fMRI Neurofeedback-Enhanced Cognitive Reappraisal Training in Depression: A Double-Blind Comparison of Left and Right vlPFC Regulation

Affective disorders are associated with maladaptive emotion regulation strategies. In particular, the left more than the right ventrolateral prefrontal cortex (vlPFC) may insufficiently regulate emotion processing, e.g., in the amygdala. A double-blind cross-over study investigated NF-supported cognitive reappraisal training in major depression (n = 42) and age- and gender-matched controls (n = 39). In a randomized order, participants trained to upregulate either the left or the right vlPFC during cognitive reappraisal of negative images on two separate days. We wanted to confirm regional specific NF effects with improved learning for left compared to right vlPFC (ClinicalTrials.gov NCT03183947). Brain responses and connectivity were studied with respect to training progress, gender, and clinical outcomes in a 4-week follow-up. Increase of vlPFC activity was stronger after NF training from the left- than the right-hemispheric ROI. This regional-specific NF effect during cognitive reappraisal was present across patients with depression and controls and supports a central role of the left vlPFC for cognitive reappraisal. Further, the activity in the left target region was associated with increased use of cognitive reappraisal strategies (r = 0.48). In the 4-week follow-up, 75% of patients with depression reported a successful application of learned strategies in everyday life and 55% a clinically meaningful symptom improvement suggesting clinical usability.

Free Working Memory through Free Recall

Volitional control is a critical component of working memory (WM), and interdependence between items in visual WM (VWM) has drawn considerable attention in the field recently. Here we assess how the precision of the probed item is affected by the other items in VWM under two different levels of volitional control. On each trial, the retrieval task was not informed to participants until the end of the encoding and delay periods, which could be one of the following: participants were requested to recall all the items sequentially in an order chosen by themselves (free recall) or in an order randomly chosen by the computer (forced recall). Compared with forced recall, free recall leads to the overall higher precision of recall and faster localization of the item to report. We also found that forced recall is associated with greater interference for the probed item from the other items in VWM. Participants tend to report the best-precision target first and the top-left target first, with the former but not the latter contributing to the observed benefit of volitional control. Altogether, freely choosing the order of recall from VWM improves human performance in memory retrieval.

Transcranial ultrasound selectively biases decision-making in primates

Transcranial focused ultrasound has the promise to evolve into a transformative noninvasive way to modulate activity of neuronal circuits deep in the brain. The approach may enable systematic and causal mapping of how individual brain circuits are involved in specific behaviors and behavioral disorders. Previous studies demonstrated neuromodulatory potential, but the effect polarity, size, and spatial specificity have been difficult to assess. Here, we engaged non-human primates (macaca mulatta) in an established task that provides a well defined framework to characterize the neuromodulatory effects. In this task, subjects decide whether to look at a right or a left target, guided by one the targets appearing first. Previous studies showed that excitation/inhibition of oculomotor circuits leads to contralateral/ipsilateral biases in this choice behavior. We found that brief, low-intensity ultrasound stimuli (300 ms, 0.6 MPa, 270 kHz) delivered to the animals’ left/right frontal eye fields bias the animals’ decisions to the right/left visual hemifield. The effect was modest, about on the order of that produced when injecting moderate amounts of potent neuromodulatory drugs into the same regions in this task. The polarity of the effects suggested a neuronal excitation within the stimulated regions. No effects were observed when we applied the same stimuli to control brain regions not involved in oculomotor target selection. Together, using an established paradigm, we found that transcranial ultrasound is capable of modulating neurons to the extent of biasing choice behavior of non-human primates. A demonstration of tangible, brain-region-specific effects on behavior of primates constitutes a critical step toward applying this noninvasive neuromodulation method in investigations of how specific neural circuits are involved in specific behaviors or disease signs.

The progressive elimination task in dogs (Canis familiaris): The case of divergence

Domestic dogs (Canis familiaris) were administered progressive elimination tasks in which they had to visit and deplete either 3 or 4 baited sites. They were brought back to the starting point after each visit. When administered a 4-choice task with small angular deviation between adjacent targets, the dogs chose first an inner target (e.g., right inner target) and the opposite outer target (e.g., the left target) as a second correct choice. So they relied on divergence; that is they chose the farthest target as the next choice. Varying angular deviation did not modulate divergence. Decreasing the number of targets (3-choice task, Experiment 2) did relax divergence, though target selection was not totally random. The dogs still chose as a first choice an inner target (i.e., the middle target) when selecting the most divergent patterns of elimination. Finally, in Experiment 3, the dogs were administered a 3-choice task with large angular deviation but in which all targets had been hidden. The dogs chose first an outer target (i.e., right or left)) and the other outer target as the second correct choice. That is they relied on divergence. The results suggest that divergence is the outcome of a flexibility/cognitive load tradeoff when facing novelty and uncertainty.

Tracking local anesthetic effects using a novel perceptual reference approach

Drug effects of loco-regional anesthetics are commonly measured by unidimensional pain rating scales. These scales require subjects to transform their perceptual correlates of stimulus intensities onto a visual, verbal, or numerical construct that uses a unitless cognitive reference frame. The conceptual understanding and execution of this magnitude estimation task may vary among individuals and populations. To circumvent inherent shortcomings of conventional experimental pain scales, this study used a novel perceptual reference approach to track subjective sensory perceptions during onset of an analgesic nerve block. In 34 male subjects, nociceptive electric stimuli of 1-ms duration were repetitively applied to left (target) and right (reference) mandibular canines every 5 s for 600 s, with a side latency of 1 ms. Stimulus strength to the target canine was programmed to evoke a tolerable pain intensity perception and remained constant at this level throughout the experiment. A dose of 0.6 ml of articaine 4% was submucosally injected at the left mental foramen. Subjects then reported drug effects by adjusting the stimulus strength (in milliamperes) to the reference tooth, so that the perceived intensity in the reference tooth was equi-intense to the target tooth. Pain and stimulus perception offsets were indicated by subjects. Thus, the current approach for matching the sensory experience in one anatomic location after regional anesthesia allows detailed tracking of evolving perceptual changes in another location. This novel perceptual reference approach facilitates direct and accurate quantification of analgesic effects with high temporal resolution. We propose using this method for future experimental investigations of analgesic/anesthetic drug efficacy.

Reach endpoint errors do not vary with movement path of the proprioceptive target

Previous research has shown that reach endpoints vary with the starting position of the reaching hand and the location of the reach target in space. We examined the effect of movement direction of a proprioceptive target-hand, immediately preceding a reach, on reach endpoints to that target. Participants reached to visual, proprioceptive (left target-hand), or visual-proprioceptive targets (left target-hand illuminated for 1 s prior to reach onset) with their right hand. Six sites served as starting and final target locations (35 target movement directions in total). Reach endpoints do not vary with the movement direction of the proprioceptive target, but instead appear to be anchored to some other reference (e.g., body). We also compared reach endpoints across the single and dual modality conditions. Overall, the pattern of reaches for visual-proprioceptive targets resembled those for proprioceptive targets, while reach precision resembled those for the visual targets. We did not, however, find evidence for integration of vision and proprioception based on a maximum-likelihood estimator in these tasks.

Hand Position Affects Saccadic Reaction Times in Monkeys and Humans

In daily life, activities requiring the hand and eye to work separately are as frequent as activities requiring tight eye–hand coordination, and we effortlessly switch from one type of activity to the other. Such flexibility is unlikely to be achieved without each effector “knowing” where the other one is at all times, even when it is static. Here, we provide behavioral evidence that the mere position of the static hand affects one eye movement parameter: saccadic reaction time. Two monkeys were trained and 11 humans instructed to perform nondelayed or delayed visually guided saccades to either a right or a left target while holding their hand at a location either near or far from the eye target. From trial to trial, target locations and hand positions varied pseudorandomly. Subjects were tested both when they could and when they could not see their hand. The main findings are 1) the presence of the static hand in the workspace did affect saccade initiation; 2) this interaction persisted when the hand was invisible; 3) it was strongly influenced by the delay duration: hand–target proximity retarded immediate saccades, whereas it could hasten delayed saccades; and 4) this held true both for humans and for each of the two monkeys. We propose that both visual and nonvisual hand position signals are used by the primates' oculomotor system for the planning and execution of saccades, and that this may result in a hand–eye competition for spatial attentional resources that explains the delay-dependent reversal observed.

Factors Affecting Personal Space toward a Group

The personal space of 160 males and 160 females was measured relative to target groups whose characteristics varied in size (1, 2, 3, 4), type of person (men, women, boy, and girl), and direction of orientation (right, front, left). Two analyses of variance were completed: (a) sex of subject × type of target person × group size × direction of facing and (b) sex of subject × direction of facing of right target × direction of facing of left target person × man-woman composition. Personal space was smaller toward groups not containing a man than for those containing a man, for groups of children than adults when approaching face to face, for groups of females than males when approaching from behind, for groups facing away than for groups facing at right angles than for groups facing toward. Although group size was involved in a significant interaction with type of person and direction of facing, it did not produce a significant main effect. Sex of subject also was not significant, showing that males and females exhibited generic social schemas in personal spacing toward groups.