Visual salience of the stop signal affects the neuronal dynamics of controlled inhibition

The voluntary control of movement is often tested by using the countermanding, or stop-signal task that sporadically requires the suppression of a movement in response to an incoming stop-signal. Neurophysiological recordings in monkeys engaged in the countermanding task have shown that dorsal premotor cortex (PMd) is implicated in movement control. An open question is whether and how the perceptual demands inherent the stop-signal affects inhibitory performance and their underlying neuronal correlates. To this aim we recorded multi-unit activity (MUA) from the PMd of two male monkeys performing a countermanding task in which the salience of the stop-signals was modulated. Consistently to what has been observed in humans, we found that less salient stimuli worsened the inhibitory performance. At the neuronal level, these behavioral results were subtended by the following modulations: when the stop-signal was not noticeable compared to the salient condition the preparatory neuronal activity in PMd started to be affected later and with a less sharp dynamic. This neuronal pattern is probably the consequence of a less efficient inhibitory command useful to interrupt the neural dynamic that supports movement generation in PMd

Visual salience of the stop-signal affects movement suppression process

We investigated how the ability to suppress an impending movement is affected by the visual salience of the stop-signal in a reaching countermanding task. We found that when the stop-signal was easy to detect, stop performance was better than when the stop-signal was difficult to detect. In an exploratory analysis, we also found that the change in salience of the stop-signal can have an effect on the speed of response in trials following the stop-signal. This effect occurred together with strategic slowing down after an error in inhibiting was committed and together with a repetition priming effect due to the stop-signal presented in the previous trial. Our results suggest the need to investigate more in depth the afferent processing stage of the inhibitory control of movement and how task demands can affect its functioning

Neuronal correlates of motivated inhibition in monkey motor cortices

The ability to rapidly inhibit actions is critical to the effective and flexible interactions with the environment, and it has been widely studied by using the countermanding (stop-signal) task. An open question is how this ability can be affected by other cognitive functions, such as motivation, and relatedly, which are the neural correlates of this influence. To address this question we designed a combined countermanding/motivation task intended to modulate the motivation to stop and to move by using the reward prospect, and we recorded the Multi-Unit Activity (MUA) by means of Utah arrays (2x48 channels) from the dorsal premotor cortex (PMd) and the primary motor cortex (M1) of a macaque monkey while engaged in the task. Indeed previous data have shown that motor cortices neuronal activity signals both movement inhibition (Mattia et al., 2013) and reward (Roesch and Olson, 2004), but it is unclear whether and how these phenomena are combined. In the countermanding/motivation task, the monkey was instructed to reach to a target after a go signal (no-stop trials) but to withhold his response when a stop-signal followed after a variable delay (stop trials). In every trial, one out of three possible reward cues (RC) was presented 1 sec before the go signal to inform about the amount of reward that would have been delivered if a correct response had been produced. RC conditions were: Go+Stop- with a higher reward for no-stop trials compared to the stop trials; Go-Stop+, with reversed reward amounts; and Go Stop with equal amounts delivered. We found that the monkey strategically adapted his behavior to the different reward prospects: reaction times (RTs) diminished and the probability of errors in the stop trials increased from Go-Stop+, to Go Stop and then to Go+Stop- conditions. Recorded MUA in both PMd and M1 was modulated by task conditions. In some channels (22/96), MUA was significantly modulated before go signal by the RC value. Of these channels, 41% showed a progressive increase of MUA after the RC presentation until movement onset; this activity was progressively higher for Go-Stop+, Go Stop and Go+Stop-. Fifty-five percent showed a decrease during the RT epoch and a further increase of MUA just before or after movement onset. Others channels (48/96) showed RC related modulations around movement onset and/or after reaching the final target but not before go signal. Interestingly, in correct stop trials, some of the channels showed an early stop-signal response which magnitude was affected by the RC value. These results suggest that motor cortices can signal and integrate motivational aspects into movement control and inhibition

Persistence of cortical neuronal activity in the dying brain

We report the presence of cortical electrical activity persisting for about 120 min after cardiac arrest. The general consensus is that interruption of brain blood flow triggers a chain of electrophysiological phenomena: oscillatory activity rises in the first tens of seconds [1], followed by a depression of both oscillatory and spiking activities, and then by a slow spreading depolarization due to the beginning of irreversible degenerative processes at the cellular level [2–4]. The spreading depolarization is characterized by direct current changes that can last up to tens of minutes and it has been described by using coarsegrained electroencephalography and electrocorticography measures. As such, low-amplitude and faster local phenomena might have been missed. To address whether some brain activity at a microscale can persist for longer periods after cardiac arrest, we recorded the intraparenchymal activity in the frontal cortex of an adult male macaque monkey using a multi-electrode miniaturized array to monitor neuronal activities during the standard end of a protocol-established euthanasia procedure. Both local field potentials (LFPs) and multi-unit activities (MUAs) [5] were recorded starting from the deep sedated state (induction by ketamine and medetomidine hydrochloride; mixture isoflurane/oxygen to effect), and well beyond the cardiorespiratory arrest caused by the intravascular bolus injection of pentothal sodium. During the initial deep anaesthesia stage, neuronal activity displayed the typical burst suppression regime with irregular LFP and MUA oscillations (Fig. 1a-b). This activity strongly reduced after cardiac arrest (Fig. 1c). However, after about 20 min, bursts of LFPs re-emerged sparse in time up to about 120 min, each displaying a peak of power at 1–3 Hz in the Fourier spectrograms. Importantly, these bursts were accompanied by a supra- and subthreshold MUA modulations giving rise to a significant time-delayed LFP-MUA coupling (see Fig. 1d). Although confined to a single subject, our results prove that the dying brain at the microscale can show electrophysiological activity for long time after cardiac arrest. Importantly, this activity appears after a period of relative silence and it is characterized by a peculiar temporal relationship between LFP and MUA in several electrodes suggesting a non-local origin. This would require a common synaptic input which in principle could be provided by brainstem structures that are typically more resistant to anoxia [4]. We think that our data contribute in posing fundamental questions about the nature of the transition to the death state. For example, what is the metabolic state associated with this process? Can spontaneous (or artificially induced) enhanced neuromodulation be of help in augmenting the resilience to global ischemia? Our finding outlines the importance of investigating the neurobiology of dying with intraparenchymal high-resolution approaches. This could help in addressing central medical questions like the definition of death, the proper timing and the adequate sedation for organ transplantation, and the development of resuscitation and recovery procedures. Whether this activity is a sign of intact brain processing needs further studies

Action selection uncertainty in the test phase of a transitive inference task: Neuronal correlates in monkey premotor cortex.

Cognitively advanced animals are able to dynamically interact with the environment. In this process, action selection could be strongly influenced by the confidence value assigned to single items in the stream of incoming sensory information. A form of dynamic representation of the environment is the organization of learned items in hierarchically ordered series. In a 6-items transitive inference task, when the list A > B > C > D > E > F is finally created, the probability of choosing B in the pair BC is lower than for the pair BE suggesting that the confidence for the value of B is variable and related to the mental representation of all other elements presented/experienced together. This relationship between performance and symbol separation is also know as symbolic distance effect. Previous work has focused on the contribution of sensory information to confidence. We explored how confidence on target value could influence action selection by measuring neuronal activity in the premotor cortex of 2 trained monkeys. We selected neurons with activity modulated by the direction of movement and we analyzed how directionality is influenced by the symbolic distance of items to compare. Our results show that directionality in premotor cortex increases with symbolic distance and uncertainty providing support to the idea that the motor system contributes to perceptual confidence

High Cervical Spinal Cord Stimulation: A One Year Follow-Up Study on Motor and Non-Motor Functions in Parkinson’s Disease

Background: The present study investigated the effectiveness of stimulation applied at cervical levels on pain and Parkinson’s disease (PD) symptoms using either tonic or burst stimulation mode. Methods: Tonic high cervical spinal cord stimulation (T-HCSCS) was applied on six PD patients suffering from low back pain and failed back surgery syndrome, while burst HCSCS (B-HCSCS) was applied in twelve PD patients to treat primarily motor deficits. Stimulation was applied percutaneously with quadripolar or octapolar electrodes. Clinical evaluation was assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H&Y) scale. Pain was evaluated by a visual analog scale. Evaluations of gait and of performance in a cognitive motor task were performed in some patients subjected to B-HCSCS. One patient who also suffered from severe autonomic cardiovascular dysfunction was investigated to evaluate the effectiveness of B-HCSCS on autonomic functions. Results: B-HCSCS was more effective and had more consistent effects than T-HCSCS in reducing pain. In addition, B-HCSCS improved UPDRS scores, including motor sub-items and tremor and H&Y score. Motor benefits appeared quickly after the beginning of B-HCSCS, in contrast to long latency improvements induced by T-HCSCS. A slight decrease of effectiveness was observed 12 months after implantation. B-HCSCS also improved gait and ability of patients to correctly perform a cognitive–motor task requiring inhibition of a prepared movement. Finally, B-HCSCS ameliorated autonomic control in the investigated patient. Conclusions: The results support a better usefulness of B-HCSCS compared to T-HCSCS in controlling pain and specific aspects of PD motor and non-motor deficits for at least one year

Effect of Motivation on Movement Control: Neural Correlates in Dorsal Premotor Cortex

The dorsal premotor cortex (PMd) is a brain area involved in the control of movement. An open question is how the motivation can modulate this function. We trained a macaque monkey to a modified version of the countermanding task, in which Go trials (~65%) require to make a movement after a go signal, while Stop trials (~35%) require to inhibit the reactive movement after a stop signal. In each trial, an initial cue (1000 msec delay) informed about the potential amount of reward that would have been delivered if a correct response would have been produced. The meaning of the cue for correct responses was different. In the Go+Stop- condition the cue indicated more reward for the Go trials and less reward for the Stop trials. The opposite was in the Go-Stop+ condition. The cue was not informative (neutral) for the GoStop condition. We found that the monkey adapted his behavior to the cue value: faster reaction times in Go trials and higher error rate in Stop trials diminished from Go+Stop-, to GoStop and then to Go-Stop+ conditions. In PMd we found that 43/74 neurons recorded distinguished between conditions: some of them started to differentiate between conditions after 500msec from the cue, others close to the go signal. Seventeen/43 neurons were directly involved in movement control and showed different responses to the stop signal presentation depending on the cue presented. These data suggest that in PMd motivational information is integrated into neural mechanism of movement control by a heterogeneous dynamic

Atrophic degeneration of cerebellum impairs both the reactive and the proactive control of movement in the stop signal paradigm

The cognitive control of movement suppression, including performance monitoring, is one of the core properties of the executive system. A complex cortical and subcortical network involving cerebral cortex, thalamus, subthalamus, and basal ganglia, has been regarded as the neural substrate of inhibition of programmed movements. By using the countermanding task, a suitable tool to explore behavioral components of movement suppression, the contribution of the cerebellum in the proactive control and monitoring of voluntary action has been recently described in patients affected by focal lesions involving in particular the cerebellar dentate nucleus. Here we evaluated the performance on the countermanding task in a group of patients with cerebellar degeneration, in which the cerebellar cortex was diffusely affected, and showed that they display additionally a longer latency in countermanding engaged movements. Overall, the present data confirm the role of the cerebellum in executive control of action inhibition by extending the contribution to reactive motor suppression