Resting state networks (RSNs) are increasingly forwarded as candidate biomarkers for neuropsychiatric disorders. Such biomarkers may provide objective measures for evaluating novel therapeutic interventions in nonhuman primates often used in translational neuroimaging research. This study aimed to characterize the RSNs of awake squirrel monkeys and compare the characteristics of those networks in adolescent and adult subjects. Twenty-seven squirrel monkeys ( n =12 adolescents [6 male/6 female] ∼2.5 years and n =15 adults [7 male/8 female] ∼9.5 years) were gradually acclimated to awake scanning procedures; whole-brain fMRI images were acquired with a 9.4 Tesla scanner. Group level independent component (ICA) analysis (30 ICs) with dual regression was used to detect and compare RSNs. Twenty ICs corresponding to physiologically meaningful networks representing a range of neural functions, including motor, sensory, reward, and cognitive processes were identified in both adolescent and adult monkeys. The reprod...

Phase-entrainment of cells by theta oscillations is thought to globally coordinate the activity of cell assemblies across different structures, such as the hippocampus and neocortex. This coordination is likely required for optimal processing of sensory input during recognition and decision-making processes. In quadruple-area ensemble recordings from male rats engaged in a multisensory discrimination task, we investigated phase-entrainment of cells by theta oscillations in areas along the cortico-hippocampal hierarchy: somatosensory barrel (S1BF), secondary visual cortex (V2L), perirhinal cortex (PER) and dorsal hippocampus (dHC). Rats discriminated between two 3D objects presented in tactile-only, visual-only or both tactile and visual modalities. During task engagement, S1BF, V2L, PER and dHC LFP signals showed coherent theta-band activity. We found phase-entrainment of single-cell spiking activity to locally recorded as well as hippocampal theta activity in S1BF, V2L, PER and dHC. While phase-entrainmen...

The medial mammillary bodies (MB) play an important role in the formation of spatial memories; their dense inputs from hippocampal and brainstem regions makes them well-placed to integrate movement-related and spatial information, that is then extended to the anterior thalamic nuclei and beyond to cortex. While the anatomical connectivity of the medial MBs has been well-studied, much less is known about their physiological properties, particularly in freely-moving animals. We therefore carried out a comprehensive characterization of medial MB electrophysiology across arousal states by concurrently recording from the medial MB and the CA1 field of the hippocampus in male rats. In agreement with previous studies, we found medial MB neurons to have firing rates modulated by running speed and angular head velocity, as well as theta-entrained firing. We extended the characterization of MB neuron electrophysiology in three key ways: 1) we identified a subset of neurons (25%) that exhibit dominant bursting activi...

Sensory stimulation is often accompanied by fluctuations at high frequencies (>30Hz) in brain signals. These could be “narrowband” oscillations in the gamma band (30-70 Hz) or non-oscillatory “broadband” high-gamma (70-150 Hz) activity. Narrowband gamma oscillations, which are induced by presenting some visual stimuli such as gratings and have been shown to weaken with healthy aging and the onset of Alzheimer's Disease, hold promise as potential biomarkers. However, since delivering visual stimuli is cumbersome as it requires head stabilization for eye tracking, an equivalent auditory paradigm could be useful. Although simple auditory stimuli have been shown to produce high-gamma activity, whether specific auditory stimuli can also produce narrowband gamma oscillations is unknown. We tested whether auditory ripple stimuli, which are considered an analogue to visual gratings, could elicit narrowband oscillations in auditory areas. We recorded 64-channel EEG from male and female (18 each) subjects while they...

A sub-lethal ischemic episode (termed preconditioning [PC]) protects neurons in the brain against a subsequent severe ischemic injury. This phenomenon is known as brain ischemic tolerance, and has received much attention from researchers because of its robust neuroprotective effects. We have previously reported that PC activates astrocytes and subsequently upregulates P2X7 receptors, thereby leading to ischemic tolerance. However, the downstream signals of P2X7 receptors that are responsible for PC-induced ischemic tolerance remain unknown. Here, we show that PC-induced P2X7 receptor-mediated lactate release from astrocytes has an indispensable role in this event. Using a transient focal cerebral ischemia model caused by middle cerebral artery occlusion, extracellular lactate levels during severe ischemia were significantly increased in mice who experienced PC; this increase was dependent on P2X7 receptors. In addition, the intracerebroventricular injection of lactate protected against cerebral ischemic in...

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...