For adaptive goal-directed action, the brain needs to monitor action performance and detect errors. The corresponding information may be conveyed via different sensory modalities; for instance, visual and proprioceptive body position cues may inform about current manual action performance. Thereby, contextual factors such as the current task set may also determine the relative importance of each sensory modality for action guidance. Here, we analysed human behavioural, functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG) data from two virtual reality (VR)-based hand-target phase matching studies to identify the neuronal correlates of performance monitoring and error processing under instructed visual or proprioceptive task sets. Our main result was a general, modality-independent response of the bilateral frontal operculum (FO) to poor phase matching accuracy, as evident from increased BOLD signal and increased gamma power. Furthermore, functional connectivity of the bilateral FO ...

The ventral striatum is implicated in the affective processing of reward, which can be divided into a motivational and a hedonic component. Here, we examined whether these two components rely on distinct neural substrates within the ventral striatum in humans (11 females and 13 males). We used a high-resolution fMRI protocol targeting the ventral striatum combined with a Pavlovian-instrumental task and a hedonic reactivity task. Both tasks involved an olfactory reward, thereby allowing us to measure Pavlovian-triggered motivation and sensory pleasure for the same reward within the same participants. Our findings show that different subregions of the ventral striatum are dissociable in their contributions to the motivational versus the hedonic component of the affective processing of reward. Parsing the neural mechanisms of the interplay between Pavlovian incentive and hedonic processes may have important implications for understanding compulsive reward-seeking behaviors such as addiction, binge-eating, or ...

In post-mitotic neurons, several tumor suppressor genes (TSGs) including p53, Rb and PTEN modulate the axon regeneration success after injury. Particularly, PTEN inhibition is a key driver of successful CNS axon regeneration after optic nerve or spinal cord injury. In contrast, in peripheral neurons, TSG influence in neuronal morphology, physiology and pathology has not been investigated to the same depth. In this study we conditionally deleted PTEN from mouse facial motoneurons ( Ptenflox/flox; Chat-Cre ) and analyzed neuronal responses in vivo with or without peripheral facial nerve injury in male and female mice. In uninjured motoneurons, PTEN loss induced somatic, axonal and nerve hypertrophy, synaptic terminal enlargement and reduction in physiological whisker movement. Despite these morphological and physiological changes, PTEN deletion positively regulated facial nerve regeneration and recovery of whisker movement after nerve injury. Regenerating PTEN deficient motoneurons upregulated P-CREB and a s...

Neurophysiological work in primates and rodents have shown the amygdala plays a central role in reward processing through connectivity with the orbitofrontal cortex (OFC) and hippocampus. However, understanding the role of oscillations in each region and their connectivity in different stages of reward processing in humans has been hampered by limitations with non-invasive methods such as poor spatial and temporal resolution. To overcome these limitations, we recorded local field potentials (LFPs) directly from the amygdala, OFC and hippocampus simultaneously in human male and female epilepsy patients performing a monetary incentive delay task. This allowed us to dissociate electrophysiological activity and connectivity patterns related to the anticipation and receipt of rewards and losses in real-time. Anticipation of reward increased high frequency gamma (HFG) (60-250 Hz) activity in the hippocampus and theta band (4-8 Hz) synchronization between amygdala and OFC, suggesting roles in memory and motivatio...

Using postsynaptically tethered calcium sensor GCaMP, we investigated spontaneous synaptic transmission at individual active zones (AZs) at the Drosophila (both sexes) neuromuscular junction. Optical monitoring of GCaMP events coupled with focal electrical recordings of synaptic currents revealed “hot spots” of spontaneous transmission, which corresponded to transient states of elevated activity at selected AZs. The elevated spontaneous activity had two temporal components, one at a timescale of minutes and the other at a subsecond timescale. We developed a three-state model of AZ preparedness for spontaneous transmission and performed Monte Carlo simulations of the release process, which produced an accurate quantitative description of the variability and time course of spontaneous transmission at individual AZs. To investigate the mechanisms of elevated activity, we first focused on the protein complexin, which binds the SNARE protein complex and serves to clamp spontaneous fusion. Overexpression of Dros...

Narrowband γ oscillations (NBG: ∼20-60 Hz) in visual cortex reflect rhythmic fluctuations in population activity generated by underlying circuits tuned for stimulus location, orientation, and color. A variety of theories posit a specific role for NBG in encoding and communicating this information within visual cortex. However, recent findings suggest a more nuanced role for NBG, given its dependence on certain stimulus feature configurations, such as coherent-oriented edges and specific hues. Motivated by these factors, we sought to quantify the independent and joint tuning properties of NBG to oriented and color stimuli using intracranial recordings from the human visual cortex (male and female). NBG was shown to display a cardinal orientation bias (horizontal) and also an end- and mid-spectral color bias (red/blue and green). When jointly probed, the cardinal bias for orientation was attenuated and an end-spectral preference for red and blue predominated. This loss of mid-spectral tuning occurred even fo...

In the article, “Modality-Specific Impairment of Hippocampal CA1 Neurons of Alzheimer's Disease Model Mice,” by Risa Takamura, Kotaro Mizuta, Yukiko Sekine, Tanvir Islam, Takashi Saito, Masaaki Sato, Masamichi Ohkura, Junichi Nakai, Toshio Ohshima, Takaomi C. Saido, and Yasunori Hayashi, which

It is clear that humans can extract statistical information from streams of visual input, yet how our brain processes sequential images into the abstract representation of the mean feature value remains poorly explored. Using multivariate pattern analyses of electroencephalography recorded while human observers viewed 10 sequentially presented Gabors of different orientations to estimate their mean orientation at the end, we investigated sequential averaging mechanism by tracking the quality of individual and mean orientation as a function of sequential position. Critically, we varied the sequential variance of Gabor orientations to understand the neural basis of perceptual mean errors occurring during a sequential averaging task. We found that the mean-orientation representation emerged at specific delays from each sequential stimulus onset and became increasingly accurate as additional Gabors were viewed. Especially in frontocentral electrodes, the neural representation of mean orientation improved more ...

Recent studies suggest an important role of the principal inhibitory neurotransmitter GABA for motor performance in the context of aging. Nonetheless, as previous magnetic resonance spectroscopy (MRS) studies primarily reported resting-state GABA levels, much less is known about transient changes in GABA levels during motor task performance and how these relate to behavior and brain activity patterns. Therefore, we investigated GABA+ levels of left primary sensorimotor cortex (SM1) acquired before, during, and after execution of a unimanual/bimanual action selection task in 30 (human) young adults (YA; age 24.5 ± 4.1, 15 male) and 30 older adults (OA; age 67.8 ± 4.9, 14 male). In addition to task-related MRS data, task-related functional magnetic resonance imaging (fMRI) data were acquired. Behavioral results indicated lower motor performance in OA as opposed to YA, particularly in complex task conditions. MRS results demonstrated lower GABA+ levels in OA as compared with YA. Furthermore, a transient task-...

Women have a higher prevalence and incidence of Alzheimer's disease (AD) than age-matched men, and loss of estrogen might be partially responsible for the higher risk of AD in aged women. While β-secretase (BACE1) plays an important role in AD pathogenesis, whether BACE1 involved the sex difference in AD pathology remains unclear. This study investigated the hypothesis that estrogen regulates BACE1 transcription via the estrogen response element (ERE) and designated pathways. Using estrogen receptor (ER) knock-out mice and mutagenesis of EREs in HEK293 cells, we demonstrated sex-specific inhibition of BACE1 transcription by estrogen via direct binding to ERE sites and ERα. We also used a repressor of estrogen receptor activity (REA) and showed that an REA–ERE complex downregulated BACE1. A chromatin immunoprecipitation assay analysis determined that all three EREs at the BACE1 promoter were required for estradiol-mediated downregulation of BACE1 transcription in mice. Last, we confirmed the impairment of t...