The nucleus accumbens (NAc) is a central component of the brain circuitry that mediates motivated behavior, including reward processing. Since the rewarding properties of social stimuli have a vital role in guiding behavior (both in humans and nonhuman animals), the nucleus accumbens is likely to contribute to the brain circuitry controlling social behavior. In rodents, prior studies have found that focal pharmacological inhibition of NAc and/or elevation of dopamine in NAc increases social interactions. However, the role of the NAc in social behavior in nonhuman primates remains unknown. We measured the social behavior of eight dyads of male macaques following (1) pharmacological inhibition of the nucleus accumbens using the GABAA agonist muscimol and (2) focal application of quinpirole, an agonist at the D2 family of dopamine receptors. Transient inhibition of the NAc with muscimol increased social behavior when drug was infused in submissive, but not dominant partners of the dyad. Focal application of q...

The cerebellum has the reputation of being a primitive part of the brain that mostly is involved in motor coordination and motor control. Older lesion studies and more recent electrophysiological studies have, however, indicated that it is involved in temporal perception and temporal expectation-building. An outstanding question is whether this temporal expectation-building cerebellar activity has functional relevance. In this study, we collected magnetoencephalographic data from 30 healthy participants performing a detection task on at-threshold stimulation that was presented at the end of a sequence of temporally regular or irregular above-threshold stimulation. We found that behavioural detection rates depended on the degree of irregularity in the sequence preceding it. We also found cerebellar responses evoked by above-threshold and at-threshold stimulation. The evoked responses to at-threshold stimulation differed significantly, depending on whether it was preceded by a regular or an irregular sequen...

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique capable of inducing neuroplasticity as measured by changes in peripheral muscle electromyography (EMG) or electroencephalography (EEG) from pre to post stimulation. However, temporal courses of neuromodulation during ongoing rTMS are unclear. Monitoring cortical dynamics via TMS-evoked responses using EMG (motor-evoked potentials; MEPs) and EEG (transcranial-evoked potentials; TEPs) during rTMS might provide further essential insights into its mode of action - temporal course of potential modulations. The objective of this study was to first evaluate the validity of online rTMS-EEG and -EMG analyses, and second to scrutinize the temporal changes of TEPs and MEPs during rTMS. As rTMS is subject to high inter-individual effect variability, we aimed for single-subject analyses of EEG changes during rTMS. 10 healthy human participants were stimulated with 1000 pulses of 1 Hz rTMS over the motor cortex while EEG an...

In many real-life scenarios, our decisions could lead to multiple outcomes that conflict in value. Hence, an appropriate neural representation of the net experienced value of conflicting outcomes, which plays a crucial role in guiding future decisions, is critical for adaptive behavior. As some recent functional neuroimaging work primarily focused on the concurrent processing of monetary gains and aversive information, very little is known regarding the integration of conflicting value signals involving monetary losses and appetitive information in the human brain. To address this critical gap, we conducted a functional MRI study involving healthy human male participants to examine the nature of integrating positive emotion and monetary losses. We employed a novel experimental design where the valence (positive or neutral) of an emotional stimulus indicated the type of outcome (loss or no-loss) in a choice task. Specifically, we probed two plausible integration patterns while processing conflicting value s...

The accumulation of amyloid-beta (Αβ) and hyperphosphorylated-tau (hp-tau) are two classical histopathological biomarkers in Alzheimer's disease (AD). However, their detailed interactions with the electro physiological changes at the meso- and macroscale are not yet fully understood. We developed a mechanistic multiscale model of AD progression, linking proteinopathy to its effects on neural activity and vice-versa. We integrated a heterodimer model of prion-like protein propagation, and a brain network model of Jansen-Rit neural masses derived from human neuroimaging data whose parameters varied due to neurotoxicity. Results showed that changes in inhibition guided the electrophysiological alterations found in AD, and these changes were mainly attributed to Αβ effects. Additionally, we found a causal disconnection between cellular hyperactivity and interregional hypersynchrony contrary to previous beliefs. Finally, we demonstrated that early Αβ and hp-tau depositions’ location determine the spatiotemporal...

In many real-life scenarios, our decisions could lead to multiple outcomes that conflict with value. Hence, an appropriate neural representation of the net experienced value of conflicting outcomes, which play a crucial role in guiding future decisions, is critical for adaptive behavior. As some recent functional neuroimaging work has primarily focused on the concurrent processing of monetary gains and aversive information, very little is known regarding the integration of conflicting value signals involving monetary losses and appetitive information in the human brain. To address this critical gap, we conducted a functional MRI study involving healthy human male participants to examine the nature of integrating positive emotion and monetary losses. We employed a novel experimental design where the valence (positive or neutral) of an emotional stimulus indicated the type of outcome (loss or no loss) in a choice task. Specifically, we probed two plausible integration patterns while processing conflicting va...

The accumulation of amyloid- β ( Aβ ) and hyperphosphorylated-tau (hp-tau) are two classical histopathological biomarkers in Alzheimer’s disease (AD). However, their detailed interactions with the electrophysiological changes at the meso- and macroscale are not yet fully understood. We developed a mechanistic multiscale model of AD progression, linking proteinopathy to its effects on neural activity and vice-versa. We integrated a heterodimer model of prion-like protein propagation and a brain network model of Jansen–Rit neural masses derived from human neuroimaging data whose parameters varied due to neurotoxicity. Results showed that changes in inhibition guided the electrophysiological alterations found in AD, and these changes were mainly attributed to Aβ effects. Additionally, we found a causal disconnection between cellular hyperactivity and interregional hypersynchrony contrary to previous beliefs. Finally, we demonstrated that early Aβ and hp-tau depositions’ location determine the spatiotemporal p...

The inferior colliculus (IC), the midbrain auditory integration center, analyzes information about social vocalizations and provides substrates for higher level processing of vocal signals. We used multichannel recordings to characterize and localize responses to social vocalizations and synthetic stimuli within the IC of female and male mice, both urethane anesthetized and unanesthetized. We compared responses to ultrasonic vocalizations (USVs) with other vocalizations in the mouse repertoire and related vocal responses to frequency tuning, IC subdivisions, and sex. Responses to lower frequency, broadband social vocalizations were widespread in IC, well represented throughout the tonotopic axis, across subdivisions, and in both sexes. Responses to USVs were much more limited. Although we observed some differences in tonal and vocal responses by sex and subdivision, representations of vocal responses by sex and subdivision were largely the same. For most units, responses to vocal signals occurred only when...

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by intrusive obsessive thoughts and compulsive behaviors. Multiple studies have shown the association of polymorphisms in the SLC1A1 gene with OCD. The most common of these OCD-associated polymorphisms increases the expression of the encoded protein, excitatory amino acid transporter 3 (EAAT3), a neuronal glutamate transporter. Previous work has shown that increased EAAT3 expression results in OCD-relevant behavioral phenotypes in rodent models. In this study, we created a novel mouse model with targeted, reversible overexpression of Slc1a1 in forebrain neurons. The mice do not have a baseline difference in repetitive behavior but show increased hyperlocomotion following a low dose of amphetamine (3 mg/kg) and increased stereotypy following a high dose of amphetamine (8 mg/kg). We next characterized the effect of amphetamine on striatal cFos response and found that amphetamine increased cFos throughout the striatum in ...

As the global elderly population grows, age-related cognitive decline is becoming an increasingly significant healthcare issue, often leading to various neuropsychiatric disorders. Among the many molecular players involved in memory, AMPA-type glutamate receptors are known to regulate learning and memory, but how their dynamics change with age and affect memory decline is not well understood. Here, we examined the in vivo properties of the AMPA-type glutamate receptor GLR-1 in the AVA interneuron of the Caenorhabditis elegans nervous system during physiological aging. We found that both total and membrane-bound GLR-1 receptor levels decrease with age in wild-type worms, regardless of their location along the axon. Using fluorescence recovery after photobleaching, we also demonstrated that a reduction in GLR-1 abundance correlates with decreased local, synaptic GLR-1 receptor dynamics. Importantly, we found that reduced GLR-1 levels strongly correlate with the age-related decline in short-term associative m...