Experts in action: why we need an embodied social brain hypothesis

The anthropoid primates are known for their intense sociality and large brain size. The idea that these might be causally related has given rise to a large body of work testing the ‘social brain hypothesis'. Here, the emphasis has been placed on the political demands of social life, and the cognitive skills that would enable animals to track the machinations of other minds in metarepresentational ways. It seems to us that this position risks losing touch with the fact that brains primarily evolved to enable the control of action, which in turn leads us to downplay or neglect the importance of the physical body in a material world full of bodies and other objects. As an alternative, we offer a view of primate brain and social evolution that is grounded in the body and action, rather than minds and metarepresentation. This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.

Hemodynamic molecular imaging of tumor-associated enzyme activity in the living brain

Molecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here, we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xenografted cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a potentially translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.

PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson’s disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Fear inoculation among snake experts

Background Fear acquisition of certain stimuli, such as snakes, is thought to be rapid, resistant to extinction, and easily transferable onto other similar objects. It has been hypothesized that due to increased survival chances, preparedness to instantly acquire fear towards evolutionary threats has been hardwired into neural pathways of the primate brain. Here, we compare participants’ fear of snakes according to experience; from those who often deal with snakes and even suffer snakebites to those unfamiliar with snakes. Methods The Snake Questionnaire-12 (SNAQ-12) and Specific Phobia Questionnaire (SPQ) were administered to three groups of participants with a different level of experience with snakes and snakebites: 1) snake experts, 2) firefighters, and 3) college students. Results This study shows that individuals more experienced with snakes demonstrate lower fear. Moreover, participants who have suffered a snakebite (either venomous or not) score lower on fear of snakes (SNAQ-12), but not of all other potentially phobic stimuli (SPQ). Conclusions Our results suggest that a harmless benign exposure might immunize people to highly biologically prepared fears of evolutionary threats, such as snakes.

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

Transcranial alternating current stimulation (tACS) is a promising but controversial method for modulating neural activity noninvasively. Much of the controversy revolves around the question of whether tACS can generate electric fields that are strong enough to entrain neuronal spiking activity. Here we show that what matters is not the electric field strength per se, but rather the strength of the stimulation relative to ongoing oscillatory entrainment. We recorded from single neurons in the cortex and subcortex of behaving non-human primates, while applying tACS at different frequencies and amplitudes. When neuronal activity was weakly locked to ongoing oscillations, tACS readily entrained single-neuron activity to specific stimulation phases. In contrast, neurons that were strongly locked to ongoing oscillations usually exhibited decreased entrainment during low-amplitude tACS. As this reduced entrainment is a property of many oscillating systems, attempts to impose an external rhythm on spiking activity may often yield precisely the opposite effect.