The WU-Minn Human Connectome Project (HCP) is a publicly-available dataset containing state-of-the-art structural magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion MRI (dMRI) for over a thousand healthy subjects. While the planned scope of the HCP included an anatomic connectome, resting-state fMRI (rs-fMRI) forms the bulk of the HCP’s current connectomic output. We address this by presenting a full-cortex connectome derived from probabilistic diffusion tractography and organized into the HCP-MMP1.0 atlas. Probabilistic methods and large sample sizes are preferable for whole-connectome mapping as they increase the fidelity of traced low-probability connections. We find that overall, connection strengths are lognormally distributed and decay exponentially with tract length, that connectivity reasonably matches macaque histologic tracing in homologous areas, that contralateral homologs and left-lateralized language areas are hyperconnected, and that hierarchical similarity influences con...

Polychlorinated biphenyls (PCBs) are enduring environmental toxicants and exposure is associated with neurodevelopmental deficits. The auditory system appears particularly sensitive, as previous work has shown that developmental PCB exposure causes both hearing loss and gross disruptions in the organization of the rat auditory cortex. However, the mechanisms underlying PCB-induced changes are not known, nor is it known whether the central effects of PCBs are a consequence of peripheral hearing loss. Here, we study changes in both peripheral and central auditory function in rats with developmental PCB exposure using a combination of optical and electrophysiological approaches. Female rats were exposed to an environmental PCB mixture in utero and until weaning. At adulthood, auditory brainstem responses (ABRs) were measured, and synaptic currents were recorded in slices from auditory cortex layer 2/3 neurons. Spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) were more frequent in PCB-exposed rats compa...

The regulation of neuronal soma size is essential for appropriate brain circuit function and its dysregulation is associated with several neurodevelopmental disorders. A defect in the dendritic growth and elaboration of motor neocortical pyramidal neurons in neonates lacking neuregulin-4 (NRG4) has previously been reported. In this study, we investigated whether the loss of NRG4 causes further morphologic defects that are specific to these neurons. We analyzed the soma size of pyramidal neurons of layer (L)2/3 and L5 of the motor cortex and a subpopulation of multipolar interneurons in this neocortical region in Nrg4 +/+ and Nrg4 −/− mice. There were significant decreases in pyramidal neuron soma size in Nrg4 −/− mice compared with Nrg4 +/+ littermates at all stages studied [postnatal day (P)10, P30, and P60]. The reduction was especially marked at P10 and in L5 pyramidal neurons. Soma size was not significantly different for multipolar interneurons at any age. This in vivo phenotype was replicated in pyra...

Motor neurons (MNs) innervating the digit muscles of the intrinsic hand (IH) and intrinsic foot (IF) control fine motor movements. The ability to reproducibly label specifically IH and IF MNs in mice would be a beneficial tool for studies focused on fine motor control. To this end, we find that a CRE knock-in mouse line of Atoh1 , a developmentally expressed basic helix-loop-helix (bHLH) transcription factor, reliably expresses CRE-dependent reporter genes in ∼60% of the IH and IF MNs. We determine that CRE-dependent expression in IH and IF MNs is ectopic because an Atoh1 mouse line driving FLPo recombinase does not label these MNs although other Atoh1 -lineage neurons in the intermediate spinal cord are reliably identified. Furthermore, the CRE-dependent reporter expression is enriched in the IH and IF MN pools with much sparser labeling of other limb-innervating MN pools such as the tibialis anterior (TA), gastrocnemius (GS), quadricep (Q), and adductor (Ad). Lastly, we find that ectopic reporter express...

Attentional selection is a function that allocates the brain’s computational resources to the most important part of a visual scene at a specific moment. Saliency map models have been proposed as computational models to predict attentional selection within a spatial location. Recent saliency map models based on deep convolutional neural networks (DCNNs) exhibit the highest performance for predicting the location of attentional selection and human gaze, which reflect overt attention. Trained DCNNs potentially provide insight into the perceptual mechanisms of biological visual systems. However, the relationship between artificial and neural representations used for determining attentional selection and gaze location remains unknown. To understand the mechanism underlying saliency map models based on DCNNs and the neural system of attentional selection, we investigated the correspondence between layers of a DCNN saliency map model and monkey visual areas for natural image representations. We compared the char...

The development of deep convolutional neural networks (CNNs) has recently led to great successes in computer vision, and CNNs have become de facto computational models of vision. However, a growing body of work suggests that they exhibit critical limitations on tasks beyond image categorization. Here, we study one such fundamental limitation, concerning the judgment of whether two simultaneously presented items are the same or different (SD) compared with a baseline assessment of their spatial relationship (SR). In both human subjects and artificial neural networks, we test the prediction that SD tasks recruit additional cortical mechanisms which underlie critical aspects of visual cognition that are not explained by current computational models. We thus recorded electroencephalography (EEG) signals from human participants engaged in the same tasks as the computational models. Importantly, in humans the two tasks were matched in terms of difficulty by an adaptive psychometric procedure; yet, on top of a mo...

A hallmark of human thought is the ability to think about not just the actual world but also about alternative ways the world could be. One way to study this contrast is through language. Language has grammatical devices for expressing possibilities and necessities, such as the words might or must . With these devices, called “modal expressions,” we can study the actual versus possible contrast in a highly controlled way. While factual utterances such as “There is a monster under my bed” update the here-and-now of a discourse model, a modal version of this sentence, “There might be a monster under my bed,” displaces from the here-and-now and merely postulates a possibility. We used magnetoencephalography (MEG) to test whether the processes of discourse updating and modal displacement dissociate in the brain. Factual and modal utterances were embedded in short narratives, and across two experiments, factual expressions increased the measured activity over modal expressions. However, the localization of the ...

The development of Parkinson’s disease (PD) causes dysfunction of the frontal cortex, which contributes to the hallmark motor symptoms and is regarded as one of the primary causes of the affective and cognitive impairments observed in PD. Treatment with L-3,4-dihydroxyphenylalanine (L-DOPA) alleviates motor symptoms but has mixed efficacy in restoring normal cognitive functions, which is further complicated by the psychoactive effects of the drug. We investigated how L-DOPA affects gene expression in the frontal cortex in an animal model of unilateral PD. We performed RNA sequencing (RNA-Seq) analysis of gene expression in the frontal cortex of rats with 6-hydroxydopamine (6-OHDA)-induced unilateral dopaminergic lesions treated with L-DOPA, for two weeks. The analysis of variance identified 48 genes with a significantly altered transcript abundance after L-DOPA treatment. We also performed a weighted gene coexpression network analysis (WGCNA), which resulted in the detection of five modules consisting of g...

Autism-associated genetic mutations may perturb the balance between stability and plasticity of synaptic connections in the brain. Here, we report an increase in the formation and stabilization of dendritic spines in the cerebral cortex of the mouse model of MECP2 -duplication syndrome, a high-penetrance form of syndromic autism. Increased stabilization is mediated entirely by spines that form cooperatively in 10-μm clusters and is observable across multiple cortical areas both spontaneously and following motor training. Excessive stability of dendritic spine clusters could contribute to behavioral rigidity and other phenotypes in syndromic autism.

Nicotine, the primary addictive substance in tobacco, is widely abused. Relapse to cues associated with nicotine results in increased glutamate release within nucleus accumbens core (NAcore), modifying synaptic plasticity of medium spiny neurons (MSNs), which contributes to reinstatement of nicotine seeking. However, the role of cholinergic interneurons (ChIs) within the NAcore in mediating these neurobehavioral processes is unknown. ChIs represent less than 1% of the accumbens neuronal population and are activated during drug seeking and reward-predicting events. Thus, we hypothesized that ChIs may play a significant role in mediating glutamatergic plasticity that underlies nicotine-seeking behavior. Using chemogenetics in transgenic rats expressing Cre under the control of the choline acetyltransferase (ChAT) promoter, ChIs were bidirectionally manipulated before cue-induced reinstatement. Following nicotine self-administration and extinction, ChIs were activated or inhibited before a cue reinstatement s...