Drift in Individual Behavioral Phenotype as a Strategy for Unpredictable Worlds Individuals, even with matched genetics and environment, show substantial phenotypic variability. This variability may be part of a bet-hedging strategy, where populations express a range of phenotypes to ensure survival in unpredictable environments. In addition to phenotypic variability between individuals (“bet-hedging”), individuals also show variability in their behavioral phenotype across time, even absent obvious external cues. There are few evolutionary theories that explain random shifts in phenotype across an animal’s life, which we term phenotypic drift. We use individuality in locomotor handedness in Drosophila melanogaster to characterize both bet-hedging and drift. We use a continuous circling assay to show that handedness spontaneously changes over timescales ranging from seconds to the lifespan of a fly. We compare the amount of behavioral drift and bet-hedging across a number of different fly strains and show independent strain-specific differences in bet-hedging and behavioral drift. We show manipulation of serotonin changes the rate of behavioral drift, indicating a potential circuit substrate controlling behavioral drift. We then develop a theoretical framework for assessing the adaptive value of phenotypic drift, demonstrating that drift may be adaptive for populations subject to selection pressures that fluctuate on timescales similar to the lifespan of an animal. We apply our model to real-world environmental signals and find patterns of fluctuations that favor random drift in behavioral phenotype, suggesting that drift may be adaptive under some real-world conditions. These results demonstrate that behavioral drift plays a role in driving variability in a population and may serve an adaptive role distinct from population level bet-hedging.
Why is anything conscious? We tackle the problem of consciousness by taking the naturally selected, embodied organism as our starting point. We provide a formalism describing how biological systems such as human bodies self-organize to hierarchically interpret unlabelled sensory information according to valence. The system is attracted and repelled at different spatial and temporal scales. This is a qualitative interpretation of an unlabelled physical state. We show how such interpretations imply behavioural policies which are differentiated from each other only by this qualitative aspect of information processing. Natural selection favours systems that actively intervene in the world to achieve homeostatic and reproductive goals. Put provocatively, death grounds meaning. This means that in living systems information processing is necessarily subjective, that is, it has quality embedded into its very core. Qualitative information processing involves interoceptive and exteroceptive classifiers, and determines priorities for self-survival. We formulate The Psychophysical Principle of Causality as a theorem, and prove generalisation optimal learning forces this valence first ontology. Qualitative good or bad processing necessarily comes before quality neutral representations of properties (i.e. “red” is constructed from valence). Under selection pressures like sophisticated predation this produces a hierarchy of selves, of which reafference and reflective self awareness are a consequence. We discuss this in light of the seminal distinction between phenomenal and access consciousness. We claim that phenomenal consciousness without access is likely common, but the reverse is implausible. Our proposal lays the foundation of a formal science of consciousness, closer to human fact than zombie fiction.
On the coupling and decoupling of mind wandering and perception: a shared metabolism account Mind wandering (MW) has been associated with reduced responsiveness to external stimuli (“perceptual decoupling”). Conversely, increased perceptual demands of a task result in reduced MW. Here we propose a neurobiological account attributing the mutually-limiting relationship of MW and perception to brain-wide limits on cerebral metabolism. Since overall cerebral metabolism is known to remain constant, despite increased mental task demands, we tested whether increased perceptual processing load in a visual task will result in reduced oxygen metabolism in MW-related medial prefrontal cortex (mPFC) regions.
Structural remodeling of the mitochondrial protein biogenesis machinery under proteostatic stress Cells have evolved organelle-specific responses to maintain protein homeostasis (proteostasis). During proteostatic stress, mitochondria down-regulate translation and enhance protein folding, yet the underlying mechanisms remain poorly defined. Here, we used cryo–electron tomography to observe the structural consequences of mitochondrial proteostatic stress within human cells. We detected protein aggregates within the mitochondrial matrix, accompanied by a marked remodeling of cristae architecture. Concomitantly, the number of mitochondrial ribosome complexes was significantly reduced. Mitochondrial Hsp60 (mHsp60), a key protein folding machine, underwent major conformational changes to favor complexes with its co-chaperone mHsp10. We visualized the interactions of mHsp60 with native substrate proteins and determined in vitro mHsp60 cryo–electron microscopy structures enabling nucleotide state assignment of the in situ structures. These data converge on a model of the mHsp60 functional cycle and its essential role in mitochondrial proteostasis. More broadly, our findings reveal structural mechanisms governing mitochondrial protein biosynthesis and their remodeling under proteostatic stress.
Most Ventral Pallidal Cholinergic Neurons Are Bursting Basal Forebrain Cholinergic Neurons with Mesocorticolimbic Connectivity Spoken language is often, if not always, understood in a context formed by the identity of the speaker. For example, we can easily make sense of an utterance such as “I’m going to have a manicure this weekend” or “The first time I got pregnant I had a hard time” when spoken by a woman, but it would be harder to understand when it is spoken by a man. Previous ERP studies have shown mixed results regarding the neurophysiological responses to such speaker–content mismatches, with some reporting an N400 effect and others a P600 effect. In an EEG experiment involving 64 participants, we used social and biological mismatches as test cases to demonstrate how these distinct ERP patterns reflect different aspects of rational inference. We showed that when the mismatch involves social stereotypes (e.g., men getting a manicure), listeners can arrive at a “literal” interpretation by integrating the content with their social knowledge, though this integration requires additional effort due to stereotype violations—resulting in an N400 effect. In contrast, when the mismatch involves biological knowledge (e.g., men getting pregnant), a “literal” interpretation becomes highly implausible or impossible, leading listeners to treat the input as potentially containing errors and engage in correction processes—resulting in a P600 effect. Supporting this rational inference framework, we found that the social N400 effect decreased as a function of the listener’s personality trait of openness (as more open-minded individuals maintain more flexible social expectations), while the biological P600 effect remained robust (as biological constraints are recognized regardless of individual personalities). Our findings help to reconcile empirical inconsistencies and reveal how rational inference shapes speaker-contextualized language comprehension. We demonstrate how listeners flexibly adapt its processing strategy based on contextual information, which may be part of the general information-processing principles of the human brain.
The effects of physical exercise on inflammation-induced maladaptive neuroplasticity in post-traumatic headache Post-traumatic headache (PTH) lack effective treatment due to the wide variety of possible brain damage that can occur, as well as the neural mechanisms of pain. However, immunity and maladaptive plasticity are involved in many hyperalgesia states, including secondary headaches. While analgesic drugs can act on specific molecular pathways, headaches involve a complex system of pain. Physical exercise can be a potent nonpharmacological modulator of the immune system and is known to play an important role in neural plasticity. However, further studies are needed to better understand the beneficial effects of physical exercise on secondary headaches and how physical exercise, the immune system, and plasticity interact with PTH. Here, we examine how immune system–induced neuroplasticity contributes to headache pathophysiology and how physical exercise might reverse these maladaptive changes
Beyond Context-Transfer Effects: Attenuated Familiarity During Virtual Reality-Based Retrieval Across Different Encoding Modalities Whereas the circumstances under which episodic memory benefits from Virtual Reality (VR)-based encoding remain elusive, preliminary findings suggest that the contributions of the underlying retrieval processes might depend on the encoding modality. Previous research indicates that engrams obtained from VR conditions elicit enhanced recollection alongside attenuated familiarity. However, it remains unclear whether this pattern depends on the congruence of the encoding and retrieval contexts. Consequently, this study examined potential context-transfer effects on the electrophysiological correlates of familiarity and recollection after VR-based and PC-based encoding. A source memory paradigm was employed to test the retrieval of objects and their encoding context, i.e., item and source memory under VR conditions. The electrophysiological results indicated attenuated familiarity of PC-based engrams reflected in the frontal old/new effect (FN400), yet the same held true for VR-based engrams. Moreover, a strong old/new effect in the late positive component (LPC) linked to recollection was evident under both conditions. In contrast, the late posterior negativity (LPN), linked to the search for and reactivation of contextual details during retrieval, was observed under neither condition. In summary, the present results indicated comparable contributions of familiarity and recollection to retrieval, independent of the encoding modality, when retrieval occurred under VR conditions. While effects on engrams retrieved without their correct source might, to some degree, depend on context-transfer effects, familiarity was attenuated across encoding modalities. Consequently, the present results demonstrate that disparities between VR- and PC-engrams depend on the combination of encoding and retrieval modalities and extend beyond context-transfer effects.
Critical Dynamics in the Association Cortex Predict Higher Intelligence in Typically Developing Children Neuronal network models have indicated that the so-called critical dynamics facilitate efficient information processing, while criticality disruptions were linked to neuropathology through excitation/inhibition (E/I) imbalances. However, there is limited empirical evidence for a relationship between critical brain dynamics and cognition in healthy children and adolescents. Here, we investigate how these dynamics relate to intelligence in a developing cohort. We recorded eyes-open resting EEG in 128 children (6–19 years, 72 female) and quantified near-critical dynamics in the alpha-band using functional excitation/inhibition ratio (fE/I) and in nonoscillatory activity using the 1/f aperiodic exponent of the power spectrum. We devised models relating intelligence to fE/I and 1/f exponent across seven Yeo7 functional brain networks ranked from lower-order sensorimotor to higher-order association networks. We observed significant correlations between fE/I and 1/f exponent and IQ in association cortices, in contrast to sensorimotor cortices. Children in the high-IQ group had fE/I ratios closer to the theoretical critical value of 1 in association cortices compared with the low-IQ group. The association–sensorimotor axis rank moderated the associations between 1/f exponent and IQ, these associations decreasing on a gradient across the hierarchy of the Yeo7 networks. Age and rank moderated the fE/I–IQ association, with the association–sensorimotor effect size gradient most visible in adolescents. Together, the results suggest that individual variation in criticality-sensitive biomarkers in association networks may be linked to IQ differences in an age-dependent manner, consistent with the hypothesis that developmental modulation of critical dynamics across the cortical hierarchy may support more efficient cognitive processing.
Most Ventral Pallidal Cholinergic Neurons Are Bursting Basal Forebrain Cholinergic Neurons with Mesocorticolimbic Connectivity The ventral pallidum (VP) lies at the intersection of basal ganglia and basal forebrain circuitry, possessing attributes of both major subcortical systems. Basal forebrain cholinergic neurons (BFCNs) are rapidly recruited by reinforcement feedback and project to cortical and subcortical forebrain targets; in contrast, striatal cholinergic cells are local interneurons exhibiting classical “pause-burst” responses to rewards. However, VP cholinergic neurons (VPCNs) are less characterized, and it is unclear whether basal forebrain and striatal-type cholinergic neurons mix in the VP. Therefore, we performed anterograde and monotranssynaptic retrograde labeling, in vitro acute slice recordings and bulk calcium recordings of VPCNs in mice of either sex. We found that VPCNs broadly interact with the mesocorticolimbic circuit that processes rewards and punishments, targeting the basolateral amygdala, the medial prefrontal cortex, and the lateral habenula while receiving inputs from the nucleus accumbens, hypothalamus, central amygdala, bed nucleus of stria terminalis, and ventral tegmental area. Bulk calcium recordings revealed that VPCNs responded to rewards, punishments, and reward-predicting cues. Acute slice recordings showed that most VPCNs resembled the bursting type of BFCNs, while a few of them were of the regular rhythmic type, which differentiated most VPCNs from striatal cholinergic interneurons. These results were confirmed by in vivo electrophysiological recordings of putative VPCNs. We conclude that VPCNs show burst firing and specialized connectivity to relay aversive and appetitive stimuli to the reinforcement circuitry, possibly implicated in mood disorders and addiction.