In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex-and agematched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed pointbased correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective painprocessing areas in patients suffering from chronic pain. The accentuated 0.12-to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system. functional MRI | insula | resting state | autonomic nervous system | human A cute pain has an important protective function and is supported by a well-known brain network comprising the insular cortex, anterior cingulate cortex (ACC), primary and secondary somatosensory cortex, and thalamus (1). When pain becomes chronic, its physiological protective function is lost. Chronic pain decreases the quality of life and interferes with the cognitive, affective, and physical functioning. Although one-fifth of the Western population suffers from chronic pain (2), the underlying brain activity is poorly understood.Extensive meta-analyses (1, 3, 4) indicate that the brain areas related to chronic and acute pain differ to some extent, but no single brain-activity pattern is specific to chronic pain. Morphometric analyses suggest gray-matter loss in many chronic pain conditions, indicating that chronic pain may alter brain structure (5), but in a reversible manner (6).Previous studies on the brain basis of chronic pain have concentrated on abnormal activation sites and strengths following external stimulation. Studies of resting-state brain activity by means of functional magnetic resonance imaging (fMRI) have shown that the connectivity within the default-mode network (7) is altered in chronic pain, together with reduced task-related deactivation within this network (8, 9). Recently, the spectra of the default-mode network were shown to contain more power at 0.05 to 0.1 Hz in patients suffering from diabetic neuropathic pain than in healthy control subjects (9).In the present study, we focused on the resting-state fluctuations and functional connectivity of the affective pain-processing areas, the insula and ACC, in chronic pain. Specifically, we recorded spontaneous fMRI sig...
According to recent functional magnetic resonance imaging (fMRI) studies, spectators of a movie may share similar spatiotemporal patterns of brain activity. We aimed to extend these findings of intersubject correlation to temporally accurate single-trial magnetoencephalography (MEG). A silent 15-min black-and-white movie was shown to eight subjects twice. We adopted a spatial filtering model and estimated its parameter values by using multi-set canonical correlation analysis (M-CCA) so that the intersubject correlation was maximized. The procedure resulted in multiple (mutually uncorrelated) time-courses with statistically significant intersubject correlations at frequencies below 10 Hz; the maximum correlation was 0.28 ± 0.075 in the ≤1 Hz band. Moreover, the 24-Hz frame rate elicited steady-state responses with statistically significant intersubject correlations up to 0.29 ± 0.12. To assess the brain origin of the across-subjects correlated signals, the time-courses were correlated with minimum-norm source current estimates (MNEs) projected to the cortex. The time series implied across-subjects synchronous activity in the early visual, posterior and inferior parietal, lateral temporo-occipital, and motor cortices, and in the superior temporal sulcus (STS) bilaterally. These findings demonstrate the capability of the proposed methodology to uncover cortical MEG signatures from single-trial signals that are consistent across spectators of a movie.
It is often implicitly assumed that the neural activation patterns revealed by hemodynamic methods, such as functional magnetic resonance imaging (fMRI), and electrophysiological methods, such as magnetoencephalography (MEG) and electroencephalography (EEG), are comparable. In early sensory processing that seems to be the case, but the assumption may not be correct in high-level cognitive tasks. For example, MEG and fMRI literature of single-word reading suggests differences in cortical activation, but direct comparisons are lacking. Here, while the same human participants performed the same reading task, analysis of MEG evoked responses and fMRI blood oxygenation level-dependent (BOLD) signals revealed marked functional and spatial differences in several cortical areas outside the visual cortex. Divergent patterns of activation were observed in the frontal and temporal cortex, in accordance with previous separate MEG and fMRI studies of reading. Furthermore, opposite stimulus effects in the MEG and fMRI measures were detected in the left occipitotemporal cortex: MEG evoked responses were stronger to letter than symbol strings, whereas the fMRI BOLD signal was stronger to symbol than letter strings. The EEG recorded simultaneously during MEG and fMRI did not indicate neurophysiological differences that could explain the observed functional discrepancies between the MEG and fMRI results. Acknowledgment of the complementary nature of hemodynamic and electrophysiological measures, as reported here in a cognitive task using evoked response analysis in MEG and BOLD signal analysis in fMRI, represents an essential step toward an informed use of multimodal imaging that reaches beyond mere combination of location and timing of neural activation.
In addition to SSEP (somatosensory evoked potentials), three different evoked responses are noted that could be useful for clinical monitoring.
Androgen deprivation and SARS-CoV-2 in men with prostate cancerWe read with great interest the very recent article by Montopoli et al., 1 which reports men with prostate cancer tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Veneto, Italy, by 1 April 2020. The authors suggest that androgen deprivation therapy (ADT) could partially protect from SARS-CoV-2 infection. 1 The biological premise for this observation is the androgen receptormediated regulation of TMPRSS2, 2 a type II transmembrane serine protease that is important for SARS-CoV-2 entry to host cells. 3 Indeed, androgens regulate TMPRSS2 expression also in a lung carcinoma cell line. 4 Encouraged by the findings of Montopoli et al., 1 we examined the health care records of patients with prostate cancer [International Classification of Diseases (ICD)-10 code C61] in the Hospital District of Helsinki and Uusimaa, Finland, using automated text mining with manual verification and structured diagnostic codes. Altogether, 352 such men were tested for SARS-CoV-2 between 7 March and 14 May 2020. A patient was classified to be on ADT if he had a history of orchiectomy, or a valid prescription for a gonadotropin-releasing hormone (GnRH) analogue, GnRH antagonist, and/or antiandrogens (flutamide, bicalutamide, enzalutamide) or the CYP17 inhibitor abiraterone before his SARS-CoV-2 test (n ¼ 134) [38%, 95% confidence interval (CI): 33%e43%]. The mean age of these 134 men was 78.4 years AE 8.1 standard deviation (range 58e96 years). The frequency of being on ADT was in agreement with that observed in a survey of a large cohort of UK men with prostate cancer. 5 Conversely, a patient was classified not to be on ADT if no records of the above conditions were found or ADT had been ceased before a SARS-CoV-2 test (n ¼ 218; mean age 76.5 years AE 9.4 standard deviation, range 51e96 years). The presence of SARS-CoV-2 RNA in nasopharyngeal swab samples was analyzed by RT-PCR (details available upon request). This study was based on register data, provided by the registry holder, Helsinki University Hospital, and therefore no ethical permission was required according to the Finnish Medical Research Act.Of the 352 prostate cancer patients, 17 (4.8%, 95% CI: 2.6%e7.0%) tested positive for SARS-CoV-2, and 6 (35%, 95% CI: 13%e58%) of them were on ADT. However, the frequency of being positive for SARS-CoV-2 was not associated with ADT [6/134 on ADT versus 11/218 not on ADT; odds ratio (OR) 0.88; 95% CI 0.32e2.44, P ¼ 0.81]. ADT was not associated with the severity of the disease, as assessed by occurrence of death or the need of intensive care (1/6 in the ADT-positive group versus 3/11 in the ADT-negative group; OR 0.53; 95% CI 0.04e6.66, P ¼ 0.63). There were no differences in possible confounding comorbidities on Letters to the Editor
Our results show that burst suppression caused by the different anesthetics can be reliably detected with our segmentation and classification methods. The analysis of normal and pathological EEG, however, should include information of the anesthetic used. Knowledge of the normal variation of the EEG is necessary in order to detect the abnormal BSP of, for instance, seizure patients.
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