Perception and propagation of activity through the cortical hierarchy is determined by neural variability

The brains of higher organisms are composed of anatomically and functionally distinct regions performing specialised tasks; but regions do not operate in isolation. Orchestration of complex behaviours requires communication between brain regions, but how neural activity dynamics are organised to facilitate reliable transmission is not well understood. We studied this process directly by generating neural activity that propagates between brain regions and drives behaviour, allowing us to assess how populations of neurons in sensory cortex cooperate to transmit information. We achieved this by imaging two hierarchically organised and densely interconnected regions, the primary and secondary somatosensory cortex (S1 and S2) in mice while performing two-photon photostimulation of S1 neurons and assigning behavioural salience to the photostimulation. We found that the probability of perception is determined not only by the strength of the photostimulation signal, but also by the variability of S1 neural activity. Therefore, maximising the signal-to-noise ratio of the stimulus representation in cortex is critical to its continued propagation downstream. Further, we show that propagated, behaviourally salient activity elicits balanced, persistent, and generalised activation of the downstream region. Hence, our work adds to existing understanding of cortical function by identifying how population activity is formatted to ensure robust transmission of information, allowing specialised brain regions to communicate and coordinate behaviour.

Respiratory function modulated during execution, observation, and imagination of walking via SII

The Mirror Neurons System (MNS) consists of brain areas active during actions execution, as well as observation-imagination of the same actions. MNS represents a potential mechanism by which we understand other's action goals. We investigated MNS activation for legs actions, and its interaction with the autonomic nervous system. We performed a physiological and fMRI investigation on the common neural structures recruited during the execution, observation, and imagination of walking, and their effects on respiratory activity. Bilateral SMA were activated by all three tasks, suggesting that these areas are responsible for the core of the MNS effect for walking. Moreover, we observed in bilateral parietal opercula (OP1, secondary somatosensory cortex-SII) evidence of an MNS subtending walking execution-observation-imagination that also modulated the respiratory function. We suggest that SII, in modulating the vegetative response during motor activity but also during observation-imagination, consists of a re-enacting function which facilitates the understanding of motor actions.

The neural correlates of grandmaternal caregiving

In many societies, grandmothers are important caregivers, and grandmaternal investment is often associated with improved grandchild well-being. Here, we present, to our knowledge, the first study to examine grandmaternal brain function. We recruited 50 grandmothers with at least one biological grandchild between 3 and 12 years old. Brain function was measured with functional magnetic resonance imaging as grandmothers viewed pictures of their grandchild, an unknown child, the same-sex parent of the grandchild, and an unknown adult. Grandmothers also completed questionnaires to measure their degree of involvement with and attachment to their grandchild. After controlling for age and familiarity of stimuli, viewing grandchild pictures activated areas involved with emotional empathy (insula and secondary somatosensory cortex) and movement (motor cortex and supplementary motor area). Grandmothers who more strongly activated areas involved with cognitive empathy (temporo-parietal junction and dorsomedial prefrontal cortex) when viewing pictures of the grandchild desired greater involvement in caring for the grandchild. Finally, compared with results from an earlier study of fathers, grandmothers more strongly activated regions involved with emotional empathy (dorsal anterior cingulate cortex, insula and secondary somatosensory cortex), and motivation (nucleus accumbens, ventral pallidum and caudate nucleus). All in all, our findings suggest that emotional empathy may be a key component of grandmaternal responses to their grandchildren.

Finger representations in primary somatosensory cortex are modulated during vibrotactile working memory

It is well-established that vibrotactile stimulations elicit Blood-oxygen-level-dependent (BOLD) responses in somatotopically organized brain regions. Whether these somatotopic maps are modulated by working memory (WM) is still unknown. In our WM experiment, participants had to compare frequencies that were separated by a delay period. Vibrotactile stimuli were sequentially applied to either their right index or little finger. Using functional MRI, we investigated whether vibrotactile WM modulated neural activity in primary somatosensory (S1), an area that is known to contain individual finger representations. Our mass-univariate results revealed the well-described network of brain regions involved in WM. Interestingly, our mass-univariate results did not demonstrate S1 to be part of this network. However, when we parametrically modulated the time-binned regressors in our GLM we found that the delay activity in S1 and secondary somatosensory cortex (S2) was reflected in a U-shaped manner. Using multi-voxel pattern analysis (MVPA), an analysis technique that is more sensitive to subtle activity differences, we found finger-specific patterns of activation in the S1 hand area during the WM delay period. These results indicate that processes underlying WM modulate finger-specific representations during our discrimination task.

A cortico-cortical pathway targets inhibitory interneurons and modulates paw movement during locomotion in mice

The primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized cortico-cortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long range inputs to this S1 area. Silencing S2 to non whisker S1 projections alters the hind paw orientation during locomotion while manipulation of the M1 projection has little effect. Using patch clamp recordings in brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory interneuron subtypes. We conclude that S2 S1 corticocortical interactions mediated by local interneurons are critical for efficient locomotion.

Mu-opioid receptor system modulates responses to vocal bonding and distress signals in humans

Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET-fMRI study (n=17) we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying sounds. MOR availability was measured with positron emission tomography using high-affinity agonist radioligand [11C]carfentanil. Haemodynamic responses to social laughter and crying sounds were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, primary and secondary motor cortex; crying sounds led to more restricted activation in auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri, and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of MOR system in modulating acute brain responses to both positive and negative social signals.

Ipsilateral stimulus encoding in primary and secondary somatosensory cortex of awake mice

Lateralization is a hallmark of somatosensory processing in the mammalian brain. However, in addition to their contralateral representation, unilateral tactile stimuli also modulate neuronal activity in somatosensory cortices of the ipsilateral hemisphere. The cellular organization and functional role of these ipsilateral stimulus responses in awake somatosensory cortices, especially regarding stimulus coding, are unknown. Here, we targeted silicon probe recordings to the vibrissa region of primary (S1) and secondary (S2) somatosensory cortex of awake head-fixed male and female mice while delivering ipsilateral and contralateral whisker stimuli. Ipsilateral stimuli drove larger and more reliable responses in S2 than in S1, and activated a larger fraction of stimulus-responsive neurons. Ipsilateral stimulus-responsive neurons were rare in layer 4 of S1, but were located in equal proportion across all layers in S2. Linear classifier analyses further revealed that decoding of the ipsilateral stimulus was more accurate in S2 than S1, while S1 decoded contralateral stimuli most accurately. These results reveal substantial encoding of ipsilateral stimuli in S1 and especially S2, consistent with the hypothesis that higher cortical areas may integrate tactile inputs across larger portions of space, spanning both sides of the body.

Short-term dynamics of long-range corticocortical synapses revealed by selective optical stimulation

Synapses are continually regulated by their own activity. In the neocortex, direct interactions between cortical areas play a central role in cognitive function, but the dynamic regulation of these long-range corticocortical synapses by activity and their impact on a postsynaptic target neuron is unclear. Here, we use an optogenetic strategy to study the connections between mouse somatosensory and motor cortex. We found that short-term synaptic facilitation was strong in both corticocortical synapses, resulting in far more sustained responses than local intra-cortical and thalamocortical connections. This facilitation was dependent on the presynaptic calcium sensor synaptotagmin-7 and altered by several optogenetic approaches. Recordings revealed that during repetitive activation, the short-term dynamics of corticocortical synapses enhanced the excitability of layer 2/3 pyramidal neurons, increasing the probability of spiking with activity. Furthermore, the properties of the connections linking primary with secondary somatosensory cortex resemble those between somatosensory-motor areas. These results reveal a synaptic mechanism by which corticocortical projections may mediate specific changes in cellular excitability over relatively extended periods.

Neocortical substrates of feelings evoked with music in the ACC, insula, and somatosensory cortex

Neurobiological models of emotion focus traditionally on limbic/paralimbic regions as neural substrates of emotion generation, and insular cortex (in conjunction with isocortical anterior cingulate cortex, ACC) as the neural substrate of feelings. An emerging view, however, highlights the importance of isocortical regions beyond insula and ACC for the subjective feeling of emotions. We used music to evoke feelings of joy and fear, and multivariate pattern analysis (MVPA) to decode representations of feeling states in functional magnetic resonance (fMRI) data of n = 24 participants. Most of the brain regions providing information about feeling representations were neocortical regions. These included, in addition to granular insula and cingulate cortex, primary and secondary somatosensory cortex, premotor cortex, frontal operculum, and auditory cortex. The multivoxel activity patterns corresponding to feeling representations emerged within a few seconds, gained in strength with increasing stimulus duration, and replicated results of a hypothesis-generating decoding analysis from an independent experiment. Our results indicate that several neocortical regions (including insula, cingulate, somatosensory and premotor cortices) are important for the generation and modulation of feeling states. We propose that secondary somatosensory cortex, which covers the parietal operculum and encroaches on the posterior insula, is of particular importance for the encoding of emotion percepts, i.e., preverbal representations of subjective feeling.