Threat and Reward Imminence Processing in the Human Brain.

In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. In addition, the extent to which aversive-related and appetitive-related processing engage distinct or overlapping circuits remains poorly understood. Here, we sought to investigate the dynamics of aversive and appetitive processing while male and female participants engaged in comparable trials involving threat avoidance or reward seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence. For example, in the aversive domain, we predicted that the bed nucleus of the stria terminalis (BST), but not the amygdala, would exhibit anticipatory responses given the role of the former in anxious apprehension. We also predicted that the periaqueductal gray (PAG) would exhibit threat-proximity responses based on its involvement in proximal-threat processes, and that the ventral striatum would exhibit threat-imminence responses given its role in threat escape in rodents. Overall, we uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the BST, PAG, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Whereas the ventral striatum generated anticipatory responses in the proximity of reward as expected, it also exhibited threat-related imminence responses. In fact, across multiple brain regions, we observed a main effect of arousal. In other words, we uncovered extensive temporally evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information regardless of valence, findings further supported by network analysis.SIGNIFICANCE STATEMENT In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. Here, we sought to investigate the dynamics of aversive/appetitive processing while participants engaged in trials involving threat avoidance or reward seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence. We uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the bed nucleus of the stria terminalis, periaqueductal gray, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Overall, we uncovered extensive temporally evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information regardless of valence.

Threat and reward imminence processing in the human brain.

In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. In addition, the extent to which aversive- and appetitive-related processing engage distinct or overlapping circuits remains poorly understood. Here, we sought to investigate the dynamics of aversive and appetitive processing while male and female participants engaged in comparable trials involving threat-avoidance or reward-seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence . For example, in the aversive domain, we predicted that the bed nucleus of the stria terminalis (BST), but not the amygdala, would exhibit anticipatory responses given the role of the former in anxious apprehension. We also predicted that the periaqueductal gray (PAG) would exhibit threat-proximity responses based on its involvement in proximal-threat processes, and that the ventral striatum would exhibit threat-imminence responses given its role in threat escape in rodents. Overall, we uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the BST, PAG, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Whereas the ventral striatum generated anticipatory responses in the proximity of reward as expected, it also exhibited threat-related imminence responses. In fact, across multiple brain regions, we observed a main effect of arousal. In other words, we uncovered extensive temporally-evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information irrespective of valence, findings further supported by network analysis. Significance Statement: In the human brain, aversive and appetitive processing have been studied with controlled stimuli in rather static settings. Here, we sought to investigate the dynamics of aversive/appetitive processing while participants engaged in trials involving threat-avoidance or reward-seeking. A central goal was to characterize the temporal evolution of responses during periods of threat or reward imminence . We uncovered imminence-related temporally increasing ("ramping") responses in multiple brain regions, including the bed nucleus of the stria terminalis, periaqueductal gray, and ventral striatum, subcortically, and dorsal anterior insula and anterior midcingulate, cortically. Overall, we uncovered extensive temporally-evolving, imminence-related processing in both the aversive and appetitive domain, suggesting that distributed brain circuits are dynamically engaged during the processing of biologically relevant information irrespective of valence.

Stimulus-induced Robust Narrow-band Gamma Oscillations in Human EEG Using Cartesian Gratings.

Stimulus-induced narrow-band gamma oscillations (20-70 Hz) are induced in the visual areas of the brain when particular visual stimuli, such as bars, gratings, or full-screen hue, are shown to the subject. Such oscillations are modulated by higher cognitive functions, like attention, and working memory, and have been shown to be abnormal in certain neuropsychiatric disorders, such as schizophrenia, autism, and Alzheimer's disease. However, although electroencephalogram (EEG) remains one of the most non-invasive, inexpensive, and accessible methods to record brain signals, some studies have failed to observe discernable gamma oscillations in human EEG. In this manuscript, we have described in detail a protocol to elicit robust gamma oscillations in human EEG. We believe that our protocol could help in developing non-invasive gamma-based biomarkers in human EEG, for the early detection of neuropsychiatric disorders.

Stimulus-Induced Narrowband Gamma Oscillations are Test-Retest Reliable in Human EEG.

Visual stimulus-induced gamma oscillations in electroencephalogram (EEG) recordings have been recently shown to be compromised in subjects with preclinical Alzheimer's Disease (AD), suggesting that gamma could be an inexpensive biomarker for AD diagnosis provided its characteristics remain consistent across multiple recordings. Previous magnetoencephalography studies in young subjects have reported consistent gamma power over recordings separated by a few weeks to months. Here, we assessed the consistency of stimulus-induced slow (20-35 Hz) and fast gamma (36-66 Hz) oscillations in subjects (n = 40) (age: 50-88 years) in EEG recordings separated by a year, and tested the consistency in the magnitude of gamma power, its temporal evolution and spectral profile. Gamma had distinct spectral/temporal characteristics across subjects, which remained consistent across recordings (average intraclass correlation of ~0.7). Alpha (8-12 Hz) and steady-state-visually evoked-potentials were also reliable. We further tested how EEG features can be used to identify 2 recordings as belonging to the same versus different subjects and found high classifier performance (AUC of ~0.89), with temporal evolution of slow gamma and spectral profile being most informative. These results suggest that EEG gamma oscillations are reliable across sessions separated over long durations and can also be a potential tool for subject identification.

Distributed and Multifaceted Effects of Threat and Safety.

In the present fMRI study, we examined how anxious apprehension is processed in the human brain. A central goal of the study was to test the prediction that a subset of brain regions would exhibit sustained response profiles during threat periods, including the anterior insula, a region implicated in anxiety disorders. A second important goal was to evaluate the responses in the amygdala and the bed nucleus of the stria terminals, regions that have been suggested to be involved in more transient and sustained threat, respectively. A total of 109 participants performed an experiment in which they encountered "threat" or "safe" trials lasting approximately 16 sec. During the former, they experienced zero to three highly unpleasant electrical stimulations, whereas in the latter, they experienced zero to three benign electrical stimulations (not perceived as unpleasant). The timing of the stimulation during trials was randomized, and as some trials contained no stimulation, stimulation delivery was uncertain. We contrasted responses during threat and safe trials that did not contain electrical stimulation, but only the potential that unpleasant (threat) or benign (safe) stimulation could occur. We employed Bayesian multilevel analysis to contrast responses to threat and safe trials in 85 brain regions implicated in threat processing. Our results revealed that the effect of anxious apprehension is distributed across the brain and that the temporal evolution of the responses is quite varied, including more transient and more sustained profiles, as well as signal increases and decreases with threat.

Gamma oscillations weaken with age in healthy elderly in human EEG.

Gamma rhythms (~20-70 â€‹Hz) are abnormal in mental disorders such as autism and schizophrenia in humans, and Alzheimer's disease (AD) models in rodents. However, the effect of normal aging on these oscillations is unknown, especially for elderly subjects in whom AD is most prevalent. In a first large-scale (236 subjects; 104 females) electroencephalogram (EEG) study on gamma oscillations in elderly subjects (aged 50-88 years), we presented full-screen visual Cartesian gratings that induced two distinct gamma oscillations (slow: 20-34 â€‹Hz and fast: 36-66 â€‹Hz). Power decreased with age for gamma, but not alpha (8-12 â€‹Hz). Reduction was more salient for fast gamma than slow. Center frequency also decreased with age for both gamma rhythms. The results were independent of microsaccades, pupillary reactivity to stimulus, and variations in power spectral density with age. Steady-state visual evoked potentials (SSVEPs) at 32 â€‹Hz also reduced with age. These results are crucial for developing gamma/SSVEP-based biomarkers of cognitive decline in elderly.

Large Visual Stimuli Induce Two Distinct Gamma Oscillations in Primate Visual Cortex.

Recent studies have shown the existence of two gamma rhythms in the hippocampus subserving different functions but, to date, primate studies in primary visual cortex have reported a single gamma rhythm. Here, we show that large visual stimuli induce a slow gamma (25-45 Hz) in area V1 of two awake adult female bonnet monkeys and in the EEG of 15 human subjects (7 males and 8 females), in addition to the traditionally known fast gamma (45-70 Hz). The two rhythms had different tuning characteristics for stimulus orientation, contrast, drift speed, and size. Further, fast gamma had short latency, strongly entrained spikes and was coherent over short distances, reflecting short-range processing, whereas slow gamma appeared to reflect long-range processing. Together, two gamma rhythms can potentially provide better coding or communication mechanisms and a more comprehensive biomarker for diagnosis of mental disorders.SIGNIFICANCE STATEMENT Gamma rhythm has been associated with high-level cognitive functions such as attention and feature binding and has been reported to be abnormal in brain disorders such as autism and schizophrenia. Unlike previous studies that have shown a single gamma rhythm in the primate visual cortex, we found that large visual gratings induce two distinct gamma oscillations in both monkey LFP and human EEG. These rhythms, termed slow (25-45 Hz) and fast (45-70 Hz), exhibited distinct tuning preferences, latencies, and coherence profiles, potentially reflecting processing at two different ranges. Multiple gamma oscillations in visual cortex may provide a richer representation of external visual stimuli and could be used for developing brain-machine interfacing applications and screening tests for neuropsychiatric disorders.