Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Treatment of Patients With Concussion

ObjectiveInvestigate the efficacy of 3 anti-Calcitonin Gene-Related Peptide monoclonal antibodies (anti-CGRP mAbs), fremanezumab, galcanezumab, and erenumab, in concussion patients with post-traumatic headache (PTH) with a migraine phenotype.BackgroundA study using monoclonal antibodies in mice with mild traumatic brain injury saw improvements in cutaneous allodynia.1 A study from Denmark using erenumab for PTH found patients had an 82% decrease in the number of headache days. This study also demonstrated that 44% of patients had a reduction in HIT-6 score = 5 after 9–12 weeks of treatment.2.Design/MethodsRetrospective chart review of patients diagnosed with PTH (n = 168) evaluated HIT-6, number of reported headache days, and the number of modifiable concussion variables (headache, dizziness, attention/concentration deficit, mood and sleep disturbance) prior to initiation of anti-CGRP mAbs and after at least 3 months of treatment were recorded.ResultsPatients saw a decrease in HIT-6 score (p < 0.0001), with a mean difference of −4.26 from pre-treatment to at least 3 months after treatment. When evaluating 5 concussion symptom categories, patients experienced x¯ = 2.35 symptoms prior to anti-CGRP mAbs treatment, and x¯ = 1.67 after at least 3 months of treatment. Patients also experienced a decrease in the number of headache days per month (<0.0001) with a mean difference of −7.25 (range 0–30) headache days per month. Seven patients experienced adverse effects (1 patient had 2 different adverse effects), including injection site rash, fatigue, constipation, and dizziness. Only one patient discontinued medication due to adverse event.ConclusionsAnti-CGRP mAbs used to treat PTH showed improved headache severity and frequency, as well as a decreased number of overall concussion symptoms. There was a subset of patients with a more robust response. Switching anti-CGRP mAbs was beneficial in some patients.

The Reaction Switching Produces A Greater Bias to Prepotent Response than Reaction Inhibition

There is a discussion about common or various mechanisms of response inhibition and response switching. To understand these mechanisms, we used a modified Go/NoGo task with three stimulus categories. The subjects were instructed to press a button in response to frequent Go stimuli, press another button in response to rare Go stimuli and hold any motor response following the presentation of NoGo stimuli. The results showed a decrease in reaction time for frequent Go, following both categories of rare stimuli and the decrease was greater following rare Go. Also, the total number of errors did not differ between Go and NoGo, however, a greater bias of error rate towards frequent Go stimuli was found for rare Go compared to NoGo. Finally, positive correlations were found between the increase in reaction time for rare Go compared to frequent Go and the number of errors for both rare Go and rare NoGo. Together, these results indicate that both rare Go and NoGo stimuli required to inhibit the prepotent response, but rare Go in comparison to NoGo stimuli also evoked a conflict between prepotent and alternative responses, which is expressed in greater response bias toward frequent Go.

Differential patterns of brain activation between hoarding disorder and obsessive-compulsive disorder during executive performance

BackgroundPreliminary evidence suggests that hoarding disorder (HD) and obsessive-compulsive disorder (OCD) may show distinct patterns of brain activation during executive performance, although results have been inconclusive regarding the specific neural correlates of their differential executive dysfunction. In the current study, we aim to evaluate differences in brain activation between patients with HD, OCD and healthy controls (HCs) during response inhibition, response switching and error processing.MethodsWe assessed 17 patients with HD, 18 patients with OCD and 19 HCs. Executive processing was assessed inside a magnetic resonance scanner by means of two variants of a cognitive control protocol (i.e. stop- and switch-signal tasks), which allowed for the assessment of the aforementioned executive domains.ResultsOCD patients performed similar to the HCs, differing only in the number of successful go trials in the switch-signal task. However, they showed an anomalous hyperactivation of the right rostral anterior cingulate cortex during error processing in the switch-signal task. Conversely, HD patients performed worse than OCD and HC participants in both tasks, showing an impulsive-like pattern of response (i.e. shorter reaction time and more commission errors). They also exhibited hyperactivation of the right lateral orbitofrontal cortex during successful response switching and abnormal deactivation of frontal regions during error processing in both tasks.ConclusionsOur results support that patients with HD and OCD present dissimilar cognitive profiles, supported by distinct neural mechanisms. Specifically, while alterations in HD resemble an impulsive pattern of response, patients with OCD present increased error processing during response conflict protocols.

Dissociable neural circuits underlie the resolution of three discrete sources of competition during task-switching

Humans perform sub-optimally when juggling more than one task, but are nonetheless required to multitask during many daily activities. Rapidly and effectively switching attentional focus between tasks is fundamental to navigating complex environments. Task-switching paradigms in conjunction with neuroimaging have identified brain networks underpinning flexible reallocation of cognitive resources and a core network of neural regions is repeatedly implicated (i.e., posterior parietal, inferior frontal, anterior cingulate, and middle frontal cortex). Performance costs such as reduced accuracy and slowed responses accompany the first execution of a task following a task-switch. These costs stem from three main sources of competition: 1) the need to reconfigure task-rules, 2) the immediate history of motor responding, and 3) whether inputs to be acted upon provide congruent or incongruent information regarding the appropriate motor response, relative to the recently “switched-away-from” task. Here, we asked whether both common (domain-general) and non-overlapping (dissociable) neural circuits were involved in resolving these three distinct sources of competition under high-demand task-switching conditions. Dissociable neural circuits were active in resolving each of the three sources of competition. No domain-general regions were implicated in all three. Rather, two regions were common across rule-switching and stimulus incongruence, and five regions to incongruence and response-switching. Each source of conflict elicited activation from many regions including the posterior cingulate, thalamus, and cerebellum, regions not commonly implicated in the task-switching literature. These results suggest that dissociable neural networks are principally responsible for resolving different sources of competition, but with partial interaction of some overlapping domain-general circuitry.

Measuring habit formation through goal-directed response switching

Reward-learning theory views habits as stimulus–response links formed through extended reward training. Accordingly, animal research has shown that actions that are initially goal-directed can become habitual after operant overtraining. However, a similar demonstration is absent in human research, which poses a serious problem for translational models of behavior. We propose that response-time (RT) switch cost after operant training can be used as a new, reliable marker for the operation of the habit system in humans. Using a new method, we show that RT switch cost demonstrates the properties that would be expected of a habitual behavior: (1) it increases with overtraining; (2) it increases when rewards are larger, and (3) it increases when time pressure is added to the task, thereby hindering the competing goal-directed system. These results offer a promising new pathway for studying the operation of the habit system in humans.

Coats’ Disease-Related Macular Edema Treated with Combined Aflibercept and Laser Photocoagulation

Purpose. To describe the clinical response of refractory macular edema associated with Coats’ disease following treatment with aflibercept and laser photocoagulation. Methods. Case report. Results. A 17-year-old female presented with decreased vision of the left eye. Ophthalmic exam demonstrated intraretinal hemorrhages and exudation with associated edema centrally. Angiographic evaluation revealed central leaking microaneurysms and peripheral capillary dropout. These findings and a systemic work-up that yielded an incidental Factor V Leiden mutation lead to a diagnosis of Coats’ disease. Initial treatment consisted of laser photocoagulation and intravitreal bevacizumab but with poor response. Switching to intravitreal aflibercept resulted in resolution of the refractory macular edema and improvement of visual acuity to 20/25 in the left eye. Conclusion. We describe a case of refractory macular edema which responded more favorably to intravitreal aflibercept compared with bevacizumab when combined with laser photocoagulation in a patient with Coats’ disease.