Altered functional connectivity has been reported in infants with prenatal exposure to opioids, which significantly interrupts and influences endogenous neurotransmitter/receptor signaling during fetal programming. Better birth outcomes and long-term developmental outcomes are associated with medication for opioid use disorder (MOUD) during pregnancy, but the neural mechanisms underlying these benefits are largely unknown. We aimed to characterize effects of prenatal opioid/other drug exposure (PODE) and the neural basis for MOUD’s reported beneficial effects by examining neonatal brain functional organization. A cohort of 109 human newborns (42 PODE, 39 with prenatal exposure to drugs excluding opioids (PDE), 28 drug-free controls; males and females) underwent resting-state fMRI at 2 weeks of age. To examine neural effects of MOUD, PODE infants were separated into subgroups based on whether mothers received MOUD (n=31) or no treatment (n=11). A novel heatmap analysis was designed to characterize PODE-asso...

Our ability to effectively retrieve complex semantic knowledge meaningfully impacts our daily lives, yet the neural processes that underly successful access and transient failures in access remain only partially understood. In this fMRI study, we contrast activation during successful semantic access, unsuccessful semantic access due to transient access-failures (i.e., ‘tip-of-the-tongue’, ‘feeling-of-knowing’), and trials where the semantic knowledge was not possessed. Twenty-four human participants (14 female) were presented 240 trivia-based questions relating to person, place, object or scholastic knowledge-domains. Analyses of the recall event indicated a relatively greater role of a dorsomedial section of the prefrontal cortex in unsuccessful semantic access and relatively greater recruitment of the pars orbitalis of the inferior frontal gyrus in successful access. Successful access was also associated with increased activation in knowledge-domain selective areas. Generally, knowledge-domain selective ...

The predisposition to engage in autonomous habitual behaviors has been associated with behavioral disorders such as obsessive-compulsive disorder and addiction. Attentional set-shifting tasks (ASSTs), that incorporate changes governing the association of discriminative stimuli with contingent reinforcement, are commonly used to measure underlying processes of cognitive/behavioral flexibility. The purpose of this study was to identify primate brain networks that mediate trait-like deficits in ASST performance using resting state functional magnetic resonance imaging (rsfMRI). A self-pacing ASST was administered to 3 cohorts of rhesus monkeys (total n=35, 18 female). Increased performance over 30 consecutive sessions segregated the monkeys into 2 populations, termed High Performers (HP, n=17) and Low Performers (LP, n=17), with one anomaly. Compared to LPs, HPs had higher rates of improving performance over sessions and completed the 8 sets/session with fewer errors. LP monkeys, on the other hand, spent most...

GABAergic inhibitory neurons, through their molecular, anatomic and physiological diversity, provide a substrate for the modulation of ongoing cortical circuit activity throughout the sleep-wake cycle. Here, we investigated neuronal activity dynamics of parvalbumin (PV), vasoactive intestinal polypeptide (VIP) and somatostatin (SST) neurons in naturally-sleeping head-restrained mice at the level of layer 2/3 of the primary somatosensory barrel cortex of mice. Through calcium-imaging and targeted single-unit loose-patch or whole-cell recordings, we found that PV action potential (AP) firing activity was largest during both NREM (non-rapid eye movement) and REM sleep stages, that VIP neurons were most active during REM sleep and that the overall activity of SST neurons remained stable throughout the sleep/wake cycle. Analysis of neuronal activity dynamics uncovered rapid decreases in PV cell firing at wake onset followed by a progressive recovery during wake. Simultaneous local field potential (LFP) recordin...

Neural substrates of evidence accumulation have been a central issue in decision-making studies because of the prominent success of the accumulation model in explaining a wide range of perceptual decision making. Since accumulation-shaped activities have been found in multiple brain regions, which are called accumulators, questions regarding functional relations among these accumulators are emerging. This study employed the deconvolution method of functional magnetic resonance imaging (fMRI) signals from human male and female participants during object-category decision tasks, taking advantage of the whole-brain coverage of fMRI with improved availability of temporal information of the deconvolved activity. We detected the accumulation activity in many non-category-selective regions over the frontal, parietal, and temporal lobes as well as category-selective regions of the categorization task. Importantly, the frontal regions mostly showed activity peaks matching the decision timing (classified as “type-A ...

The activity of primary auditory cortex (A1) neurons is modulated not only by sensory inputs but also by other task-related variables in associative learning. However, it is unclear how A1 neural activity changes dynamically in response to these variables during the learning process of associative memory tasks. Therefore, we developed an associative memory task using auditory stimuli in rats. In this task, rats were required to associate tone frequencies (high and low) with a choice of ports (right or left) to obtain a reward. The activity of A1 neurons in the rats during the learning process of the task was recorded. A1 neurons increased their firing rates either when the rats were presented with a high or low tone (frequency-selective cells) before they chose either the left or right port (choice-direction cells), or when they received a reward after choosing either the left or right port (reward-direction cells). Furthermore, the proportion of frequency-selective cells and reward-direction cells increas...

Aphasia is a prevalent cognitive syndrome caused by stroke. The rarity of premorbid imaging and heterogeneity of lesion obscures the links between the local effects of the lesion, global anatomical network organization, and aphasia symptoms. We applied a simulated attack approach in humans to examine the effects of 39 stroke lesions (16 females) on anatomical network topology by simulating their effects in a control sample of 36 healthy (15 females) brain networks. We focused on measures of global network organization thought to support overall brain function and resilience in the whole brain and within the left hemisphere. After removing lesion volume from the network topology measures and behavioral scores (the Western Aphasia Battery Aphasia Quotient; WAB-AQ, four behavioral factor scores obtained from a neuropsychological battery, and a factor sum), we compared the behavioral variance accounted for by simulated post-stroke connectomes to that observed in the randomly permuted data. Global measures of a...

In multi-segmented locomotion, coordination of all appendages is crucial for the generation of a proper motor output. In running for example, leg coordination is mainly based on the central interaction of rhythm generating networks, called central pattern generators (CPGs). In slower forms of locomotion, however, sensory feedback, which originates from sensory organs that detect changes in position, velocity and load of the legs’ segments, has been shown to play a more crucial role. How exactly sensory feedback influences the activity of the CPGs to establish functional neuronal connectivity is not yet fully understood. Using the female stick insect Carausius morosus , we show for the first time that a long-range caudo-rostral sensory connection exists and highlight that load as sensory signal is sufficient to entrain rhythmic motoneuron (MN) activity in the most rostral segment. So far, mainly rostro-caudal influencing pathways have been investigated where the strength of activation, expressed by the MN a...

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. In male and female mice, we demonstrate that VTA and SNc microglia exhibit unique and premature responses to aging, compared with cortex and NAc microglia. This is associated with localized VTA/SNc neuroinflammation that may compromise synaptic function as early as middle age. Surprisingly, systemic inflammation, local neuron d...