Current projects

1. Sensory processing deficits and aberrant neural oscillations in veterans with posttraumatic stress symtpoms

Post-traumatic stress disorder (PTSD) is a pervasive psychological disorder characterized by a plethora of low- and high-order aberrations in response to environmental stimuli. While emphasis has largely been placed on top-down processes involving emotion-regulation and cognitive deficits, recent studies have demonstrated aberrant sensory processes in the patients with PTSD. Furthermore, recent electroencephalography (EEG) work from our lab has asserted that veterans with PTSD demonstrate decreased alpha oscillations, a neural index of sensory gating, in the posterior sensory systems at rest. This deficient bottom-up inhibition from hyperactive sensory systems would overload frontal control processing suggesting an additional mechanism of PTSD pathology stemming from sensory processing deficits. The proposed study seeks to investigate this deficiency by measuring resting-state alpha activity through EEG recordings in veterans and examining how it contributes to sensory processing anomalies and post-traumatic stress (PTS) symptoms.

2. Alpha-frequency transcranial alternating current stimulation (tACS) induces plastic increases in posterior-frontal network connectivity

Despite accruing evidence for the effect transcranial alternating current stimulation (tACS) has on cortical oscillations, little remains known about the influence tACS has on inter-areal oscillatory dynamics. Furthermore, while efforts to assess within-session aftereffects persist, long-term modulatory effects, especially changes in inter-areal connectivity, remain to be elucidated. Utilizing a multi-session, randomized control tACS paradigm, we are evalutating the effects repeated stimulation at an individual’s peak alpha frequency (IAF) has on intrinsic posterior alpha activity over the span of 4 days. Spectral Granger Causality was employed to further assess plastic changes in long-range network communication between posterior sensory and frontal executive control systems, while mood and sensory sensitivity ratings assessed effects on affective and sensory processes.

Current projects

1. Mechanism-based Transcranial Alternating Current Stimulation (tACS) for Suicide Prevention in the Military

Suicide rates in the military have increased substantially over the past decade; in veterans, suicide rates, especially in male veterans, have risen to almost double the rate of civilians, despite extensive prevention efforts by the U.S. Army. Causes for depression are extremely complex and multifaceted, posing particular challenge for suicide prevention. To mitigate these complex and potentially independent psychological and physiological processes in the pathway to suicide, it has become imperative to develop mechanism-based and specific, targeted intervention protocols. Towards that end, the current proposal aims to develop a novel, mechanism-based neuromodulation treatment, using transcranial alternating current stimulation (tACS). Importantly, this treatment is designed to target a specific high-risk group that is strongly represented by the military population. That is, based on interdisciplinary research in our lab and others, we have isolated a special, intersected set of social, psychological and biological (neural) risk factors, commonly observed in military personnel. The multiplicative effects of these risks combined would present a strong suicide risk in these vulnerable individuals. Furthermore, recent technological advancements in transcranial stimulation have brought forward the technology of transcranial alternating current stimulation (tACS), a safe, noninvasive neuromodulation approach. Unlike a variety of transcranial electrical or magnetic stimulation techniques used in neuropsychiatric treatments, tACS is only recently adopted to modulate specific neural oscillations and network connectivity, allowing for precise targeting of pathology (e.g., alpha oscillations in PTSD). Research has shown strong potential of tACS in selectively entraining and enhancing endogenous neural oscillations, especially at their peak frequencies. Evidence also suggests neural plasticity resulting from tACS, which is critical for efficacious clinical applications. Therefore, by simulating the intrinsic alpha oscillations, tACS can introduce plastic changes in the brain, resulting in sustained long-term augmentation of alpha activity.Therefore, based on this novel tripartite risk model of suicide (stress, distress intolerance and alpha deficits), which is particularly relevant to military personnel, the current proposal aims to target a specific subset of high-risk military personnel by precisely eradicating the biological root (alpha deficits) of their vulnerability to suicide.

Current projects

1. Defining the human olfactory network: a functional connectome analysis

Until recently, most human neuroanatomy has been inferred from rodent and monkey data; however, as noninvasive neuroimaging techniques and analytical methods have developed, researchers have begun to bridge the gap between animal models and the human brain. Here we seek to identify and explore the understudied olfactory network utilizing the open-source Human Connectome Project (HCP) resting-state functional magnetic resonance imaging (rs-fMRI) dataset. Our analysis revealed the functional integration of novel cortical substrates not present in non-human animal models, while also confirming established connectivity between more ancestral brain regions. Additional analyses used Graph Theory to characterize the network properties and relate odor processing ability to these properties in an independently collected dataset.

Current projects

1. Alpha Matters: Alpha Oscillatory Activity Correlates With Sensory Profile Measures and Modulates Sound Perception

It has long been suspected that alpha oscillations (8-12Hz) play an important role in the inhibition of irrelevant sensory input, and are thus involved in sensory gating and processing. We set out to investigate whether intrinsic (baseline) levels of alpha power in the parieto- occipital cortex correlate with the way an individual processes neutral as well as unpleasant sounds of varying intensities. It was found that posterior alpha power is negatively correlated with perceived loudness of sounds. Moreover, for quiet stimuli, alpha power was positively correlated with rated pleasantness of sounds.

Current projects

1. Enhanced olfactory sensory perception of threat in anxiety: An event-related fMRI study

The current conceptualization of threat processing in anxiety emphasizes emotional hyper-reactivity, which mediates various debilitating symptoms and derangements in anxiety disorders. Here, we investigated olfactory sensory perception of threat as an alternative account for anxiety genesis. Combining an event-related functional magnetic resonance imaging paradigm with an olfactory discrimination task, we examined how anxiety modulates basic perception of olfactory threats at behavioral and neural levels. In spite of subthreshold presentation of negative and neutral odors, a positive systemic association emerged between negative odor discrimination accuracy and anxiety levels. In parallel, the right olfactory primary (piriform) cortex indicated augmented response to subthreshold negative (vs. neutral) odors as a function of individual differences in anxiety. Using a psychophysiological (PPI) analysis, we further demonstrated amplified functional connectivity between the piriform cortex and emotion-related regions (amygdala and hippocampus) in response to negative odor, particularly in anxiety. Finally, anxiety also intensified skin conductance response to negative (vs. neutral) odor, indicating potentiated emotional arousal to subliminal olfactory threat in anxiety. Together, these findings elucidate exaggerated processing of olfactory threat in anxiety across behavioral, autonomic physiological, and neural domains. Critically, our data emphasized anxiety-related hyper-sensitivity of the primary olfactory cortex and basic olfactory perception in response to threat, supporting a novel neurosensory account that may underlie the deleterious symptoms of anxiety.

2. An fMRI investigation of olfactory alliesthesia: Enhanced olfactory sensory acuity in anxiety

The current literature offers little information about threat processing in senses other than vision. Among all senses, olfaction has nonetheless a uniquely intimate relationship with emotion. Moreover, accruing evidence suggests that olfactory dysfunction is associated with emotional disorders in addition to schizophrenia, meriting deliberate investigation of olfactory threat processing to uncover an olfactory-specific etiological mechanism of anxiety. Importantly, olfactory hedonic evaluation tends to depend on the perceiver’s internal state (i.e., olfactory alliesthesia). As such, anxiety as an internal state can negatively shift odor valence and confront anxious people with increased olfactory stress in everyday life. Combining experimental provocation of anxiety with fMRI techniques, we tested the hypothesis that anxiety improves olfactory acuity such that initially undetectable/negligible nuisance odors become perceptible, accompanied by enhanced activation of the emotion network in the brain and augmented autonomic arousal in the periphery. This is the first study to extricate the neural mechanisms of anxiety-state-dependent olfactory encoding, a system that could potentially mediate fundamental anxiety pathology.

3. Olfactory-visual synthesis sharpens subthreshold threat perception: an fMRI study

As noted above, all species equipped with multiple senses integrate them to optimize perception and action. This process is especially prominent when minimal sensory information is available. In line with our overarching theorization of aberrant threat perception in anxiety, we examined the hypothesis that crossmodal synergy of threat perception is particularly elevated in anxiety, such that concordant multisensory threat signals, even though individually unnoticeable, become evident in anxious people. This model may stand as a highly novel pathological mechanism for anxiety, by exposing people to otherwise unnoticeable sensory stressors and thus fueling anxious response. In this fMRI study, we presented subthreshold threat cues through both faces and odors that contained either neutral or subtle negative emotion, where the bimodal inputs are either concordant or disconcordant in the affective content, forming a 2-by-2 factorial design. This project represents the first study to elucidate the neural basis of crossmodal (olfactory-visual) synergy in perceiving otherwise undetectable threat in faces and smells. Notably, this work addresses a key question in basic affective neuroscience research by integrating multimodal representations of threat. Furthermore, to examine the modulatory effect of anxiety, we measured subjects’ anxiety levels (trait and state) based on self-report inventories, and recorded skin conductance response data during fMRI scanning to further specify anxiety-related responses.

Current projects

1. Hemispheric asymmetry and visuo-olfactory integration in perceiving subthreshold fearful expressions

Multisensory integration is ubiquitous, facilitating perception beyond the limit of individual senses. This mechanism is especially salient when individual sensory input is weak, potentially fusing undetectable traces into a tangible percept (“the principle of inverse effectiveness”). Nevertheless, it is unclear how this rule applies to threat perception, synthesizing elusive, discrete traces of a threat into a discernible danger signal. In light of hemispheric asymmetry in threat processing, we combined parafoveal stimulus presentation and the contralateral P1 event-related potential to investigate how aversive olfactory inputs enhance visual perception of highly degraded, subthreshold fearful expressions. The dominant right hemisphere exhibited early visual discrimination between subtle fear and neutral expressions, independently of accompanying odors. In the left hemisphere, differential visual processing occurred only at the convergence of negative odors and minute facial fear, highlighting the success and necessity of visuo-olfactory threat integration in this disadvantaged hemisphere. Reaction time data from a subsequent dot-detection task complemented these neural findings, revealing odor-dependent and hemisphere-specific modulation of spatial attention to facial expressions. Our evidence thus indicates crossmodal threat integration in basic visual perception that captures minimal threat information, especially in the “blind” right hemifield. Critically, this interaction between multisensory synergy and hemispheric asymmetry in threat perception may underlie the multifaceted fear experiences in everyday life, optimizing responses to maximize ecological interest in the face of danger.

2. Olfactory-visual synthesis sharpens subthreshold threat perception: an fMRI study

As noted above, all species equipped with multiple senses integrate them to optimize perception and action. This process is especially prominent when minimal sensory information is available. In line with our overarching theorization of aberrant threat perception in anxiety, we examined the hypothesis that crossmodal synergy of threat perception is particularly elevated in anxiety, such that concordant multisensory threat signals, even though individually unnoticeable, become evident in anxious people. This model may stand as a highly novel pathological mechanism for anxiety, by exposing people to otherwise unnoticeable sensory stressors and thus fueling anxious response. In this fMRI study, we presented subthreshold threat cues through both faces and odors that contained either neutral or subtle negative emotion, where the bimodal inputs are either concordant or disconcordant in the affective content, forming a 2-by-2 factorial design. This project represents the first study to elucidate the neural basis of crossmodal (olfactory-visual) synergy in perceiving otherwise undetectable threat in faces and smells. Notably, this work addresses a key question in basic affective neuroscience research by integrating multimodal representations of threat. Furthermore, to examine the modulatory effect of anxiety, we measured subjects’ anxiety levels (trait and state) based on self-report inventories, and recorded skin conductance response data during fMRI scanning to further specify anxiety-related responses.

Current projects

1. From early specialization to later generalization: Dynamic perceptual categorization of individual threat emotions.

Object perception typically follows a hierarchical progression from simple to complex and from general to specific, but it is unclear how individual threat emotions are categorized in perceptual processing. Using visual event-related potentials in a “looming” paradigm, we demonstrate that two threat subtypes—fear and disgust—engage distinct initial visual encoding (104 ms), succeeded by convergent visual analysis in downstream inferior temporal cortex (>540 ms). That fear enhanced and disgust suppressed early sensory response, relative to neutral emotion, coincides with opposite behavioral and autonomic reflexes these two threats typically elicit. By contrast, the later perceptual confluence of fear and disgust, corroborated by comparable exaggeration in perceived object looming in both conditions, highlights general threat categorization in later perceptual processing to guide motivationally appropriate behavior. Therefore, contrary to standard object perception, human threat perception engages an initial mandatory specialization of individual threats, followed by context-dependent generalization at a later stage.

Current projects

1. Parametric depiction of early and late processing of fear and disgust in various intensities

In real life, we experience threat in differing intensities, ranging from a mild threat of confronting an unfriendly face to the extreme threat of facing death. Strikingly, how humans respond to varying levels of threat has hardly been systemically studied, especially in terms of the underlying neural mechanisms. Here, combining morphing techniques and brain electrophysiology, we varied the percentage of a fearful face mixed in a neutral face from 2% to 30% (in increments of 4%) to parametrically delineate early and late analysis of threat emotions, and to associate threat processing with individual levels of anxiety. Behavioral data suggested a clear sigmoid function between fear detection rate and fear intensity level. Importantly, we uncovered a fear detection threshold shift due to anxiety: anxious individuals exhibited a lower threshold (i.e. lower fear intensity) than non-anxious participants, highlighting a perceptual acuity to threat. Interestingly, the P3 event-related potential indicated a clear linear function between P3 amplitude and fear intensity, accentuating a parametric tacking system in later visual perception of threat.

2. Hemispheric asymmetry and visuo-olfactory integration in perceiving subthreshold fearful expressions

Multisensory integration is ubiquitous, facilitating perception beyond the limit of individual senses. This mechanism is especially salient when individual sensory input is weak, potentially fusing undetectable traces into a tangible percept (“the principle of inverse effectiveness”). Nevertheless, it is unclear how this rule applies to threat perception, synthesizing elusive, discrete traces of a threat into a discernible danger signal. In light of hemispheric asymmetry in threat processing, we combined parafoveal stimulus presentation and the contralateral P1 event-related potential to investigate how aversive olfactory inputs enhance visual perception of highly degraded, subthreshold fearful expressions. The dominant right hemisphere exhibited early visual discrimination between subtle fear and neutral expressions, independently of accompanying odors. In the left hemisphere, differential visual processing occurred only at the convergence of negative odors and minute facial fear, highlighting the success and necessity of visuo-olfactory threat integration in this disadvantaged hemisphere. Reaction time data from a subsequent dot-detection task complemented these neural findings, revealing odor-dependent and hemisphere-specific modulation of spatial attention to facial expressions. Our evidence thus indicates crossmodal threat integration in basic visual perception that captures minimal threat information, especially in the “blind” right hemifield. Critically, this interaction between multisensory synergy and hemispheric asymmetry in threat perception may underlie the multifaceted fear experiences in everyday life, optimizing responses to maximize ecological interest in the face of danger.

3. From early specialization to later generalization: Dynamic perceptual categorization of individual threat emotions

Object perception typically follows a hierarchical progression from simple to complex and from general to specific, but it is unclear how individual threat emotions are categorized in perceptual processing. Using visual event-related potentials in a “looming” paradigm, we demonstrate that two threat subtypes—fear and disgust—engage distinct initial visual encoding (104 ms), succeeded by convergent visual analysis in downstream inferior temporal cortex (>540 ms). That fear enhanced and disgust suppressed early sensory response, relative to neutral emotion, coincides with opposite behavioral and autonomic reflexes these two threats typically elicit. By contrast, the later perceptual confluence of fear and disgust, corroborated by comparable exaggeration in perceived object looming in both conditions, highlights general threat categorization in later perceptual processing to guide motivationally appropriate behavior. Therefore, contrary to standard object perception, human threat perception engages an initial mandatory specialization of individual

Current projects

1. Enhanced olfactory sensory perception of threat in anxiety: An event-related fMRI study

The current conceptualization of threat processing in anxiety emphasizes emotional hyper-reactivity, which mediates various debilitating symptoms and derangements in anxiety disorders. Here, we investigated olfactory sensory perception of threat as an alternative account for anxiety genesis. Combining an event-related functional magnetic resonance imaging paradigm with an olfactory discrimination task, we examined how anxiety modulates basic perception of olfactory threats at behavioral and neural levels. In spite of subthreshold presentation of negative and neutral odors, a positive systemic association emerged between negative odor discrimination accuracy and anxiety levels. In parallel, the right olfactory primary (piriform) cortex indicated augmented response to subthreshold negative (vs. neutral) odors as a function of individual differences in anxiety. Using a psychophysiological (PPI) analysis, we further demonstrated amplified functional connectivity between the piriform cortex and emotion-related regions (amygdala and hippocampus) in response to negative odor, particularly in anxiety. Finally, anxiety also intensified skin conductance response to negative (vs. neutral) odor, indicating potentiated emotional arousal to subliminal olfactory threat in anxiety. Together, these findings elucidate exaggerated processing of olfactory threat in anxiety across behavioral, autonomic physiological, and neural domains. Critically, our data emphasized anxiety-related hyper-sensitivity of the primary olfactory cortex and basic olfactory perception in response to threat, supporting a novel neurosensory account that may underlie the deleterious symptoms of anxiety.

2. Hemispheric asymmetry and visuo-olfactory integration in perceiving subthreshold fearful expressions

Multisensory integration is ubiquitous, facilitating perception beyond the limit of individual senses. This mechanism is especially salient when individual sensory input is weak, potentially fusing undetectable traces into a tangible percept (“the principle of inverse effectiveness”). Nevertheless, it is unclear how this rule applies to threat perception, synthesizing elusive, discrete traces of a threat into a discernible danger signal. In light of hemispheric asymmetry in threat processing, we combined parafoveal stimulus presentation and the contralateral P1 event-related potential to investigate how aversive olfactory inputs enhance visual perception of highly degraded, subthreshold fearful expressions. The dominant right hemisphere exhibited early visual discrimination between subtle fear and neutral expressions, independently of accompanying odors. In the left hemisphere, differential visual processing occurred only at the convergence of negative odors and minute facial fear, highlighting the success and necessity of visuo-olfactory threat integration in this disadvantaged hemisphere. Reaction time data from a subsequent dot-detection task complemented these neural findings, revealing odor-dependent and hemisphere-specific modulation of spatial attention to facial expressions. Our evidence thus indicates crossmodal threat integration in basic visual perception that captures minimal threat information, especially in the “blind” right hemifield. Critically, this interaction between multisensory synergy and hemispheric asymmetry in threat perception may underlie the multifaceted fear experiences in everyday life, optimizing responses to maximize ecological interest in the face of danger.

3. Parametric depiction of early and late processing of fear and disgust in various intensities

In real life, we experience threat in differing intensities, ranging from a mild threat of confronting an unfriendly face to the extreme threat of facing death. Strikingly, how humans respond to varying levels of threat has hardly been systemically studied, especially in terms of the underlying neural mechanisms. Here, combining morphing techniques and brain electrophysiology, we varied the percentage of a fearful face mixed in a neutral face from 2% to 30% (in increments of 4%) to parametrically delineate early and late analysis of threat emotions, and to associate threat processing with individual levels of anxiety. Behavioral data suggested a clear sigmoid function between fear detection rate and fear intensity level. Importantly, we uncovered a fear detection threshold shift due to anxiety: anxious individuals exhibited a lower threshold (i.e. lower fear intensity) than non-anxious participants, highlighting a perceptual acuity to threat. Interestingly, the P3 event-related potential indicated a clear linear function between P3 amplitude and fear intensity, accentuating a parametric tacking system in later visual perception of threat.

4. An fMRI investigation of olfactory alliesthesia: Enhanced olfactory sensory acuity in anxiety

The current literature offers little information about threat processing in senses other than vision. Among all senses, olfaction has nonetheless a uniquely intimate relationship with emotion. Moreover, accruing evidence suggests that olfactory dysfunction is associated with emotional disorders in addition to schizophrenia, meriting deliberate investigation of olfactory threat processing to uncover an olfactory-specific etiological mechanism of anxiety. Importantly, olfactory hedonic evaluation tends to depend on the perceiver’s internal state (i.e., olfactory alliesthesia). As such, anxiety as an internal state can negatively shift odor valence and confront anxious people with increased olfactory stress in everyday life. Combining experimental provocation of anxiety with fMRI techniques, we tested the hypothesis that anxiety improves olfactory acuity such that initially undetectable/negligible nuisance odors become perceptible, accompanied by enhanced activation of the emotion network in the brain and augmented autonomic arousal in the periphery. This is the first study to extricate the neural mechanisms of anxiety-state-dependent olfactory encoding, a system that could potentially mediate fundamental anxiety pathology.