Tim M. Tierney

FIACH: A biophysical model for automatic retrospective noise control in fMRI

Different noise sources in fMRI acquisition can lead to spurious false positives and reduced sensitivity. We have developed a biophysically-based model (named FIACH: Functional Image Artefact Correction Heuristic) which extends current retrospective noise control methods in fMRI. FIACH can be applied to both General Linear Model (GLM) and resting state functional connectivity MRI (rs-fcMRI) studies. FIACH is a two-step procedure involving the identification and correction of non-physiological large amplitude temporal signal changes and spatial regions of high temporal instability. We have demonstrated its efficacy in a sample of 42 healthy children while performing language tasks that include overt speech with known activations. We demonstrate large improvements in sensitivity when FIACH is compared with current methods of retrospective correction. FIACH reduces the confounding effects of noise and increases the studys power by explaining significant variance that is not contained within the commonly used motion parameters. The method is particularly useful in detecting activations in inferior temporal regions which have proven problematic for fMRI. We have shown greater reproducibility and robustness of fMRI responses using FIACH in the context of task induced motion. In a clinical setting this will translate to increasing the reliability and sensitivity of fMRI used for the identification of language lateralisation and eloquent cortex. FIACH can benefit studies of cognitive development in young children, patient populations and older adults.

Moving magnetoencephalography towards real-world applications with a wearable system

Imaging human brain function with techniques such as magnetoencephalography typically requires a subject to perform tasks while their head remains still within a restrictive scanner. This artificial environment makes the technique inaccessible to many people, and limits the experimental questions that can be addressed. For example, it has been difficult to apply neuroimaging to investigation of the neural substrates of cognitive development in babies and children, or to study processes in adults that require unconstrained head movement (such as spatial navigation). Here we describe a magnetoencephalography system that can be worn like a helmet, allowing free and natural movement during scanning. This is possible owing to the integration of quantum sensors, which do not rely on superconducting technology, with a system for nulling background magnetic fields. We demonstrate human electrophysiological measurement at millisecond resolution while subjects make natural movements, including head nodding, stretching, drinking and playing a ball game. Our results compare well to those of the current state-of-the-art, even when subjects make large head movements. The system opens up new possibilities for scanning any subject or patient group, with myriad applications such as characterization of the neurodevelopmental connectome, imaging subjects moving naturally in a virtual environment and investigating the pathophysiology of movement disorders.

Phase–amplitude coupling and the BOLD signal: A simultaneous intracranial EEG (icEEG) - fMRI study in humans performing a finger-tapping task

Abstract Although it has been consistently found that local blood‐oxygen‐level‐dependent (BOLD) changes are better modelled by a combination of the power of multiple EEG frequency bands rather than by the power of a unique band alone, the local electro‐haemodynamic coupling function is not yet fully characterised. Electrophysiological studies have revealed that the strength of the coupling between the phase of low‐ and the amplitude of high‐ frequency EEG activities (phase–amplitude coupling ‐ PAC) has an important role in brain function in general, and in preparation and execution of movement in particular. Using electrocorticographic (ECoG) and functional magnetic resonance imaging (fMRI) data recorded simultaneously in humans performing a finger‐tapping task, we investigated the single‐trial relationship between the amplitude of the BOLD signal and the strength of PAC and the power of &agr;, &bgr;, and &ggr; bands, at a local level. In line with previous studies, we found a positive correlation for the &ggr; band, and negative correlations for the PAC&bgr;&ggr; strength, and the &agr; and &bgr; bands. More importantly, we found that the PAC&bgr;&ggr; strength explained variance of the amplitude of the BOLD signal that was not explained by a combination of the &agr;, &bgr;, and &ggr; band powers. Our main finding sheds further light on the distinct nature of PAC as a functionally relevant mechanism and suggests that the sensitivity of EEG‐informed fMRI studies may increase by including the PAC strength in the BOLD signal model, in addition to the power of the low‐ and high‐ frequency EEG bands. HighlightsFirst study of single‐trial correlations between the phase amplitude coupling strength and BOLD.Intracranial EEG and fMRI data simultaneously recorded in humans during a motor task.PAC&bgr;&ggr; strength explains variance of BOLD in addition a combination of &agr;, &bgr;, and &ggr; band powers.

Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children

Background Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the “resting state”; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work’s motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population Methods Forty-six children with focal epilepsy and 20 controls (6–18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies (“rest sessions”), for another two sessions, subjects watched a child friendly stimulation i.e. movie (“movie sessions”). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject. Findings Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance. Conclusions A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without sedation. Our data suggest that ~20 minutes is the optimal length of scanning for EEG-fMRI studies in children with frequent IED. The efficiency of the fMRI design derived from spontaneous IED generation is an important factor for producing concordant results.

Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy.

Patients with focal epilepsy have been shown to have reduced functional connectivity in intrinsic connectivity networks (ICNs), which has been related to neurocognitive development and outcome. However, the relationship between interictal epileptiform discharges (IEDs) and changes in ICNs remains unclear, with evidence both for and against their influence. EEG‐fMRI data was obtained in 27 children with focal epilepsy (mixed localisation and aetiologies) and 17 controls. A natural stimulus task (cartoon blocks verses blocks where the subject was told “please wait”) was used to enhance the connectivity within networks corresponding to ICNs while reducing potential confounds of vigilance and motion. Our primary hypothesis was that the functional connectivity within visual and attention networks would be reduced in patients with epilepsy. We further hypothesized that controlling for the effects of IEDs would increase the connectivity in the patient group. The key findings were: (1) Patients with mixed epileptic foci showed a common connectivity reduction in lateral visual and attentional networks compared with controls. (2) Having controlled for the effects of IEDs there were no connectivity differences between patients and controls. (3) A comparison within patients revealed reduced connectivity between the attentional network and basal ganglia associated with interictal epileptiform discharges. We also found that the task activations were reduced in epilepsy patients but that this was unrelated to IED occurrence. Unexpectedly, connectivity changes in ICNs were strongly associated with the transient effects of interictal epileptiform discharges. Interictal epileptiform discharges were shown to have a pervasive transient influence on the brains functional organisation. Hum Brain Mapp 38:221–236, 2017.

A study of the electro-haemodynamic coupling using simultaneously acquired intracranial EEG and fMRI data in humans.

In current fMRI studies designed to map BOLD changes related to interictal epileptiform discharges (IED), which are recorded on simultaneous EEG, the information contained in the morphology and field extent of the EEG events is exclusively used for their classification. Usually, a BOLD predictor based on IED onset times alone is constructed, effectively treating all events as identical. We used intracranial EEG (icEEG)-fMRI data simultaneously recorded in humans to investigate the effect of including any of the features: amplitude, width (duration), slope of the rising phase, energy (area under the curve), or spatial field extent (number of contacts over which the sharp wave was observed) of the fast wave of the IED (the sharp wave), into the BOLD model, to better understand the neurophysiological origin of sharp wave-related BOLD changes, in the immediate vicinity of the recording contacts. Among the features considered, the width was the only one found to explain a significant amount of additional variance, suggesting that the amplitude of the BOLD signal depends more on the duration of the underlying field potential (reflected in the sharp wave width) than on the degree of neuronal activity synchrony (reflected in the sharp wave amplitude), and, consequently, that including inter-event variations of the sharp wave width in the BOLD signal model may increase the sensitivity of forthcoming EEG-fMRI studies of epileptic activity.

Combined EEG-fMRI and ESI improves localisation of paediatric focal epilepsy

Surgical treatment in epilepsy is effective if the epileptogenic zone (EZ) can be correctly localized and characterized. Here we use simultaneous electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) data to derive EEG‐fMRI and electrical source imaging (ESI) maps. Their yield and their individual and combined ability to (1) localize the EZ and (2) predict seizure outcome were then evaluated.

Combined electroencephalography–functional magnetic resonance imaging and electrical source imaging improves localization of pediatric focal epilepsy

Surgical treatment in epilepsy is effective if the epileptogenic zone (EZ) can be correctly localized and characterized. Here we use simultaneous electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) data to derive EEG‐fMRI and electrical source imaging (ESI) maps. Their yield and their individual and combined ability to (1) localize the EZ and (2) predict seizure outcome were then evaluated.

Thalamic volume reduction in drug-naive patients with new-onset genetic generalized epilepsy

Patients with genetic generalized epilepsy (GGE) have subtle morphologic abnormalities of the brain revealed with magnetic resonance imaging (MRI), particularly in the thalamus. However, it is unclear whether morphologic abnormalities of the brain in GGE are a consequence of repeated seizures over the duration of the disease, or are a consequence of treatment with antiepileptic drugs (AEDs), or are independent of these factors. Therefore, we measured brain morphometry in a cohort of AED‐naive patients with GGE at disease onset. We hypothesize that drug‐naive patients at disease onset have gray matter changes compared to age‐matched healthy controls.

Using optically-pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum

We test the feasibility of an optically pumped magnetometer-magnetoencephalographic (OP-MEG) system for the measurement of human cerebellar activity. This is to our knowledge the first study investigating the human cerebellar electrophysiology using OPMs. As a proof of principle, we use an air-puff stimulus to the eyeball in order to elicit cerebellar activity that is well characterised in non-human models. In three subjects, we observe an evoked component at approx. 50ms post-stimulus, followed by a second component at approx. 85-115 ms post-stimulus. Source inversion localises both components in the cerebellum, while control experiments exclude potential sources elsewhere. We also assess the induced oscillations, with time-frequency decompositions, and identify the source in the occipital lobe, a region expected to be active in our paradigm. We conclude that the OP-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum.