Central effects of erenumab in migraine patients

Neurology ◽  
2020 ◽  
Vol 95 (20) ◽  
pp. e2794-e2802 ◽  
Author(s):  
Christian Ziegeler ◽  
Jan Mehnert ◽  
Katharina Asmussen ◽  
Arne May
Keyword(s):  
Middle Temporal Gyrus ◽  
Migraine Treatment ◽  
Cgrp Receptor ◽  
Central Effects ◽  
Lingual Gyrus ◽  
Fmri Study ◽  
Calcitonin Gene ◽  
Central Mode ◽  
The Right ◽  
Hypothalamic Activation

ObjectiveTo determine whether erenumab, a new monoclonal antibody to the calcitonin gene-related peptide (CGRP) receptor, exerts functional central effects in migraineurs by performing functional imaging scans on patients treated with erenumab.MethodsWe conducted an fMRI study on 27 patients with migraine using a well-established trigeminal nociceptive paradigm, examining patients before and 2 weeks after administration of the CGRP receptor antibody erenumab 70 mg.ResultsComparing both visit days in all patients (n = 27) revealed that erenumab leads to a decrease in activation in the right thalamus (i.e., contralateral to the stimulated side), right middle temporal gyrus, right lingual gyrus, left operculum, and several clusters on both sides of the cerebellum. Furthermore, when responders (n = 9) and nonresponders (n = 8) of the respective same headache state were compared, we found a significant reduction of hypothalamic activation after the administration of erenumab in responders only (t = 4.78; contrast estimate 29.79 [90% confidence interval 19.53–40.05]). This finding of reduced hypothalamic activation was confirmed when absolute headache days was used as a regressor.InterpretationThese findings suggest that erenumab may not be an exclusively peripheral migraine treatment but has additional central effects. Whether this is due to secondary changes after peripheral modulation of sensory input or indeed represents a direct central mode of action is discussed.

scholarly journals Effect of Calcitonin Gene-Related Peptide Receptor Antagonists on Migraine Treatment: A Meta-Analysis

2021 ◽  
Author(s):  
Jiyoung Kim ◽  
Kyoungjune Pak ◽  
Gha-Hyun Lee ◽  
Jae Wook Cho ◽  
Hyun-Woo kim
Keyword(s):  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Treatment ◽  
Acute Migraine ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists ◽  
Acute Migraine Treatment

Abstract Background: The pathophysiology of migraine has been researched incessantly, and it has been suggested that calcitonin gene-related peptide (CGRP) is associated with migraine attacks. CGRP receptor blockers are attracting attention for migraine prevention and treatment of acute episodes, and CGRP receptor antagonists have been shown to be effective in treating acute migraine headaches. This meta-analysis aimed to assess the effect of available CGRP receptor antagonists, focusing on their therapeutic doses for acute migraine treatment.Methods: We performed a systematic search of MEDLINE (from inception to March 2021) and EMBASE (from inception to March 2021) for English publications using the keywords “migraine” and “Calcitonin gene-related peptide,” limited to human studies.Results: Five studies that focused on examining the effects of CGRP receptor antagonists on acute migraine treatment met the eligibility criteria for this meta-analysis. The pooled analysis demonstrated that the CGRP receptor antagonist improved freedom from pain (OR=2.066, 95% confidence interval [CI] 1.766–2.418, I2=0%), absence of bothersome symptoms (OR=1.606, 95% CI=1.408–1.830, I2=0%), pain relief (OR=1.791, 95% CI=1.598–2.008, I2=0%), and freedom from nausea (OR=1.361, 95% CI=1.196–1.548, I2=0%), significantly more than the placebo. Conclusions: CGRP receptor antagonists are effective for acute migraine treatment and are expected to be used clinically as emerging therapeutic agents.

scholarly journals Processing of Targets in Smooth or Apparent Motion Along the Vertical in the Human Brain: An fMRI Study

2010 ◽  
Vol 103 (1) ◽  
pp. 360-370 ◽  
Author(s):  
Vincenzo Maffei ◽  
Emiliano Macaluso ◽  
Iole Indovina ◽  
Guy Orban ◽  
Francesco Lacquaniti
Keyword(s):  
Apparent Motion ◽  
Visual Motion ◽  
Brain Activity ◽  
Activity Patterns ◽  
Vertical Motion ◽  
Constant Speed ◽  
Lingual Gyrus ◽  
Fmri Study ◽  
Smooth Motion ◽  
The Right

Neural substrates for processing constant speed visual motion have been extensively studied. Less is known about the brain activity patterns when the target speed changes continuously, for instance under the influence of gravity. Using functional MRI (fMRI), here we compared brain responses to accelerating/decelerating targets with the responses to constant speed targets. The target could move along the vertical under gravity (1 g), under reversed gravity (−1 g), or at constant speed (0 g). In the first experiment, subjects observed targets moving in smooth motion and responded to a GO signal delivered at a random time after target arrival. As expected, we found that the timing of the motor responses did not depend significantly on the specific motion law. Therefore brain activity in the contrast between different motion laws was not related to motor timing responses. Average BOLD signals were significantly greater for 1 g targets than either 0 g or −1 g targets in a distributed network including bilateral insulae, left lingual gyrus, and brain stem. Moreover, in these regions, the mean activity decreased monotonically from 1 g to 0 g and to −1 g. In the second experiment, subjects intercepted 1 g, 0 g, and −1 g targets either in smooth motion (RM) or in long-range apparent motion (LAM). We found that the sites in the right insula and left lingual gyrus, which were selectively engaged by 1 g targets in the first experiment, were also significantly more active during 1 g trials than during −1 g trials both in RM and LAM. The activity in 0 g trials was again intermediate between that in 1 g trials and that in −1 g trials. Therefore in these regions the global activity modulation with the law of vertical motion appears to hold for both RM and LAM. Instead, a region in the inferior parietal lobule showed a preference for visual gravitational motion only in LAM but not RM.

scholarly journals Migraine therapeutics differentially modulate the CGRP pathway

Cephalalgia ◽  
2021 ◽  
Vol 41 (5) ◽  
pp. 499-514
Author(s):  
Minoti Bhakta ◽  
Trang Vuong ◽  
Tetsuya Taura ◽  
David S Wilson ◽  
Jennifer R Stratton ◽  
...  
Keyword(s):  
Small Molecule ◽  
Therapeutic Agents ◽  
Camp Signaling ◽  
Migraine Treatment ◽  
Cgrp Receptor ◽  
Calcitonin Gene ◽  
Migraine Pathogenesis ◽  
Cgrp Receptor Antagonists ◽  
Receptor Family

Background The clinical efficacy of migraine therapeutic agents directed towards the calcitonin-gene related peptide (CGRP) pathway has confirmed the key role of this axis in migraine pathogenesis. Three antibodies against CGRP – fremanezumab, galcanezumab and eptinezumab – and one antibody against the CGRP receptor, erenumab, are clinically approved therapeutics for the prevention of migraine. In addition, two small molecule CGRP receptor antagonists, ubrogepant and rimegepant, are approved for acute migraine treatment. Targeting either the CGRP ligand or receptor is efficacious for migraine treatment; however, a comparison of the mechanism of action of these therapeutic agents is lacking in the literature. Methods To gain insights into the potential differences between these CGRP pathway therapeutics, we compared the effect of a CGRP ligand antibody (fremanezumab), a CGRP receptor antibody (erenumab) and a CGRP receptor small molecule antagonist (telcagepant) using a combination of binding, functional and imaging assays. Results Erenumab and telcagepant antagonized CGRP, adrenomedullin and intermedin cAMP signaling at the canonical human CGRP receptor. In contrast, fremanezumab only antagonized CGRP-induced cAMP signaling at the human CGRP receptor. In addition, erenumab, but not fremanezumab, bound and internalized at the canonical human CGRP receptor. Interestingly, erenumab also bound and internalized at the human AMY1 receptor, a CGRP receptor family member. Both erenumab and telcagepant antagonized amylin-induced cAMP signaling at the AMY1 receptor while fremanezumab did not affect amylin responses. Conclusion The therapeutic effect of agents targeting the CGRP ligand versus receptor for migraine prevention (antibodies) or acute treatment (gepants) may involve distinct mechanisms of action. These findings suggest that differing mechanisms could affect efficacy, safety, and/or tolerability in migraine patients.

scholarly journals Frequency-specific alterations of the resting-state BOLD signals in nocturnal enuresis: an fMRI Study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiangyu Zheng ◽  
Jiawei Sun ◽  
Yating Lv ◽  
Mengxing Wang ◽  
Xiaoxia Du ◽  
...  
Keyword(s):  
Resting State ◽  
Nocturnal Enuresis ◽  
Medical Center ◽  
Blood Oxygen Level Dependent ◽  
Middle Temporal Gyrus ◽  
Blood Oxygen Level ◽  
Middle Temporal ◽  
School Of Medicine ◽  
Fmri Study ◽  
The Right

AbstractResting state functional magnetic resonance imaging studies of nocturnal enuresis have focused primarily on regional metrics in the blood oxygen level dependent (BOLD) signal ranging from 0.01 to 0.08 Hz. However, it remains unclear how local metrics show in sub-frequency band. 129 children with nocturnal enuresis (NE) and 37 healthy controls were included in this study. The patients were diagnosed by the pediatricians in Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, according to the criteria from International Children's Continence Society (ICCS). Questionnaires were used to evaluate the symptoms of enuresis and completed by the participants. In this study, fALFF, ReHo and PerAF were calculated within five different frequency bands: typical band (0.01–0.08 Hz), slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz), and slow-2 (0.198–0.25 Hz). In the typical band, ReHo increased in the left insula and the right thalamus, while fALFF decreased in the right insula in children with NE. Besides, PerAF was increased in the right middle temporal gyrus in these children. The results regarding ReHo, fALFF and PerAF in the typical band was similar to those in slow-5 band, respectively. A correlation was found between the PerAF value of the right middle temporal gyrus and scores of the urinary intention-related wakefulness. Results in other bands were either negative or in white matter. NE children might have abnormal intrinsic neural oscillations mainly on slow-5 bands.

scholarly journals The Effects of Music Intervention on Functional Connectivity Strength of the Brain in Schizophrenia

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Mi Yang ◽  
Hui He ◽  
Mingjun Duan ◽  
Xi Chen ◽  
Xin Chang ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State Fmri ◽  
Middle Temporal Gyrus ◽  
Therapeutic Effects ◽  
Music Intervention ◽  
Functional Connection ◽  
Fmri Study ◽  
Functional Connectivity Strength ◽  
The Right ◽  
Connectivity Strength

Schizophrenia is often associated with behavior abnormality in the cognitive and affective domain. Music intervention is used as a complementary treatment for improving symptoms in patients with schizophrenia. However, the neurophysiological correlates of these remissions remain poorly understood. Here, we investigated the effects of music intervention in neural circuits through functional magnetic resonance imaging (fMRI) study in schizophrenic subjects. Under the standard care, patients were randomly assigned to music and non-music interventions (MTSZ, UMTSZ) for 1 month. Resting-state fMRI were acquired over three time points (baseline, 1 month, and 6 months later) in patients and analyzed using functional connectivity strength (FCS) and seed-based functional connection (FC) approaches. At baseline, compared with healthy controls, decreased FCS in the right middle temporal gyrus (MTG) was observed in patients. However, after music intervention, the functional circuitry of the right MTG, which was related with the function of emotion and sensorimotor, was improved in MTSZ. Furthermore, the FC increments were significantly correlated with the improvement of symptoms, while vanishing 6 months later. Together, these findings provided evidence that music intervention might positively modulate the functional connectivity of MTG in patients with schizophrenia; such changes might be associated with the observed therapeutic effects of music intervention on neurocognitive function. This trial is registered with ChiCTR-OPC-14005339.

Disgust Processing in Phobia of Blood-Injection-Injury

2003 ◽  
Vol 17 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Anne Schienle ◽  
Axel Schäfer ◽  
Rudolf Stark ◽  
Bertram Walter ◽  
Peter Kirsch ◽  
...  
Keyword(s):  
Inferior Frontal Gyrus ◽  
Self Report ◽  
Dynamic Responses ◽  
Left Inferior Frontal Gyrus ◽  
Injection Injury ◽  
Lingual Gyrus ◽  
Fmri Study ◽  
Blood Injection ◽  
The Right ◽  
Bii Phobia

Abstract An elevated disgust sensitivity (DS) is considered to be a vulnerability factor for the development of a blood-injection-injury (BII) phobia. Within the present functional Magnetic Resonance Imaging (fMRI) study, 12 female BII phobics were scanned while viewing alternating blocks of 40 disgust-inducing, 40 fear-inducing, and 40 affectively neutral pictures. Each block lasted 60s and was repeated six times during the experiment. All scenes were phobia-irrelevant. Afterwards, the subjects gave affective ratings for the pictures and described their DS on a self-report measure for different areas (e.g., poor hygiene, unusual food, death/deformation). The responses were compared with those of 12 nonphobic females. The BII phobics showed a stronger occipital activation within the right cuneus and lingual gyrus during the first viewing of the disgusting pictures. Aside from this finding, which could be interpreted as reflecting increased attention, there was little evidence for a generally elevated DS in BII phobia. On the DS questionnaire, the patients had indicated a greater reactivity only for disorder-relevant contents (death/deformation). Further, both groups gave similar disgust ratings for the pictures and showed comparable brain-dynamic responses over all blocks of the disgust condition, which included the activation of both amygdalae and the left inferior frontal gyrus.

Anomalous Auditory Cortex Activations in Colored Hearing Synaesthetes: An fMRI-Study

2011 ◽  
Vol 24 (4) ◽  
pp. 391-405 ◽  
Author(s):  
Ursula Stiegemann ◽  
Henning Scheich ◽  
Birgit Gaschler-Markefski ◽  
Gregor Szycik ◽  
Hinderk Meiners Emrich ◽  
...  
Keyword(s):  
Occipital Lobe ◽  
Superior Temporal Gyrus ◽  
Normal Subjects ◽  
Middle Temporal Gyrus ◽  
Word Condition ◽  
Color Processing ◽  
Tone Condition ◽  
Fmri Study ◽  
The Right ◽  
Left Middle Temporal Gyrus

AbstractColor percept induction in synaesthetes by hearing words was previously shown to involve activation of visual and specifically color processing cortex areas. While this provides a rationale for the origin of the anomalous color percept the question of mechanism of this crossmodal activation remains unclear. We pursued this question with fMRI in color hearing synaesthetes by exposing subjects to words and tones. Brain activations in word condition accompanied by highly reliable color percepts were compared with activations in tone condition with only occasional color percepts and both contrasted to activations in normal subjects under the same stimulus conditions. This revealed that already the tone condition similar to the word condition caused abnormally high activations in various cortical areas even though synaesthetic percepts were more rare. Such tone activations were significantly larger than in normal subjects in visual areas of the right occipital lobe, the fusiform gyrus, and the left middle temporal gyrus and in auditory areas of the left superior temporal gyrus. These auditory areas showed strong word and tone activation alike and not the typically lower tone than word activation in normal subjects. Taken together these results are interpreted in favour of the disinhibited feedback hypothesis as the neurophysiological basis of genuine synaesthesia.

Improvement in prefrontal thalamic connectivity during the early course of the illness in recent-onset psychosis: a 12-month longitudinal follow-up resting-state fMRI study

2020 ◽  
pp. 1-9
Author(s):  
Daniel Bergé ◽  
Tyler A. Lesh ◽  
Jason Smucny ◽  
Cameron S. Carter
Keyword(s):  
Resting State ◽  
Resting State Fmri ◽  
Functional Changes ◽  
Recent Onset ◽  
Fmri Study ◽  
Clinical Meaning ◽  
Mixed Pattern ◽  
The Right ◽  
Over Time

Abstract Background Previous research in resting-state functional magnetic resonance imaging (rs-fMRI) has shown a mixed pattern of disrupted thalamocortical connectivity in psychosis. The clinical meaning of these findings and their stability over time remains unclear. We aimed to study thalamocortical connectivity longitudinally over a 1-year period in participants with recent-onset psychosis. Methods To this purpose, 129 individuals with recent-onset psychosis and 87 controls were clinically evaluated and scanned using rs-fMRI. Among them, 43 patients and 40 controls were re-scanned and re-evaluated 12 months later. Functional connectivity between the thalamus and the rest of the brain was calculated using a seed to voxel approach, and then compared between groups and correlated with clinical features cross-sectionally and longitudinally. Results At baseline, participants with recent-onset psychosis showed increased connectivity (compared to controls) between the thalamus and somatosensory and temporal regions (k = 653, T = 5.712), as well as decreased connectivity between the thalamus and left cerebellum and right prefrontal cortex (PFC; k = 201, T = −4.700). Longitudinal analyses revealed increased connectivity over time in recent-onset psychosis (relative to controls) in the right middle frontal gyrus. Conclusions Our results support the concept of abnormal thalamic connectivity as a core feature in psychosis. In agreement with a non-degenerative model of illness in which functional changes occur early in development and do not deteriorate over time, no evidence of progressive deterioration of connectivity during early psychosis was observed. Indeed, regionally increased connectivity between thalamus and PFC was observed.

Assessment of the neuronal underpinnings of cognitive impairment in bipolar disorder with a picture encoding paradigm and methodological lessons learnt

2021 ◽  
pp. 026988112110085
Author(s):  
JZ Petersen ◽  
J Macoveanu ◽  
HL Kjærstad ◽  
GM Knudsen ◽  
LV Kessing ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Impairment ◽  
Neuronal Activity ◽  
Cognitive Impairments ◽  
Hierarchical Cluster ◽  
Small Region ◽  
Middle Temporal Gyrus ◽  
Recall Accuracy ◽  
Fmri Study

Background: Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the neurocircuitry abnormalities underlying these deficits and their change with illness progression. Aims: This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm. Methods: Remitted patients with BD ( n=153) and healthy controls ( n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients ( n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients’ neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s). Results: Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period. Conclusion: Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.

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