Binocular disparity provides critical information about three-dimensional (3D) structures to support perception and action. In the past decade significant progress has been made in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high-field (7T) functional imaging at submillimeter resolution to examine fine-scale BOLD fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We tested for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception [i.e., correlated random dot stereograms (RDS)] versus those that do not (i.e., anticorrelated RDS). Using multivoxel pattern anal...

Decision-making not only requires agents to decide what to choose but also how much information to sample before committing to a choice. Previously established frameworks for economic choice argue for a deliberative process of evidence accumulation across time. These tacitly acknowledge a role of information sampling in that decisions are only made once sufficient evidence is acquired, yet few experiments have explicitly placed information sampling under the participant's control. Here, we use fMRI to investigate the neural basis of information sampling in economic choice by allowing participants ( n = 30, sex not recorded) to actively sample information in a multistep decision task. We show that medial frontal cortex (MFC) activity is predictive of further information sampling before choice. Choice difficulty (inverse value difference, keeping sensory difficulty constant) was also encoded in MFC, but this effect was explained away by the inclusion of information sampling as a coregressor in the general li...

When encoding new episodic memories, visual and semantic processing is proposed to make distinct contributions to accurate memory and memory distortions. Here, we used fMRI and preregistered representational similarity analysis to uncover the representations that predict true and false recognition of unfamiliar objects. Two semantic models captured coarse-grained taxonomic categories and specific object features, respectively, while two perceptual models embodied low-level visual properties. Twenty-eight female and male participants encoded images of objects during fMRI scanning, and later had to discriminate studied objects from similar lures and novel objects in a recognition memory test. Both perceptual and semantic models predicted true memory. When studied objects were later identified correctly, neural patterns corresponded to low-level visual representations of these object images in the early visual cortex, lingual, and fusiform gyri. In a similar fashion, alignment of neural patterns with fine-gra...

Hippocampus and prefrontal cortex (PFC) circuits are thought to play a prominent role in human episodic memory, but the precise nature, and electrophysiological basis, of directed information flow between these regions and their role in verbal memory formation has remained elusive. Here we investigate nonlinear causal interactions between hippocampus and lateral PFC using intracranial EEG recordings (26 participants, 16 females) during verbal memory encoding and recall tasks. Direction-specific information theoretic analysis revealed higher causal information flow from the hippocampus to PFC than in the reverse direction. Crucially, this pattern was observed during both memory encoding and recall, and the strength of causal interactions was significantly greater during memory task performance than resting baseline. Further analyses revealed frequency specificity of interactions with greater causal information flow from hippocampus to the PFC in the delta-theta frequency band (0.5-8 Hz); in contrast, PFC to...

High molecular weight hyaluronan (HMWH), a well-established treatment for osteoarthritis pain, is anti-hyperalgesic in preclinical models of inflammatory and neuropathic pain. HMWH-induced anti-hyperalgesia is mediated by its action at cluster of differentiation 44 (CD44), the cognate hyaluronan receptor, which can signal via phosphoinositide 3-kinase (PI3K), a large family of kinases involved in diverse cell functions. We demonstrate that intrathecal administration of an oligodeoxynucleotide (ODN) antisense to mRNA for PI3Kγ (a Class I PI3K isoform) expressed in dorsal root ganglia (DRGs), and intradermal administration of a PI3Kγ-selective inhibitor (AS605240), markedly attenuates HMWH-induced anti-prostaglandin E2 (PGE2) hyperalgesia, in male and female rats. Intradermal administration of inhibitors of mammalian target of rapamycin (mTOR; rapamycin) and protein kinase B (AKT; AKT Inhibitor IV), signaling molecules downstream of PI3Kγ, also attenuates HMWH-induced anti-hyperalgesia. In vitro patch-clamp ...

Naoki Hisamoto, Yoshiki Sakai, Kohei Ohta, Tatsuhiro Shimizu, Chun Li, et al. (see pages [8309–8320][1]) A major impediment to axon regeneration in the adult CNS is the loss of axons' intrinsic ability to grow. Deciphering the signaling cascades required for axon regeneration in the PNS and in

The connectome of the brain has a great impact on the function of the brain as the structure of the connectome affects the speed and efficiency of information transfer. As a highly energy-consuming organ, an efficient network structure is essential. A previous study has shown consistent overall brain connectivity across a large variety of species. This connectivity conservation was explained by a balance between interhemispheric and intrahemispheric connections; that is, spices with highly connected hemispheres appear to have weaker interhemisphere connections. This study examines this connectivity trade-off in the human brain using diffusion-based tractography and network analysis in the Human Connectome Project (970 subjects, 527 female). We explore the biological origins of this phenomenon, heritability, and the effect on cognitive measures. The proportion of commissural fibers in the brain had a negative correlation to hemispheric efficiency, pointing to a trade-off between inner hemispheric and inter...

The postinjury regenerative capacity of neurons is known to be mediated by a complex interaction of intrinsic regenerative pathways and external cues. In Caenorhabditis elegans , the initiation of axon regeneration is regulated by the nonmuscle myosin light chain-4 (MLC-4) phosphorylation signaling pathway. In this study, we have identified svh-16 / cdk-14 , a mammalian CDK14 homolog, as a positive regulator of axon regeneration in motor neurons. We then isolated the CDK-14-binding protein MIG-5/Disheveled (Dsh) and found that EGL-20/Wnt and the MIG-1/Frizzled receptor (Fz) are required for efficient axon regeneration. Further, we demonstrate that CDK-14 activates EPHX-1, the C. elegans homolog of the mammalian ephexin Rho-type GTPase guanine nucleotide exchange factor (GEF), in a kinase-independent manner. EPHX-1 functions as a GEF for the CDC-42 GTPase, inhibiting myosin phosphatase, which maintains MLC-4 phosphorylation. These results suggest that CDK14 activates the RhoGEF–CDC42–MLC phosphorylation axi...

Age-related hearing loss (presbycusis) is a chronic health condition that affects 1/3 of the world’s population. One hallmark of presbycusis is a difficulty hearing in noisy environments. Presbycusis can be separated into two components: alterations of peripheral mechanotransduction of sound in the cochlea, and central alterations of auditory processing areas of the brain. While the effects of the aging cochlea in hearing loss have been well studied, the role of the aging brain in hearing loss is less well understood. Therefore, to examine how age-related central processing changes affect hearing in noisy environments, we used a mouse model (Thy1-GCaMP6s X CBA mice) that has excellent peripheral hearing in old age. We used in vivo 2-photon Ca2+ imaging to measure the responses of neuronal populations in auditory cortex (ACtx) of adult (2-6 months, 9 male, 6 female, 4,180 neurons) and aging (15-17 months, 6 male, 3 female, 1055 neurons) while listening to tones in noisy backgrounds. We found that ACtx neuro...

Inhibitory synaptic mechanisms oppose epileptic network activity in the brain. The breakdown in this inhibitory restraint and propagation of seizure activity has been linked to the overwhelming of feedforward inhibition, which is provided in large part by parvalbumin-expressing (PV) interneurons in the cortex. The underlying cellular processes therefore represent potential targets for understanding and preventing the propagation of seizure activity. Here we use an optogenetic strategy to test the hypothesis that depolarization block in PV interneurons is a significant factor during the loss of inhibitory restraint. Depolarization block results from the inactivation of voltage-gated sodium channels and leads to impaired action potential firing. We used focal NMDA stimulation to elicit reproducible epileptiform discharges in hippocampal organotypic brain slices from male and female mice, and combined this with targeted recordings from defined neuronal populations. Simultaneous patch-clamp recordings from PV ...