Macaque anterior cingulate cortex deactivation impairs performance and alters lateral prefrontal oscillatory activities in a rule-switching task.

In primates, both the dorsal anterior cingulate cortex (dACC) and the dorsolateral prefrontal cortex (dlPFC) are key regions of the frontoparietal cognitive control network. To study the role of the dACC and its communication with the dlPFC in cognitive control, we recorded local field potentials (LFPs) from the dlPFC before and during the reversible deactivation of the dACC, in macaque monkeys engaging in uncued switches between 2 stimulus-response rules, namely prosaccade and antisaccade. Cryogenic dACC deactivation impaired response accuracy during maintenance of-but not the initial switching to-the cognitively demanding antisaccade rule, which coincided with a reduction in task-related theta activity and the correct-error (C-E) difference in dlPFC beta-band power. During both rule switching and maintenance, dACC deactivation prolonged the animals' reaction time and reduced task-related alpha power in the dlPFC. Our findings support a role of the dACC in prefrontal oscillatory activities that are involved the maintenance of a new, challenging task rule.

Neural correlates for task switching in the macaque superior colliculus.

Successful task switching requires a network of brain areas to select, maintain, implement, and execute the appropriate task. Although frontoparietal brain areas are thought to play a critical role in task switching by selecting and encoding task rules and exerting top-down control, how brain areas closer to the execution of tasks participate in task switching is unclear. The superior colliculus (SC) integrates information from various brain areas to generate saccades and is likely influenced by task switching. Here, we investigated switch costs in nonhuman primates and their neural correlates in the activity of SC saccade-related neurons in monkeys performing cued, randomly interleaved pro- and anti-saccade trials. We predicted that behavioral switch costs would be associated with differential modulations of SC activity in trials on which the task was switched vs. repeated, with activity on the current trial resembling that associated with the task set of the previous trial when a switch occurred. We observed both error rate and reaction time switch costs and changes in the discharge rate and timing of activity in SC neurons between switch and repeat trials. These changes were present later in the task only after fixation on the cue stimuli but before saccade onset. These results further establish switch costs in macaque monkeys and suggest that SC activity is modulated by task-switching processes in a manner inconsistent with the concept of task set inertia.NEW & NOTEWORTHY Task-switching behavior and superior colliculus (SC) activity were investigated in nonhuman primates performing randomly interleaved pro- and anti-saccade tasks. Here, we report error rate and reaction time switch costs in macaque monkeys and associated differences in stimulus-related activity of saccade-related neurons in the SC. These results provide a neural correlate for task switching and suggest that the SC is modulated by task-switching processes and may reflect the completion of task set reconfiguration.

Dorsolateral Prefrontal Cortex Deactivation in Monkeys Reduces Preparatory Beta and Gamma Power in the Superior Colliculus.

Cognitive control requires the selection and maintenance of task-relevant stimulus-response associations, or rules. The dorsolateral prefrontal cortex (DLPFC) has been implicated by lesion, functional imaging, and neurophysiological studies to be involved in encoding rules, but the mechanisms by which it modulates other brain areas are poorly understood. Here, the functional relationship of the DLPFC with the superior colliculus (SC) was investigated by bilaterally deactivating the DLPFC while recording local field potentials (LFPs) in the SC in monkeys performing an interleaved pro- and antisaccade task. Event-related LFPs showed differences between pro- and antisaccades and responded prominently to stimulus presentation. LFP power after stimulus onset was higher for correct saccades than erroneous saccades. Deactivation of the DLPFC did not affect stimulus onset related LFP activity, but reduced high beta (20-30 Hz) and high gamma (60-150 Hz) power during the preparatory period for both pro- and antisaccades. Spike rate during the preparatory period was positively correlated with gamma power and this relationship was attenuated by DLPFC deactivation. These results suggest that top-down control of the SC by the DLPFC may be mediated by beta oscillations.

Stable Task Representations under Attentional Load Revealed with Multivariate Pattern Analysis of Human Brain Activity.

Performing multiple tasks concurrently places a load on limited attentional resources and results in disrupted task performance. Although human neuroimaging studies have investigated the neural correlates of attentional load, how attentional load affects task processing is poorly understood. Here, task-related neural activity was investigated using fMRI with conventional univariate analysis and multivariate pattern analysis (MVPA) while participants performed blocks of prosaccades and antisaccades, either with or without a rapid serial visual presentation (RSVP) task. Performing prosaccades and antisaccades with RSVP increased error rates and RTs, decreased mean activation in frontoparietal brain areas associated with oculomotor control, and eliminated differences in activation between prosaccades and antisaccades. However, task identity could be decoded from spatial patterns of activation both in the absence and presence of an attentional load. Furthermore, in the FEFs and intraparietal sulcus, these spatial representations were found to be similar using cross-trial-type MVPA, which suggests stability under attentional load. These results demonstrate that attentional load may disrupt the strength of task-related neural activity, rather than the identity of task representations.

Insight into motor control and motor impairment from stroke and beta oscillations.

Beta oscillations are associated with motor function and are thought to play a role in movement impairment. In a recent magnetoencephalography (MEG) study, Rossiter et al. (J Neurophysiol 112: 2053-2058, 2014) found a disruption in the modulation of movement-related beta oscillations in stroke patients that correlated with motor impairment. We discuss how beta oscillatory measures characterize motor impairment, the implications of stroke variability, and the potential role of GABA in modulating oscillations following stroke and during stroke recovery.

An Eye on the First Surgical Side: Appreciating the Potential Impacts of a Second DBS Lead on Ipsilateral Symptoms.

Clinical Vignette: A 63-year-old man with severe essential tremor underwent staged bilateral ventralis intermedius (Vim) deep brain stimulation (DBS). Left Vim DBS resulted in improved right upper extremity tremor control. Months later, the addition of right Vim DBS to the other brain hemisphere was associated with acute worsening of the right upper extremity tremor. Clinical Dilemma: In staged bilateral Vim DBS, second lead implantation may possibly alter ipsilateral tremor control. While ipsilateral improvement is common, rarely, it can disrupt previously achieved benefit. Clinical Solution: DBS programming, including an increase in left Vim DBS amplitude, re-established and enhanced bilateral tremor control. Gap in Knowledge: The mechanisms underlying changes in ipsilateral tremor control following a second lead implantation are unknown. In this case, worsening and subsequent improvement after optimization highlight the potential impact of DBS implantation on the ipsilateral side. Expert Commentary: After staged bilateral Vim DBS, clinicians should keep an eye on the first or original DBS side and carefully monitor for emergent side effects or worsening in tremor. Ipsilateral effects resulting from DBS implantation present a reprogramming opportunity with a potential to further optimize clinical outcomes. Highlights: This case report highlights the potential for ipsilateral tremor worsening following staged bilateral DBS and provides valuable insights into troubleshooting and reprogramming strategies. The report emphasizes the importance of vigilant monitoring and individualized management in optimizing clinical outcomes for patients undergoing staged bilateral DBS for essential tremor.

Current perspectives on tractography-guided deep brain stimulation for the treatment of mood disorders.

INTRODUCTION: Deep brain stimulation (DBS) is an emerging therapy for mood disorders, particularly treatment-resistant depression (TRD). Different brain areas implicated in depression-related brain networks have been investigated as DBS targets and variable clinical outcomes highlight the importance of target identification. Tractography has provided insight into how DBS modulates disorder-related brain networks and is being increasingly used to guide DBS for psychiatric disorders. AREAS COVERED: In this perspective, an overview of the current state of DBS for TRD and the principles of tractography is provided. Next, a comprehensive review of DBS targets is presented with a focus on tractography. Finally, the challenges and future directions of tractography-guided DBS are discussed. EXPERT OPINION: Tractography-guided DBS is a promising tool for improving DBS outcomes for mood disorders. Tractography is particularly useful for targeting patient-specific white matter tracts that are not visible using conventional structural MRI. Developments in tractography methods will help refine DBS targeting for TRD and may facilitate symptom-specific precision neuromodulation. Ultimately, the standardization of tractography methods will be essential to transforming DBS into an established therapy for mood disorders.

The effects of attentional load on saccadic task switching.

Everyday life requires the ability to flexibly switch between tasks. Often, task switching is accompanied by concurrent cognitive activities that compete for limited attentional resources. This study aimed to characterize the effects of attentional load on task switching. In experiment 1, participants performed an interleaved pro-saccade and anti-saccade task. In experiment 2, participants performed an interleaved pro-saccade and anti-saccade task simultaneously with a rapid serial visual presentation task that has been shown to create an attentional load. Error rates and reaction times of pro-saccades and anti-saccades were analysed for both experiments separately and together. Overall, error rates and reaction times increased with attentional load. With attentional load, switches to pro-saccades were associated with increased error rates and reaction times, whereas switches to anti-saccades were only associated with increased error rates. We propose that attentional load interferes with neural task-set representation and that the resulting executive control is different for the dominant and non-dominant task.

What can fMRI tell us about functional variability in the oculomotor system and saccade performance?

Eye movement behavior is variable, and the brain's oculomotor circuitry may not always function consistently. In a recent fMRI study, Ozyurt and Greenlee (2011) correlated the activation strength of cortical and striatal brain regions with inter- and intraindividual variability in saccade performance. We discuss the design and implications of this study with regard to the differences between inter- and intraindividual variability, and the link between the BOLD signal and oculomotor activity.

Myoclonus and cerebellar ataxia associated with COVID-19: a case report and systematic review.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in December 2019, neurological manifestations have been recognized as potential complications. Relatively rare movement disorders associated with COVID-19 are increasingly reported in case reports or case series. Here, we present a case and systematic review of myoclonus and cerebellar ataxia associated with COVID-19. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline using the PubMed and Ovid MEDLINE databases, from November 1, 2019 to December 6, 2020. RESULTS: 51 cases of myoclonus or ataxia associated with COVID-19, including our case, were identified from 32 publications. The mean age was 59.6 years, ranging from 26 to 88 years, and 21.6% were female. Myoclonus was multifocal or generalized and had an acute onset, usually within 1 month of COVID-19 symptoms. Myoclonus occurred in isolation (46.7%), or with ataxia (40.0%) or cognitive changes (30.0%). Most cases improved within 2 months, and treatment included anti-epileptic medications or immunotherapy. Ataxia had an acute onset, usually within 1 month of COVID-19 symptoms, but could be an initial symptom. Concurrent neurological symptoms included cognitive changes (45.5%), myoclonus (36.4%), or a Miller Fisher syndrome variant (21.2%). Most cases improved within 2 months, either spontaneously or with immunotherapy. CONCLUSIONS: This systematic review highlights myoclonus and ataxia as rare and treatable post-infectious or para-infectious, immune-mediated phenomena associated with COVID-19. The natural history is unknown and future investigation is needed to further characterize these movement disorders and COVID-19.

The Amplatzer™ Cardiac Plug 2 for left atrial appendage occlusion: novel features and first-in-man experience.

Percutaneous left atrial appendage (LAA) closure is becoming a frequently performed procedure for patients with atrial fibrillation and high haemorrhagic risk. The Amplatzer™ Cardiac Plug (ACP) is one of the most commonly used devices for this purpose. Despite high success rate and low procedure risk associated with the ACP, a second generation of the device is now available. The new ACP has been designed to facilitate the implantation process, improve sealing performance and further reduce the risk of complications. The present report focuses on the novel features of the second generation of the Amplatzer™ Cardiac Plug (ACP 2 or Amulet™) and describes the first-in-man experience.

Word wins over face: emotional Stroop effect activates the frontal cortical network.

The prefrontal cortex (PFC) has been implicated in higher order cognitive control of behavior. Sometimes such control is executed through suppression of an unwanted response in order to avoid conflict. Conflict occurs when two simultaneously competing processes lead to different behavioral outcomes, as seen in tasks such as the anti-saccade, go/no-go, and the Stroop task. We set out to examine whether different types of stimuli in a modified emotional Stroop task would cause similar interference effects as the original Stroop-color/word, and whether the required suppression mechanism(s) would recruit similar regions of the medial PFC (mPFC). By using emotional words and emotional faces in this Stroop experiment, we examined the two well-learned automatic behaviors of word reading and recognition of face expressions. In our emotional Stroop paradigm, words were processed faster than face expressions with incongruent trials yielding longer reaction times and larger number of errors compared to the congruent trials. This novel Stroop effect activated the anterior and inferior regions of the mPFC, namely the anterior cingulate cortex, inferior frontal gyrus as well as the superior frontal gyrus. Our results suggest that prepotent behaviors such as reading and recognition of face expressions are stimulus-dependent and perhaps hierarchical, hence recruiting distinct regions of the mPFC. Moreover, the faster processing of word reading compared to reporting face expressions is indicative of the formation of stronger stimulus-response associations of an over-learned behavior compared to an instinctive one, which could alternatively be explained through the distinction between awareness and selective attention.