A quantitative comparison of atlas parcellations on the human superior temporal sulcus.

The superior temporal sulcus (STS) has a functional topography that has been difficult to characterize through traditional approaches. Automated atlas parcellations may be one solution while also being beneficial for both dimensional reduction and standardizing regions of interest, but they yield very different boundary definitions along the STS. Here we evaluate how well machine learning classifiers can correctly identify six social cognitive tasks from STS activation patterns dimensionally reduced using four popular atlases (Glasser et al., 2016; Gordon et al., 2016; Power et al., 2011 as projected onto the surface by Arslan et al., 2018; Schaefer et al., 2018). Functional data was summarized within each STS parcel in one of four ways, then subjected to leave-one-subject-out cross-validation SVM classification. We found that the classifiers could readily label conditions when data was parcellated using any of the four atlases, evidence that dimensional reduction to parcels did not compromise functional fingerprints. Mean activation for the social conditions was the most effective metric for classification in the right STS, whereas all the metrics classified equally well in the left STS. Interestingly, even atlases constructed from random parcellation schemes (null atlases) classified the conditions with high accuracy. We therefore conclude that the complex activation maps on the STS are readily differentiated at a coarse granular level, despite a strict topography having not yet been identified. Further work is required to identify what features have greatest potential to improve the utility of atlases in replacing functional localizers.

Configuration of the action observation network depends on the goals of the observer.

Observing the actions of others engages a core action observation network (AON) that includes the bilateral inferior frontal cortex (IFC), posterior superior temporal sulcus (pSTS) and inferior parietal lobule (IPL) (Caspers et al., 2010). Each region in the AON has functional properties that are heterogeneous and include representing the perceptual properties of action, predicting action outcomes and making inferences as to the goals of the actor. Critically, recent evidence shows that neural representations within the pSTS are sharpened when attending to the kinematics of the actor, such that the top-down guided attention reshapes underlying neural representations. In this study we evaluate how attention alters network connectivity within the AON as a system. Cues directed participant's attention to the goal, kinematics, or identity depicted in short action animations while brain responses were measured by fMRI. We identified those parcels within the AON with functional connectivity modulated by task. Results show that connectivity between the right pSTS and right IFC, and bilateral extended STS (STS+) were modulated during action observation such that connections were strengthened when the participant was attending to the action than goal. This finding is contrasted by the univariate results, which no univariate modulations in these brain regions except for right IFC. Using the functional networks defined by Yeo et al. (2011), we identified the parcels that are modulated by the attention to consist mainly of the fronto-parietal control network and default mode networks. These results are consistent with models of top-down feedback from executive system in the IFC to pSTS and implicates a right lateralized dual pathway model for action observation when focused on whole-body kinematics.

The PyMVPA BIDS-App: a robust multivariate pattern analysis pipeline for fMRI data.

With the advent of multivariate pattern analysis (MVPA) as an important analytic approach to fMRI, new insights into the functional organization of the brain have emerged. Several software packages have been developed to perform MVPA analysis, but deploying them comes with the cost of adjusting data to individual idiosyncrasies associated with each package. Here we describe PyMVPA BIDS-App, a fast and robust pipeline based on the data organization of the BIDS standard that performs multivariate analyses using powerful functionality of PyMVPA. The app runs flexibly with blocked and event-related fMRI experimental designs, is capable of performing classification as well as representational similarity analysis, and works both within regions of interest or on the whole brain through searchlights. In addition, the app accepts as input both volumetric and surface-based data. Inspections into the intermediate stages of the analyses are available and the readability of final results are facilitated through visualizations. The PyMVPA BIDS-App is designed to be accessible to novice users, while also offering more control to experts through command-line arguments in a highly reproducible environment.

When shapes are more than shapes: perceptual, developmental, and neurophysiological basis for attributions of animacy and theory of mind.

Among a variety of entities in their environment, what do humans consider alive or animate and how does this attribution of animacy promote development of more abstract levels of mentalizing? By decontextualizing the environment of bodily features, we review how physical movements give rise to perceived animacy in Heider-Simmel style animations. We discuss the developmental course of how perceived animacy shapes our interpretation of the social world, and specifically discuss when and how children transition from perceiving actions as goal-directed to attributing behaviors to unobservable mental states. This transition from a teleological stance, asserting a goal-oriented interpretation to an agent's actions, to a mentalistic stance allows older children to reason about more complex actions guided by hidden beliefs. The acquisition of these more complex cognitive behaviors happens developmentally at the same time neural systems for social cognition are coming online in young children. We review perceptual, developmental, and neural evidence to identify the joint cognitive and neural changes associated with when children begin to mentalize and how this ability is instantiated in the brain.

Optimizing multivariate pattern classification in rapid event-related designs.

BACKGROUND: Multivariate pattern analysis (MVPA or pattern decoding) has attracted considerable attention as a sensitive analytic tool for investigations using functional magnetic resonance imaging (fMRI) data. With the introduction of MVPA, however, has come a proliferation of methodological choices confronting the researcher, with few studies to date offering guidance from the vantage point of controlled datasets detached from specific experimental hypotheses. NEW METHOD: We investigated the impact of four data processing steps on support vector machine (SVM) classification performance aimed at maximizing information capture in the presence of common noise sources. The four techniques included: trial averaging (classifying on separate trial estimates versus condition-based averages), within-run mean centering (centering the data or not), method of cost selection (using a fixed or tuned cost value), and motion-related denoising approach (comparing no denoising versus a variety of nuisance regressions capturing motion-related reference signals). The impact of these approaches was evaluated on real fMRI data from two control ROIs, as well as on simulated pattern data constructed with carefully controlled voxel- and trial-level noise components. RESULTS: We find significant improvements in classification performance across both real and simulated datasets with run-wise trial averaging and mean centering. When averaging trials within conditions of each run, we note a simultaneous increase in the between-subject variability of SVM classification accuracies which we attribute to the reduced size of the test set used to assess the classifier's prediction error. Therefore, we propose a hybrid technique whereby randomly sampled subsets of trials are averaged per run and demonstrate that it helps mitigate the tradeoff between improving signal-to-noise ratio by averaging and losing exemplars in the test set. COMPARISON WITH EXISTING METHODS: Though a handful of empirical studies have employed run-based trial averaging, mean centering, or their combination, such studies have done so without theoretical justification or rigorous testing using control ROIs. CONCLUSIONS: Therefore, we intend this study to serve as a practical guide for researchers wishing to optimize pattern decoding without risk of introducing spurious results.

Perks of blindness: Enhanced verbal memory span in blind over sighted adults.

Blind individuals commonly use verbal encoding (i.e. text-to-speech) and memory-based strategies (i.e. serial recall) for situations in which sighted individuals use vision (i.e. finding items). These strategies may serve to train cognitive systems responsible for maintaining and manipulating verbal information. To test this hypothesis, we investigate whether early visual deprivation is linked to improved verbal short-term and working memory abilities, and thus might illustrate experience-dependent plasticity in memory systems. We also test whether the sensory modality for encoding information influences performance. Our data show that blind adults recalled more items on a verbal short-term memory span task than sighted participants. Furthermore, blind individuals performed equally well on auditory forward and backward conditions despite the fact that recalling items in reverse order is more difficult for the general population. However, the benefits of recalling items in reverse order did not extend to the tactile domain, specifically, a braille version of the short-term memory digit span task in blind individuals. Furthermore, we observed no differences between blind and sighted individuals on a more demanding auditory n-back task evaluating more complex working memory processes. We conclude that the memory benefits associated with blindness might be restricted to auditory-verbal short-term memory and likely reflect strategy use and practice.

CRISPR in Your Kitchen: an At-Home CRISPR Kit to Edit Genes in Saccharomyces cerevisiae Used during a Remote Lab Course.

The use of CRISPR-based experiments in an undergraduate course is appealing because of the ease of editing, and the relevance of CRISPR to current research. Before the COVID-19 pandemic, we developed an in-person lab for a high-enrollment course that allowed students to design and conduct CRISPR editing experiments in budding yeast, Saccharomyces cerevisiae. Post pandemic, the lab course moved online, and we lost the hands-on component. We subsequently developed an at-home kit that contained all the necessary materials for students to grow and transform S. cerevisiae with the DNA molecules necessary for CRISPR-Cas9 induced editing. Our at-home kits cost approximately $70 each to produce and were shipped to over 600 students during the 2020 to 2021 academic year. By adding the at-home experimental work to our remote, online lab course, students were able to generate loss-of-function mutants in ADE2 (causing a red color phenotype). Students were able to send edited yeast samples back to campus for sequencing, allowing for characterization of the different mutations that can occur due to CRISPR-Cas9 induced editing. Here, we described the protocol to produce and use the kits and summarized the student experience of using the at-home kit in a large enrollment, remote lab course. These kits provided opportunities to engage students in hands-on experimentation during a remote course and could also be used to reach learners in other domains, such as high schools and outreach programs.

Distinct cerebellar regions for body motion discrimination.

Visual processing of human movements is critical for adaptive social behavior. Cerebellar activations have been observed during biological motion discrimination in prior neuroimaging studies, and cerebellar lesions may be detrimental for this task. However, whether the cerebellum plays a causal role in biological motion discrimination has never been tested. Here, we addressed this issue in three different experiments by interfering with the posterior cerebellar lobe using transcranial magnetic stimulation (TMS) during a biological discrimination task. In Experiments 1 and 2, we found that TMS delivered at onset of the visual stimuli over the vermis (vermal lobule VI), but not over the left cerebellar hemisphere (left lobule VI/Crus I), interfered with participants' ability to distinguish biological from scrambled motion compared to stimulation of a control site (vertex). Interestingly, when stimulation was delivered at a later time point (300 ms after stimulus onset), participants performed worse when TMS was delivered over the left cerebellar hemisphere compared to the vermis and the vertex (Experiment 3). Our data show that the posterior cerebellum is causally involved in biological motion discrimination and suggest that different sectors of the posterior cerebellar lobe may contribute to the task at different time points.

Attention network modulation via tRNS correlates with attention gain.

Transcranial random noise stimulation (tRNS) can enhance vision in the healthy and diseased brain. Yet, the impact of multi-day tRNS on large-scale cortical networks is still unknown. We investigated the impact of tRNS coupled with behavioral training on resting-state functional connectivity and attention. We trained human subjects for 4 consecutive days on two attention tasks, while receiving tRNS over the intraparietal sulci, the middle temporal areas, or Sham stimulation. We measured resting-state functional connectivity of nodes of the dorsal and ventral attention network (DVAN) before and after training. We found a strong behavioral improvement and increased connectivity within the DVAN after parietal stimulation only. Crucially, behavioral improvement positively correlated with connectivity measures. We conclude changes in connectivity are a marker for the enduring effect of tRNS upon behavior. Our results suggest that tRNS has strong potential to augment cognitive capacity in healthy individuals and promote recovery in the neurological population.

Examining vocal attractiveness through articulatory working space.

Robust gender differences exist in the acoustic correlates of clearly articulated speech, with females, on average, producing speech that is acoustically and phonetically more distinct than that of males. This study investigates the relationship between several acoustic correlates of clear speech and subjective ratings of vocal attractiveness. Talkers were recorded producing vowels in /bVd/ context and sentences containing the four corner vowels. Multiple measures of working vowel space were computed from continuously sampled formant trajectories and were combined with measures of speech timing known to co-vary with clear articulation. Partial least squares regression (PLS-R) modeling was used to predict ratings of vocal attractiveness for male and female talkers based on the acoustic measures. PLS components that loaded on size and shape measures of working vowel space-including the quadrilateral vowel space area, convex hull area, and bivariate spread of formants-along with measures of speech timing were highly successful at predicting attractiveness in female talkers producing /bVd/ words. These findings are consistent with a number of hypotheses regarding human attractiveness judgments, including the role of sexual dimorphism in mate selection, the significance of traits signalling underlying health, and perceptual fluency accounts of preferences.

Top-Down Attention Guidance Shapes Action Encoding in the pSTS.

The posterior superior temporal sulcus (pSTS) is a brain region characterized by perceptual representations of human body actions that promote the understanding of observed behavior. Increasingly, action observation is recognized as being strongly shaped by the expectations of the observer (Kilner 2011; Koster-Hale and Saxe 2013; Patel et al. 2019). Therefore, to characterize top-down influences on action observation, we evaluated the statistical structure of multivariate activation patterns from the action observation network (AON) while observers attended to the different dimensions of action vignettes (the action kinematics, goal, or identity of avatars jumping or crouching). Decoding accuracy varied as a function of attention instruction in the right pSTS and left inferior frontal cortex (IFC), with the right pSTS classifying actions most accurately when observers attended to the action kinematics and the left IFC classifying most accurately when observed attended to the actor's goal. Functional connectivity also increased between the right pSTS and right IFC when observers attended to the actions portrayed in the vignettes. Our findings are evidence that the attentive state of the viewer modulates sensory representations in the pSTS, consistent with proposals that the pSTS occupies an interstitial zone mediating top-down context and bottom-up perceptual cues during action observation.

Understanding diaschisis models of attention dysfunction with rTMS.

Visual attentive tracking requires a balance of excitation and inhibition across large-scale frontoparietal cortical networks. Using methods borrowed from network science, we characterize the induced changes in network dynamics following low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) as an inhibitory noninvasive brain stimulation protocol delivered over the intraparietal sulcus. When participants engaged in visual tracking, we observed a highly stable network configuration of six distinct communities, each with characteristic properties in node dynamics. Stimulation to parietal cortex had no significant impact on the dynamics of the parietal community, which already exhibited increased flexibility and promiscuity relative to the other communities. The impact of rTMS, however, was apparent distal from the stimulation site in lateral prefrontal cortex. rTMS temporarily induced stronger allegiance within and between nodal motifs (increased recruitment and integration) in dorsolateral and ventrolateral prefrontal cortex, which returned to baseline levels within 15 min. These findings illustrate the distributed nature by which inhibitory rTMS perturbs network communities and is preliminary evidence for downstream cortical interactions when using noninvasive brain stimulation for behavioral augmentations.

Prolonged Neuromodulation of Cortical Networks Following Low-Frequency rTMS and Its Potential for Clinical Interventions.

Non-invasive brain stimulation safely induces persistent large-scale neural modulation in functionally connected brain circuits. Interruption models of repetitive transcranial magnetic stimulation (rTMS) capitalize on the acute impact of brain stimulation, which decays over minutes. However, rTMS also induces longer-lasting impact on cortical functions, evident by the use of multi-session rTMS in clinical population for therapeutic purposes. Defining the persistent cortical dynamics induced by rTMS is complicated by the complex balance of excitation and inhibition among functionally connected networks. Nonetheless, it is these neuronal dynamic responses that are essential for the development of new neuromodulatory protocols for translational applications. We will review evidence of prolonged changes of cortical response, tens of minutes following one session of low frequency rTMS over the cortex. We will focus on the different methods which resulted in prolonged behavioral and brain changes, such as the combination of brain stimulation techniques, and individually tailored stimulation protocols. We will also highlight studies which apply these methods in multi-session stimulation practices to extend stimulation impact into weeks and months. Our data and others' indicate that delayed cortical dynamics may persist much longer than previously thought and have potential as an extended temporal window during which cortical plasticity may be enhanced.

Functional connectivity in ASD: Atypical pathways in brain networks supporting action observation and joint attention.

Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication, including attending to and interpreting social cues, initiating and responding to joint attention, and engaging in abstract social cognitive reasoning. Current studies emphasize a underconnectivity in ASD, particularly for brain systems that support abstract social reasoning and introspective thought. Here, we evaluate intrinsic connectivity in children with ASD, targeting brain systems that support the developmental precursors to social reasoning, namely perception of social cues and joint attention. Using resting state fMRI made available through the Autism Brain Imaging Data Exchange (ABIDE), we compute functional connectivity within and between nodes in the action observation, attention and social cognitive networks in children and adolescents with ASD. We also compare connectivity strength to observational assessments that explicitly evaluate severity of ASD on two distinct subdomains using the ADOS-Revised schedule: social affective (SA) and restricted, repetitive behaviors (RRB). Compared to age-matched controls, children with ASD have decreased functional connectivity in a number of connections in the action observation network, particularly in the lateral occipital cortex (LOTC) and fusiform gyrus (FG). Distinct patterns of connections were also correlated with symptom severity on the two subdomains of the ADOS. ADOS-SA severity most strongly correlated with connectivity to the left TPJ, while ADOS-RRB severity correlated with connectivity to the dMPFC. We conclude that atypical connectivity in the action observation system may underlie some of the more complex deficits in social cognitive systems in ASD.

Multivariate pattern analysis of the human pSTS: A comparison of three prototypical localizers.

The posterior extent of the human superior temporal sulcus (pSTS) is an important cortical region for detecting animacy, attributing agency to others, and decoding goal-directed behavior. Theoretical accounts attribute these cognitive skills to unique neural populations that have been difficult to identify empirically (Hein and Knight, 2008). The aim of this study is to evaluate the multivariate statistical structure of pSTS activation patterns when viewing different social cues. We identified a core conjunction region on pSTS from univariate responses with preference for point-light biological motion, faces and the attribution of social concepts to simple animated shapes. In a multivariate analysis, we characterized the similarity structure of the resulting activation patterns after controlling for variance in the activation profile elicited by form and motion features. We found strong antagonistic activation profiles between the social conditions and their localizer controls, a harbinger of why these canonical localizers are so effective, even in individual subjects. We also found unique patterns of similarity between the three core social conditions. Our findings are consistent with the Shultz et al. (2015) model of pSTS function in which separate neural populations exist for animacy detection from body parts versus for extracting intentional cues from movement.

Feature-based attentional tuning during biological motion detection measured with SSVEP.

Performance in detection tasks can be improved by directing attention to task-relevant features. In this study, we evaluate the direction tuning of selective attention to motion features when observers detect point-light biological motion in noise. Feature-based attention strategy is assessed by capitalizing on the sensitivity of unattended steady-state visual-evoked potential (SSVEP) to the spreading of feature-based attention to unattended regions of space. Participants monitored for the presence of a point-light walker embedded in uniform dynamic noise in the center of the screen. We analyzed the phase-locked electroencephalogram response to a flickering random-dot kinematogram (RDK) in an unattended peripheral annulus for the 1 s prior to the onset of the target. We found the highest SSVEP power to originate from electrodes over posterior parietal cortex (PPC), with power modulated by the direction of motion in the unattended annulus. The SSVEP was strongest on trials in which the unattended motion was opposite the facing direction of the walker, consistent with the backstroke of the feet and with the global direction of perceived background motion from a translating walker. Coherence between electrodes over PPC and other brain regions successfully predicted individual participant's d-prime, with the highest regression coefficients at electrodes over ventrolateral prefrontal cortex (VLPFC). The findings are evidence that functional connectivity between frontal and parietal cortex promote perceptual feature-based attention, and subsequent perceptual sensitivity, when segregating point-light figures from masking surround.

Investigation of autistic traits through strategic decision-making in games with adaptive agents.

Autism Spectrum Disorders are characterized by difficulties in communicating and cooperating with other people. Impairment in Theory of Mind (ToM), the ability to infer what another person is thinking, may contribute to these social deficits. The present study assesses the relationship between autistic traits and decision-making in a socioeconomic game environment that measures ToM and cooperation. We quantified participant strategy during game play with computer agents that simulated aspects of ToM or fixed strategy agents with static behaviors or heuristics. Individuals with higher Autism Quotient (AQ) scores cooperated less than subjects with low AQ scores with the ToM agents. In contrast, subjects with higher AQ scores cooperated more with fixed strategy agents. Additionally, subjects with higher AQ scores spent more time than low AQ subjects signaling cooperative intent in games with fixed strategy agents while spending less time signaling cooperation with adaptive agents, indicating a preference toward systemizing behaviors in the face of uncertainty. We conclude that individuals with high levels of autistic traits are less likely to utilize ToM as a cognitive strategy, even when it is beneficial, to achieve a desired outcome.

Network Connectivity of the Right STS in Three Social Perception Localizers.

The posterior STS (pSTS) is an important brain region for perceptual analysis of social cognitive cues. This study seeks to characterize the pattern of network connectivity emerging from the pSTS in three core social perception localizers: biological motion perception, gaze recognition, and the interpretation of moving geometric shapes as animate. We identified brain regions associated with all three of these localizers and computed the functional connectivity pattern between them and the pSTS using a partial correlations metric that characterizes network connectivity. We find a core pattern of cortical connectivity that supports the hypothesis that the pSTS serves as a hub of the social brain network. The right pSTS was the most highly connected of the brain regions measured, with many long-range connections to pFC. Unlike other highly connected regions, connectivity to the pSTS was distinctly lateralized. We conclude that the functional importance of right pSTS is revealed when considering its role in the large-scale network of brain regions involved in various aspects of social cognition.

The Pivotal Role of the Right Parietal Lobe in Temporal Attention.

The visual system is extremely efficient at detecting events across time even at very fast presentation rates; however, discriminating the identity of those events is much slower and requires attention over time, a mechanism with a much coarser resolution [Cavanagh, P., Battelli, L., & Holcombe, A. O. Dynamic attention. In A. C. Nobre & S. Kastner (Eds.), The Oxford handbook of attention (pp. 652-675). Oxford: Oxford University Press, 2013]. Patients affected by right parietal lesion, including the TPJ, are severely impaired in discriminating events across time in both visual fields [Battelli, L., Cavanagh, P., & Thornton, I. M. Perception of biological motion in parietal patients. Neuropsychologia, 41, 1808-1816, 2003]. One way to test this ability is to use a simultaneity judgment task, whereby participants are asked to indicate whether two events occurred simultaneously or not. We psychophysically varied the frequency rate of four flickering disks, and on most of the trials, one disk (either in the left or right visual field) was flickering out-of-phase relative to the others. We asked participants to report whether two left-or-right-presented disks were simultaneous or not. We tested a total of 23 right and left parietal lesion patients in Experiment 1, and only right parietal patients showed impairment in both visual fields while their low-level visual functions were normal. Importantly, to causally link the right TPJ to the relative timing processing, we ran a TMS experiment on healthy participants. Participants underwent three stimulation sessions and performed the same simultaneity judgment task before and after 20 min of low-frequency inhibitory TMS over right TPJ, left TPJ, or early visual area as a control. rTMS over the right TPJ caused a bilateral impairment in the simultaneity judgment task, whereas rTMS over left TPJ or over early visual area did not affect performance. Altogether, our results directly link the right TPJ to the processing of relative time.