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The hypothalamus communicated with the frontal lobe, parietal lobe, and cingulate gyrus in CH development.
Source publication
Background
The peripheral and central origins of pain in cluster headache (CH) have been a matter of much debate. The development and application of functional imaging techniques have provided more evidence supporting the hypothesis that CH is not a disorder exclusively peripheral in origin, and in fact central regions might be more important. Even...
Similar publications
In the human cortex, event-related potentials (ERPs) are triggered in response to sensory, cognitive or motor stimuli. Due to the inherent difficulties of conducting invasive mechanistic studies in human subjects, little is known as to the precise neurophysiological mechanisms that lead to their manifestation. By contrast, although much is known ab...
Citations
... Additionally altered during and after the bout, particularly on the affected side, were lemniscal somatosensory evoked responses (97) and evoked potentials elicited peripherally by transcranial magnetic stimulation over the motor region (under GABAergic control) (98). The latencies of event-related cognitive evoked potentials were also observed to be differently altered during the active period compared to the remission period in CH patients, underscoring the multidimensional involvement of recurrent and severe pain such as CH (99)(100)(101)(102). ...
Background
Despite advances in neuroimaging and electrophysiology, cluster headache’s pathogenesis remains unclear. This review will examine clinical neurophysiology studies, including electrophysiological and functional neuroimaging, to determine if they might help us construct a neurophysiological model of cluster headache.
Results
Clinical, biochemical, and electrophysiological research have implicated the trigeminal-parasympathetic system in cluster headache pain generation, although the order in which these two systems are activated, which may be somewhat independent, is unknown. Electrophysiology and neuroimaging have found one or more central factors that may cause seasonal and circadian attacks. The well-known posterior hypothalamus, with its primary circadian pacemaker suprachiasmatic nucleus, the brainstem monoaminergic systems, the midbrain, with an emphasis on the dopaminergic system, especially when cluster headache is chronic, and the descending pain control systems appear to be involved. Functional connection investigations have verified electrophysiological evidence of functional changes in distant brain regions connecting to wide cerebral networks other than pain.
Conclusion
We propose that under the impact of external time, an inherited misalignment between the primary circadian pacemaker suprachiasmatic nucleus and other secondary extra- suprachiasmatic nucleus clocks may promote disturbance of the body’s internal physiological clock, lowering the threshold for bout recurrence.
... Neuroimaging has significantly facilitated our understanding of putative brain mechanisms underpinning CH [4][5][6][7]. Functional magnetic resonance imaging (fMRI) and in particular blood-oxygen-level dependent (BOLD) fMRI, can describe differences in activity and connectivity between CH patients and healthy controls [8], both in the resting state and during headache attacks [9,10], pointing towards the hypothalamus as a key area involved in triggering headache attacks during bouts, as well as in marking the beginning and end of bouts in episodic CH patients, causing the circadian nature of CH symptoms. Nevertheless, these findings continue to be debated, as it remains unclear whether results incorporate the hypothalamus and/or the neighbouring ventral tegmental area (VTA) as the areas responsible for those differences [11]. ...
Background
Cluster headache is an excruciating disorder with no cure. Greater occipital nerve blockades can transiently suppress attacks in approximately 50% of patients, however, its mechanism of action remains uncertain, and there are no reliable predictors of treatment response. To address this, we investigated the effect of occipital nerve blockade on regional cerebral blood flow (rCBF), an index of brain activity, and differences between treatment responders and non-responders. Finally, we compared baseline perfusion maps from patients to a matched group of healthy controls.
Methods
21 male, treatment-naive patients were recruited while in a cluster headache bout. During a pain-free phase between headaches, patients underwent pseudo-continuous arterial spin labelled MRI assessments to provide quantitative indices of rCBF. MRIs were performed prior to and 7-to-21 days following treatment. Patients also recorded the frequency of their headache attacks in a daily paper diary. Neuropsychological assessment including anxiety, depression and quality of life measures was performed in a first, scanning free session for each patient.
Results
Following treatment, patients demonstrated relative rCBF reductions in posterior temporal gyrus, cerebellum and caudate, and rCBF increases in occipital cortex. Responders demonstrated relative rCBF increases, compared to non-responders, in medial prefrontal cortex and lateral occipital cortex at baseline, but relative reductions in cingulate and middle temporal cortices. rCBF was increased in patients compared to healthy controls in cerebellum and hippocampus, but reduced in orbitofrontal cortex, insula and middle temporal gyrus.
Conclusions
We provide new mechanistic insights regarding the aetiology of cluster headache, the mechanisms of action of occipital nerve blockades and potential predictors of treatment response. Future investigation should determine whether observed effects are reproducible and extend to other headache disorders.
... Neuroimaging has signi cantly facilitated our understanding of putative brain mechanisms underpinning CH. [4][5][6][7] Functional magnetic resonance imaging (fMRI) and in particular blood-oxygen-level dependent (BOLD) fMRI, can describe differences in activity and connectivity between CH patients and healthy controls, [8] both in the resting state and during headache attacks. [9,10] Nevertheless, chronic pain largely relates to spontaneous, low frequency uctuations, for which arterial spin labelling (ASL) is more optimally sensitive, as it can identify changes in low frequency brain activity via quanti cation of regional cerebral blood ow (rCBF) as a proxy of resting brain activity in relation to chronic pain. ...
Background: Cluster headache is an excruciating disorder with no cure. Greater occipital nerve blockades can transiently suppress attacks in approximately 50% of patients, however, its mechanism of action remains uncertain, and there are no reliable predictors of treatment response. To address this, we investigated the effect of occipital nerve blockade on regional cerebral blood flow (rCBF), an index of brain activity, and differences between treatment responders and non-responders. Finally, we compared baseline perfusion maps from patients to a matched group of healthy controls. Methods: 21 male, treatment-naive patients were recruited while in a cluster headache bout. During a pain-free phase between headaches, patients underwent pseudo-continuous arterial spin labelled MRI assessments to provide quantitative indices of rCBF. MRIs were performed prior to and 8-to-22 days following treatment. Patients also recorded the frequency of their headache attacks in a daily paper diary. Neuropsychological assessment including anxiety, depression and quality of life measures was performed in a first, scanning free session for each patient. Results: Following treatment, patients demonstrated relative rCBF reductions in posterior temporal gyrus, cerebellum and caudate, and rCBF increases in occipital cortex. Responders demonstrated relative rCBF increases, compared to non-responders, in medial prefrontal cortex and lateral occipital cortex at baseline, but relative reductions in cingulate and middle temporal cortices. rCBF was increased in patients compared to healthy controls in cerebellum and hippocampus, but reduced in orbitofrontal cortex, insula and middle temporal gyrus. Conclusions: We provide new mechanistic insights regarding the aetiology of cluster headache, the mechanisms of action of occipital nerve blockades and potential predictors of treatment response. Future investigation should determine whether observed effects are reproducible and extend to other headache disorders.
... No significant correlations were found between ERP data and disease duration, attack duration and daily frequency of attacks in the different group of patients (33,34). In one visual ERP study, P300 amplitude was decreased in CH patients in comparison with HCs, irrespective of the headache side (35). ...
“Cluster headache and other trigeminal autonomic cephalalgias” is a category of primary headaches characterized by strictly unilateral headache with concomitant ipsilateral facial autonomic features. Their pathophysiology is not fully understood. Many neurophysiological techniques have been used in attempts to disentangle the pathophysiological mechanisms underlying these elusive brain disorders. Overall, these investigations have revealed side-to-side differences, in virtually all the sensory modalities explored (both pain-related and non-pain-related), in patients (almost always cluster headache patients) versus healthy controls. Signs of peripheral and central sensitization of the trigeminal system, as well as of the extracephalic spinal pain processing system, have been detected using blink and lower limb withdrawal reflexes in cluster headache. In some cases, acute or prophylactic treatments can reverse these dysfunctions. The use of improved selection criteria and more refined neurophysiological techniques, especially if combined with neuroimaging data, should lead to greater understanding of the nature of the brain dysfunction in trigeminal autonomic cephalalgias.
... This disorganized connectivity could be a consequence of white matter microstructural alteration described in CH [85]. Lastly, cognitive processing studies employing event-related potentials are useful in elucidating cortical activation time courses during cognitive processing [86,87]. The hypothalamic dysfunction might also explain the habituation deficit of the brainstem and the general sensitization of pain processing detected in patients with CH [88]. ...
Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.
... Several neurophysiological studies have shown altered pain perception and decreased pain thresholds in patients with cluster headache, suggesting dysfunction of the pain control system [84][85][86][87] . Furthermore, neurophysio logical studies have implicated deficits in supraspinal pain control, such as the diffuse noxious inhibitory controls (neuronal pathways that underlie the physiological inhibition of pain by another painful stimulus) in cluster headache 88,89 . Dysfunction of the descending pain control system may facilitate primary headache disorders, including cluster headache, by disinhibiting or facilitating nociceptive signalling 90 . ...
Cluster headache is an excruciating, strictly one-sided pain syndrome with attacks that last between 15 minutes and 180 minutes and that are accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. The pain is so severe that female patients describe each attack as worse than childbirth. The past decade has seen remarkable progress in the understanding of the pathophysiological background of cluster headache and has implicated the brain, particularly the hypothalamus, as the generator of both the pain and the autonomic symptoms. Anatomical connections between the hypothalamus and the trigeminovascular system, as well as the parasympathetic nervous system, have also been implicated in cluster headache pathophysiology. The diagnosis of cluster headache involves excluding other primary headaches and secondary headaches and is based primarily on the patient's symptoms. Remarkable progress has been achieved in developing effective treatment options for single cluster attacks and in developing preventive measures, which include pharmacological therapies and neuromodulation.
... Two principal electrophysiological markers have been considered as an objective index of cognitive processing: latency and amplitude. It is widely accepted that P3 latency reflects the length of stimulus evaluation processes [21], when two choice reaction time (RT) is required and its amplitude is largely determined by stimulus relevance, the amount of attention allocated to the stimulus, working memory and the task's complexity [22,23]. ...
Background
The aim of this study was to evaluate the changes in the cognitive performance of migraine patients using a comprehensive series of cognitive/behavioral and electrophysiological tests.
Method
A randomized, cross-sectional, within subject approach was used to compare neuropsychological and electrophysiological evaluations from migrane-affected and healthy subjects.
Results
Thirty-four patients with migraine (6 males, 28 females, average 36 years old) were included. Migraineurs performed worse in the majority of the Montreal Cognitive Assessment (MoCA) (p = 0.007) compared to the healthy subjects, significantly in language (p = 0.005), memory (p = 0.006), executive functions (p = 0.042), calculation (p = 0.018) and orientation (p = 0.012). Migraineurs had a lower score on the memory trial of the Rey–Osterrieth complex figure test (ROCF) (p = 0.012). The P3 latency in Fz, Cz, Pz was prolonged in migraineurs compared with the normal control group (P < 0.001). In addition, we analyzed significant correlations between MoCA score and the duration of migraine. We also observed that a decrease in the MoCA-executive functions and calculation score and in the ROCF-recall score were both correlated to the frequency of migraine. Migraineurs were more anxious than healthy subjects (p = 0.001), which is independent of cognitive testing. Differences were unrelated to age, gender and literacy.
Conclusions
Cognitive performance decreases during migraine, and cognitive dysfunction can be related to the duration and frequency of a migraine attack.
... Prolonged P300 latencies in CH patients during the cluster period was demonstrated by Evers et al. [11,16] and because P300 latency is an indicator of cognitive performance, the authors concluded that CH has a central origin. [17] Similarly, evidence of dysfunction in the cognitive processing of CH patients was demonstrated in a study by Wang et al. [18] in which the authors found a significantly reduced P300 amplitudes in patients as compared to controls with no significant difference between the side of pain and the contralateral side. The authors hypothesized that there was a dysfunction of the supraspinal control of pain in CH and possibly supported by an abnormal hypothalamic function with abnormal amplitudes seen equally on both affected and nonaffected sides. ...
Background : Patients suffering from primary headaches such as migraine, tension-type headache, and cluster headache frequently report cognitive problems, particularly with attention and memory. The aim of this study was to see if there was a link between pain intensity and cognitive function in people who had primary headaches.
Methods : This cross-sectional study included 69 primary headache patients (37 migraines, 27 tension-type headaches and 5 cluster headaches; age range 18–80 year). Migraine, tension-type headache and cluster headache diagnosis were determined according to the International Classification of Headache Disorders 3 rd edition beta version (ICHD-3 beta) diagnostic criteria. All eligible subjects underwent cognitive function examination using Montreal Cognitive Assessment Indonesian version (MoCA-INA), Trail Making test A (TMT-A), Trail Making test B (TMT-B), Trail Making test C (TMT-C), Forward Digit Span and Backward Digit Span. The intensity of pain was assessed using Numeric Rating Scale (NRS).
Results : There were 69 primary headache patients included in this study, 52 (75.4%) patients had abnormal MoCA-INA, 52(75.4%) patients had abnormal Forward Digit Span and 48(69.6%) patients had abnormal Backward Digit Span. There was significant correlation between pain intensity and cognitive function in migraine, TTH and cluster headaches patients. The MoCA-INA, Forward Digit Span and Backward Digit Span had negative correlations with pain intensity, whereas TMT A-time, TMT A-error, TMT B-time and TMT B-error had positive correlation.
Conclusion : There were significant associations between pain intensity of and cognitive function in primary headaches with p<0.05. It is suggested that the more severe pain intensity, the more impair of cognitive function.
