What you saw a while ago determines what you see now: The effect and temporal dynamics of awareness priming on implicit behavior The perceptual content (e.g., seen a happy vs. seen a sad face) and also subjective visibility (e.g., whether the stimulus is visible or not) of a given (liminal) stimulus is influenced by the history of previously consciously experienced stimuli. This effect on subjective visibility, termed awareness priming, suggests that findings from a large body of literature on unconscious processing might be confounded by conscious awareness. However, those literatures on unconscious processing used implicit behavioral measures of unconscious processing. The challenge is only valid if previous visible stimuli (not just physically salient) also affect implicit behavior, e.g., response priming. Here, we used Continuous Flash Suppression (CFS) to probe the limits and temporal dynamics of awareness priming effect. We showed that prior conscious exposure to two Chinese words increases both visibility and discrimination accuracy, and also improves the response priming of words presented just at the visibility threshold. A correlation analysis revealed that this effect is only driven by the high visibility of the previous stimuli but not high physical saliency. Our results strongly validated the challenge from awareness priming to the literature on unconscious processing. Moreover, we found a different temporal dynamic for how previous visible exposure to a word affects current perception: previous short-term exposure (1-10 back trials) to a visible word only enhances discrimination accuracy of the same word in the current trial, whereas long-term exposure (10-30 back trials) exclusively elevates visibility. This novel finding suggests that areas higher in the processing hierarchy, with larger temporal receptive field, contribute to consciousness, while areas lower in the cortical hierarchy contribute to objective discrimination.
Encoding surprise by retinal ganglion cells The efficient coding hypothesis posits that early sensory neurons transmit maximal information about sensory stimuli, given internal constraints. A central prediction of this theory is that neurons should preferentially encode stimuli that are most surprising. Previous studies suggest this may be the case in early visual areas, where many neurons respond strongly to rare or surprising stimuli. For example, previous research showed that when presented with a rhythmic sequence of full-field flashes, many retinal ganglion cells (RGCs) respond strongly at the instance the flash sequence stops, and when another flash would be expected. This phenomenon is called the ‘omitted stimulus response’. However, it is not known whether the responses of these cells varies in a graded way depending on the level of stimulus surprise. To investigate this, we presented retinal neurons with extended sequences of stochastic flashes. With this stimulus, the surprise associated with a particular flash/silence, could be quantified analytically, and varied in a graded manner depending on the previous sequences of flashes and silences. Interestingly, we found that RGC responses could be well explained by a simple normative model, which described how they optimally combined their prior expectations and recent stimulus history, so as to encode surprise. Further, much of the diversity in RGC responses could be explained by the model, due to the different prior expectations that different neurons had about the stimulus statistics. These results suggest that even as early as the retina many cells encode surprise, relative to their own, internally generated expectations.
The emergence of the width of subjective temporality: the self-simulational theory of temporal extension from the perspective of the free energy principle The self-simulational theory of temporal extension describes an information-theoretically formalized mechanism by which the width of subjective temporality emerges from the architecture of self-modelling. In this paper, the perspective of the free energy principle will be assumed, to cast the emergence of subjective temporality, along with a mechanism for duration estimation, from first principles of the physics of self-organization. Building on the transparent inferential format of self-modelling, it will be explained why subjective temporality feels like a genuine dimension, in which our life unfolds, as opposed to a mere mental construct, such as the mental number line. Using active inference, a deep parametric generative model of temporal inference is simulated, which realizes the described dynamics on a computational level. Two biases (i.e. variations) of time-perception naturally emerge from the simulation. This concerns the intentional binding effect (i.e. the subjective compression of the temporal interval between voluntarily initiated actions and subsequent sensory consequences) and empirically documented alterations of subjective time experience in deep and concentrated states of meditative absorption. Generally, numerous systematic and domain-specific variations of subjective time experience are computationally explained, as enabled by integration with current active inference accounts mapping onto the respective domains. This concerns the temporality modulating role of negative valence, impulsivity, boredom, flow-states, and near death-experiences, amongst others. The self-simulational theory of temporal extension, from the perspective of the free energy principle, explains how the subjective temporal Now emerges and varies from first principles, accounting for why sometimes, subjective time seems to fly, and sometimes, moments feel like eternities.
CA1 Engram Cell Dynamics Before and After Learning A fundamental question in neuroscience is how memory formation shapes brain activity at the level of populations of neurons. Recent studies of hippocampal engram cells, identified by immediate-early genes (IEGs) induced by learning, propose that these populations act as a neuronal substrate for memory storage. The current framework for engram formation proposes that cells join ensembles based on increased intrinsic excitability, and that after initial learning, they co-activate to support memory retrieval. However, direct evidence of how engram population dynamics evolve across learning is limited. Here we combined activity-dependent genetic tagging and two-photon calcium imaging to characterize CA1 engram population activity before and after learning. We observed that spontaneous activity two days before learning predicted genetic tagging, consistent with a model in which spontaneous fluctuations bias cells into forming engram assemblies. Surprisingly, we were unable to detect increased spontaneous activity rates or pairwise correlations amongst tagged CA1 neurons after learning. These results were consistent with computational network models that incorporate strong and specific inhibitory connections, supporting the idea that excitatory/inhibitory balance in CA1 may play a key role in engram dynamics. Together these results highlight a potential role for slow time scale excitability fluctuations in driving engram formation and suggest that excitatory-inhibitory balance may regulate engram cell co-activation
Spaced training activates Miro/Milton-dependent mitochondrial dynamics in neuronal axons to sustain long-term memory Neurons have differential and fluctuating energy needs across distinct cellular compartments, shaped by brain electrochemical activity associated with cognition. In vitro studies show that mitochondria transport from soma to axons is key to maintaining neuronal energy homeostasis. Nevertheless, whether the spatial distribution of neuronal mitochondria is dynamically adjusted in vivo in an experience-dependent manner remains unknown. In Drosophila, associative long-term memory (LTM) formation is initiated by an early and persistent upregulation of mitochondrial pyruvate flux in the axonal compartment of neurons in the mushroom body (MB). Through behavior experiments, super-resolution analysis of mitochondria morphology in the neuronal soma and in vivo mitochondrial fluorescence recovery after photobleaching (FRAP) measurements in the axons, we show that LTM induction, contrary to shorter-lived memories, is sustained by the departure of some mitochondria from MB neuronal soma and increased mitochondrial dynamics in the axonal compartment. Accordingly, impairing mitochondrial dynamics abolished the increased pyruvate consumption, specifically after spaced training and in the MB axonal compartment, thereby preventing LTM formation. Our results thus promote reorganization of the mitochondrial network in neurons as an integral step in elaborating high-order cognitive processes.
Precise cortical contributions to sensorimotor feedback control during reactive balance The role of the cortex in shaping automatic whole-body motor behaviors such as walking and balance is poorly understood. Gait and balance are typically mediated through subcortical circuits, with the cortex becoming engaged as needed on an individual basis by task difficulty and complexity. However, we lack a mechanistic understanding of how increased cortical contribution to whole-body movements shapes motor output. Here we use reactive balance recovery as a paradigm to identify relationships between hierarchical control mechanisms and their engagement across balance tasks of increasing difficulty in young adults. We hypothesize that parallel sensorimotor feedback loops engaging subcortical and cortical circuits contribute to balance-correcting muscle activity, and that the involvement of cortical circuits increases with balance challenge. We decomposed balance-correcting muscle activity based on hypothesized subcortically- and cortically-mediated feedback components driven by similar sensory information, but with different loop delays. The initial balance-correcting muscle activity was engaged at all levels of balance difficulty. Its onset latency was consistent with subcortical sensorimotor loops observed in the lower limb. An even later, presumed, cortically-mediated burst of muscle activity became additionally engaged as balance task difficulty increased, at latencies consistent with longer transcortical sensorimotor loops. We further demonstrate that evoked cortical activity in central midline areas measured using electroencephalography (EEG) can be explained by a similar sensory transformation as muscle activity but at a delay consistent with its role in a transcortical loop driving later cortical contributions to balance-correcting muscle activity. These results demonstrate that a neuromechanical model of muscle activity can be used to infer cortical contributions to muscle activity without recording brain activity. Our model may provide a useful framework for evaluating changes in cortical contributions to balance that are associated with falls in older adults and in neurological disorders such as Parkinson’s disease.
Evolutionarily conserved neural responses to affective touch in monkeys transcend consciousness and change with age Affective touch—a slow, gentle, and pleasant form of touch—activates a different neural network than which is activated during discriminative touch in humans. Affective touch perception is enabled by specialized low-threshold mechanoreceptors in the skin with unmyelinated fibers called C tactile (CT) afferents. These CT afferents are conserved across mammalian species, including macaque monkeys. However, it is unknown whether the neural representation of affective touch is the same across species and whether affective touch’s capacity to activate the hubs of the brain that compute socioaffective information requires conscious perception. Here, we used functional MRI to assess the preferential activation of neural hubs by slow (affective) vs. fast (discriminative) touch in anesthetized rhesus monkeys (Macaca mulatta). The insula, anterior cingulate cortex (ACC), amygdala, and secondary somatosensory cortex were all significantly more active during slow touch relative to fast touch, suggesting homologous activation of the interoceptive-allostatic network across primate species during affective touch. Further, we found that neural responses to affective vs. discriminative touch in the insula and ACC (the primary cortical hubs for interoceptive processing) changed significantly with age. Insula and ACC in younger animals differentiated between slow and fast touch, while activity was comparable between conditions for aged monkeys (equivalent to >70 y in humans). These results, together with prior studies establishing conserved peripheral nervous system mechanisms of affective touch transduction, suggest that neural responses to affective touch are evolutionarily conserved in monkeys, significantly impacted in old age, and do not necessitate conscious experience of touch.
An attentional and working memory theory of hallucination vulnerability in frontotemporal dementia The rate and prevalence of hallucinations in behavioural variant frontotemporal dementia (bvFTD) is well established. The mechanisms for underlying vulnerability however are the least well described compared with other neuropsychiatric conditions, despite significantly complicating the diagnostic process. As such, this present study aimed to provide a detailed characterisation of the neural, cognitive and behavioural profile associated with a predisposition to hallucinatory experiences in bvFTD.
In total, 153 patients with bvFTD were recruited sequentially to this study. A group of patients with well characterised hallucinations and good quality volumetric MRI scans (n = 23) were genetically and demographically matched to a group without hallucinations (n = 23) and a healthy control cohort (n = 23). All patients were assessed at their initial visit by means of a detailed clinical interview, a comprehensive battery of neuropsychological tests and MRI. Data was analysed according to three levels: 1) the relationship between neural structures, cognition, behaviour and hallucinations in bvFTD; 2) the impact of the C9orf72 expansion; and 3) hallucination subtype on expression of hallucinations.
Basic and complex attentional (including divided attention and working memory) and visual function measures differed between groups (all p < .001) with hallucinators demonstrating poorer performance, along with evidence of structural changes centred on the prefrontal cortex, caudate and cerebellum (corrected for False Discovery Rate at p < .05 with a cluster threshold of 100 contiguous voxels). Attentional processes were also implicated in C9orf72 carriers with hallucinations with structural changes selectively involving the thalamus. Patients with visual hallucinations in isolation showed a similar pattern with emphasis on cerebellar atrophy.
Our findings provided novel insights that attentional and visual function subsystems and related distributed brain structures are implicated in the generation of hallucinations in bvFTD, that dissociate across C9orf72, sporadic bvFTD and for the visual subtype of hallucinations. This loading on attentional and working memory measures is in line with current mechanistic models of hallucination that frequently suggested a failure of integration of cognitive and perceptual processes. We therefore propose a novel cognitive and neural model for hallucination predisposition in bvFTD that aligns with a transdiagnostic model for hallucinations across neurodegeneration and psychiatry.