Altered physiological brain variation in drug‐resistant epilepsy

Abstract

IntroductionFunctional magnetic resonance imaging (fMRI) combined with simultaneous electroencephalography (EEG‐fMRI) has become a major tool in mapping epilepsy sources. In the absence of detectable epileptiform activity, the resting state fMRI may still detect changes in the blood oxygen level‐dependent signal, suggesting intrinsic alterations in the underlying brain physiology.MethodsIn this study, we used coefficient of variation (CV) of critically sampled 10 Hz ultra‐fast fMRI (magnetoencephalography, MREG) signal to compare physiological variance between healthy controls (n = 10) and patients (n = 10) with drug‐resistant epilepsy (DRE).ResultsWe showed highly significant voxel‐level (p < 0.01, TFCE‐corrected) increase in the physiological variance in DRE patients. At individual level, the elevations range over three standard deviations (σ) above the control mean (μ) CVMREG values solely in DRE patients, enabling patient‐specific mapping of elevated physiological variance. The most apparent differences in group‐level analysis are found on white matter, brainstem, and cerebellum. Respiratory (0.12–0.4 Hz) and very‐low‐frequency (VLF = 0.009–0.1 Hz) signal variances were most affected.ConclusionsThe CVMREG increase was not explained by head motion or physiological cardiorespiratory activity, that is, it seems to be linked to intrinsic physiological pulsations. We suggest that intrinsic brain pulsations play a role in DRE and that critically sampled fMRI may provide a powerful tool for their identification.

Respiratory-related brain pulsations are increased in epilepsy—a two-centre functional MRI study

“…Due to scheduling reasons and/or subject compliance, some acquisitions had to be shortened to 5 min. To enable a consistent analysis, only the first 5 min from every dataset was used, similarly to previous work ( Kananen et al , 2018 ). Furthermore, the usage of the first 5 min minimized the vigilance drops of the subjects ( Kiviniemi et al , 2016 ; Kananen et al , 2018 ).…”

“…Previously, these physiological pulsations have been regarded as artefacts with little relevance to the underlying pathology. However, these fluctuations are the driving forces of brain CSF pulsations and have been linked to several neurological diseases including epilepsy ( Kananen et al , 2018 ; Sun et al , 2018 ; Rajna et al , 2019 ). In particular, differences in the amplitude and variance in physiological BOLD signal fluctuations, as quantified by the coefficient of variation (CV), have been reported in different conditions, e.g.…”

“…In particular, differences in the amplitude and variance in physiological BOLD signal fluctuations, as quantified by the coefficient of variation (CV), have been reported in different conditions, e.g. in acute ischaemic stroke ( Khalil et al , 2017 ), Alzheimer’s disease ( Makedonov et al , 2016 ; Tuovinen et al , 2017 ), small vessel disease ( Makedonov et al , 2013 ) and epilepsy ( Kananen et al , 2018 ). CV measures become more accurate when calculated over large distributions including thousands of samples and thus benefit from the high temporal resolution of MREG in the characterization of BOLD signal properties in frequency sub-bands of interest.…”

“…Our group published a preliminary study measuring physiological pulsations in patients with intractable epilepsy suggesting that pulsations were altered in patients compared to controls ( Kananen et al , 2018 ). In this study, we aim to replicate these findings in a larger group of patients, additionally introducing patient data with new onset epilepsy, thus allowing the exclusion of the effect of antiepileptic drugs (AEDs) as a cause of the observed change in brain pulsations.…”

3D Multi-Resolution Optical Flow Analysis of Cardiovascular Pulse Propagation in Human Brain

“…There is also prior evidence suggesting that the physiological noise in functional MR imaging (FMRI) signals are altered in dementia [15], [16]. Recently, drug resistant epilepsy linked to glymphatic AQP4 water channel abnormality, was shown in [17] to have abnormal respiratory brain pulsations in addition to cardiovascular pulsation changes.…”