Time Course Of Neural Activity Research Articles

8607 Gender Affirming Hormone Therapy: Influence of Brain Network Connectivity Changes on Affect

Abstract Disclosure: J. Andreano: None. A. Lopez: None. M. Misra: None. Background: Previous research indicates that acute gonadal treatments and fluctuations in ovarian hormone levels over the course of the menstrual cycle can alter patterns of communication between brain regions, as well as producing significant changes in self-reported affect. Recent research from our laboratory indicates changes in both brain connectivity and affect with gender affirming hormone therapy (GAHT). However, the relationship between these changes with GAHT are not well understood. Additionally, it is difficult to separate influences of GAHT and transgender identity in understanding differences in connectvity and affect from cisgender controls. A better understanding of the influence of GAHT on intrinsic network connectivity could point the way towards improved GAHT treatment regimens that minimize affective side effects. Objective: To assess relationships between changes in brain network connectivity and affective changes following GAHT, identifying regions in which changes of connectivity are associated with changes in self-reported affect, and to examine differences in brain network connectivity between transgender participants and cisgender controls. Methods: 14 transgender individuals receiving GAHT (estradiol n =7, testosterone n = 7)) were scanned using functional magnetic imaging (fMRI) at rest at two timepoints: baseline, prior to treatment, and 6 months into GAHT. Additionally, 20 cisgender controls (10 male, 10 female) were scanned once each. The time course of neural activity was computed for each voxel in the brain, then tested for correlation with each other voxel to develop a whole-brain connectome for each participant. Maps of average connectivity to two seeds known to associate with two major networks in the brain (posterior cingulate cortex for Default Mode Network, and anterior insula for Salience Network) were then generated for each participant. Within transgender participants, these maps were then compared between the baseline and 6 month timepoints. Additionally, baseline scans were also compared to scans from cisgender controls corresponding to biological sex. Results: Within-subjects analyses of transgender participants showed diverse associations between changes in seed-based connectivity and changes in self-reported anxiety and depression following GAHT in both the default mode and salience networks. Between subjects comparisons showed significantly higher connectivity within the salience network in trans men relative to cis women, as well as greater inter-network connectivity in this group. In contrast, cis men showed greater connectivity within both default mode and salience networks relative to trans women. Conclusions: Changes in affect following GAHT appear related to GAHT-induced changes in network connectivity; these influences appear independent of differences between cis and transgender individuals. Presentation: 6/2/2024

SAT412 Effects Of Gender-Affirming Hormone Therapy On The Connectivity Of Intrinsic Brain Networks

Abstract Disclosure: C.C. Pedreira: None. S. Tchir-Bourgeois: None. S. Tuli: None. A. Giancola: None. C. Loxton: None. A.S. Keuroghlian: None. M. Misra: None. J.M. Andreano: None. Background: Previous research has indicated that both acute gonadal hormone treatments and fluctuations in ovarian hormone levels over the course of the menstrual cycle can significantly alter patterns of communication between brain regions, particularly regions involved in affective processing. However, the neural effects of prolonged exogenous gonadal hormone exposure, as in gender-affirming hormone therapy (GAHT), are not presently well-understood. A better understanding of the influence of GAHT on intrinsic network connectivity could point the way towards improved GAHT treatment regimens that minimize affective side effects.Objective: To characterize the effects of estradiol and testosterone treatments in GAH on patterns of connectivity within and between the brain’s intrinsic networks.Methods: 5 transgender individuals receiving GAHT (estradiol n =3, testosterone n = 2) were scanned using functional magnetic imaging (fMRI) at rest at two timepoints: baseline, prior to treatment, and 6 months into GAHT. The time course of neural activity was computed for each voxel in the brain, then tested for correlation with each other voxel to develop a whole-brain connectome for each participant. Connectomes were then analyzed in two ways: 1) maps of average connectivity to two regions of interest found in previous research to differ between cis and transgender people (the anterior insula and temporal pole) were generated for each participant. These maps were then compared between baseline and 6-month timepoints. 2) Overall network structure of the brain was generated a priori for each participant at each timepoint using a community detection algorithm. Network assignments were then compared between timepoints, noting regions whose connectivity shifted between networks after GAHT.Results: 2 of 3 participants treated with estradiol exhibited a significant reduction of connectivity to the anterior insula throughout the brain, most notably within the medial temporal lobe and cingulate cortex. Both participants receiving testosterone treatment showed reduced anterior insula connectivity, although connectivity to the cingulate cortex, particularly the mid-cingulate, was preserved. Estradiol did not significantly affect connectivity of the frontal pole, although testosterone produced a widespread reduction in frontal pole connectivity. Community detection analysis indicated a shift in connectivity to the salience network from the default mode network in the medial temporal lobe following estradiol treatment. Testosterone treatment was associated with greater connectivity in medial frontal regions to the frontoparietal network. Conclusions: Preliminary evidence indicates that both estradiol and testosterone treatment can produce significant changes in the connectivity of affective regions in the brain, as well as reorganization of the brain’s network structure. Presentation: Saturday, June 17, 2023

Temporal Dynamics of Brain Activity Predicting Sense of Agency over Muscle Movements.

Our muscles are the primary means through which we affect the external world, and the sense of agency (SoA) over the action through those muscles is fundamental to our self-awareness. However, SoA research to date has focused almost exclusively on agency over action outcomes rather than over the musculature itself, as it was believed that SoA over the musculature could not be manipulated directly. Drawing on methods from human-computer interaction and adaptive experimentation, we use human-in-the-loop Bayesian optimization to tune the timing of electrical muscle stimulation so as to robustly elicit a SoA over electrically actuated muscle movements in male and female human subjects. We use time-resolved decoding of subjects' EEG to estimate the time course of neural activity which predicts reported agency on a trial-by-trial basis. Like paradigms which assess SoA over action consequences, we found that the late (post-conscious) neural activity predicts SoA. Unlike typical paradigms, however, we also find patterns of early (sensorimotor) activity with distinct temporal dynamics predicts agency over muscle movements, suggesting that the "neural correlates of agency" may depend on the level of abstraction (i.e., direct sensorimotor feedback versus downstream consequences) most relevant to a given agency judgment. Moreover, fractal analysis of the EEG suggests that SoA-contingent dynamics of neural activity may modulate the sensitivity of the motor system to external input.SIGNIFICANCE STATEMENT The sense of agency, the feeling of "I did that," when directing one's own musculature is a core feature of human experience. We show that we can robustly manipulate the sense of agency over electrically actuated muscle movements, and we investigate the time course of neural activity that predicts the sense of agency over these actuated movements. We find evidence of two distinct neural processes: a transient sequence of patterns that begins in the early sensorineural response to muscle stimulation and a later, sustained signature of agency. These results shed light on the neural mechanisms by which we experience our movements as volitional.

Take your time: Slow brain rhythms predict fluid intelligence

Evidence is mixed whether fluid intelligence (Gf) is associated with increased or decreased alpha and beta band activity (7–30 Hz). Moreover, the Gf relationship with the delta and theta band activity (1–7 Hz) is unknown. We recorded electroencephalographic (EEG) data in 160 healthy adults solving Raven's Advanced Progressive Matrices with a randomized item order to control for item difficulty unaffected by sequential effects. The participants studied each matrix for 30 s before the response bank onset, so we could track the time course of neural activity during problem solving. We measured Gf using six tests. Gf positively correlated with the delta band power, while there was no correlation with the theta band power. For almost all of the participants, we identified the specific slow rhythm frequency, which varied in power as a function of item difficulty. We observed that the lower this frequency, the higher Gf, but only in men. Finally, the alpha and low-beta activity correlated negatively with Gf after we had filtered out the activity during idle intervals (the latter reflecting waiting for the response bank). Overall, the brain activity in the delta, alpha, and beta bands explained 22.6% of Gf variance.

Dimensionality reduction of calcium-imaged neuronal population activity.

Calcium imaging has been widely adopted for its ability to record from large neuronal populations. To summarize the time course of neural activity, dimensionality reduction methods, which have been applied extensively to population spiking activity, may be particularly useful. However, it is unclear if the dimensionality reduction methods applied to spiking activity are appropriate for calcium imaging. We thus carried out a systematic study of design choices based on standard dimensionality reduction methods. We also developed a method to perform deconvolution and dimensionality reduction simultaneously (Calcium Imaging Linear Dynamical System, CILDS). CILDS most accurately recovered the single-trial, low-dimensional time courses from simulated calcium imaging data. CILDS also outperformed the other methods on calcium imaging recordings from larval zebrafish and mice. More broadly, this study represents a foundation for summarizing calcium imaging recordings of large neuronal populations using dimensionality reduction in diverse experimental settings.

Autohrf-an R package for generating data-informed event models for general linear modeling of task-based fMRI data.

The analysis of task-related fMRI data at the level of individual participants is commonly based on general linear modeling (GLM), which allows us to estimate the extent to which the BOLD signal can be explained by the task response predictors specified in the event model. The predictors are constructed by convolving the hypothesized time course of neural activity with an assumed hemodynamic response function (HRF). However, our assumptions about the components of brain activity, including their onset and duration, may be incorrect. Their timing may also differ across brain regions or from person to person, leading to inappropriate or suboptimal models, poor fit of the model to actual data, and invalid estimates of brain activity. Here, we present an approach that uses theoretically driven models of task response to define constraints on which the final model is computationally derived using actual fMRI data. Specifically, we developed autohrf-an R package that enables the evaluation and data-driven estimation of event models for GLM analysis. The highlight of the package is the automated parameter search that uses genetic algorithms to find the onset and duration of task predictors that result in the highest fitness of GLM based on the fMRI signal under predefined constraints. We evaluated the usefulness of the autohrf package on two original datasets of task-related fMRI activity, a slow event-related spatial working memory study and a mixed state-item study using the flanker task, and on a simulated slow event-related working memory data. Our results suggest that autohrf can be used to efficiently construct and evaluate better task-related brain activity models to gain a deeper understanding of BOLD task response and improve the validity of model estimates. Our study also highlights the sensitivity of fMRI analysis with GLM to precise event model specification and the need for model evaluation, especially in complex and overlapping event designs.

The Precentral Gyrus Contributions to the Early Time-Course of Grapheme-to-Phoneme Conversion.

As part of silent reading models, visual orthographic information is transduced into an auditory phonological code in a process of grapheme-to-phoneme conversion (GPC). This process is often identified with lateral temporal-parietal regions associated with auditory phoneme encoding. However, the role of articulatory phonemic representations and the precentral gyrus in GPC is ambiguous. Though the precentral gyrus is implicated in many functional MRI studies of reading, it is not clear if the time course of activity in this region is consistent with the precentral gyrus being involved in GPC. We recorded cortical electrophysiology during a bimodal match/mismatch task from eight patients with perisylvian subdural electrodes to examine the time course of neural activity during a task that necessitated GPC. Patients made a match/mismatch decision between a 3-letter string and the following auditory bi-phoneme. We characterized the distribution and timing of evoked broadband high gamma (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus emerged with a high concentration of broadband high gamma responses to visual and auditory language as well as mismatch effects. The pars opercularis, supramarginal gyrus, and superior temporal gyrus were also involved. The precentral gyrus showed strong phase-locking with the caudal fusiform gyrus during letter-string presentation and with surrounding perisylvian cortex during the bimodal visual-auditory comparison period. These findings hint at a role for precentral cortex in transducing visual into auditory codes during silent reading.

Time Course of Homeostatic Structural Plasticity in Response to Optogenetic Stimulation in Mouse Anterior Cingulate Cortex.

Plasticity is the mechanistic basis of development, aging, learning, and memory, both in healthy and pathological brains. Structural plasticity is rarely accounted for in computational network models due to a lack of insight into the underlying neuronal mechanisms and processes. Little is known about how the rewiring of networks is dynamically regulated. To inform such models, we characterized the time course of neural activity, the expression of synaptic proteins, and neural morphology employing an in vivo optogenetic mouse model. We stimulated pyramidal neurons in the anterior cingulate cortex of mice and harvested their brains at 1.5 h, 24 h, and $48\,\mathrm{h}$ after stimulation. Stimulus-induced cortical hyperactivity persisted up to 1.5 h and decayed to baseline after $24\,\mathrm{h}$ indicated by c-Fos expression. The synaptic proteins VGLUT1 and PSD-95, in contrast, were upregulated at $24\,\mathrm{h}$ and downregulated at $48\,\mathrm{h}$, respectively. Spine density and spine head volume were also increased at $24\,\mathrm{h}$ and decreased at $48\,\mathrm{h}$. This specific sequence of events reflects a continuous joint evolution of activity and connectivity that is characteristic of the model of homeostatic structural plasticity. Our computer simulations thus corroborate the observed empirical evidence from our animal experiments.

Time matters: Feature-specific prioritization follows feature integration in visual object processing

Objects represent a fundamental selection unit of visual attention. However, at odds with the integrated competition account, our recent study demonstrated that attentional facilitation of constituent features does not spread automatically within an object, but instead depends on the specific task relevance of each feature. Here, we employed a novel experimental design, allowing simultaneous electrophysiological measurements of the allocation of attention to two distinct features (rotation and color) within one object (a square) during both trial-wise and block-wise cued shifts of attention. This was possible through the presentation of a square that evokes two distinct steady-state visual evoked potentials (SSVEPs) for its rotation and its color changes, respectively. Given the continuous oscillatory nature of SSVEPs, we were able to investigate the time course of neural activity in the early visual cortex of the human brain when subjects attended to one of the two features, compared to when the whole object was attended. This approach enabled us to uncover feature-based mechanisms of attention within one object, as well as their interaction with object-based mechanisms. Both behavioral and electrophysiological results indicate a biphasic process composed of an early transient integration of the constituent object features, followed by sustained mechanisms of feature selection with amplification of the to-be-attended feature, followed temporally by suppression of the to-be-ignored feature.

Putting our heads together: interpersonal neural synchronization as a biological mechanism for shared intentionality.

Shared intentionality, or collaborative interactions in which individuals have a shared goal and must coordinate their efforts, is a core component of human interaction. However, the biological bases of shared intentionality and, specifically, the processes by which the brain adjusts to the sharing of common goals, remain largely unknown. Using functional near infrared spectroscopy (fNIRS), coordination of cerebral hemodynamic activation was found in subject pairs when completing a puzzle together in contrast to a condition in which subjects completed identical but individual puzzles (same intention without shared intentionality). Interpersonal neural coordination was also greater when completing a puzzle together compared to two control conditions including the observation of another pair completing the same puzzle task or watching a movie with a partner (shared experience). Further, permutation testing revealed that the time course of neural activation of one subject predicted that of their partner, but not that of others completing the identical puzzle in different partner sets. Results indicate unique brain-to-brain coupling specific to shared intentionality beyond what has been previously found by investigating the fundamentals of social exchange.

Slow Wave Activity Related to Working Memory Maintenance in the N-Back Task

Abstract. Working memory supports our ability to maintain goal-relevant information that guides cognition in the face of distraction or competing tasks. The N-back task has been widely used in cognitive neuroscience to examine the functional neuroanatomy of working memory. Fewer studies have capitalized on the temporal resolution of event-related brain potentials (ERPs) to examine the time course of neural activity in the N-back task. The primary goal of the current study was to characterize slow wave activity observed in the response-to-stimulus interval in the N-back task that may be related to maintenance of information between trials in the task. In three experiments, we examined the effects of N-back load, interference, and response accuracy on the amplitude of the P3b following stimulus onset and slow wave activity elicited in the response-to-stimulus interval. Consistent with previous research, the amplitude of the P3b decreased as N-back load increased. Slow wave activity over the frontal and posterior regions of the scalp was sensitive to N-back load and was insensitive to interference or response accuracy. Together these findings lead to the suggestion that slow wave activity observed in the response-to-stimulus interval is related to the maintenance of information between trials in the 1-back task.

Mapping of language brain areas in patients with brain tumors.

Language cortex in the human brain shows high variability among normal individuals and may exhibit a considerable shift from its original position due to tumor growth. Mapping the precise location of language areas is important before surgery to avoid postoperative language deficits. In this paper, the Magnetoencephalography (MEG) recording and the MRI scanning of six brain tumorous subjects are used to localize the language specific areas. MEG recordings were performed during two silent reading tasks; silent word reading and silent picture naming. MEG source imaging is performed using distributed source modeling technique called CLARA ("Classical LORETA Analysis Recursively Applied"). Estimated MEG sources are overlaid on individual MRI of each patient to improve interpretation of MEG source imaging results. The results show successful identification of the essential language areas and clear definition of the time course of neural activation connecting them.

The time-course of cortico-limbic neural responses to air hunger

Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼45mmHg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (VT) was alternated every 90s between high VT (0.96±0.23L) that provided respiratory comfort (12±6% full scale) and low VT (0.48±0.08L) which evoked air hunger (56±11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research.

Interindividual synchronization of brain activity during live verbal communication

Verbal social interaction plays an important role both in the etiology and treatment of psychiatric disorders. However, the neural basis of social interaction has primarily been studied in the individual brain, neglecting the inter-individual perspective. Here, we show inter-individual neuronal coupling of brain activity during live verbal interaction, by investigating 11 pairs of good female friends who were instructed to speak about autobiographical life events during simultaneous fMRI acquisition. The analysis revealed that the time course of neural activity in areas associated with speech production was coupled with the time course of neural activity in the interlocutor's auditory cortex. This shows the feasibility of the new methodology, which may help elucidate basic reciprocal mechanisms of social interaction and the underpinnings of disordered communication. In particular, it may serve to study the process of psychotherapy on a neuronal level.

Time course of word production does not support a parallel input architecture

Hickok's enterprise to unify psycholinguistic and motor control models is highly stimulating. Nonetheless, there are problems of the model with respect to the time course of neural activation in word production, the flexibility for continuous speech, and the need for non-motor feedback.

Temporal Dynamics of Disgust and Morality: An Event-Related Potential Study

Disgust is argued to be an emotion that motivates the avoidance of disease-causing entities in the physical domain and unacceptable behaviors in the social-moral domain. Empirical work from behavioral, physiological and brain imaging studies suggests moral judgments are strongly modulated by disgust feelings. Yet, it remains unclear how they are related in the time course of neural processing. Examining the temporal order of disgust emotion and morality could help to clarify the role of disgust in moral judgments. In the present research, a Go/No-Go paradigm was employed to evoke lateralized readiness potentials (LRPs) to investigate the temporal order of physical disgust and moral information processing. Participants were asked to give a “yes” or “no” response regarding the physical disgust and moral wrongness of a social act. The results showed that the evaluation of moral information was processed prior to that of physical disgust information. This suggests that moral information is available earlier than physical disgust, and provides more data on the biological heterogeneity between disgust and morality in terms of the time course of neural activity. The findings implicate that physical disgust emotion may not be necessary for people to make moral judgments. They also suggest that some of our moral experience may be more fundamental (than physical disgust experience) to our survival and development, as humans spend a considerable amount of time engaging in social interaction.

Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness

The neurophysiological mechanisms by which anesthetic drugs cause loss of consciousness are poorly understood. Anesthetic actions at the molecular, cellular, and systems levels have been studied in detail at steady states of deep general anesthesia. However, little is known about how anesthetics alter neural activity during the transition into unconsciousness. We recorded simultaneous multiscale neural activity from human cortex, including ensembles of single neurons, local field potentials, and intracranial electrocorticograms, during induction of general anesthesia. We analyzed local and global neuronal network changes that occurred simultaneously with loss of consciousness. We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (<1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space. Local (<4 mm) neuronal populations maintain the millisecond-scale connectivity patterns observed in the awake state, and spike rates fluctuate and can reach baseline levels. However, neuronal spiking occurs only within a limited slow oscillation-phase window and is silent otherwise, fragmenting the time course of neural activity. Unexpectedly, we found that these slow oscillations occur asynchronously across cortex, disrupting functional connectivity between cortical areas. We conclude that the onset of slow oscillations is a neural correlate of propofol-induced loss of consciousness, marking a shift to cortical dynamics in which local neuronal networks remain intact but become functionally isolated in time and space.

Cortical activity during speech and non-speech oromotor tasks: A magnetoencephalography (MEG) study

We used whole-head magnetoencephalography to investigate cortical activity during two oromotor activities foundational to speech production. 13 adults performed mouth opening and phoneme (/pa/) production tasks to a visual cue. Jaw movements were tracked with an ultrasound-emitting device. Trials were time-locked to both stimulus onset and peak of jaw displacement. An event-related beamformer source reconstruction algorithm was used to detect areas of cortical activity for each condition. Beamformer output was submitted to iterative K-means clustering analyses. The time course of neural activity at each cluster centroid was computed for each individual and condition. Peaks were identified and latencies submitted for statistical analysis to reveal the relative timing of activity in each brain region. Stimulus locked activations for the mouth open task included a progression from left cuneus to left frontal and then right pre-central gyrus. Phoneme generation revealed the same sequence but with bilateral frontal activation. When time locked to jaw displacement, the mouth open condition showed left frontal followed by right frontal–temporal areas. Phoneme generation showed a complicated sequence of bilateral temporal and frontal areas. This study used three unique approaches (beamforming, clustering and jaw tracking) to demonstrate the temporal progression of neural activations that underlie the motor control of two simple oromotor tasks. These findings have implications for understanding clinical conditions with deficits in articulatory control or motor speech planning.

Direct recordings in human cortex reveal the dynamics of gamma-band [50–150Hz] activity during pursuit eye movement control

The time course of neural activity in human brain regions involved in mediating pursuit eye movements is unclear. To address this question, we recorded intracerebral electroencephalography activity in eight epileptic patients while they performed a pursuit task that dissociates reactive, predictive and inhibited pursuits. A sustained gamma band (50-150 Hz) activity corresponding to pursuit maintenance was observed in the pursuit (and not saccade) area of the frontal eye field (FEF), in the ventral intraparietal sulcus (VIPS) and in occipital areas. The latency of gamma increase was found to precede target onset in FEF and VIPS, suggesting that those areas could also be involved during pursuit preparation/initiation. During pursuit inhibition, a sustained gamma band response was observed within prefrontal areas (pre-supplementary-motor-area, dorso-lateral prefrontal and frontopolar cortex). This study describes for the first time the dynamics of the neural activity in four areas of the pursuit system, not previously available in humans. These findings provide novel timing constraints to current models of the human pursuit system and establish the relevance of direct recordings to precisely relate eye movement behavior with neural activity in humans.

Orexinergic signaling mediates light-induced neuronal activation in the dorsal raphe nucleus

Seasonal affective disorder (SAD), a major depressive disorder recurring in the fall and winter, is caused by the reduction of light in the environment, and its depressive symptoms can be alleviated by bright light therapy. Both circadian and monoaminergic systems have been implicated in the etiology of SAD. However, the underlying neural pathways through which light regulates mood are not well understood. The present study utilized a diurnal rodent model, Arvicanthis niloticus, to explore the neural pathways mediating the effects of light on brain regions involved in mood regulation. Animals kept in constant darkness received light exposure in early subjective day, the time when light therapy is usually applied. The time course of neural activity following light exposure was assessed using Fos protein as a marker in the following brain regions/cells: the suprachiasmatic nucleus (SCN), orexin neurons in the perifornical-lateral hypothalamic area (PF-LHA) and the dorsal raphe nucleus (DRN). A light-induced increase in Fos expression was observed in orexin neurons and the DRN, but not in the SCN. As the DRN is densely innervated by orexinergic inputs, the involvement of orexinergic signaling in mediating the effects of light on the DRN was tested in the second experiment. The animals were injected with the selective orexin receptor type 1 (OXR1) antagonist SB-334867 prior to the light exposure. The treatment of SB-334867 significantly inhibited the Fos induction in the DRN. The results collectively point to the role of orexin neurons in mediating the effects of light on the mood-regulating monoaminergic areas, suggesting an orexinergic pathway that underlies light-dependent mood fluctuation and the beneficial effects of light therapy.