Jorge Arrubla

Imaging the where and when of tic generation and resting state networks in adult Tourette patients

Introduction: Tourette syndrome (TS) is a neuropsychiatric disorder with the core phenomenon of tics, whose origin and temporal pattern are unclear. We investigated the When and Where of tic generation and resting state networks (RSNs) via functional magnetic resonance imaging (fMRI). Methods: Tic-related activity and the underlying RSNs in adult TS were studied within one fMRI session. Participants were instructed to lie in the scanner and to let tics occur freely. Tic onset times, as determined by video-observance were used as regressors and added to preceding time-bins of 1 s duration each to detect prior activation. RSN were identified by independent component analysis (ICA) and correlated to disease severity by the means of dual regression. Results: Two seconds before a tic, the supplementary motor area (SMA), ventral primary motor cortex, primary sensorimotor cortex and parietal operculum exhibited activation; 1 s before a tic, the anterior cingulate, putamen, insula, amygdala, cerebellum and the extrastriatal-visual cortex exhibited activation; with tic-onset, the thalamus, central operculum, primary motor and somatosensory cortices exhibited activation. Analysis of resting state data resulted in 21 components including the so-called default-mode network. Network strength in those regions in SMA of two premotor ICA maps that were also active prior to tic occurrence, correlated significantly with disease severity according to the Yale Global Tic Severity Scale (YGTTS) scores. Discussion: We demonstrate that the temporal pattern of tic generation follows the cortico-striato-thalamo-cortical circuit, and that cortical structures precede subcortical activation. The analysis of spontaneous fluctuations highlights the role of cortical premotor structures. Our study corroborates the notion of TS as a network disorder in which abnormal RSN activity might contribute to the generation of tics in SMA.

The Default Mode Network and EEG Regional Spectral Power: A Simultaneous fMRI-EEG Study

Electroencephalography (EEG) frequencies have been linked to specific functions as an “electrophysiological signature” of a function. A combination of oscillatory rhythms has also been described for specific functions, with or without predominance of one specific frequency-band. In a simultaneous fMRI-EEG study at 3 T we studied the relationship between the default mode network (DMN) and the power of EEG frequency bands. As a methodological approach, we applied Multivariate Exploratory Linear Optimized Decomposition into Independent Components (MELODIC) and dual regression analysis for fMRI resting state data. EEG power for the alpha, beta, delta and theta-bands were extracted from the structures forming the DMN in a region-of-interest approach by applying Low Resolution Electromagnetic Tomography (LORETA). A strong link between the spontaneous BOLD response of the left parahippocampal gyrus and the delta-band extracted from the anterior cingulate cortex was found. A positive correlation between the beta-1 frequency power extracted from the posterior cingulate cortex (PCC) and the spontaneous BOLD response of the right supplementary motor cortex was also established. The beta-2 frequency power extracted from the PCC and the precuneus showed a positive correlation with the BOLD response of the right frontal cortex. Our results support the notion of beta-band activity governing the “status quo” in cognitive and motor setup. The highly significant correlation found between the delta power within the DMN and the parahippocampal gyrus is in line with the association of delta frequencies with memory processes. We assumed “ongoing activity” during “resting state” in bringing events from the past to the mind, in which the parahippocampal gyrus is a relevant structure. Our data demonstrate that spontaneous BOLD fluctuations within the DMN are associated with different EEG-bands and strengthen the conclusion that this network is characterized by a specific electrophysiological signature created by combination of different brain rhythms subserving different putative functions.

Advances in multimodal neuroimaging: hybrid MR-PET and MR-PET-EEG at 3 T and 9.4 T.

Multi-modal MR-PET-EEG data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. The three modalities complement each other well; structural-functional imaging being the domain of MRI, molecular imaging with specific tracers is the strength of PET, and EEG provides a temporal dimension where the other two modalities are weak. The utility of hybrid MR-PET at 3 T in a clinical setting is presented and critically discussed. The potential problems and the putative gains to be accrued from hybrid imaging at 9.4 T, with examples from the human brain, are outlined. Steps on the road to 9.4 T multi-modal MR-PET-EEG are also illustrated. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented, setting the stage for hybrid imaging at ultra-high field. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are presented. Examples of tumour imaging on a 3 T MR-PET system are presented and discussed. Finally, the perspectives for multi-modal imaging are discussed based on two on-going studies, the first comparing MR and PET methods for the measurement of perfusion and the second which looks at tumour delineation based on MRI contrasts but the knowledge of tumour extent is based on simultaneously acquired PET data.

Simultaneous EEG-fMRI acquisition at low, high and ultra-high magnetic fields up to 9.4 T: perspectives and challenges.

In this perspectives article we highlight the advantages of simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). As MRI moves towards using ultra-high magnetic fields in the quest for increased signal-to-noise, the question arises whether combined EEG-fMRI measurements are feasible at magnetic fields of 7 T and higher. We describe the challenges of MRI-EEG at 1.5, 3, 7 and 9.4 T and review the proposed solutions. In an outlook, we discuss further developments such as simultaneous trimodal imaging using MR, positron emission tomography (PET) and EEG under the same physiological conditions in the same subject.

EEG acquisition in ultra-high static magnetic fields up to 9.4 T

The simultaneous acquisition of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data has gained momentum in recent years due to the synergistic effects of the two modalities with regard to temporal and spatial resolution. Currently, only EEG-data recorded in fields of up to 7 T have been reported. We investigated the feasibility of recording EEG inside a 9.4 T static magnetic field, specifically to determine whether meaningful EEG information could be recovered from the data after removal of the cardiac-related artefact. EEG-data were recorded reliably and reproducibly at 9.4 T and the cardiac-related artefact increased in amplitude with increasing B0, as expected. Furthermore, we were able to correct for the cardiac-related artefact and identify auditory event related responses at 9.4 T in 75% of subjects using independent component analysis (ICA). Also by means of ICA we detected event related spectral perturbations (ERSP) in subjects at 9.4 T in response to opening/closing the eyes comparable with the response at 0 T. Overall our results suggest that it is possible to record meaningful EEG data at ultra-high magnetic fields. The simultaneous EEG-fMRI approach at ultra-high-fields opens up the horizon for investigating brain dynamics at a superb spatial resolution and a temporal resolution in the millisecond domain.

Recording visual evoked potentials and auditory evoked P300 at 9.4T static magnetic field.

Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has shown a number of advantages that make this multimodal technique superior to fMRI alone. The feasibility of recording EEG at ultra-high static magnetic field up to 9.4T was recently demonstrated and promises to be implemented soon in fMRI studies at ultra high magnetic fields. Recording visual evoked potentials are expected to be amongst the most simple for simultaneous EEG/fMRI at ultra-high magnetic field due to the easy assessment of the visual cortex. Auditory evoked P300 measurements are of interest since it is believed that they represent the earliest stage of cognitive processing. In this study, we investigate the feasibility of recording visual evoked potentials and auditory evoked P300 in a 9.4T static magnetic field. For this purpose, EEG data were recorded from 26 healthy volunteers inside a 9.4T MR scanner using a 32-channel MR compatible EEG system. Visual stimulation and auditory oddball paradigm were presented in order to elicit evoked related potentials (ERP). Recordings made outside the scanner were performed using the same stimuli and EEG system for comparison purposes. We were able to retrieve visual P100 and auditory P300 evoked potentials at 9.4T static magnetic field after correction of the ballistocardiogram artefact using independent component analysis. The latencies of the ERPs recorded at 9.4T were not different from those recorded at 0T. The amplitudes of ERPs were higher at 9.4T when compared to recordings at 0T. Nevertheless, it seems that the increased amplitudes of the ERPs are due to the effect of the ultra-high field on the EEG recording system rather than alteration in the intrinsic processes that generate the electrophysiological responses.

GABA concentration in posterior cingulate cortex predicts putamen response during resting state fMRI.

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA) and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI). In this study GABA concentration in the posterior cingulate cortex (PCC) was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS) from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio) were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting state.

Attention to detail: Why considering task demands is essential for single-trial analysis of bold correlates of the visual p1 and n1

Single-trial fluctuations in the EEG signal have been shown to temporally correlate with the fMRI BOLD response and are valuable for modeling trial-to-trial fluctuations in responses. The P1 and N1 components of the visual ERP are sensitive to different attentional modulations, suggesting that different aspects of stimulus processing can be modeled with these ERP parameters. As such, different patterns of BOLD covariation for P1 and N1 informed regressors would be expected; however, current findings are equivocal. We investigate the effects of variations in attention on P1 and N1 informed BOLD activation in a visual oddball task. Simultaneous EEG-fMRI data were recorded from 13 healthy participants during three conditions of a visual oddball task: Passive, Count, and Respond. We show that the P1 and N1 components of the visual ERP can be used in the integration-by-prediction method of EEG-fMRI data integration to highlight brain regions related to target detection and response production. Our data suggest that the P1 component of the ERP reflects changes in sensory encoding of stimulus features and is more informative for the Passive and Count conditions. The N1, on the other hand, was more informative for the Respond condition, suggesting that it can be used to model the processing of stimulus, meaning specifically discriminating one type of stimulus from another, and processes involved in integrating sensory information with response selection. Our results show that an understanding of the underlying electrophysiology is necessary for a thorough interpretation of EEG-informed fMRI analysis.

Fine motor skills in adult Tourette patients are task-dependent.

BackgroundTourette syndrome is a neuropsychiatric disorder characterized by motor and phonic tics. Deficient motor inhibition underlying tics is one of the main hypotheses in its pathophysiology. Therefore the question arises whether this supposed deficient motor inhibition affects also voluntary movements. Despite severe motor tics, different personalities who suffer from Tourette perform successfully as neurosurgeon, pilot or professional basketball player.MethodsFor the investigation of fine motor skills we conducted a motor performance test battery in an adult Tourette sample and an age matched group of healthy controls.ResultsThe Tourette patients showed a significant lower performance in the categories steadiness of both hands and aiming of the right hand in comparison to the healthy controls. A comparison of patients’ subgroup without comorbidities or medication and healthy controls revealed a significant difference in the category steadiness of the right hand.ConclusionsOur results show that steadiness and visuomotor integration of fine motor skills are altered in our adult sample but not precision and speed of movements. This alteration pattern might be the clinical vignette of complex adaptations in the excitability of the motor system on the basis of altered cortical and subcortical components. The structurally and functionally altered neuronal components could encompass orbitofrontal, ventrolateral prefrontal and parietal cortices, the anterior cingulate, amygdala, primary motor and sensorimotor areas including altered corticospinal projections, the corpus callosum and the basal ganglia.

Cortical response variation with different sound pressure levels: A combined event-related potentials and FMRI study

Introduction Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs). Methods EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data. Results The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs. Discussion The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects.