RESUMEN
Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.
Asunto(s)
Electroencefalografía , Estimulación Magnética Transcraneal , Masculino , Humanos , Femenino , Ritmo Teta/fisiología , Lóbulo Parietal/fisiología , Corteza Prefrontal/fisiología , Memoria a Corto Plazo/fisiologíaRESUMEN
Lacosamide enhances slow inactivation of voltage-gated sodium channels and can lead to dose-dependent PR interval prolongation. Previously, lacosamide has been associated with second-degree atrioventricular (AV) heart block in the context of multiple medical comorbidities and/or in the elderly with multimorbidity on other dromotropic agents. We report a case of second-degree AV block occurring in a healthy, athletic young adult. The patient had baseline bradycardia with no known cardiac comorbidities. He was exquisitely sensitive to lacosamide with EKG and telemetry changes developing on the order of hours after receiving intravenous lacosamide. Lacosamide was subsequently stopped, the second-degree AV block was no longer present and EKG returned to baseline. We hypothesize that his sensitivity to lacosamide-induced AV block was possibly secondary to his baseline bradycardia with early repolarization changes. The case underscores the importance of surveillance cardiac monitoring. While medical comorbidities and an older age may portend a greater risk of PR prolongation, routine EKGs should be considered in all patients receiving lacosamide.
RESUMEN
Aggression is a complex behavior that is essential for survival. Of the various forms of aggression, impulsive violent displays without prior planning or deliberation are referred to as affective aggression. Affective aggression is thought to be caused by aberrant perceptions of, and consequent responses to, threat. Understanding the neuronal networks that regulate affective aggression is pivotal to development of novel approaches to treat chronic affective aggression. Here, we provide a detailed anatomical map of neuronal activity in the forebrain of two inbred lines of mice that were selected for low (NC100) and high (NC900) affective aggression. Attack behavior was induced in male NC900 mice by exposure to an unfamiliar male in a novel environment. Forebrain maps of c-Fos+ nuclei, which are surrogates for neuronal activity during behavior, were then generated and analyzed. NC100 males rarely exhibited affective aggression in response to the same stimulus, thus their forebrain c-Fos maps were utilized to identify unique patterns of neuronal activity in NC900s. Quantitative results indicated robust differences in the distribution patterns and densities of c-Fos+ nuclei in distinct thalamic, subthalamic, and amygdaloid nuclei, together with unique patterns of neuronal activity in the nucleus accumbens and the frontal cortices. Our findings implicate these areas as foci regulating differential behavioral responses to an unfamiliar male in NC900 mice when expressing affective aggression. Based on the highly conserved patterns of connections and organization of neuronal limbic structures from mice to humans, we speculate that neuronal activities in analogous networks may be disrupted in humans prone to maladaptive affective aggression.