Biology subjects

Pack, C. C.

Publications and source records attributed to Pack, C. C..

16 recordsLinked to original sources

bioRxiv2026

Reassessing Choice Probability: What 59 Macaque Studies Tell Us About Decision-Related Activity in Visual Cortex

Choice probability (CP) quantifies the trial-by-trial covariation between a sensory neurons response and perceptual reports. Despite extensive interest in CP as a window into how perception is linked to the activity of sensory neurons, the usefulness of CP remains debated. On one hand, reported CP magnitudes vary widely across seemingly equivalent studies, questioning its utility as a metric. On the other hand, the absence of clear patterns in CP variability has made it difficult to use it to adjudicate between competing models of visual perception. Here, we performed a meta-analysis of 150 CP estimates from 59 macaque neurophysiology studies to identify factors that systematically influence CP. We confirmed the positive relationship between CP and neuronal sensitivity both across and within individual studies. When controlled for sensitivity, we found remarkable consistency in CP across varying tasks and brain regions with two notable exceptions. First, CPs were higher in tasks involving bistable percepts, reinforcing the link between CP magnitude and subjective perception. Second, CPs were smaller in area V1, supporting prior suggestions about V1s special role in visual processing. We further found a significant effect of stimulus duration on CP, providing evidence against strictly feedforward models and favoring models with substantial feedback and recurrent processing. Finally, we offer recommendations for future studies to enhance the cross-study comparability and theoretical utility of choice signals as the field transitions to large-scale population recordings. More broadly, our findings demonstrate the benefits of meta-studies that expose patterns across many different tasks and animals - yielding insights that complement large-scale population recordings.

neuroscience↗

bioRxiv2025

The curriculum effect in visual learning: the role of readout dimensionality

Generalization of visual perceptual learning (VPL) to unseen conditions varies across tasks. Previous work suggests that training curriculum may be integral to generalization, yet a theoretical explanation is lacking. We propose an explanatory theory of visual learning generalization and curriculum effects by leveraging an artificial neural network (ANN) model of VPL in comparison with humans. We found that easy-to-hard sequential training improved generalization in both humans and ANNs. However, when easy and hard conditions were interleaved, humans and ANNs showed different behaviours: while ANNs performed worse than with sequential training, humans maintained good performance but with large inter-individual variability. Investigating ANN models trained with different curricula, we demonstrated that models relying on low-dimensional neural populations showed superior generalization. This readout subspace dimensionality was directly determined by curriculum: learners who learned from easy tasks early formed lower-dimensional subspaces and generalized better. Our theory provides a mechanistic framework linking curriculum design to VPL generalization through neural population dimensionality. Author SummaryLearning new skills is fundamental to humans and animals. However, a key challenge in learning is generalization: applying learned skills to new situations not encountered during training. While it is well known that training curriculum affects how well we generalize, the underlying mechanisms remain poorly understood. What makes certain training curricula more effective than others? Why do some learners generalize better than others even with similar training? We developed a computational theory to explain how curriculum design influences generalization in visual learning. Using a combination of human behavioural experiments and artificial neural network modeling, we posit that easy-to-hard training sequences lead learners to focus on fewer, more essential visual features. This creates low-dimensional neural representations that are robust and generalize well to new conditions. Importantly, we found this benefit even extends to learners who spontaneously adopt easy-to-hard strategies on their own, without explicit curriculum design. Our theory provides a mechanistic link between curriculum structure, neural population dynamics, and generalization performance. Moreover, these findings offer practical guidelines for designing effective training programs in education and rehabilitation.

neuroscience↗

bioRxiv2025

Decision signals in the absence of spiking activity in primate visual cortex

Fluctuations in single-neuron activity in sensory cortex often correlate with perceptual decisions. This kind of correlation has been hypothesized to reflect a causal influence of sensory signals on decisions, a feedback influence of decisions on sensory signals, and various other factors as well. To disentangle these different possibilities, we have examined local field potentials (LFPs) recorded from the middle temporal (MT) area of non-human primates performing a motion discrimination task. Compared to single-neuron spiking, LFPs have the advantage of being decomposable into different frequencies that are associated with different anatomical sources of input. More importantly, they persist when spiking activity is inactivated, which precludes a causal influence of the corresponding neural activity on behavior. We found that high frequency (70-150 Hz) LFP power was correlated with perceptual decisions and that this correlation disappeared when spikes were inactivated, consistent with a causal role for this frequency band in decision making. These signals overlapped in time with decision signals in lower gamma-band power (30-70 Hz), which persisted after spiking inactivation, suggesting a non-causal, feedback input. Interestingly, lower-frequency LFP signals (5-30 Hz) reflected both impending perceptual decisions and the outcome of previous trials. Our results therefore reveal that neural activity multiplexes different sources of information about perceptual decisions and that these types of information can be estimated reliably from different LFP frequencies.

neuroscience↗

bioRxiv2025

The flexible contribution of cortical area V4 to visual perception

Humans and other primates are capable of learning to recognize new visual stimuli throughout their lifetimes. Most theoretical models assume that such learning occurs through the adjustment of the large number of synaptic weights connecting the visual cortex to downstream decision-making areas. While this approach to learning can optimize performance on behavioral tasks, it can also be costly in terms of time and energy. An alternative hypothesis is that the brain favors simpler learning rules that do not necessarily optimize the readout of information from visual cortical neurons. Here we have examined these hypotheses by reversibly inactivating visual area V4 in non-human primates at different stages of training on shape discrimination tasks. We find that V4 inactivation generally has a behavioral effect for only a subset of the stimuli that are encoded in the V4 population activity, specifically those that can be represented efficiently in the population firing rate. As a result, there is little relationship between neural measures of discriminability and the causal contribution of V4 neurons to a particular task. This pattern of results can be explained by incorporating a strong inductive bias for simpler perceptual readouts into existing theoretical frameworks. Such a simplicity bias is suboptimal in the sense that it ignores information that could theoretically be extracted from the neural population, but it has the likely advantage of facilitating efficient learning on ecologically-relevant timescales.

neuroscience↗

bioRxiv2025

Brain stimulation preferentially influences long-range projections in primates

Advances in brain stimulation have made it possible to target smaller and smaller regions for electromagnetic stimulation, in the hopes of producing increasingly focal neural effects. However, the brain is extensively interconnected, and the neurons comprising those connections may themselves be particularly susceptible to neurostimulation. Here, we test this hypothesis by identifying long-range projections in single-unit recordings from non-human primates receiving transcranial alternating current stimulation (tACS). We find that putative long-range projections are more strongly affected by stimulation than other cells. Specifically, they are both more entrained on average and account for occurrences of extremely strong entrainment. Since stimulation appears to target the edges, rather than nodes, of neural networks, it may be necessary to rethink how neurostimulation strategies are designed.

neuroscience↗

bioRxiv2024

Stimulus-dependent delay of perceptual filling-in by microsaccades

Perception is a function of both stimulus features and active sensory sampling. The illusion of perceptual filling-in occurs when eye gaze is kept still: visual boundary perception may fail, causing adjacent visual features to remarkably merge into one uniform visual surface. Microsaccades-small, involuntary eye movements during gaze fixation-counteract perceptual filling-in, but the mechanisms underlying this process are not well understood. We investigated whether microsaccade efficacy for preventing filling-in depends on two boundary properties, color contrast and retinal eccentricity (distance from gaze center). Twenty-one human participants (male and female) fixated on a point until they experienced filling-in between two isoluminant colored surfaces. We found that increased color contrast independently extends the duration before filling-in but does not alter the impact of individual microsaccades. Conversely, lower eccentricity delayed filling-in only by increasing microsaccade efficacy. We propose that microsaccades facilitate stable boundary perception via a transient retinal motion signal that scales with eccentricity but is invariant to boundary contrast. These results shed light on how incessant eye movements integrate with ongoing stimulus processing to stabilize perceptual detail, with implications for visual rehabilitation and the optimization of visual presentations in virtual and augmented reality environments. Significance StatementTo perceive, sense organs actively sample the environment--for example, by touching, sniffing, or moving the eyes. Visual sampling persists even when gaze is fixed on a single point: involuntary microsaccades continuously move the eye in small jumps. We investigated a previously documented observation that microsaccades prevent illusory fading of perceived visual boundaries during fixation. We discovered that despite being connected, microsaccades and fading are sensitive to different stimulus features. Boundaries separating surfaces with more distinct colors inherently took longer to fade. Boundaries closer to the center of vision also took longer to fade, but only because microsaccades were more effective. These findings reveal new insight into how pervasive sensory sampling delivers a stable and detailed perceptual experience.

neuroscience↗

bioRxiv2024

Feature selectivity of corticocortical feedback along the primate dorsal visual pathway

Anatomical studies have revealed a prominent role for feedback projections in the primate visual cortex. Theoretical models suggest that these projections support important brain functions, like attention, prediction, and learning. However, these models make different predictions about the relationship between feedback connectivity and neuronal stimulus selectivity. We have therefore performed simultaneous recordings in different regions of the primate dorsal visual pathway. Specifically, we recorded neural activity from the medial superior temporal (MST) area, and one of its main feedback targets, the middle temporal (MT) area. We estimated functional connectivity from correlations in the single-neuron spike trains and performed electrical microstimulation in MST to determine its causal influence on MT. Both methods revealed that inhibitory feedback occurred more commonly when the source and target neurons had very different stimulus preferences. At the same time, the strength of feedback suppression was greater for neurons with similar preferences. Excitatory feedback projections, in contrast, showed no consistent relationship with stimulus preferences. These results suggest that corticocortical feedback could play a role in shaping sensory responses according to behavioral or environmental context.

neuroscience↗

bioRxiv2023

Temporal interference stimulation disrupts spike timing in the primate brain

Electrical stimulation can regulate brain activity, producing clear clinical benefits, but focal and effective neuromodulation often requires surgically implanted electrodes. Recent studies argue that temporal interference (TI) stimulation may provide similar outcomes non-invasively. During TI, scalp electrodes generate multiple electrical fields in the brain, modulating neural activity only where they overlap. Despite considerable enthusiasm for this approach, little empirical evidence demonstrates its effectiveness, especially under conditions suitable for human use. Here, using single-neuron recordings in non-human primates, we show that TI reliably alters the timing of spiking activity. However, we find that the strategies which improve the focality of TI -- high frequencies, multiple electrodes, and amplitude-modulated waveforms -- also limit its effectiveness. Combined, they make TI 80% weaker than other forms of non-invasive brain stimulation. Although this is too weak to cause widespread neuronal entrainment, it may be ideally suited for disrupting pathological synchronization, a hallmark of many neurological disorders.

neuroscience↗

bioRxiv2023

Decision-related activity and movement selection in primate visual cortex

Fluctuations in the activity of sensory neurons often predict perceptual decisions. This connection can be quantified with a metric called choice probability (CP), and there has been a longstanding debate about whether CP reflects a causal influence on decisions, or an echo of decision-making activity elsewhere in the brain. Here we show that CP can actually reflect a third variable, namely the movement used to indicate the decision. In a standard visual motion discrimination task, neurons in the middle temporal (MT) area of the primate visual cortex responded more strongly during trials in which the animals executed a saccade toward their receptive fields, and less strongly for saccades directed away from the receptive fields. The resulting trial-to-trial variability accounted for much of the CP observed across the neuronal population, and it arose through training. Surprisingly, the learned association between MT activity and oculomotor selection was causal, as pharmacological inactivation of MT neurons biased behavioral responses away from the corresponding receptive field locations. These results demonstrate that training on a task with fixed sensorimotor contingencies introduces movement-related activity in sensory brain regions, and that this plasticity can shape the neural circuitry of perceptual decision-making.

animal behavior and cognition↗

bioRxiv2023

Asymmetric stimulus representations bias visual perceptual learning

The primate visual cortex contains various regions that exhibit specialization for different stimulus properties, such as motion, shape, and color. Within each region there is often further specialization, such that particular stimulus features, such as horizontal and vertical orientations, are overrepresented. These asymmetries are associated with well-known perceptual biases, but little is known about how they influence visual learning. Most theories would predict that learning is optimal, in the sense that it is unaffected by these asymmetries. But other approaches to learning would result in specific patterns of perceptual biases. To distinguish between these possibilities, we trained human observers to discriminate between expanding and contracting motion patterns, which have a highly asymmetrical representation in visual cortex. Observers exhibited biased percepts of these stimuli, and these biases were affected by training in ways that were often suboptimal. We simulated different neural network models and found that a learning rule that involved only adjustments to decision criteria, rather than connection weights, could account for our data. These results suggest that cortical asymmetries influence visual perception and that human observers often rely on suboptimal strategies for learning.

neuroscience↗

bioRxiv2022

Tracking the dynamics of perisaccadic visual signals with magnetoencephalography

Many brain functions are difficult to localize, as they involve distributed networks that reconfigure themselves on short timescales. One example is the integration of oculomotor and visual signals that occurs with each eye movement: The brain must combine motor signals about the eye displacement with retinal signals, to infer the structure of the surrounding environment. Our understanding of this process comes primarily from single-neuron recordings, which are limited in spatial extent, or fMRI measurements, which have poor temporal resolution. We have therefore studied visual processing during eye movements, using magnetoencephalography (MEG), which affords high spatiotemporal resolution. Human subjects performed a task in which they reported the orientation of a visual stimulus while executing a saccade. After removal of eye movement artifacts, time-frequency analysis revealed a signal that propagated in the beta-frequency band from parietal cortex to visual cortex. This signal had the characteristics of perisaccadic "remapping", a neural signature of the integration of oculomotor and visual signals. These results reveal a novel mechanism of visual perception and demonstrate that MEG can provide a useful window into distributed brain functions.

neuroscience↗

bioRxiv2021

tACS competes with ongoing oscillations for control of spike-timing in the primate brain.

Transcranial alternating current stimulation (tACS) is commonly used to enhance brain rhythms, in the hopes of improving behavioral performance. Unfortunately, these interventions often yield highly variable results. Here, we identify a key source of this variability by recording from single neurons in alert non-human primates. We find that, rather than enhancing rhythmic activity, tACS appears to compete with the brains endogenous oscillations for control of spike timing. Specifically, when the strength of stimulation is weak relative to endogenous oscillations, tACS actually decreases the rhythmicity of spiking. However, when stimulation is comparatively stronger, tACS imposes its own rhythm on spiking activity. Thus the effect of tACS depends categorically on the strength of neural entrainment to endogenous oscillations, which varies greatly across behavioral states and brain regions. Without carefully considering these factors, attempts to impose external rhythms on specific brain regions may often yield precisely the opposite of the intended effect.

neuroscience↗

bioRxiv2021

A cortical circuit for abrupt visual learning in the primate brain

Visual plasticity declines sharply after the critical period, yet we easily learn to recognize new faces and places even as adults. Such learning is often characterized by a "moment of insight", an abrupt and dramatic improvement in recognition. The mechanisms that support abrupt learning are unknown, but one hypothesis is that they involve changes in synchronization between brain regions. To test this hypothesis, we used a behavioral task in which non-human primates rapidly learned to recognize novel images and to associate them with specific responses. Simultaneous recordings from inferotemporal and prefrontal cortices revealed a transient synchronization of neural activity between these areas that peaked around the moment of insight. Synchronization was strongest between inferotemporal sites that encoded images and reward-sensitive prefrontal sites. Moreover, its magnitude intensified gradually over image exposures, suggesting that abrupt learning culminates from the search for informative signals within a circuit linking sensory information to task demands.

neuroscience↗

bioRxiv2021

Your head is there to move you around: Goal-driven models of the primate dorsal pathway

Neurons in the dorsal visual pathway of the mammalian brain are selective for motion stimuli, with the complexity of stimulus representations increasing along the hierarchy. This progression is similar to that of the ventral visual pathway, which is well characterized by artificial neural networks (ANNs) optimized for object recognition. In contrast, there are no image-computable models of the dorsal stream with comparable explanatory power. We hypothesized that the properties of dorsal stream neurons could be explained by a simple learning objective: the need for an organism to orient itself during self-motion. To test this hypothesis, we trained a 3D ResNet to predict an agents self-motion parameters from visual stimuli in a simulated environment. We found that the responses in this network accounted well for the selectivity of neurons in a large database of single-neuron recordings from the dorsal visual stream of non-human primates. In contrast, ANNs trained on an action recognition dataset through supervised or self-supervised learning could not explain responses in the dorsal stream, despite also being trained on naturalistic videos with moving objects. These results demonstrate that an ecologically relevant cost function can account for dorsal stream properties in the primate brain.

neuroscience↗

bioRxiv2019

tACS entrains neural activity while somatosensory input is blocked

Transcranial alternating current stimulation (tACS) modulates brain activity by passing electrical current through electrodes that are attached to the scalp. Because it is safe and non-invasive, it holds great promise as a tool for basic research and clinical treatment. However, little is known about how tACS ultimately influences neural activity. One hypothesis is that tACS affects neural responses directly, by producing electrical fields that interact with the brains endogenous electrical activity. Since the shape and location of these electric fields can be controlled, stimulation could be targeted at brain regions associated with particular behaviors or symptoms. However, an alternative hypothesis is that tACS affects neural activity indirectly, via peripheral sensory afferents. In particular, it has often been hypothesized that tACS acts on nerve fibers in the skin, which in turn provide rhythmic input to central neurons. In this case, there would be little possibility of targeted brain stimulation, as the regions modulated by tACS would depend entirely on the somatosensory pathways originating in the skin around the stimulating electrodes. Here, we directly test these competing hypotheses by recording single-unit activity in the hippocampus and visual cortex of monkeys receiving tACS. We find that tACS entrains neuronal activity in both regions, so that cells fire synchronously with the stimulation. Blocking somatosensory input with a topical anesthetic does not significantly alter these neural entrainment effects. These data are therefore consistent with the direct stimulation hypothesis and suggest that peripheral somatosensory stimulation is not required for tACS to entrain neurons.

neuroscience↗

bioRxiv2017

A unifying motif for spatial and directional surround suppression

In the visual system, the response to a stimulus in a neurons receptive field can be modulated by stimulus context, and the strength of these contextual influences vary with stimulus intensity. Recent work has shown how a theoretical model, the stabilized supralinear network (SSN), can account for such modulatory influences, using a small set of computational mechanisms. While the predictions of the SSN have been confirmed in primary visual cortex (V1), its computational principles apply with equal validity to any cortical structure. We have therefore tested the generality of the SSN by examining modulatory influences in the middle temporal area (MT) of the macaque visual cortex, using electrophysiological recordings and pharmacological manipulations. We developed a novel stimulus that can be adjusted parametrically to be larger or smaller in the space of all possible motion directions. We found, as predicted by the SSN, that MT neurons integrate across motion directions for low-contrast stimuli, but that they exhibit suppression by the same stimuli when they are high in contrast. These results are analogous to those found in visual cortex when stimulus size is varied in the space domain. We further tested the mechanisms of inhibition using pharmacologically manipulations of inhibitory efficacy. As predicted by the SSN, local manipulation of inhibitory strength altered firing rates, but did not change the strength of surround suppression. These results are consistent with the idea that the SSN can account for modulatory influences along different stimulus dimensions and in different cortical areas.\n\nSignificance StatementVisual neurons are selective for specific stimulus features in a region of visual space known as the receptive field, but can be modulated by stimuli outside of the receptive field. The SSN model has been proposed to account for these and other modulatory influences, and tested in V1. As this model is not specific to any particular stimulus feature or brain region, we wondered whether similar modulatory influences might be observed for other stimulus dimensions and other regions. We tested for specific patterns of modulatory influences in the domain of motion direction, using electrophysiological recordings from MT. Our data confirm the predictions of the SSN in MT, suggesting that the SSN computations might be a generic feature of sensory cortex.

neuroscience↗