Leor N. Katz

Dissociated functional significance of decision-related activity in the primate dorsal stream

During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making, with strong correlations between their response fluctuations and the animal’s choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding. The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions.

Differential effects of deep TMS of the prefrontal cortex on apathy and depression

BACKGROUND Apathy is one hallmark of major depression (MDD). It is distinguished by lack of emotion, whereas other aspects of depression involve considerable emotional distress. Investigating both apathy and depression may increase the degree of treatment efficacy for both ailments together and apart. OBJECTIVE Evaluate the differential effects of deep transcranial magnetic stimulation (DTMS) over the prefrontal cortex (PFC) on apathy and other aspects of depression in patients suffering from a depressive episode. METHODS Fifty-four treatment-resistant MDD patients were evaluated with the Hamilton Rating Scale for Depression (HRSD), and then treated with DTMS. Apathy-related items from HRSD (ApHRSD) were compared with the remaining items from HRSD (DepHRSD). Antidepressant medications were withdrawn and active DTMS treatment was administered at 20 Hz, 5 days a week for 4 weeks. Changes in HRSD were recorded. Primary efficacy time point was 1 week after the end of active treatment. RESULTS At screening, ApHRSD distribution was unimodal (moderate apathy), with low correlation (r = 0.17) between ApHRSD and DepHRSD. After treatment, a third had remitted apathy, and the correlation between ApHRSD and DepHRSD had dramatically increased (r = 0.83). Severe ApHRSD (≥ 7) at screening correlated with nonremission for both ApHRSD (R(2) = 0.1993, P = .0012) and DepHRSD (R(2) = 0.0860, P = .0334). CONCLUSIONS DTMS over the PFC improved both apathy and depression similarly. However, DTMS did not lead to MDD remission if ApHRSD at screening was ≥ 7 of 12. Further investigation using a larger sample will determine whether screening apathy at baseline could be used to predict efficacy of DTMS in MDD patients.

Eye Movements, Visual Search and Scene Memory, in an Immersive Virtual Environment

Visual memory has been demonstrated to play a role in both visual search and attentional prioritization in natural scenes. However, it has been studied predominantly in experimental paradigms using multiple two-dimensional images. Natural experience, however, entails prolonged immersion in a limited number of three-dimensional environments. The goal of the present experiment was to recreate circumstances comparable to natural visual experience in order to evaluate the role of scene memory in guiding eye movements in a natural environment. Subjects performed a continuous visual-search task within an immersive virtual-reality environment over three days. We found that, similar to two-dimensional contexts, viewers rapidly learn the location of objects in the environment over time, and use spatial memory to guide search. Incidental fixations did not provide obvious benefit to subsequent search, suggesting that semantic contextual cues may often be just as efficient, or that many incidentally fixated items are not held in memory in the absence of a specific task. On the third day of the experience in the environment, previous search items changed in color. These items were fixated upon with increased probability relative to control objects, suggesting that memory-guided prioritization (or Surprise) may be a robust mechanisms for attracting gaze to novel features of natural environments, in addition to task factors and simple spatial saliency.

Functional dissection of signal and noise in MT and LIP during decision-making

During perceptual decision-making, responses in the middle temporal (MT) and lateral intraparietal (LIP) areas appear to map onto theoretically defined quantities, with MT representing instantaneous motion evidence and LIP reflecting the accumulated evidence. However, several aspects of the transformation between the two areas have not been empirically tested. We therefore performed multistage systems identification analyses of the simultaneous activity of MT and LIP during individual decisions. We found that monkeys based their choices on evidence presented in early epochs of the motion stimulus and that substantial early weighting of motion was present in MT responses. LIP responses recapitulated MT early weighting and contained a choice-dependent buildup that was distinguishable from motion integration. Furthermore, trial-by-trial variability in LIP did not depend on MT activity. These results identify important deviations from idealizations of MT and LIP and motivate inquiry into sensorimotor computations that may intervene between MT and LIP.

Cross-species comparison of anticipatory and stimulus-driven neck muscle activity well before saccadic gaze shifts in humans and nonhuman primates

Recent studies have described a phenomenon wherein the onset of a peripheral visual stimulus elicits short-latency (<100 ms) stimulus-locked recruitment (SLR) of neck muscles in nonhuman primates (NHPs), well before any saccadic gaze shift. The SLR is thought to arise from visual responses within the intermediate layers of the superior colliculus (SCi), hence neck muscle recordings may reflect presaccadic activity within the SCi, even in humans. We obtained bilateral intramuscular recordings from splenius capitis (SPL, an ipsilateral head-turning muscle) from 28 human subjects performing leftward or rightward visually guided eye-head gaze shifts. Evidence of an SLR was obtained in 16/55 (29%) of samples; we also observed examples where the SLR was present only unilaterally. We compared these human results with those recorded from a sample of eight NHPs from which recordings of both SPL and deeper suboccipital muscles were available. Using the same criteria, evidence of an SLR was obtained in 8/14 (57%) of SPL recordings, but in 26/29 (90%) of recordings from suboccipital muscles. Thus, both species-specific and muscle-specific factors contribute to the low SLR prevalence in human SPL. Regardless of the presence of the SLR, neck muscle activity in both human SPL and in NHPs became predictive of the reaction time of the ensuing saccade gaze shift ∼70 ms after target appearance; such pregaze recruitment likely reflects developing SCi activity, even if the tectoreticulospinal pathway does not reliably relay visually related activity to SPL in humans.

Decision-related perturbations of decision-irrelevant eye movements

Significance Studies using limb movements to probe cognitive states have suggested an interactive model of cognition and motor action. Despite ample evidence showing that the neural activity in oculomotor brain circuits is correlated with the formation of decisions about where to move the eyes, it is not known whether there are interactions between such decision-related activity and decision-irrelevant oculomotor processing. By probing the oculomotor system with a decision-irrelevant saccadic eye movement during decision formation, we found that saccade metrics are affected by the strength and direction of motion evidence. Our results suggest that decision signals continuously flow into the oculomotor system during decision making, and further extend the interactive model of cognition and action into the oculomotor system. It is well established that ongoing cognitive functions affect the trajectories of limb movements mediated by corticospinal circuits, suggesting an interaction between cognition and motor action. Although there are also many demonstrations that decision formation is reflected in the ongoing neural activity in oculomotor brain circuits, it is not known whether the decision-related activity in those oculomotor structures interacts with eye movements that are decision irrelevant. Here we tested for an interaction between decisions and instructed saccades unrelated to the perceptual decision. Observers performed a direction-discrimination decision-making task, but made decision-irrelevant saccades before registering their motion decision with a button press. Probing the oculomotor circuits with these decision-irrelevant saccades during decision making revealed that saccade reaction times and peak velocities were influenced in proportion to motion strength, and depended on the directional congruence between decisions about visual motion and decision-irrelevant saccades. These interactions disappeared when observers passively viewed the motion stimulus but still made the same instructed saccades, and when manual reaction times were measured instead of saccade reaction times, confirming that these interactions result from decision formation as opposed to visual stimulation, and are specific to the oculomotor system. Our results demonstrate that oculomotor function can be affected by decision formation, even when decisions are communicated without eye movements, and that this interaction has a directionally specific component. These results not only imply a continuous and interactive mixture of motor and decision signals in oculomotor structures, but also suggest nonmotor recruitment of oculomotor machinery in decision making.

A Distinct Mechanism of Temporal Integration for Motion through Depth

Temporal integration of visual motion has been studied extensively within the frontoparallel plane (i.e., 2D). However, the majority of motion occurs within a 3D environment, and it is unknown whether the principles from 2D motion processing generalize to more realistic 3D motion. We therefore characterized and compared temporal integration underlying 2D (left/right) and 3D (toward/away) direction discrimination in human observers, varying motion coherence across a range of viewing durations. The resulting discrimination-versus-duration functions followed three stages, as follows: (1) a steep improvement during the first ∼150 ms, likely reflecting early sensory processing; (2) a subsequent, more gradual benefit of increasing duration over several hundreds of milliseconds, consistent with some form of temporal integration underlying decision formation; and (3) a final stage in which performance ceased to improve with duration over ∼1 s, which is consistent with an upper limit on integration. As previously found, improvements in 2D direction discrimination with time were consistent with near-perfect integration. In contrast, 3D motion sensitivity was lower overall and exhibited a substantial departure from perfect integration. These results confirm that there are overall differences in sensitivity for 2D and 3D motion that are consistent with a sensory difference between binocular and dichoptic sensory mechanisms. They also reveal a difference at the integration stage, in which 3D motion is not accumulated as perfectly as in the 2D motion model system.

The Role of the Lateral Intraparietal Area in (the Study of) Decision Making

Over the past two decades, neurophysiological responses in the lateral intraparietal area (LIP) have received extensive study for insight into decision making. In a parallel manner, inferred cognitive processes have enriched interpretations of LIP activity. Because of this bidirectional interplay between physiology and cognition, LIP has served as fertile ground for developing quantitative models that link neural activity with decision making. These models stand as some of the most important frameworks for linking brain and mind, and they are now mature enough to be evaluated in finer detail and integrated with other lines of investigation of LIP function. Here, we focus on the relationship between LIP responses and known sensory and motor events in perceptual decision-making tasks, as assessed by correlative and causal methods. The resulting sensorimotor-focused approach offers an account of LIP activity as a multiplexed amalgam of sensory, cognitive, and motor-related activity, with a complex and often indirect relationship to decision processes. Our data-driven focus on multiplexing (and de-multiplexing) of various response components can complement decision-focused models and provides more detailed insight into how neural signals might relate to cognitive processes such as decision making.

Strategic and Dynamic Temporal Weighting for Perceptual Decisions in Humans and Macaques

Abstract Perceptual decision-making is often modeled as the accumulation of sensory evidence over time. Recent studies using psychophysical reverse correlation have shown that even though the sensory evidence is stationary over time, subjects may exhibit a time-varying weighting strategy, weighting some stimulus epochs more heavily than others. While previous work has explained time-varying weighting as a consequence of static decision mechanisms (e.g., decision bound or leak), here we show that time-varying weighting can reflect strategic adaptation to stimulus statistics, and thus can readily take a number of forms. We characterized the temporal weighting strategies of humans and macaques performing a motion discrimination task in which the amount of information carried by the motion stimulus was manipulated over time. Both species could adapt their temporal weighting strategy to match the time-varying statistics of the sensory stimulus. When early stimulus epochs had higher mean motion strength than late, subjects adopted a pronounced early weighting strategy, where early information was weighted more heavily in guiding perceptual decisions. When the mean motion strength was greater in later stimulus epochs, in contrast, subjects shifted to a marked late weighting strategy. These results demonstrate that perceptual decisions involve a temporally flexible weighting process in both humans and monkeys, and introduce a paradigm with which to manipulate sensory weighting in decision-making tasks.