single spatiotemporal ICA decomposition for each subject (Tsai et al., 2006), concurrently identifying both the spatial source distribution of each cortical source and its event-related dynamics. Applied to the stop-signal task data, both approaches gave IC clusters that separately accounted for EEG processes expected in stop-signal tasks, including pre/postcentral mu rhythms, anterior-cingulate theta rhythm, and right-inferior frontal responses, the EMSICA clusters exhibiting more tightly correlated source areas and time-frequency features.

Optogenetic stimulation in the medial prefrontal cortex modulates stimulus valence from rewarding and aversive to neutral states.

Introduction: Understanding the modulations of the medial prefrontal cortex (mPFC) in the valence of the stimulus from rewarding and aversive status to neutral status is crucial for the development of novel treatments for drug addiction. This study addressed this issue and examined whether optogenetic ChR2 photostimulation in the cingulate, prelimbic, and infralimbic cortices of the mPFC regulated the valence of saccharin solution consumption from the rewarding property, the aversive property induced by morphine's conditioning, and the neutral states via saccharin extinction processes after morphine's conditioning. Methods: All rats received virus infection, buried optical fiber, optical stimulation, water deprivation, and saccharin solution consumption phases. In Experiment 1, rats were given ChR2 virus infection into the cingulate cortex (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL) to influence the rewarding saccharin solution consumption under photostimulation. In Experiment 2, rats were given ChR2 or EYFP virus infection into the Cg1, PrL, and IL to alter the saccharin solution consumption in the morphine-induced aversively conditioned taste aversion (CTA) and the saccharin solution consumption in the neutral state following the extinction process under photostimulation. Later, the immunohistochemical staining with c-Fos protein was performed for the Cg1, IL, PrL, nucleus accumbens core, nucleus accumbens shell, central amygdala, basolateral amygdala, ventral tegmental area, and dentate gyrus. Results: The results showed that optogenetic PrL stimulation decreased the rewarding valence of saccharin solution consumption and increased the morphine-induced, aversive valence of saccharin solution consumption. PrL stimulation decreased the neutral valence of saccharin solution consumption via the extinction process. Cg1 optogenetic stimulation increased the rewarding valence of saccharin solution consumption and the aversive valence of saccharin solution consumption induced by morphine in conditioning. Optogenetic IL stimulation increased the aversive valence of saccharin solution consumption induced by morphine via conditioning. Conclusion: Altogether, optogenetic stimulation in the subareas of the mPFC modulated the reward, aversion, and neutral valences of the stimulus and altered neuronal activity in the mPFC, amygdala, nucleus accumbens, and hippocampus. Notably, the change of valence was temporary alternation during light-on related to the light-off periods. However, the findings may provide insights in the development of novel treatments for addictive symptoms.

Age-Related Differences in the Neural Processing of Idioms: A Positive Perspective.

We examined whether older adults benefit from a larger mental-lexicon size and world knowledge to process idioms, one of few abilities that do not stop developing until later adulthood. Participants viewed four-character sequences presented one at a time that combined to form (1) frequent idioms, (2) infrequent idioms, (3) random sequences, or (4) perceptual controls, and judged whether the four-character sequence was an idiom. Compared to their younger counterparts, older adults had higher accuracy for frequent idioms and equivalent accuracy for infrequent idioms. Compared to random sequences, when processing frequent and infrequent idioms, older adults showed higher activations in brain regions related to sematic representation than younger adults, suggesting that older adults devoted more cognitive resources to processing idioms. Also, higher activations in the articulation-related brain regions indicate that older adults adopted the thinking-aloud strategy in the idiom judgment task. These results suggest re-organized neural computational involvement in older adults' language representations due to life-long experiences. The current study provides evidence for the alternative view that aging may not necessarily be solely accompanied by decline.

The Medial Prefrontal Cortex, Nucleus Accumbens, Basolateral Amygdala, and Hippocampus Regulate the Amelioration of Environmental Enrichment and Cue in Fear Behavior in the Animal Model of PTSD.

A growing body of evidence showed that environmental enrichment (EE) ameliorated footshock-induced fear behavior of posttraumatic stress disorder (PTSD). However, no research comprehensively tested the effect of EE, cue, and the combination of EE and cue in footshock-induced fear behavior of PTSD symptoms. The present study addressed this issue and examined whether the medial prefrontal cortex (mPFC, including the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), and infralimbic cortex (IL)), the nucleus accumbens (NAc), the basolateral amygdala (BLA), and the hippocampus (e.g., CA1, CA3, and dentate gyrus (DG)) regulated the amelioration of the EE, cue, or the combination of EE and cue. The results showed that EE or cue could reduce fear behavior. The combination of EE and cue revealed a stronger decrease in fear behavior. The cue stimulus may play an occasion setting or a conditioned stimulus to modulate the reduction in fear behavior induced by footshock. Regarding the reduction of the EE in fear behavior, the Cg1 and IL of the mPFC and the NAc upregulated the c-Fos expression; however, the BLA downregulated the c-Fos expression. The mPFC (i.e., the Cg1, PrL, and IL) and the hippocampus (i.e., the CA1, CA3, and DG) downregulated the c-Fos expression in the suppression of the cue in fear behavior. The interaction of EE and cue in reduction of fear behavior occurred in the Cg1 and NAc for the c-Fos expression. The data of c-Fos mRNA were similar to the findings of the c-Fos protein expression. These findings related to the EE and cue modulations in fear behavior may develop a novel nonpharmacological treatment in PTSD.

EEG-correlates of trait anxiety in the stop-signal paradigm.

The relationship between trait anxiety and event-related EEG oscillatory reactions in the stop-signal paradigm was studied in 15 non-clinical subjects with average age of 26 years (13 men). In the paradigm, subjects responded to target stimuli by pressing one of the two choice buttons. In 30 out of 130 trials, target presentation was followed by a stop-signal, indicating that subjects had to refrain from a prepared motor response. The subject's level of anxiety was assessed using the State Trait Anxiety Inventory. Wide-band desynchronization (8-25 Hz) was found before button-press. It was sustained after the subjects pressed the button at 7-14 Hz frequency range. Also, synchronization at 15-25 Hz band occurred in 400-1400 ms after the button-press. Synchronization at lower frequencies (1-7 Hz) was also found during 0-700 ms after the stop-signal onset. Also, desynchronization at 8-20 Hz was found in 300-800 ms after stop-signal onset. The group with higher anxiety showed desynchronization at 10-13 Hz in 0-800 ms after the button-press, whereas the group with lower anxiety showed synchronization at the same frequency range. In 0-600 ms after stop-signal onset, desynchronization at 8-13 Hz was observed in the group with higher anxiety, whereas the group with lower anxiety demonstrated synchronization or weak desynchronization. Our findings support the Eysenck et al. [M.W. Eysenck, N. Derakshan, R. Santos, M.G. Calvo, Anxiety and cognitive performance: attentional control theory, Emotion 7(2) (2007) 336-356] theory that subjects with higher anxiety have more attentional control over reaction and increased use of processing resources as compared with lower anxiety subjects.

Lingering Sound: Event-Related Phase-Amplitude Coupling and Phase-Locking in Fronto-Temporo-Parietal Functional Networks During Memory Retrieval of Music Melodies.

Brain oscillations and connectivity have emerged as promising measures of evaluating memory processes, including encoding, maintenance, and retrieval, as well as the related executive function. Although many studies have addressed the neural mechanisms underlying working memory, most of these studies have focused on the visual modality. Neurodynamics and functional connectivity related to auditory working memory are yet to be established. In this study, we explored the dynamic of high density (128-channel) electroencephalography (EEG) in a musical delayed match-to-sample task (DMST), in which 36 participants were recruited and were instructed to recognize and distinguish the target melodies from similar distractors. Event-related spectral perturbations (ERSPs), event-related phase-amplitude couplings (ERPACs), and phase-locking values (PLVs) were used to determine the corresponding brain oscillations and connectivity. First, we observed that low-frequency oscillations in the frontal, temporal, and parietal regions were increased during the processing of both target and distracting melodies. Second, the cross-frequency coupling between low-frequency phases and high-frequency amplitudes was elevated in the frontal and parietal regions when the participants were distinguishing between the target from distractor, suggesting that the phase-amplitude coupling could be an indicator of neural mechanisms underlying memory retrieval. Finally, phase-locking, an index evaluating brain functional connectivity, revealed that there was fronto-temporal phase-locking in the theta band and fronto-parietal phase-locking in the alpha band during the recognition of the two stimuli. These findings suggest the existence of functional connectivity and the phase-amplitude coupling in the neocortex during musical memory retrieval, and provide a highly resolved timeline to evaluate brain dynamics. Furthermore, the inter-regional phase-locking and phase-amplitude coupling among the frontal, temporal and parietal regions occurred at the very beginning of musical memory retrieval, which might reflect the precise timing when cognitive resources were involved in the retrieval of targets and the rejection of similar distractors. To the best of our knowledge, this is the first EEG study employing a naturalistic task to study auditory memory processes and functional connectivity during memory retrieval, results of which can shed light on the use of natural stimuli in studies that are closer to the real-life applications of cognitive evaluations, mental treatments, and brain-computer interface.

Conscious and Non-conscious Representations of Emotional Faces in Asperger's Syndrome.

Several neuroimaging studies have suggested that the low spatial frequency content in an emotional face mainly activates the amygdala, pulvinar, and superior colliculus especially with fearful faces(1-3). These regions constitute the limbic structure in non-conscious perception of emotions and modulate cortical activity either directly or indirectly(2). In contrast, the conscious representation of emotions is more pronounced in the anterior cingulate, prefrontal cortex, and somatosensory cortex for directing voluntary attention to details in faces(3,4). Asperger's syndrome (AS)(5,6) represents an atypical mental disturbance that affects sensory, affective and communicative abilities, without interfering with normal linguistic skills and intellectual ability. Several studies have found that functional deficits in the neural circuitry important for facial emotion recognition can partly explain social communication failure in patients with AS(7-9). In order to clarify the interplay between conscious and non-conscious representations of emotional faces in AS, an EEG experimental protocol is designed with two tasks involving emotionality evaluation of either photograph or line-drawing faces. A pilot study is introduced for selecting face stimuli that minimize the differences in reaction times and scores assigned to facial emotions between the pretested patients with AS and IQ/gender-matched healthy controls. Information from the pretested patients was used to develop the scoring system used for the emotionality evaluation. Research into facial emotions and visual stimuli with different spatial frequency contents has reached discrepant findings depending on the demographic characteristics of participants and task demands(2). The experimental protocol is intended to clarify deficits in patients with AS in processing emotional faces when compared with healthy controls by controlling for factors unrelated to recognition of facial emotions, such as task difficulty, IQ and gender.

Face recognition in Asperger syndrome: a study on EEG spectral power changes.

EEG reactions in emotional face recognition were studied in five participants with Asperger syndrome (AS) and seven control subjects. Control subjects showed a spectral power increase following the stimulus onset in two time-frequency intervals-(1) 150-300ms in the 1-16Hz frequency range and (2) 300-650ms in the 1-8Hz range. Also, alpha/beta desynchronization occurred 400-1000ms after the stimulus onset with maximal amplitude in the posterior region. Theta synchronization (4-8Hz) was weaker in the AS group than in the control group, but beta2 desynchronization was stronger in the AS group. The results were interpreted in terms of automatic and voluntary control of perception.

MR image segmentation using a power transformation approach.

This study proposes a segmentation method for brain MR images using a distribution transformation approach. The method extends traditional Gaussian mixtures expectation-maximization segmentation to a power transformed version of mixed intensity distributions, which includes Gaussian mixtures as a special case. As MR intensities tend to exhibit non-Gaussianity due to partial volume effects, the proposed method is designed to fit non-Gaussian tissue intensity distributions. One advantage of the method is that it is intuitively appealing and computationally simple. To avoid performance degradation caused by intensity inhomogeneity, different methods for correcting bias fields were applied prior to image segmentation, and their correction effects on the segmentation results were examined in the empirical study. The partitions of brain tissues (i.e., gray and white matter) resulting from the method were validated and evaluated against manual segmentation results based on 38 real T1-weighted image volumes from the internet brain segmentation repository, and 18 simulated image volumes from BrainWeb. The Jaccard and Dice similarity indexes were computed to evaluate the performance of the proposed approach relative to the expert segmentations. Empirical results suggested that the proposed segmentation method yielded higher similarity measures for both gray matter and white matter as compared with those based on the traditional segmentation using the Gaussian mixtures approach.

A method for generating reproducible evidence in fMRI studies.

Insights into cognitive neuroscience from neuroimaging techniques are now required to go beyond the localisation of well-known cognitive functions. Fundamental to this is the notion of reproducibility of experimental outcomes. This paper addresses the central issue that functional magnetic resonance imaging (fMRI) experiments will produce more desirable information if researchers begin to search for reproducible evidence rather than only p value significance. The study proposes a methodology for investigating reproducible evidence without conducting separate fMRI experiments. The reproducible evidence is gathered from the separate runs within the study. The associated empirical Bayes and ROC extensions of the linear model provide parameter estimates to determine reproducibility. Empirical applications of the methodology suggest that reproducible evidence is robust to small sample sizes and sensitive to both the magnitude and persistency of brain activation. It is demonstrated that research findings in fMRI studies would be more compelling with supporting reproducible evidence in addition to standard hypothesis testing evidence.

Mapping single-trial EEG records on the cortical surface through a spatiotemporal modality.

Event-related potentials (ERPs) induced by visual perception and cognitive tasks have been extensively studied in neuropsychological experiments. ERP activities time-locked to stimulus presentation and task performance are often observed separately at individual scalp channels based on averaged time series across epochs and experimental subjects. An analysis using averaged EEG dynamics could discount information regarding interdependency between ongoing EEG and salient ERP features. Advanced tools such as independent component analysis (ICA) have been developed for decomposing collections of single-trial EEG records into separate features. Those features (or independent components) can then be mapped onto the cortical surface using source localization algorithms to visualize brain activation maps and to study between-subject consistency. In this study, we propose a statistical framework for estimating the time course of spatiotemporally independent EEG components simultaneously with their cortical distributions. Within this framework, we implemented Bayesian spatiotemporal analysis for imaging the sources of EEG features on the cortical surface. The framework allows researchers to include prior knowledge regarding spatial locations as well as spatiotemporal independence of different EEG sources. The use of the Electromagnetic Spatiotemporal ICA (EMSICA) method is illustrated by mapping event-related EEG dynamics induced by events in a visual two-back continuous performance task. The proposed method successfully identified several interesting components with plausible corresponding cortical activation topographies, including processes contributing to the late positive complex (LPC) located in central parietal, frontal midline, and anterior cingulate cortex, to atypical mu rhythms associated with the precentral gyrus, and to the central posterior alpha activity in the precuneus.