Anatomical organization of the primate cortex varies as a function of total brain size, where possession of a larger brain is accompanied by disproportionate expansion of associative cortices alongside a relative contraction of sensorimotor systems. However, equivalent scaling maps are not yet available for regional white matter anatomy. Here, we use three large-scale neuroimaging datasets to examine how regional white matter volume (WMV) scales with interindividual variation in brain volume amongst typically developing humans (combined N = 2391; 1247 females, 1144 males). We show that WMV scaling is regionally heterogeneous: larger brains have relatively greater WMV in anterior and posterior regions of cortical white matter, as well as the genu and splenium of the corpus callosum, but relatively less WMV in most subcortical regions. Furthermore, regions of positive WMV scaling tend to connect previously-defined regions of positive gray matter scaling in the cortex – revealing a coordinated coupling of reg...

Recognising speech in background noise is a strenuous daily activity, yet most humans can master it. An explanation of how the human brain deals with such sensory uncertainty during speech recognition is to-date missing. Previous work has shown that recognition of speech without background noise involves modulation of the auditory thalamus (medial geniculate body, MGB): There are higher responses in left MGB for speech recognition tasks that require tracking of fast-varying stimulus properties in contrast to relatively constant stimulus properties (e.g., speaker identity tasks) despite the same stimulus input. Here we tested the hypotheses that (i) this task-dependent modulation for speech recognition increases in parallel with the sensory uncertainty in the speech signal, i.e., the amount of background noise and that (ii) this increase is present in the ventral MGB, which corresponds to the primary sensory part of the auditory thalamus. In accordance with our hypothesis, we show—by using ultra-high-resolu...

Many patients with chronic pain conditions suffer from depression. The mechanisms underlying pain-induced depression are still unclear. There are critical links of medial prefrontal cortex (mPFC) synaptic function to depression, with signaling through the endocannabinoid (eCB) system as an important contributor. We hypothesized that afferent noxious inputs after injury compromise activity-dependent eCB signaling in the mPFC, resulting in depression. Depression-like behaviors were tested in male and female rats with traumatic neuropathy (spared nerve injury, SNI) and neuronal activity in the mPFC was monitored using the immediate early gene, c-Fos, and in vivo electrophysiological recordings. mPFC eCB concentrations were determined using mass spectrometry while behavioral and electrophysiological experiments were employed to evaluate role of alterations in eCB signaling in depression after pain. SNI-induced pain induced the development of depression phenotypes in both male and female rats. Pyramidal neurons...

Attributing outcomes to your own actions or to external causes is essential for appropriately learning which actions lead to reward and which actions do not. Our previous work showed that this type of credit assignment is best explained by a Bayesian reinforcement learning model which posits that beliefs about the causal structure of the environment modulate reward prediction errors (RPEs) during action value updating. In this study, we investigated the brain networks underlying reinforcement learning that are influenced by causal beliefs using functional magnetic resonance imaging (fMRI) while human participants (n = 31; 13 males, 18 females) completed a behavioral task that manipulated beliefs about causal structure. We found evidence that RPEs modulated by causal beliefs are represented in dorsal striatum, while standard (unmodulated) RPEs are represented in ventral striatum. Further analyses revealed that beliefs about causal structure are represented in anterior insula and inferior frontal gyrus. Fina...

Not all movements require the motor cortex for execution. Intriguingly, dependence on motor cortex of a given movement is not fixed, but instead can dynamically change over the course of long-term learning. For instance, rodent forelimb movements that initially require motor cortex can become independent of the motor cortex after an extended period of training. However, it remains unclear whether long-term neural changes rendering the motor cortex dispensable are a simple function of the training length. To address this issue, we trained mice (both male and female) to perform two distinct forelimb movements, forward versus downward reaches with a joystick, concomitantly over several weeks and then, compared the involvement of the motor cortex between the two movements. Most mice achieved different levels of motor performance between the two movements after long-term training. Of the two movements, the one that achieved higher trial-to-trial consistency (i.e., consistent-direction movement) was significantl...

The mouse auditory cortex is comprised of several auditory fields spanning the dorso-ventral axis of the temporal lobe. The ventral most auditory field is the temporal association cortex (TeA), which remains largely unstudied. Using Neuropixels probes, we simultaneously recorded from primary auditory cortex (AUDp), secondary auditory cortex (AUDv) and TeA, characterizing neuronal responses to pure tones and frequency modulated (FM) sweeps in awake head-restrained female mice. As compared to primary and secondary auditory cortices, single unit responses to pure tones in TeA were sparser, delayed and prolonged. Responses to FMs were also sparser. Population analysis showed that the sparser responses in TeA render it less sensitive to pure tones, yet more sensitive to FMs. When characterizing responses to pure tones under anesthesia, the distinct signature of TeA was changed considerably as compared to that in awake mice, implying that responses in TeA are strongly modulated by non-feedforward connections. To...

Spinal neuronal mechanisms regulate recovered involuntary micturition after spinal cord injury (SCI). It is recently discovered that dopamine (DA) is synthesized in the rat injured spinal cord and is involved in lower urinary tract (LUT) activity. To fully understand the role of spinal DA-ergic machinery in micturition, we examined urodynamic responses in female rats during pharmacological modulation of the DA pathway. Three to four weeks after complete thoracic SCI, L-DOPA administered intravenously during bladder cystometrogram and external urethral sphincter (EUS) electromyography reduced bladder overactivity and increased the duration of EUS bursting, leading to remarkably improved voiding efficiency. Apomorphine, a non-selective dopamine receptor (DR) agonist, or quinpirole, a selective DR2 agonist, induced similar responses whereas a specific DR2 antagonist remoxipride alone only had minimal effects. Meanwhile, administration of SCH 23390, a DR1 antagonist, reduced voiding efficiency by increasing to...

Our visual environment is complicated and our cognitive capacity is limited. As a result, we must strategically ignore some stimuli in order to prioritize others. Common-sense suggests that foreknowledge of distractor characteristics, like location or color, might help us ignore these objects. But empirical studies have provided mixed evidence, often showing that knowing about a distractor before it appears counter-intuitively leads to its attentional selection. What has looked like strategic distractor suppression in the past is now commonly explained as a product of prior experience and implicit statistical learning, and the long-standing notion that distractor suppression is reflected in alpha-band oscillatory brain activity has been challenged by results appearing to link alpha to target resolution. Can we strategically, proactively suppress distractors? And, if so, does this involve alpha? Here, we use concurrent recording of human EEG and eye movements in optimized experimental designs to identify be...

The dorsal region of the bed nucleus of the stria terminalis (dBNST) receives substantial dopaminergic input which overlaps with norepinephrine input implicated in stress responses. Using ex vivo fast scan cyclic voltammetry in male C57BL6 mouse brain slices, we demonstrate that electrically stimulated dBNST catecholamine signals are of substantially lower magnitude and have slower uptake rates compared with caudate signals. Dopamine terminal autoreceptor activation inhibited roughly half of the catecholamine transient, and noradrenergic autoreceptor activation produced an ∼30% inhibition. Dopamine transporter blockade with either cocaine or GBR12909 significantly augmented catecholamine signal duration. We optogenetically targeted dopamine terminals in the dBNST of transgenic ( TH:Cre ) mice of either sex and, using ex vivo whole-cell electrophysiology, we demonstrate that optically stimulated dopamine release induces slow outward membrane currents and an associated hyperpolarization response in a subset ...

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. We found that TA-LTP was impaired in male fmr1 KO mice. Although there were no significant differences in basal synaptic transmission, synaptically evoked dendritic calcium signals were smaller in KO neurons. Using dendritic recording, we found no difference in complex spikes or pharmacologically isolated Ca2+ spikes; however, the threshold for fast, Na+-dependent dendritic spikes was depolarized in fmr1 KO mice. Cell-attached patch-clamp recordings found no difference in Na+ channels between wild-type and fmr1 KO CA1 dendrites. Dendritic spike threshold and TA-LTP were restored by blocking A-type K+ channels with either 150 µm B...