Brain responsivity to emotional faces differs in men and women with and without a history of alcohol use disorder

Inclusion of women in research on Alcohol Use Disorder (AUD) has shown that gender differences contribute to unique profiles of cognitive, emotional, and neuropsychological dysfunction. We employed functional magnetic resonance imaging (fMRI) of abstinent individuals with a history of AUD (21 women [AUDw], 21 men [AUDm]) and demographically similar non-AUD control (NC) participants without AUD (21 women [NCw], 21 men [NCm]) to explore how gender and AUD interact to influence brain responses during emotional processing and memory. Participants completed a delayed match-to-sample emotional face memory fMRI task, and brain activation contrasts between a fixation stimulus and pictures of emotional face elicited a similar overall pattern of activation for all four groups. Significant Group by Gender interactions revealed two activation clusters. A cluster in an anterior portion of the middle and superior temporal gyrus, elicited lower activation to the fixation stimulus than to faces for the AUDw as compared to the NCw; that abnormality was more pronounced than the one observed for men. Another cluster in the medial portion of the superior frontal cortex elicited higher activation to the faces by AUDm than NCm, a difference that was more evident than the one observed for women. Together, these findings have added new evidence of AUD-related gender differences in neural responses to facial expressions of emotion.

Involuntary Markers of Saliency and Surprise Revealed by Oculomotor Inhibition in Response to Auditory Sequences

Our eyes move constantly but are often inhibited momentarily in response to external stimuli. The properties of this Oculomotor-Inhibition (OMI) depend on the stimulus saliency, anticipation, and attention. Previous studies have shown prolonged saccadic inhibition for auditory oddballs; however, they required active counting of the oddballs. Here we investigated whether the OMI response to auditory deviants can provide a quantitative measure of deviance strength (auditory pitch difference) and investigated its dependence on the Inter-Stimulus Interval (ISI), without requesting a voluntary attention to the deviant stimulus. Observers fixated on a central fixation stimulus and passively listened to repeated short sequences of pure tones that contained a deviant tone either regularly or with 20% probability (the Oddball paradigm). The results showed, as in previous studies, prolonged microsaccade inhibition following the deviant tone. Moreover, the inhibition onset latency was shorter in proportion to the pitch deviance (the saliency effect) and the release was significantly longer for rare deviants (the surprise effect) as long as the ISI was short (<2.5s). Taken together, these results suggest that OMI provides involuntary markers of saliency and surprise, which can be obtained without the observer’s response.

Methods for chair restraint and training of the common marmoset on oculomotor tasks

The oculomotor system is the most thoroughly understood sensorimotor system in the brain, due in large part to electrophysiological studies carried out in macaque monkeys trained to perform oculomotor tasks. A disadvantage of the macaque model is that many cortical oculomotor areas of interest lie within sulci, making high-density array and laminar recordings impractical. Many techniques of molecular biology developed in rodents, such as optogenetic manipulation of neuronal subtypes, are also limited in this species. The common marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to frontoparietal oculomotor areas, and may bridge the gap between systems neuroscience in macaques and molecular techniques. Techniques for restraint, training, and neural recording in these animals have been well developed in auditory neuroscience. Those for oculomotor neuroscience, however, remain at a relatively early stage. In this article we provide details of a custom-designed restraint chair for marmosets, a combination head restraint/recording chamber allowing access to cortical oculomotor areas and providing stability suitable for eye movement and neural recordings, as well as a training protocol for oculomotor tasks. We additionally report the results of a psychophysical study in marmosets trained to perform a saccade task using these methods, showing that, as in rhesus and humans, marmosets exhibit a “gap effect,” a decrease in reaction time when the fixation stimulus is removed before the onset of a visual saccade target. These results are the first evidence of this effect in marmosets and support the common marmoset model for neurophysiological investigations of oculomotor control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in behaving primates has provided a wealth of information regarding the neural circuits underlying the control of eye movements. Such studies require restraint of the animal within a primate chair, head fixation, methods of acclimating the animals to this restraint, and the use of operant conditioning methods for training on oculomotor tasks. In contrast to the macaque model, relatively few studies have reported in detail methods for use in the common marmoset. In this report we detail custom-designed equipment and methods by which we have used to successfully train head-restrained marmosets to perform basic oculomotor tasks.

Asymmetrical representation of the upper and lower visual fields in oculomotor maps

The striate area devoted to the lower visual field (LVF) is larger than that devoted to the upper visual field (UVF). A similar anatomical asymmetry also exists in the LGN. Here we take advantage of two experimental tasks that are known to modulate the direction and amplitude of saccades to demonstrate a visual field asymmetry in oculomotor maps. Participants made visually guided saccades. In Experiment 1, the saccade target was accompanied by a visual distractor. The distractor's presence modulated the direction of saccades, and this effect was much stronger for LVF targets. In Experiment 2, the temporal gap between the offset of the fixation stimulus and the onset of the saccade target was manipulated. This manipulation modulated the amplitude of saccades and this modulation was stronger for saccades towards UVF targets. Taken together, these results suggest that the representation of both meridians and eccentricities in the LVF is compressed in oculomotor maps.

Prestimulus Interhemispheric Coupling of Brain Rhythms Predicts Cognitive–Motor Performance in Healthy Humans

Physiological and neuroimaging studies suggest that human actions are characterized by time-varying engagement of functional distributed networks within the brain. In this study, we investigated whether specific prestimulus interhemispheric connectivity, as a measure of synchronized network between the two hemispheres, could lead to a better performance (as revealed by RT) in a simple visuomotor task. Eighteen healthy adults underwent EEG recording during a visual go/no-go task. In the go/no-go task, a central fixation stimulus was followed by a green (50% of probability) or red visual stimulus. Participants had to press the mouse button after the green stimuli (go trials). Interhemispheric coupling was evaluated by the spectral coherence among all the electrodes covering one hemisphere and matched with those on the other. The frequency bands of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz), and gamma (30–40 Hz). The task-related results showed that interhemispheric connectivity decreased in delta and increased in alpha band. Furthermore, we observed positive delta and negative alpha correlations with the RT; namely, the faster the RT, the lower delta and the higher alpha connection between the two hemispheres. These results suggested that the best performance is anticipated by the better functional coupling of cortical circuits involved during the processing of the sensorimotor information, occurring between the two hemispheres pending cognitive go/no-go task.

Which Visual Pathways Cause Fixation-Related Inhibition?

Visual stimuli can both inhibit and activate motor mechanisms. In one well-known example, the latency of saccadic eye movements is prolonged in the presence of a fixation stimulus, relative to the case in which the fixation stimulus disappears before the target appears. This automatic sensory-motor effect, known as the gap effect or fixation-offset effect, has been associated with inhibitory connections within the superior colliculus (SC). Visual information is provided to the SC and other oculomotor areas, such as the frontal eye fields (FEF), mainly by the magnocellular geniculostriate pathway, and also by the retinotectal pathway. We tested whether signals in these pathways are necessary to create fixation-related inhibition, by using stimuli invisible to them. We found that such stimuli, visible only to short-wave–sensitive cones (S cones), do produce fixation-related inhibition (including when warning effects were equated). We also demonstrate that this fixation-related inhibition cannot be explained by residual activation of luminance pathways and must be caused by a route separate from that of luminance fixation signals. Thus there are at least two routes that cause fixation-related inhibition, and direct sensory input to the SC or FEF by the magnocellular or retinotectal pathways is not required. We discuss the implications that there may be both cortical and collicular mechanisms.

Visual and Saccade-Related Activity in Macaque Posterior Cingulate Cortex

Previous neurophysiological studies have reported that neurons in posterior cingulate cortex (PCC) respond after eye movements, and that these responses may vary with ambient illumination. In monkeys, PCC neurons also respond after the illumination of large visual patterns but not after the illumination of small visual targets on either reflexive saccade tasks or peripheral attention tasks. These observations suggest that neuronal activity in PCC is modulated by behavioral context, which varies with the timing and spatial distribution of visual and oculomotor events. To test this hypothesis, we measured the spatial and temporal response properties of single PCC neurons in monkeys performing saccades in which target location and movement timing varied unpredictably. Specifically, an unsignaled delay between target onset and movement onset permitted us to temporally dissociate changes in PCC activity associated with either event. Response fields constructed from these data demonstrated that many PCC neurons were activated after the illumination of small contralateral visual targets, as well as after the onset of contraversive saccades guided by those targets. In addition, the PCC population maintained selectivity for small contralateral targets during delays of up to 600 ms. Overall, PCC activation was highly variable trial to trial and selective for a broad range of directions and amplitudes. Planar functions described response fields nearly as well as broadly tuned 2-dimensional Gaussian functions. Additionally, the overall responsiveness of PCC neurons decreased during delays when both a fixation stimulus and a saccade target were visible, suggesting a modulation by divided attention. Finally, the strength of the neuronal response after target onset was correlated with saccade accuracy on delayed-saccade trials. Thus PCC neurons may signal salient visual and oculomotor events, consistent with a role in visual orienting and attention.

Human Midbrain Sensitivity to Cognitive Feedback and Uncertainty During Classification Learning

Mesencephalic dopaminergic system (MDS) neurons may participate in learning by providing a prediction error signal to their targets, which include ventral striatal, orbital, and medial frontal regions, as well as by showing sensitivity to the degree of uncertainty associated with individual stimuli. We investigated the mechanisms of probabilistic classification learning in humans using functional magnetic resonance imaging to examine the effects of feedback and uncertainty. The design was optimized for separating neural responses to stimulus, delay, and negative and positive feedback components. Compared with fixation, stimulus and feedback activated brain regions consistent with the MDS, whereas the delay period did not. Midbrain activity was significantly different for negative versus positive feedback (consistent with coding of the “prediction error”) and was reliably correlated with the degree of uncertainty as well as with activity in MDS target regions. Purely cognitive feedback apparently engages the same regions as rewarding stimuli, consistent with a broader characterization of this network.

Preparatory Set Associated With Pro-Saccades and Anti-Saccades in Humans Investigated With Event-Related fMRI

Previous studies have shown that the BOLD functional MRI (fMRI) signal is increased in several cortical areas when subjects perform anti-saccades compared with pro-saccades. It remains unknown, however, whether this increase is due to an increased cortical motor signal for anti-saccades or due to differences in preparatory set between pro- and anti-saccade trials. To address this question, we measured event-related fMRI in a paradigm that allowed us to separate instruction-related brain activity from saccade-related brain activity. In this paradigm, the instruction to either generate a pro-saccade or an anti-saccade was conveyed by a switch in the color of the central fixation stimulus and preceded the presentation of a peripheral stimulus by either 6, 10, or 14 s. Cortical areas were functionally mapped using the general linear model comparing standard pro- and anti-saccade blocks with fixation blocks. When the trials were aligned on the onset of the instruction stimulus, bilateral frontal eye fields and right hemisphere dorsolateral prefrontal cortex showed an increased signal during the instruction period on anti-saccade trials as compared with pro-saccade trials. When the trials were aligned on the movement stimulus and the instruction period activity was subtracted, there were no differences between pro- and anti-saccades. This finding suggests that the increased cortical activation found in previous blocked designs originates predominately from differences in preparatory set and not from differences in the motor signal between pro- and anti-saccades.

Saccadic Inhibition in Voluntary and Reflexive Saccades

The present study investigated saccadic inhibition in both voluntary and stimulus-elicited saccades. Two experiments examined saccadic inhibition caused by an irrelevant flash occurring subsequent to target onset. In each trial, participants were required to perform a single saccade following the presentation of a black target on a gray background, 4° to the left or to the right of screen center. In some trials (flash trials), after a variable delay, a 33-msec flash was displayed at the top and bottom third of the monitor (these regions turned white). In all experimental conditions, histograms of flash-to-saccade latencies documented a decrease in saccadic frequency, forming a dip, time-locked to the flash and occurring as early as 60—70 msec following its onset. The fast latency of this effect strongly suggests a low-level, reflex-like, oculomotor effect, which was referred to as saccadic inhibition. A novel procedure was developed to allow comparisons of saccadic inhibition even across conditions, which in the absence of a flash (no-flash trials) produce dissimilar saccadic reaction times (SRTs) distributions. Experiment 1 examined the effects of the fixation stimulus on saccadic inhibition by contrasting three conditions: a gap condition (fixation stimulus disappeared 200 msec prior to target onset), a step condition (offset of the fixation stimulus was simultaneous with target onset), and an overlap condition (the fixation stimulus remained on for the duration of the trial). The overlap condition produced substantially stronger saccadic inhibition, relative to the gap and the step conditions. Experiment 2 contrasted the saccadic inhibition effect obtained for prosaccades (saccades aimed at the target) with the effect obtained for antisaccades (i.e., saccades aimed away from the same target). The onset of saccadic inhibition was earlier, and its magnitude was stronger, for antisaccades, relative to prosaccades. The plausibility that the superior colliculus is the neurophysiological locus of the saccadic inhibition effect was explored.