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Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1-2 headache days/month), 2 (3-4), 3 (5-7), 4 (8-10), 5 (11-14), 6 (15-19), 7 (20-24), and 8 (25-30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2-3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3-7 on the left side (5-24 days/month; L: r = -0.31, p = 0.004) and groups 3-8 on the right side ( r = -0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1-3 ( r = 0.34, p = 0.020) and groups 3-6 ( r = -0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine. [ABSTRACT FROM AUTHOR]

Background: To gain a comprehensive understanding of the altered sensory processing in patients with migraine, in this study, we developed an electroencephalography (EEG) protocol for examining brainstem and cortical responses to sensory stimulation. Furthermore, machine learning techniques were employed to identify neural signatures from evoked brainstem-cortex activation and their interactions, facilitating the identification of the presence and subtype of migraine., Methods: This study analysed 1,000-epoch-averaged somatosensory evoked responses from 342 participants, comprising 113 healthy controls (HCs), 106 patients with chronic migraine (CM), and 123 patients with episodic migraine (EM). Activation amplitude and effective connectivity were obtained using weighted minimum norm estimates with spectral Granger causality analysis. This study used support vector machine algorithms to develop classification models; multimodal data (amplitude, connectivity, and scores of psychometric assessments) were applied to assess the reliability and generalisability of the identification results from the classification models., Results: The findings revealed that patients with migraine exhibited reduced amplitudes for responses in both the brainstem and cortical regions and increased effective connectivity between these regions in the gamma and high-gamma frequency bands. The classification model with characteristic features performed well in distinguishing patients with CM from HCs, achieving an accuracy of 81.8% and an area under the curve (AUC) of 0.86 during training and an accuracy of 76.2% and an AUC of 0.89 during independent testing. Similarly, the model effectively identified patients with EM, with an accuracy of 77.5% and an AUC of 0.84 during training and an accuracy of 87% and an AUC of 0.88 during independent testing. Additionally, the model successfully differentiated patients with CM from patients with EM, with an accuracy of 70.5% and an AUC of 0.73 during training and an accuracy of 72.7% and an AUC of 0.74 during independent testing., Conclusion: Altered brainstem-cortex activation and interaction are characteristic of the abnormal sensory processing in migraine. Combining evoked activity analysis with machine learning offers a reliable and generalisable tool for identifying patients with migraine and for assessing the severity of their condition. Thus, this approach is an effective and rapid diagnostic tool for clinicians., (© 2024. The Author(s).)

To determine specific resting-state network patterns underlying alterations in chronic migraine, we employed oscillatory connectivity and machine learning techniques to distinguish patients with chronic migraine from healthy controls and patients with other pain disorders. This cross-sectional study included 350 participants (70 healthy controls, 100 patients with chronic migraine, 40 patients with chronic migraine with comorbid fibromyalgia, 35 patients with fibromyalgia, 30 patients with chronic tension-type headache, and 75 patients with episodic migraine). We collected resting-state magnetoencephalographic data for analysis. Source-based oscillatory connectivity within each network, including the pain-related network, default mode network, sensorimotor network, visual network, and insula to default mode network, was examined to determine intrinsic connectivity across a frequency range of 1-40 Hz. Features were extracted to establish and validate classification models constructed using machine learning algorithms. The findings indicated that oscillatory connectivity revealed brain network abnormalities in patients with chronic migraine compared with healthy controls, and that oscillatory connectivity exhibited distinct patterns between various pain disorders. After the incorporation of network features, the best classification model demonstrated excellent performance in distinguishing patients with chronic migraine from healthy controls, achieving high accuracy on both training and testing datasets (accuracy > 92.6% and area under the curve > 0.93). Moreover, in validation tests, classification models exhibited high accuracy in discriminating patients with chronic migraine from all other groups of patients (accuracy > 75.7% and area under the curve > 0.8). In conclusion, oscillatory synchrony within the pain-related network and default mode network corresponded to altered neurophysiological processes in patients with chronic migraine. Thus, these networks can serve as pivotal signatures in the model for identifying patients with chronic migraine, providing reliable and generalisable results. This approach may facilitate the objective and individualised diagnosis of migraine., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Objectives: This study investigated brain morphometry changes associated with fatigue severity in fibromyalgia (FM)., Methods: Clinical profiles and brain-MRI data were collected in patients with FM. Patients were divided into three groups based on their fatigue severity. Using voxel-based morphometry analysis and trend analysis, neural substrates showing volumetric changes associated with fatigue severity across the three groups were identified. Their seed-to-voxel structural covariance (SC) networks with the whole brain were studied in distribution and strength., Results: Among the 138 enrolled patients with FM, 23, 57, and 58 were categorised into the mild, moderate, and severe fatigue groups, respectively. The number of musculoskeletal pain regions and intensity of pain were not associated with fatigue severity, but somatic symptoms and psychiatric distress, including waking unrefreshed, depression, and anxiety, were associated with fatigue severity. After adjusting for anxiety and depression, decreased bilateral thalamic volumes were associated with higher fatigue severity. The SC distributions of the thalamic seed were more widespread to the frontal, parietal, subcortical, and limbic regions in patients with higher fatigue severity. In addition, increased right inferior temporal cortex volumes were associated with higher fatigue severity. The SC distributions of the right inferior temporal seed were more over the temporal cortex and the SC strengths of the seed were higher with the bilateral occipital cortex in patients with higher fatigue severity., Conclusions: The thalamus and the right inferior temporal cortex are implicated in the manifestation of fatigue severity in FM. Future therapeutic strategies targeting these regions are worthy of investigation.

Background: Sphenopalatine ganglion (SPG) is a peripheral structure that plays an important role in cluster headache (CH). Hence, a reliable method to measure the volume of SPG is crucial for studying the peripheral mechanism of CH. Additionally, the association between the clinical profiles and the morphology of the SPG in CH remains undetermined. This study aims to use the manual measurement of SPG volume to investigate its associations with CH, including headache laterality, cranial autonomic symptoms (CASs), presence of restlessness or agitation, and other clinical profiles., Methods: We prospectively recruited consecutive CH patients at a tertiary medical center between April 2020 and April 2022. A total of eighty side-locked, in-bout, episodic CH patients and 40 non-headache healthy controls received 1.5 T brain MRI focusing on structural neuroimaging of the SPG. The manual measurement process for SPG was under axial and sagittal FIESTA imaging, with reference T2 weight images (sagittal and axial) for localization. The inter-observer agreement of the SPG volume (both sides of the SPG from CH patients and controls) between the two observers was calculated. In CH patients, clinical profiles and the number of CASs (range 0-5) were recorded to analyze their association with SPG volume., Results: The inter-observer agreement between the two raters was excellent for the new SPG volumetry method at 0.88 (95% CI: 0.84-0.90, p < 0.001). The mean [SD] SPG volume was larger in CH patients than in non-headache controls (35.89 [12.94] vs. 26.13 [8.62] μL, p < 0.001). In CH patients, the SPG volume was larger on the pain side than on the non-pain side (38.87 [14.71] vs. 32.91 [12.70] μL, p < 0.001). The number of CASs was positively moderately correlated with the pain-side SPG volume (Pearson r = 0.320, p = 0.004) but not the non-pain side SPG volume (Pearson r = 0.207, p = 0.066)., Conclusions: This proof-of-concept study successfully measured the SPG volume and demonstrated its associations with symptomatology in patients with episodic CH. The direct measurement of SPG provide insights into studies on peripheral mechanism of CH., (© 2022. The Author(s).)

Migraine and epilepsy share in many ways with regard to their clinical presentation and pathophysiological mechanisms. A state of central hyper-excitability or hyper-responsivity is fundamental in their pathophysiology. Antiepileptic drugs (AEDs) have long been used for migraine prevention, other than for seizure control. Evidence from numerous clinical trials has well demonstrated the therapeutic effects of some of the AEDs in this regard. In this paper, we will first discuss the clinical similarity between migraine and epilepsy. Then, to address the rationale of AEDs usage in migraine prevention, we focus on those electrophysiological studies conducted in patients with migraine demonstrating evidence of central hyper-excitability or hyper-responsivity. Although controversies remain, three common findings are derived from the literature: (1) cortical hyper-excitability, (2) impaired intra-cortical inhibition or increased intra-cortical facilitation, and (3) dis-habituation (hyper-responsivity). Each single feature may actually represent one of the different manifestations derived from an overall central excitation/inhibition imbalance. Finally, we review those studies addressing the therapeutic effects of AEDs and the associated alteration in central excitability. These studies provided direct evidence that effective prevention by AEDs is associated with the restoration of excitation/inhibition imbalance., (© 2020 Elsevier B.V. All rights reserved.)

In an attempt to develop safe and robust methods for monitoring migraineurs' brain states, we explores the feasibility of using white, red, green and blue LED lights flickering around their critical flicker fusion (CFF) frequencies as foveal visual stimuli for inducing steady-state visual evoked potentials (SSVEP) and causing discernible habituation trends. After comparing the habituation indices, the multi-scale entropies and the time dependent intrinsic correlations of their SSVEP signals, we reached a tentative conclusion that sharp red and white light pulses flickering barely above their CFF frequencies can replace commonly used 13Hz stimuli to effectively cause SSVEP habituation among normal subjects. Empirical results showed that consecutive short bursts of light can produce more consistent responses than a single prolonged stimulation. Since these high frequency stimuli do not run the risk of triggering migraine or seizure attacks, further tests of these stimuli on migraine patients are warranted in order to verify their effectiveness.

"Noxious stimulation over the foot can evoke a nociceptive flexor reflex (NR) in the lower limb especially for tibialis anterior muscle (TA). Components of NR include the monosynaptic fast latency NRII, and the polysynaptic slow latency NRIII, supposedly a spinal segmental reflex influenced by the supraspinal control. Pain perception is quantified by visual analogous scale (VAS) and has been reported to be related to NRIII. Previous papers have reported the long lasting effect of transcranial magnetic stimulation (TMS), as well as TMS suppressing pain perception. The purpose of this study was to investigate the immediate and prolonged effect of a single-pulse TMS to suppress NR and pain. NRIII was provoked at right TA by a train of electrical stimulation on the right toe in 10 healthy subjects. TMS was delivered over the vertex area to evoke right anterior tibialis muscle activity. A sham TMS from different directions of the coil was performed on the next day. The NRIII amplitude and VAS were measured. As a result, the amplitude of NRIII was significantly decreased than the control 50 ms pre-stimulation (0.20 ± 0.13 mA vs . 0.65 ± 0.42 mV, P = 0.016), 100 ms pre-stimulation (0.10 ± 0.10 mA vs . 0.65 ± 0.42 mV, P = 0.001), 15 min post-stimulation (0.12 ± 0.09 mA vs . 0.65 ± 0.42 mV, P = 0.004), and 30 min post-stimulation (0.41 ± 0.21 mA vs . 0.65 ± 0.42 mV, P = 0.046). VAS was diminished compared with the control 50 ms pre-stimulation (3.3 ± 0.9 vs . 5.4 ± 1.3, P = 0.002), 100 ms pre-stimulation (2.6 ± 0.5 vs . 5.4 ± 1.3, P < 0.001) and 15 min post-stimulation (3.5 ± 0.9 vs . 5.4 ± 1.3, P = 0.046). The NRIII amplitude was well correlated with VAS in reduction during the TMS condition and 15 min after electrical stimulation (P < 0.001). The sham TMS did not suppress NRIII or VAS. In conclusion, our results indicate that NRIII and the nociception can be inhibited by one single pulse TMS and such an effect can last for a period of time."

Purpose: Fatigue may be induced by drug. Here, we reported that patients had fatigue after medication with colchicines., Method: Eight patients (8 Males, age: 42-72 years old) had fatigue but without weakness as their chief complaints. They all described an inability to maintain a sustained effort, which was ameliorated by rest., Results: The course of fatigue was insidious and progressive (mean 3.1 2.3 months, range 1-7 months) along with medication of colchicines (mean 20.3 5.5 months, range 11-28 months). Fatigue severity scale (patient: before drug withdrawal 5.41 0.19; 4 weeks after drug withdrawal 2.46 0.28; control 2.12 0.45) showed fatigue as their most disabling symptom, sometimes preventing them to carry on professional as well as socio-familial activities. The plasma creatine kinase elevated in these 8 patients before withdrawal of colchicines and returned to normal range in each subject 4 weeks after drug withdrawal. A probable diagnosis of drug-induced fatigue was made when symptom subsided after colchicines were discontinued., Conclusion: It is emphasized that side effect of drug should be considered as a differential diagnosis of fatigue in patients having colchicines. Early recognition and diagnosis will prevent serious muscle damage.

Background: We investigated the characteristics and correlates of high-frequency oscillations (HFOs) of somatosensory evoked potentials (SEPs)., Methods: Subjects were 26 healthy volunteers. SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. HFOs were obtained by digitally filtering raw SEPs from 500 to 1000 Hz, and their amplitudes and area-under-curve, duration, and number of negative peaks were measured. We also measured amplitudes of the N20 onset-peak (N20o-p), and N20 peak-P25 peak (N20p-P25p)., Results: In normal subjects, several oscillation potentials were observed at the latency of 0 to 10 ms after the onset of N20. The mean number of negative peaks of total HFOs was 6.96 +/- 1.20 (early phase 3.36 +/- 0.62; late phase 3.60 +/- 1.14). The mean maximal amplitude of total HFOs was 0.16 +/- 0.07 microV (early phase 0.14 +/- 0.05 microV; late phase 0.15 +/- 0.07 microV). The mean duration of total HFOs was 10.19 +/- 1.98 ms (early phase 4.89 +/- 1.04 ms; late phase 5.31 +/- 1.95 ms). The mean area of total HFOs was 567.54 +/- 227.86 microV x ms (early phase 268.46 +/- 98.40 microV x ms; late phase 299.08 +/- 183.44 microV x ms). The amplitude ratio was 7.30 +/- 3.32% of HFOearly/N20o-p, 3.19 +/- 1.55% of HFOlate/N20-P25, and 3.54 +/- 1.84% of HFOtotal/N20p-P25. During the test, the amplitude of HFO was significantly reduced by drowsiness., Conclusions: In waking subjects, a burst of low-amplitude HFO can be extracted from the N20.

Electrical stimulation may produce excitation or inhibition of the motor neurons, as represented the blink reflex and masseter silent period in response to trigeminal nerve stimulation. Clinically, a light touch on the palm may evoke a mentalis muscle response (MMR), i.e. a palmomental reflex. In this study, we attempted to characterize the MMR to median nerve stimulation. Electrical stimulation was applied at the median nerve with recordings at the mentalis muscles. An inhibition study was done with continuous stimuli during muscle contraction (I1 and I2 of MMRaverage). Excitation was done with a single shot during muscle relaxation (MMRsingle) or by continuous stimuli during muscle contraction (E1 and E2 of MMRaverage). The characteristic differences between MMRaverage and MMRsingle were as follows: earlier onset latencies of MMRaverage (MMRaverage < 45 ms; MMRsingle > 60 ms), and a lower amplitude of MMRaverage (MMRaverage < 50 microV; MMRsingle > 150 microV). The receptive field of MMRsingle was widespread over the body surface and that of MMRaverage was limited to the trigeminal, median and index digital nerves. Series of stimuli usually significantly decreased the amplitude of MMRsingle, as a phenomenon of habituation. On the other hand, it was difficult to evoke the earlier response (i.e. MMRaverage) without continuous stimuli and an average technique. MMRaverage had the components of both excitation (E) and inhibition (I); for example, E1-I1-E2-I2 or I1-E2-I2. E2 was the most consistent component. In patients with dorsal column dysfunction, median nerve stimulation could successfully elicit MMRsingle, but not MMRaverage. Contrarily, in patients with pain sensory loss, it was more difficult to reproduce MMRsingle than MMRaverage. It seemed that MMRaverage and MMRsingle did not have equivalents across the different modalities of stimulation.

Two male patients were diagnosed with adrenomyeloneuropathy. Their chief problems were progressive spastic paraparesis, sensory impairment, hyperpigmentation and testis atrophy. Transcranial magnetic stimulation (TMS) does not easily elicit motor-evoked potentials (MEPs) in patients with a central nervous system dysfunction, even though a few methods, such as contraction of the target muscles and the Jendrassik maneuver (JM), are used in the attempt to facilitate them. In these two patients, we used a conditioning method (prior electrical stimulation over the cutaneous nerve of the left index finger) in order to facilitate MEPs, elicited by TMS, in the left tibialis anterior muscle. In patient 1, facilitation of MEPs was present at conditioning-test (C-T) intervals in the range 60-220 ms, with the maximal MEP recorded at C-T 160 ms; in patient 2, it occurred in the C-T interval range 110-140 ms, with the maximal MEP recorded at C-T 130 ms. By means of conditioning electrical stimulation, we can facilitate MEPs elicited by TMS in those subjects in whom MEPs are minimal or difficult to elicit even using the conventional JM or muscle contraction. The facilitation of MEPs by conditioning stimuli allowed us not only to assess central motor conduction time, but also to demonstrate the preserved continuity of the corticospinal tract in these two patients.

Mitochondrial diseases are heterogeneous disorders affecting multiple systems. Here, we presented the findings of multimodal evoked potential (EP) studies of three siblings with a specific A8344G mutation of mitochondrial DNA. One of them had DM and another two had a history of encephalopathy. Visual EPs were abnormal in one patient and motor, somatosensory and brainstem auditory EPs were observed in all three patients. Our EP studies showed that the A8344G mutation of mitochondrial DNA involved multiple levels of the central nervous system even though there were no correlated symptoms. Therefore EP is an adjunct of methods to detect the functional disturbance and to screen the distribution of the involvement of the nervous system in mitochondrial diseases.