Human lesions and animal studies link the claustrum to perception, salience, sleep and pain.

The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role of the claustrum remains unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of signs and symptoms, including changes in cognitive, perceptual and motor abilities; electrical activity; mental state; and sleep. The wide range of symptoms observed following claustral lesions do not provide compelling evidence to support prominent current theories of claustrum function such as multisensory integration or salience computation. Conversely, the lesions studies support the hypothesis that the claustrum regulates cortical excitability. We argue that the claustrum is connected to, or part of, multiple brain networks that perform both fundamental and higher cognitive functions. As a multifunctional node in numerous networks, this may explain the manifold effects of claustrum damage on brain and behaviour.

Goal-Dependent Use of Temporal Regularities to Orient Attention under Spatial and Action Uncertainty.

The temporal regularities in our environments support the proactive dynamic anticipation of relevant events. In visual attention, one important outstanding question is whether temporal predictions must be linked to predictions about spatial locations or motor plans to facilitate behaviour. To test this, we developed a task for manipulating temporal expectations and task relevance of visual stimuli appearing within rapidly presented streams, while stimulus location and responding hand remained uncertain. Differently coloured stimuli appeared in one of two concurrent (left and right) streams with distinct temporal probability structures. Targets were defined by colour on a trial-by-trial basis and appeared equiprobably in either stream, requiring a localisation response. Across two experiments, participants were faster and more accurate at detecting temporally predictable targets compared to temporally unpredictable targets. We conclude that temporal expectations learned incidentally from temporal regularities can be called upon flexibly in a goal-driven manner to guide behaviour. Moreover, we show that visual temporal attention can facilitate performance in the absence of concomitant spatial or motor expectations in dynamically unfolding contexts.

Transient beta activity and cortico-muscular connectivity during sustained motor behaviour.

Neural oscillations are thought to play a central role in orchestrating activity states between distant neural populations. For example, during isometric contraction, 13-30 Hz beta activity becomes phase coupled between the motor cortex and the contralateral muscle. This and related observations have led to the proposal that beta activity and connectivity sustain stable cognitive and motor states - or the 'status quo' - in the brain. Recently, however, beta activity at the single-trial level has been shown to be short-lived - though so far this has been reported for regional beta activity in tasks without sustained motor demands. Here, we measured magnetoencephalography (MEG) and electromyography (EMG) in 18 human participants performing a sustained isometric contraction (gripping) task. If cortico-muscular beta connectivity is directly responsible for sustaining a stable motor state, then beta activity within single trials should be (or become) sustained in this context. In contrast, we found that motor beta activity and connectivity with the downstream muscle were transient. Moreover, we found that sustained motor requirements did not prolong beta-event duration in comparison to rest. These findings suggest that neural synchronisation between the brain and the muscle involves short 'bursts' of frequency-specific connectivity, even when task demands - and motor behaviour - are sustained.

Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice.

Chronic pain is a widespread debilitating condition affecting millions of people worldwide. Although several pharmacological treatments for relieving chronic pain have been developed, they require frequent chronic administration and are often associated with severe adverse events, including overdose and addiction. Persistent increased sensitization of neuronal subpopulations of the peripheral and central nervous system has been recognized as a central mechanism mediating chronic pain, suggesting that inhibition of specific neuronal subpopulations might produce antinociceptive effects. We leveraged the neurotoxic properties of the botulinum toxin to specifically silence key pain-processing neurons in the spinal cords of mice. We show that a single intrathecal injection of botulinum toxin conjugates produced long-lasting pain relief in mouse models of inflammatory and neuropathic pain without toxic side effects. Our results suggest that this strategy might be a safe and effective approach for relieving chronic pain while avoiding the adverse events associated with repeated chronic drug administration.