Search

Dysfunctional sociability is a core symptom in autism spectrum disorder (ASD) that may arise from neural-network dysconnectivity between multiple brain regions. However, pathogenic neural-network mechanisms underlying social dysfunction are largely unknown. Here, we demonstrate that circuit-selective mutation (ctMUT) of ASD-risk Shank3 gene within a unidirectional projection from the prefrontal cortex to the basolateral amygdala alters spine morphology and excitatory-inhibitory balance of the circuit. Shank3 ctMUT mice show reduced sociability as well as elevated neural activity and its amplitude variability, which is consistent with the neuroimaging results from human ASD patients. Moreover, the circuit hyper-activity disrupts the temporal correlation of socially tuned neurons to the events of social interactions. Finally, optogenetic circuit activation in wild-type mice partially recapitulates the reduced sociability of Shank3 ctMUT mice, while circuit inhibition in Shank3 ctMUT mice partially rescues social behavior. Collectively, these results highlight a circuit-level pathogenic mechanism of Shank3 mutation that drives social dysfunction. Accepted version Source info: CP-COMMUNITY-D-21-00183

The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors “stimulus type” (action, static control, and dynamic control), “stereopsis” (present, absent) and “viewpoint” (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior.

To investigate the cross-modal transfer of movement patterns necessary to perform melodies on the piano, 22 non-musicians learned to play short sequences on a piano keyboard by (1) merely listening and replaying (vision of own fingers occluded) or (2) merely observing silent finger movements and replaying (on a silent keyboard). After training, participants recognized with above chance accuracy (1) audio-motor learned sequences upon visual presentation (89±17%), and (2) visuo-motor learned sequences upon auditory presentation (77±22%). The recognition rates for visual presentation significantly exceeded those for auditory presentation (p.05). fMRI revealed that observing finger movements corresponding to audio-motor trained melodies is associated with stronger activation in the left rolandic operculum than observing untrained sequences. This region was also involved in silent execution of sequences, suggesting that a link to motor representations may play a role in cross-modal transfer from audio-motor training condition to visual recognition. No significant differences in brain activity were found during listening to visuo-motor trained compared to untrained melodies. Cross-modal transfer was stronger from the audio-motor training condition to visual recognition and this is discussed in relation to the fact that non-musicians are familiar with how their finger movements look (motor-to-vision transformation), but not with how they sound on a piano (motor-to-sound transformation).

Previous functional magnetic resonance imaging (fMRI) research on action observation has emphasized the role of putative mirror neuron areas such as Broca's area, ventral premotor cortex, and the inferior parietal lobule. However, recent evidence suggests action observation involves many distributed cortical regions, including dorsal premotor and superior parietal cortex. How these different regions relate to traditional mirror neuron areas, and whether traditional mirror neuron areas play a special role in action representation, is unclear. Here we use multi-voxel pattern analysis (MVPA) to show that action representations, including observation, imagery, and execution of reaching movements: (1) are distributed across both dorsal (superior) and ventral (inferior) premotor and parietal areas; (2) can be decoded from areas that are jointly activated by observation, execution, and imagery of reaching movements, even in cases of equal-amplitude blood oxygen level-dependent (BOLD) responses; and (3) can be equally accurately classified from either posterior parietal or frontal (premotor and inferior frontal) regions. These results challenge the presumed dominance of traditional mirror neuron areas such as Broca's area in action observation and action representation more generally. Unlike traditional univariate fMRI analyses, MVPA was able to discriminate between imagined and observed movements from previously indistinguishable BOLD activations in commonly activated regions, suggesting finer-grained distributed patterns of activation.

The tonotopic representations within the primary auditory cortex (PAC) have been successfully mapped with ultra-high field fMRI. Here, we compared the reliability of this tonotopic mapping paradigm at 7 T with 1.5 mm spatial resolution with maps acquired at 3 T with the same stimulation paradigm, but with spatial resolutions of 1.8 and 2.4 mm. For all subjects, the mirror-symmetric gradients within PAC were highly similar at 7 T and 3 T and across renderings at different spatial resolutions; albeit with lower percent signal changes at 3 T. In contrast, the frequency maps outside PAC tended to suffer from a reduced BOLD contrast-to-noise ratio at 3 T for a 1.8 mm voxel size, while robust at 2.4 mm and at 1.5 mm at 7 T. Overall, our results showed the robustness of the phase-encoding paradigm used here to map tonotopic representations across scanners.