The intraparietal sulcus (IPS) has been implicated in numerous functions that range from representation of visual stimuli to action planning, but its role in abstract decision-making has been unclear, in part because low-level functions often act as confounds. Here, we address this problem using a task that dissociates abstract decision-making from sensory salience, attentional control, motor planning, and motor output. Functional MRI data were collected from healthy female and male human subjects while they performed a policy abstraction task requiring use of a more abstract (second-order) rule to select between two less abstract (first order) rules that informed the motor response. By identifying IPS subdivisions with preferential connectivity to prefrontal regions that are differentially responsive to task abstraction, we found that a caudal IPS (cIPS) subregion with strongest connectivity to the pre-premotor cortex was preferentially active for second-order cues, whereas a rostral IPS subregion (rIPS) ...

In recent years research on natural speech processing has benefited from recognizing that low frequency cortical activity tracks the amplitude envelope of natural speech. However, it remains unclear to what extent this tracking reflects speech-specific processing beyond the analysis of the stimulus acoustics. In the present study, we aimed to disentangle contributions to cortical envelope tracking that reflect general acoustic processing from those that are functionally related to processing speech. To do so, we recorded EEG from subjects as they listened to “auditory chimeras” – stimuli comprised of the temporal fine structure (TFS) of one speech stimulus modulated by the amplitude envelope (ENV) of another speech stimulus. By varying the number of frequency bands used in making the chimeras, we obtained some control over which speech stimulus was recognized by the listener. No matter which stimulus was recognized, envelope tracking was always strongest for the ENV stimulus, indicating a dominant contribu...

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement sleep (NREM). Recently, cortical ripples in humans have been shown to enfold the replay of neuron firing patterns during cued recall. Here, using intracranial recordings from 18 patients (12 female), we show that cortical ripples also occur during NREM in humans, with similar density, oscillation frequency (∼90 Hz), duration, and amplitude to waking. Ripples occurred in all cortical regions with similar characteristics, unrelated to putative hippocampal connectivity, and were less dense and robust in higher association areas. Putative pyramidal and interneuron spiking phase-locked to cortical ripples during NREM, with phase delays consistent with ripple generation through pyramidal-interneuron feedback. Cortical ripples were smaller in amplitude than hippocampal ripples, but were similar in density, frequency, and duration. Cortical ...

Opsin-3 ( Opn3 , encephalopsin) was the first nonvisual opsin gene discovered in mammals. Since then, several Opn3 functions have been described, and in two cases (adipose tissue, smooth muscle) light sensing activity is implicated. In addition to peripheral tissues, Opn3 is robustly expressed within the central nervous system, for which it derives its name. Despite this expression, no studies have investigated developmental or adult CNS consequences of Opn3 loss-of-function. Here, the behavioral consequences of mice deficient in Opn3 were investigated. Opn3 -deficient mice perform comparably to wild-type mice in measures of motor coordination, socialization, anxiety-like behavior, and various aspects of learning and memory. However, Opn3 -deficient mice have an attenuated acoustic startle reflex (ASR) relative to littermates. This deficit is not because of changes in hearing sensitivity, although Opn3 was shown to be expressed in auditory and vestibular structures, including cochlear outer hair cells. Int...

In real-world decision-making scenarios, negative consequences do not always occur immediately after a choice. This delay between action and outcome drives the underestimation, or “delay discounting”, of punishment. While the neural substrates underlying sensitivity to immediate punishment have been well-studied, there has been minimal investigation of delayed consequences. Here, we assessed the role of lateral orbitofrontal cortex (LOFC) and basolateral amygdala (BLA), two regions implicated in cost/benefit decision-making, in sensitivity to delayed vs immediate punishment. The delayed punishment decision-making task (DPDT) was used to measure delay discounting of punishment in rodents. During DPDT, rats choose between a small, single pellet reward and a large, three pellet reward accompanied by a mild foot shock. As the task progresses, the shock is preceded by a delay that systematically increases or decreases throughout the session. We observed that rats avoid choices associated with immediate punishme...

Anterolateral system (AS) neurons transmit pain signals from the spinal cord to the brain. Their morphology, anatomy and physiological properties have been extensively characterised and suggest that specific AS neurons and their brain targets are concerned with the discriminatory aspects of noxious stimuli, such as their location or intensity, and their motivational/emotive dimension. Among the recently unravelled molecular markers of AS neurons is the developmentally-expressed transcription factor Phox2a, affording us the opportunity to selectively disrupt the embryonic wiring of AS neurons to gain insights into the logic of their adult function. Since mice with a spinal cord-specific loss of the netrin-1 receptor DCC have increased AS neuron innervation of ipsilateral brain targets and defective noxious stimulus localisation or topognosis, we generated mice of either sex carrying a deletion of Dcc in Phox2a neurons. Such DccPhox2a mice displayed impaired topognosis along the rostrocaudal axis, but with l...

A question relevant to nicotine addiction is how nicotine and other nicotinic receptor membrane-permeant ligands, such as the anti-smoking drug varenicline (Chantix), distribute in brain. Ligands, like varenicline, with high pKa and high-affinity for α4β2-type nicotinic receptors (α4β2Rs) are trapped in intracellular acidic vesicles containing α4β2Rs in vitro . Nicotine, with lower pKa and α4β2R affinity, is not trapped. Here, we extend our results by imaging nicotinic PET ligands in vivo in male and female mouse brain and identifying the trapping brain organelle in vitro as Golgi satellites (GSats). Two PET 18F-labelled imaging ligands were chosen: [18F]2-FA85380 (2-FA) with varenicline-like pKa and affinity and [18F]Nifene with nicotine-like pKa and affinity. [18F]2-FA PET-imaging kinetics were very slow consistent with 2-FA trapping in α4β2R-containing GSats. In contrast, [18F]Nifene kinetics were rapid, consistent with its binding to α4β2Rs but no trapping. Specific [18F]2-FA and [18F]Nifene signals we...

Habituation is a conserved adaptive process essential for incoming information assessment, which drives behavioral response decrement to recurrent inconsequential stimuli and does not involve sensory adaptation, or fatigue. Although the molecular mechanisms underlying the process are not well understood, habituation has been reported defective in a number of disorders including schizophrenia. We demonstrate that loss of furin1 , the Drosophila homolog of a gene whose transcriptional downregulation has been linked to schizophrenia, results in defective habituation to recurrent footshocks in mixed sex populations. The deficit is reversible by transgenic expression of the Drosophila or human Furin in adult α,/β, mushroom body neurons and by acute oral delivery of the typical antipsychotic Haloperidol and the atypical Clozapine, which are commonly used to treat schizophrenic patients. The results validate the proposed contribution of Furin downregulation in schizophrenia and suggest that defective footshock ha...

Distinct computations are performed at multiple brain regions during the encoding of spatial environments. Neural representations in the hippocampal, entorhinal and head direction (HD) networks during spatial navigation have been clearly documented, while the representational properties of the Subicular Complex (SC) are relatively under-explored, even though it has extensive anatomical connections with various brain regions involved in spatial information processing. We simultaneously recorded single units from different sub-regions of the SC in male rats while they ran clockwise on a centrally placed textured circular track (four different textures, each covering a quadrant), surrounded by six distal cues. The neural activity was monitored in standard sessions by maintaining the same configuration between the cues, while in cue manipulation sessions, the distal and local cues were either rotated in opposite directions to create a mismatch between them, or the distal cues were removed. We report a highly c...

There is currently no robust method to evaluate how built environment design affects our emotion. Understanding emotion is significant, as it influences cognitive processes, behaviour, and wellbeing, and is linked to the functioning of physiological systems. As mental health problems are becoming more prevalent, and exposure to indoor environments is increasing, it is important we develop rigorous methods to understand whether design elements in our environment affect emotion. This study examines whether the scale of interior built environments modulate neural networks involved in emotion regulation. Using a cave automatic virtual environment and controlling for indoor environmental quality, 66 adults (31 female, aged 18-55) were exposed to context-neutral enclosed indoor room scenes to understand whether built environment scale affected self-report, autonomic nervous system, and central nervous system correlates of emotion. Our results revealed enlarged scale increased electroencephalography (EEG) power i...