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Bogadhi, A. R.

Publications and source records attributed to Bogadhi, A. R..

11 recordsLinked to original sources

Pharmacobehavioral space of MoSeq syllables significantly overlaps with scalar locomotion features

"Revealing the structure of pharmacobehavioral space through motion sequencing" by Wiltschko et al. (2020) has been highly influential in behavioral phenotyping research. In a cohort of nearly 700 mice, the authors demonstrated that Motion Sequencing (MoSeq) could distinguish behavioral effects across a large and diverse set of neuroactive and psychoactive compounds. A central conclusion of the study is that MoSeq syllable features substantially outperform more traditional scalar behavioral features in treatment classification tasks. Although this comparison is not emphasized outside the Results section, the reported advantage corresponds to an increase in classification performance exceeding 50% relative to scalar feature representations. While reproducing parts of the analysis using the publicly available dataset, we found that much of this apparent performance difference can be attributed to differences in preprocessing, classifier selection, and hyperparameter optimization. Under alternative, but comparably standard, analytical choices, the performance gap between scalar features and MoSeq syllables was reduced to approximately 11%. Furthermore, in our reanalysis, the performance advantage of MoSeq syllables became statistically significant primarily in highly dense pharmacobehavioral spaces. These findings do not contradict the utility of MoSeq syllables. Rather, they suggest that the magnitude and generality of their advantage over simpler scalar features may depend strongly on analytical methodology and dataset structure. This distinction is practically relevant, as scalar feature approaches are substantially less computationally demanding and often easier to interpret biologically. Consequently, for laboratories with limited computational resources or for studies focused on specific treatment effects, conventional scalar representations may provide a competitive and more accessible alternative. Our findings highlight the importance of analytical standardization and reproducibility in comparative behavioral representation studies.

animal behavior and cognition↗

Comparison of multiple video tracking-based behavioral summary approaches for compound discrimination

The rapidly increasing number of video tracking-based behavioral summary tools and methods raises the question as to the most suitable approaches for pharmacological fingerprinting in pre-clinical research. We have recently shown that social context has a strong effect on behavioral syntax in mice, further suggesting that treatment effects can be context dependent. Here, we aim to answer the question whether there is an optimal combination of context and behavioral summary method for effect detection and discrimination of different psychoactive substances in a controlled environment. To this end, we applied eight different treatment-dosage pairs (amphetamine 1.5,3,6 mg/kg; modafinil 5,10,50 mg/kg; seltorexant 3,10 mg/kg) and evaluated five different approaches to behavioral summary: parametric aggregation, unsupervised segmentation in Keypoint-MoSeq (KPMS) & Variational Animal Motion Encoding (VAME), and supervised segmentation in Simple Behavioral Analysis (SimBA) & A-SOiD, across two different contexts (Solitary & Social) in 314 recordings of freely moving mice in an open-field arena. Surprisingly, our results show no significant differences in performance across models and context. Across treatment effect detection to treatment-dose discrimination, all models showed performance significantly above chance that was insensitive to various data limitations and extensions. Overall, our study shows that under the tested conditions and treatments, the choice of a behavioral summary model does not meaningfully affect the description of treatment effects. Simple aggregate measures from tracking data and machine learning based behavioral summary approaches that are expensive, in terms of training data and computational resources, performed equally well. Our findings taken together with literature suggest that the fuller decomposition of complex behavior through unsupervised machine learning might be necessary for the description of large-scale datasets but does not necessarily align with the goals present in smaller-scale treatment discrimination tasks common in pre-clinical research.

animal behavior and cognition↗

Much stronger coarse-to-fine visual processing in primate superior colliculus than primary visual cortex neurons

The visual system optimizes its signal processing properties to efficiently encode natural scenes. The superior colliculus (SC) and primary visual cortex (V1) both play important roles in visual-motor processing, and they both exhibit qualitatively similar visual responses. However, it is not clear whether the SC simply inherits V1s efficient coding image processing optimizations or not, especially given that the SC receives a substantial amount of direct anatomical inputs from V1. Here, by performing matched experiments in the two brain areas, as well as with the same visual stimuli and in the same experimental animals, we show that the dynamics of coarse-to-fine visual image processing in the SC are much stronger than those in V1. In the SC, visual response latencies, being fastest for coarse patterns, are dictated by image spatial frequency, independently of the spatial frequency tuning curves of the neurons. On the other hand, V1 visual response latencies are largely dominated by visual response sensitivity, which is itself much more broadband than in the SC. These observations remain fundamentally unchanged in active vision gaze-shift scenarios eliciting visual reafferent responses in both brain areas. Our results suggest that coarse-to-fine visual image processing dynamics are most observable, and thus most relevant, in visually-responsive neurons driving foveating eye movements, like in the SC. Besides explaining behavioral evidence for saccadic facilitation by images that are consistent with the statistics of natural scenes, these results indicate that coarse-to-fine visual processing dynamics are much more of a collicular than a cortical visual phenomenon.

neuroscience↗

Social Context Restructures Behavioral Syntax in Mice

The study of social behavior in mice has grown increasingly relevant for unraveling associated brain circuits and advancing the development of treatments for psychiatric symptoms involving social withdrawal or social anxiety. However, a data-driven understanding of behavior and its modulation in solitary and social contexts is lacking. In this study, we employed motion sequencing ("MoSeq") to decompose mouse behaviors into discrete units ("Syllables") and investigate whether--and how--the behavioral repertoire differs between solitary and dyadic (social) settings. Our results reveal that social context significantly modulates a minority (25%) of syllables, containing predominantly stationary and undirected behaviors. Notably, these changes are associated with spatial proximity to another mouse rather than active social contact. Interestingly, a network analysis of syllable transitions shows that context-sensitive syllables exhibit altered network influence, independent of the number of connected syllables, suggesting a regulatory role. Furthermore, syllable composition changes significantly during social contact events with two distinct sequence families governing approach and withdrawal behaviors. However, no unique syllable sequences mapped to specific social interactions. Overall, our findings suggest that a subset of syllables drives contextual behavioral adaptation in mice, potentially facilitating transitions within the broader behavioral repertoire. This highlights the utility of MoSeq in dissecting nuanced, context-dependent behavioral dynamics.

animal behavior and cognition↗

Sensory tuning in neuronal movement commands

Movement control is critical for successful interaction with our environment. However, movement does not occur in complete isolation of sensation, and this is particularly true of eye movements. Here we show that the neuronal eye movement commands emitted by the superior colliculus, a structure classically associated with oculomotor control, encompass a robust visual sensory representation of eye movement targets. Thus, similar saccades towards different images are associated with different saccade-related "motor" bursts. Such sensory tuning in superior colliculus saccade motor commands appeared for all image manipulations that we tested, from simple visual features to real-life object images, and it was also strongest in the most motor neurons in the deeper collicular layers. Visual-feature discrimination performance in the motor commands was also stronger than in visual responses. Comparing superior colliculus motor command feature discrimination performance to that in the primary visual cortex during steady gaze fixation revealed that collicular motor bursts possess a reliable peri-saccadic sensory representation of the peripheral saccade targets visual appearance, exactly when retinal input is most uncertain. Consistent with this, we found that peri-saccadic perception is altered as a function of saccade target visual features. Therefore, superior colliculus neuronal movement commands likely serve a fundamentally sensory function.

neuroscience↗

Faster detection of "darks" than "brights" by monkey superior colliculus neurons

Visual processing is segregated into ON and OFF channels as early as in the retina, and the superficial (output) layers of the primary visual cortex are dominated by neurons preferring dark stimuli. However, it is not clear how the timing of neural processing differs between "darks" and "brights" in general, especially in light of psychophysical evidence; it is also equally not clear how subcortical visual pathways that are critical for active orienting represent stimuli of positive (luminance increments) and negative (luminance decrements) contrast polarity. Here, we recorded from all visually-responsive neuron types in the superior colliculus (SC) of two male rhesus macaque monkeys. We presented a disc (0.51 deg radius) within the response fields (RFs) of neurons, and we varied, across trials, stimulus Weber contrast relative to a gray background. We also varied contrast polarity. There was a large diversity of preferences for darks and brights across the population. However, regardless of individual neural sensitivity, most neurons responded significantly earlier to dark than bright stimuli. This resulted in a dissociation between neural preference and visual response onset latency: a neuron could exhibit a weaker response to a dark stimulus than to a bright stimulus of the same contrast, but it would still have an earlier response to the dark stimulus. Our results highlight an additional candidate visual neural pathway for explaining behavioral differences between the processing of darks and brights, and they demonstrate the importance of temporal aspects in the visual neural code for orienting eye movements. Significance statementObjects in our environment, such as birds flying across a bright sky, often project shadows (or images darker than the surround) on our retina. We studied how primate superior colliculus (SC) neurons visually process such dark stimuli. We found that the overall population of SC neurons represented both dark and bright stimuli equally well, as evidenced by a relatively equal distribution of neurons that were either more or less sensitive to darks. However, independent of sensitivity, the great majority of neurons detected dark stimuli earlier than bright stimuli, evidenced by a smaller response latency for the dark stimuli. Thus, SC neural response latency can be dissociated from response sensitivity, and it favors the faster detection of dark image contrasts.

neuroscience↗

Express detection and discrimination of visual objects by primate superior colliculus neurons

Primate superior colliculus (SC) neurons exhibit rich visual feature tuning properties and are implicated in a subcortical network hypothesized to mediate fast threat and/or conspecific detection. However, the mechanisms through which generalized object detection may be mediated by SC neurons remain unclear. Here we explored whether, and how quickly, SC neurons detect and discriminate real-life object stimuli. We presented experimentally-controlled gray-scale images of seven different object categories within the response fields (RFs) of SC neurons, and we also presented a variety of luminance- and spectral-matched image controls. We found that all of our functionally-identified SC neuron types preferentially detected real-life objects even in their very first stimulus-evoked visual bursts (starting within approximately 50 ms from image onset). Intriguingly, even visually-responsive motor-related neurons exhibited such robust early object detection, and they also preferentially discriminated between object categories in their initial visual bursts. We further identified spatial frequency information in visual images as a critical source for early object detection and discrimination by SC neurons. Our results demonstrate rapid and robust SC processing of visual objects, and they underline how the visual processing capabilities of the primate SC support perception and action.

neuroscience↗

Task-irrelevant visual forms facilitate covert and overt spatial selection

Covert and overt spatial selection behaviors are guided by both visual saliency maps derived from early visual features as well as priority maps reflecting high-level cognitive factors. However, whether mid-level perceptual processes associated with visual form recognition contribute to covert and overt spatial selection behaviors remains unclear. We hypothesized that if peripheral visual forms contribute to spatial selection behaviors, then they should do so even when the visual forms are task-irrelevant. We tested this hypothesis in male and female human subjects as well as in male macaque monkeys performing a visual detection task. In this task, subjects reported the detection of a supra-threshold target spot presented on top of one of two peripheral images, and they did so with either a speeded manual button press (humans) or a speeded saccadic eye movement response (humans and monkeys). Crucially, the two images, one with a visual form and the other with a partially phase-scrambled visual form, were completely irrelevant to the task. In both manual (covert) and oculomotor (overt) response modalities, and in both humans and monkeys, response times were faster when the target was congruent with a visual form than when it was incongruent. Importantly, incongruent targets were associated with almost all errors, suggesting that forms automatically captured selection behaviors. These findings demonstrate that mid-level perceptual processes associated with visual form recognition contribute to covert and overt spatial selection. This indicates that neural circuits associated with target selection, such as the superior colliculus, may have privileged access to visual form information. Significance statementSpatial selection of visual information either with (overt) or without (covert) foveating eye movements is critical to primate behavior. However, it is still not clear whether spatial maps in sensorimotor regions known to guide overt and covert spatial selection are influenced by peripheral visual forms. We probed the ability of humans and monkeys to perform overt and covert target selection in the presence of spatially congruent or incongruent visual forms. Even when completely task-irrelevant, images of visual objects had a dramatic effect on target selection, acting much like spatial cues used in spatial attention tasks. Our results demonstrate that traditional brain circuits for orienting behaviors, such as the superior colliculus, likely have privileged access to visual object representations.

neuroscience↗

Midbrain activity supports high-level visual properties in primate temporal cortex

The evolution of the primate brain is marked by a dramatic increase in the number of neocortical areas that process visual information 1. This cortical expansion supports two hallmarks of high-level primate vision - the ability to selectively attend to particular visual features 2 and the ability to recognize a seemingly limitless number of complex visual objects 3. Given their prominent roles in high-level vision for primates, it is commonly assumed that these cortical processes supersede the earlier versions of these functions accomplished by the evolutionarily older brain structures that lie beneath the cortex. Contrary to this view, here we show that the superior colliculus (SC), a midbrain structure conserved across all vertebrates 4, is necessary for the normal expression of attention-related modulation and object selectivity in a newly identified region of macaque temporal cortex. Using a combination of psychophysics, causal perturbations and fMRI, we identified a localized region in the temporal cortex that is functionally dependent on the SC. Targeted electrophysiological recordings in this cortical region revealed neurons with strong attention-related modulation that was markedly reduced during attention deficits caused by SC inactivation. Many of these neurons also exhibited selectivity for particular visual objects, and this selectivity was also reduced during SC inactivation. Thus, the SC exerts a causal influence on high-level visual processing in cortex at a surprisingly late stage where attention and object selectivity converge, perhaps determined by the elemental forms of perceptual processing the SC has supported since before there was a neocortex.

neuroscience↗

Focal disruption of temporal cortex in macaque during midbrain-induced neglect

Spatial neglect is a common clinical syndrome involving disruption of the brains attention-related circuitry, including the dorsocaudal temporal cortex. While neglect is readily modeled in macaques, the absence of evidence for temporal cortex involvement has suggested a fundamental difference from humans. To map the neurological expression of spatial neglect in macaques, we measured attention-related fMRI activity across the cerebral cortex during experimental induction of neglect through reversible inactivation of the superior colliculus. During inactivation, monkeys exhibited hallmark attentional deficits of neglect in tasks using either moving or static stimuli. The behavioral deficits were accompanied by marked reductions in fMRI attentional modulation that were strongest in a small region on the floor of the superior temporal sulcus. Notably, direct inactivation of this mid-STS cortical region caused similar neglect-like spatial attention deficits. These results identify a putative macaque homolog to temporal cortex structures known to play a central role in human neglect.\n\nHighlightsO_LIDuring neglect the mid-STS cortex shows largest reduction in attentional modulation\nC_LIO_LIThe mid-STS cortex is selectively affected with static as well as dynamic stimuli\nC_LIO_LIMid-STS cortex is affected during neglect caused by SC or FEF inactivation\nC_LIO_LIInactivation of mid-STS cortex itself causes neglect without eye movement deficits\nC_LI\n\nIn BriefUsing fMRI in macaques performing attention tasks combined with reversible inactivations, Bogadhi et al. provide causal evidence that a region on the floor of the superior temporal sulcus is a crucial node in the cortical control of covert selective attention and a putative homolog to temporal cortex regions in humans implicated in spatial neglect.

neuroscience↗

Brain regions modulated during covert visual attention in the macaque

Neurophysiology studies of covert visual attention in monkeys have emphasized the modulation of sensory neural responses in the visual cortex. At the same time, electrophysiological correlates of attention have been reported in other cortical and subcortical structures, and recent fMRI studies have identified regions across the brain modulated by attention. Here we used fMRI in two monkeys performing covert attention tasks to reproduce and extend these findings in order to help establish a more complete list of brain structures involved in the control of attention. As expected from previous studies, we found attention-related modulation in frontal, parietal and visual cortical areas as well as the superior colliculus and pulvinar. We also found significant attention-related modulation in cortical regions not traditionally linked to attention - mid-STS areas (anterior FST and parts of IPa, PGa, TPO), as well as the caudate nucleus. A control experiment using a second-order orientation stimulus showed that the observed modulation in a subset of these mid-STS areas did not depend on visual motion. These results identify the mid-STS areas (anterior FST and parts of IPa, PGa, TPO) and caudate nucleus as potentially important brain regions in the control of covert visual attention in monkeys.

animal behavior and cognition↗