Neurodesk: an accessible, flexible and portable data analysis environment for reproducible neuroimaging.

Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.

Wearable OPM-MEG: A changing landscape for epilepsy.

Magnetoencephalography with optically pumped magnometers (OPM-MEG) is an emerging and novel, cost-effective wearable system that can simultaneously record neuronal activity with high temporal resolution ("when" neuronal activity occurs) and spatial resolution ("where" neuronal activity occurs). This paper will first outline recent methodological advances in OPM-MEG compared to conventional superconducting quantum interference device (SQUID)-MEG before discussing how OPM-MEG can become a valuable and noninvasive clinical support tool in epilepsy surgery evaluation. Although OPM-MEG and SQUID-MEG share similar data features, OPM-MEG is a wearable design that fits children and adults, and it is also robust to head motion within a magnetically shielded room. This means that OPM-MEG can potentially extend the application of MEG into the neurobiology of severe childhood epilepsies with intellectual disabilities (e.g., epileptic encephalopathies) without sedation. It is worth noting that most OPM-MEG sensors are heated, which may become an issue with large OPM sensor arrays (OPM-MEG currently has fewer sensors than SQUID-MEG). Future implementation of triaxial sensors may alleviate the need for large OPM sensor arrays. OPM-MEG designs allowing both awake and sleep recording are essential for potential long-term epilepsy monitoring.

Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy: A single-institution retrospective review.

OBJECTIVE: The aim of this report is to present our clinical experience of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in localizing the epileptogenic focus, and to evaluate the clinical impact and challenges associated with the use of EEG-fMRI in pharmacoresistant focal epilepsy. METHODS: We identified EEG-fMRI studies (n = 118) in people with focal epilepsy performed at our center from 2003 to 2018. Participants were referred from our Comprehensive Epilepsy Program in an exploratory research effort to address often difficult clinical questions, due to complex and difficult-to-localize epilepsy. We assessed the success of each study, the clinical utility of the result, and when surgery was performed, the postoperative outcome. RESULTS: Overall, 50% of EEG-fMRI studies were successful, meaning that data were of good quality and interictal epileptiform discharges were recorded. With an altered recruitment strategy since 2012 with increased inclusion of patients who were inpatients for video-EEG monitoring, we found that this patients in this selected group were more likely to have epileptic discharges detected during EEG-fMRI (96% of inpatients vs 29% of outpatients, P<.0001). To date, 48% (57 of 118) of patients have undergone epilepsy surgery. In 10 cases (17% of the 59 successful studies) the EEG-fMRI result had a "critical impact" on the surgical decision. These patients were difficult to localize because of subtle abnormalities, apparently normal MRI, or extensive structural abnormalities. All 10 had a good seizure outcome at 1 year after surgery (mean follow-up 6.5 years). SIGNIFICANCE: EEG-fMRI results can assist identification of the epileptogenic focus in otherwise difficult-to-localize cases of pharmacoresistant focal epilepsy. Surgery determined largely by localization from the EEG-fMRI result can lead to good seizure outcomes. A limitation of this study is its retrospective design with nonconsecutive recruitment. Prospective clinical trials with well-defined inclusion criteria are needed to determine the overall benefit of EEG-fMRI for preoperative localization and postoperative outcome in focal epilepsy.

Combined Isoflurane-Remifentanil Anaesthesia Permits Resting-State fMRI in Children with Severe Epilepsy and Intellectual Disability.

Head motion is a significant barrier to functional MRI (fMRI) in patients who are unable to tolerate awake scanning, including young children or those with cognitive and behavioural impairments. General anaesthesia minimises motion and ensures patient comfort, however the optimal anaesthesia regimen for fMRI in the paediatric setting is unknown. In this study, we tested the feasibility of anaesthetised fMRI in 11 patients (mean age = 9.8 years) with Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy associated with intellectual disability. fMRI was acquired during clinically-indicated MRI sessions using a synergistic anaesthesia regimen we typically administer for epilepsy neurosurgery: combined low-dose isoflurane (≤ 0.8% end-tidal concentration) with remifentanil (≤ 0.1 mcg/kg/min). Using group-level independent component analysis, we assessed the presence of resting-state networks by spatially comparing results in the anaesthetised patients to resting-state network templates from the 'Generation R' study of 536 similarly-aged non-anaesthetised healthy children (Muetzel et al. in Hum Brain Mapp 37(12):4286-4300, 2016). Numerous resting-state networks commonly studied in non-anaesthetised healthy children were readily identifiable in the anaesthetised patients, including the default-mode, sensorimotor, and frontoparietal networks. Independent component time-courses associated with these networks showed spectral characteristics suggestive of a neuronal origin of fMRI signal fluctuations, including high dynamic range and temporal frequency power predominantly below 0.1 Hz. These results demonstrate the technical feasibility of anaesthetised fMRI in children, suggesting that combined isoflurane-remifentanil anaesthesia may be an effective strategy to extend the emerging clinical applications of resting-state fMRI (for example, neurosurgical planning) to the variety of patient groups who may otherwise be impractical to scan.

Dynamic coupling between fMRI local connectivity and interictal EEG in focal epilepsy: A wavelet analysis approach.

Simultaneous scalp EEG-fMRI recording is a noninvasive neuroimaging technique for combining electrophysiological and hemodynamic aspects of brain function. Despite the time-varying nature of both measurements, their relationship is usually considered as time-invariant. The aim of this study was to detect direct associations between scalp-recorded EEG and regional changes of hemodynamic brain connectivity in focal epilepsy through a time-frequency paradigm. To do so, we developed a voxel-wise framework that analyses wavelet coherence between dynamic regional phase synchrony (DRePS, calculated from fMRI) and band amplitude fluctuation (BAF) of a target EEG electrode with dominant interictal epileptiform discharges (IEDs). As a proof of concept, we applied this framework to seven patients with focal epilepsy. The analysis produced patient-specific spatial maps of DRePS-BAF coupling, which highlight regions with a strong link between EEG power and local fMRI connectivity. Although we observed DRePS-BAF coupling proximate to the suspected seizure onset zone in some patients, our results suggest that DRePS-BAF is more likely to identify wider 'epileptic networks'. We also compared DRePS-BAF with standard EEG-fMRI analysis based on general linear modelling (GLM). There was, in general, little overlap between the DRePS-BAF maps and GLM maps. However, in some subjects the spatial clusters revealed by these two analyses appeared to be adjacent, particularly in medial posterior cortices. Our findings suggest that (1) there is a strong time-varying relationship between local fMRI connectivity and interictal EEG power in focal epilepsy, and (2) that DRePS-BAF reflect different aspects of epileptic network activity than standard EEG-fMRI analysis. These two techniques, therefore, appear to be complementary. Hum Brain Mapp 38:5356-5374, 2017. © 2017 Wiley Periodicals, Inc.

Thalamocortical functional connectivity in Lennox-Gastaut syndrome is abnormally enhanced in executive-control and default-mode networks.

OBJECTIVE: To identify abnormal thalamocortical circuits in the severe epilepsy of Lennox-Gastaut syndrome (LGS) that may explain the shared electroclinical phenotype and provide potential treatment targets. METHODS: Twenty patients with a diagnosis of LGS (mean age = 28.5 years) and 26 healthy controls (mean age = 27.6 years) were compared using task-free functional magnetic resonance imaging (MRI). The thalamus was parcellated according to functional connectivity with 10 cortical networks derived using group-level independent component analysis. For each cortical network, we assessed between-group differences in thalamic functional connectivity strength using nonparametric permutation-based tests. Anatomical locations were identified by quantifying spatial overlap with a histologically informed thalamic MRI atlas. RESULTS: In both groups, posterior thalamic regions showed functional connectivity with visual, auditory, and sensorimotor networks, whereas anterior, medial, and dorsal thalamic regions were connected with networks of distributed association cortex (including the default-mode, anterior-salience, and executive-control networks). Four cortical networks (left and right executive-control network; ventral and dorsal default-mode network) showed significantly enhanced thalamic functional connectivity strength in patients relative to controls. Abnormal connectivity was maximal in mediodorsal and ventrolateral thalamic nuclei. SIGNIFICANCE: Specific thalamocortical circuits are affected in LGS. Functional connectivity is abnormally enhanced between the mediodorsal and ventrolateral thalamus and the default-mode and executive-control networks, thalamocortical circuits that normally support diverse cognitive processes. In contrast, thalamic regions connecting with primary and sensory cortical networks appear to be less affected. Our previous neuroimaging studies show that epileptic activity in LGS is expressed via the default-mode and executive-control networks. Results of the present study suggest that the mediodorsal and ventrolateral thalamus may be candidate targets for modulating abnormal network behavior underlying LGS, potentially via emerging thalamic neurostimulation therapies.

Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome.

We previously observed that adults with Lennox-Gastaut syndrome (LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging (fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography (EEG) was acquired during presurgical fMRI. Presurgical and postsurgical functional connectivity were compared using (1) graph theoretical analyses of small-world network organization and node-wise strength; and (2) seed-based analyses of connectivity within and between five functional networks. To explore the specificity of these postsurgical network changes, connectivity was further compared to nine children with LGS who did not undergo surgery. The presurgical EEG-fMRI revealed diffuse activation of association cortex during interictal discharges. Following surgery and seizure control, functional connectivity showed increased small-world organization, stronger connectivity in subcortical structures, and greater within-network integration/between-network segregation. These changes suggest network improvement, and diverged sharply from the comparison group of nonoperated children. Following surgery, this child with LGS achieved seizure control and showed extensive reorganization of networks that underpin cognition. This case illustrates that the epileptic process of LGS can directly contribute to abnormal network organization, and that this network disruption may be reversible.

Dynamic regional phase synchrony (DRePS): An Instantaneous Measure of Local fMRI Connectivity Within Spatially Clustered Brain Areas.

Dynamic functional brain connectivity analysis is a fast expanding field in computational neuroscience research with the promise of elucidating brain network interactions. Sliding temporal window based approaches are commonly used in order to explore dynamic behavior of brain networks in task-free functional magnetic resonance imaging (fMRI) data. However, the low effective temporal resolution of sliding window methods fail to capture the full dynamics of brain activity at each time point. These also require subjective decisions regarding window size and window overlap. In this study, we introduce dynamic regional phase synchrony (DRePS), a novel analysis approach that measures mean local instantaneous phase coherence within adjacent fMRI voxels. We evaluate the DRePS framework on simulated data showing that the proposed measure is able to estimate synchrony at higher temporal resolution than sliding windows of local connectivity. We applied DRePS analysis to task-free fMRI data of 20 control subjects, revealing ultra-slow dynamics of local connectivity in different brain areas. Spatial clustering based on the DRePS feature time series reveals biologically congruent local phase synchrony networks (LPSNs). Taken together, our results demonstrate three main findings. Firstly, DRePS has increased temporal sensitivity compared to sliding window correlation analysis in capturing locally synchronous events. Secondly, DRePS of task-free fMRI reveals ultra-slow fluctuations of ∼0.002-0.02 Hz. Lastly, LPSNs provide plausible spatial information about time-varying brain local phase synchrony. With the DRePS method, we introduce a framework for interrogating brain local connectivity, which can potentially provide biomarkers of human brain function in health and disease. Hum Brain Mapp 37:1970-1985, 2016. © 2016 Wiley Periodicals, Inc.

Abnormal cognitive network interactions in Lennox-Gastaut syndrome: A potential mechanism of epileptic encephalopathy.

OBJECTIVE: In patients with Lennox-Gastaut syndrome (LGS), recurrent epileptic activity is thought to contribute to impaired cognition (epileptic encephalopathy). Using concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI), we recently showed that epileptiform discharges in LGS recruit large-scale networks that normally support key cognitive processes. In LGS, given that epileptic activity engages cognitive networks, and cognition is pervasively impaired, we hypothesized that cognitive network interactions in LGS are persistently abnormal. METHODS: We studied 15 LGS patients (mean age ± 1 standard deviation [SD] = 28.7 ± 10.6 years) and 17 healthy controls (mean age ± 1 SD = 27.6 ± 6.6 years) using task-free EEG-fMRI. Four networks of interest (default-mode, dorsal attention, executive control, and anterior salience) were defined using group-level independent components analysis (ICA). Functional connectivity within and between networks was determined for each subject, and then LGS network interactions were compared to network behavior in the control group. To test whether group differences were present in periods without scalp-detectable epileptiform discharges (i.e., persistent), we separately assessed discharge-affected and discharge-unaffected epochs in six patients with sufficient data for this analysis. RESULTS: In LGS, cognitive networks showed (1) reduced within-network integration, including weaker connectivity within the default-mode network, and (2) impaired between-network segregation, including stronger connectivity between the default-mode and dorsal attention networks. Abnormal interactions were present during fMRI periods with and without discharges, indicating that impaired network behavior may endure during periods without scalp-detectable epileptic activity. SIGNIFICANCE: In LGS, cognitive network interactions are persistently abnormal. Given that cognition typically worsens with the onset of LGS, and may improve after seizure control, our findings are consistent with the hypothesis that the epileptic process in LGS may initiate and perhaps sustain abnormal network behavior. We propose that epileptic encephalopathy may be a consequence of persistently disrupted cognitive network interactions.

Resting state functional connectivity changes induced by prior brain state are not network specific.

Resting state functional connectivity (rFC) is used to identify functionally related brain areas without requiring subjects to perform specific tasks. Previous work suggests that prior brain state, as determined by the activity engaged in immediately prior to collection of resting state data, can influence the networks recovered by rFC analyses. We determined the prevalence and network specificity of rFC changes induced by manipulations of prior state (including an unstructured (unconstrained) state, and language and motor tasks). Three blocks of rest data (one after each of the specified prior states) were acquired on each of 25 subjects. We hypothesised that prior state induced changes in rFC would be greatest within the networks most actively recruited by that prior state. Changes in rFC were greatest following the motor task and, contrary to our hypothesis, were not network specific. This was demonstrated by comparing (1) the timecourses within a set of ROIs selected on the basis of task-related de/activation, and (2) seed-based whole brain voxel-wise connectivity maps, seeded from local maxima in the task-related de/activation maps. Changes in connectivity strength tended to manifest as increases in rFC relative to that in the unstructured rest state, with change maps resembling partially complete maps of the primary sensory cortices and the cognitive control network. The majority of rFC changes occurred in areas moderately (but not weakly) connected to the seeds. Constrained prior states were associated with lower across-participant variance in rFC. This systematic investigation of the effect of prior brain state on rFC indicates that the rFC changes induced by prior brain state occur both in brain networks related to that brain activity and in networks nominally unrelated to that brain activity.

Brain regions with abnormal network properties in severe epilepsy of Lennox-Gastaut phenotype: Multivariate analysis of task-free fMRI.

OBJECTIVE: Lennox-Gastaut syndrome, and the similar but less tightly defined Lennox-Gastaut phenotype, describe patients with severe epilepsy, generalized epileptic discharges, and variable intellectual disability. Our previous functional neuroimaging studies suggest that abnormal diffuse association network activity underlies the epileptic discharges of this clinical phenotype. Herein we use a data-driven multivariate approach to determine the spatial changes in local and global networks of patients with severe epilepsy of the Lennox-Gastaut phenotype. METHODS: We studied 9 adult patients and 14 controls. In 20 min of task-free blood oxygen level-dependent functional magnetic resonance imaging data, two metrics of functional connectivity were studied: Regional homogeneity or local connectivity, a measure of concordance between each voxel to a focal cluster of adjacent voxels; and eigenvector centrality, a global connectivity estimate designed to detect important neural hubs. Multivariate pattern analysis of these data in a machine-learning framework was used to identify spatial features that classified disease subjects. RESULTS: Multivariate pattern analysis was 95.7% accurate in classifying subjects for both local and global connectivity measures (22/23 subjects correctly classified). Maximal discriminating features were the following: increased local connectivity in frontoinsular and intraparietal areas; increased global connectivity in posterior association areas; decreased local connectivity in sensory (visual and auditory) and medial frontal cortices; and decreased global connectivity in the cingulate cortex, striatum, hippocampus, and pons. SIGNIFICANCE: Using a data-driven analysis method in task-free functional magnetic resonance imaging, we show increased connectivity in critical areas of association cortex and decreased connectivity in primary cortex. This supports previous findings of a critical role for these association cortical regions as a final common pathway in generating the Lennox-Gastaut phenotype. Abnormal function of these areas is likely to be important in explaining the intellectual problems characteristic of this disorder.

Randomized comparison trial of density and context of upper limb intensive group versus individualized occupational therapy for children with unilateral cerebral palsy.

AIM: To determine whether short-term intensive group-based therapy combining modified constraint-induced movement therapy and bimanual therapy (hybrid-CIMT) is more effective than an equal total dose of distributed individualized occupational therapy (standard care) on upper limb motor and individualized outcomes. METHOD: Fifty-three children with unilateral cerebral palsy (69% males; mean age 7y 10mo, SD 2y 4mo; Manual Ability Classification System level I, n=24; level II, n=23) were randomly allocated, and 44 received either hybrid-CIMT (n=25) or standard care (n=19). Standard care comprised six weekly occupational therapy sessions and a 12-week home programme. Outcomes were assessed at baseline, 13 weeks, and 26 weeks after treatment. RESULTS: Groups were equivalent at baseline. Standard care achieved greater gains on satisfaction with occupational performance after intervention (estimated mean difference -1.2, 95% CI -2.2 to -0.1; p=0.04) and Assisting Hand Assessment at 26 weeks (estimated mean difference 3.1, 95% CI 0.2-6.0; p=0.04). Both groups demonstrated significant improvements in dexterity of the impaired upper limb, and bimanual and occupational performance over time. The differences between groups were not clinically meaningful. INTERPRETATION: There were no differences between the two models of therapy delivery. Group-based intensive camps may not be readily available; however, individualized standard care augmented with a home programme may offer an effective alternative but needs to be provided at a sufficient dose.

Lennox-Gastaut syndrome and phenotype: secondary network epilepsies.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electroclinical features despite diverse etiologies. We previously found common cerebral networks involved during slow spike-and-wave (SSW) and generalized paroxysmal fast activity (PFA), characteristic interictal discharges. Some patients have a Lennox-Gastaut-like phenotype and cortical lesions. We wished to explore the interaction between cerebral networks and lesions in this group. METHODS: 3 Tesla electroencephalography-functional magnetic resonance imaging (EEG-fMRI) on six subjects with Lennox-Gastaut phenotype and a structural lesion. Timings of SSW and PFA events were used in an event-related fMRI analysis, and to estimate the time course of the hemodynamic response from key regions. RESULTS: (1) PFA-robust fMRI signal increases were observed in frontal and parietal association cortical areas, thalamus, and pons, with simultaneous increases in both "attention" and resting-state (default mode) networks, a highly unusual pattern. (2) SSW showed mixed increased and decreased fMRI activity, with preevent increases in association cortex and thalamus, and then prominent postevent reduction. There was decreased fMRI activity in primary cortical areas. (3) Lesion-variable fMRI increases were observed during PFA and SSW discharges. Three subjects who proceeded to lesionectomy are >1 year seizure-free. SIGNIFICANCE: We conceptualize Lennox-Gastaut phenotype as a being a network epilepsy, where key cerebral networks become autonomously unstable. Epileptiform activity in Lennox-Gastaut phenotype, and by implication in LGS, appears to be amplified and expressed through association cortical areas, possibly because the attention and default-mode networks are widely interconnected, fundamental brain networks. Seizure freedom in the subjects who proceeded to lesionectomy suggests that cortical lesions are able to establish and maintain this abnormal unstable network behavior. LGS may be considered a secondary network epilepsy because the unifying epileptic manifestations of the disorder, including PFA and SSW, reflect network dysfunction, rather than the specific initiating process.

Work productivity, quality of life, and care needs: An unfolding epilepsy burden revealed in the Australian Epilepsy Project pilot study.

OBJECTIVE: Epilepsy is a common and serious neurological disorder. This cross-sectional analysis addresses the burden of epilepsy at different stages of the disease. METHODS: This pilot study is embedded within the Australian Epilepsy Project (AEP), aiming to provide epilepsy support through a national network of dedicated sites. For this analysis, adults aged 18-65 years with first unprovoked seizure (FUS), newly diagnosed epilepsy (NDE), or drug-resistant epilepsy (DRE) were recruited between February-August 2022. Baseline clinicodemographic data were collected from the participants who completed questionnaires to assess their quality of life (QOLIE-31, EQ-5D-5L), work productivity (Work Productivity and Activity Impairment [WPAI]), and care needs. Univariate analysis and multivariate regression was performed. RESULTS: 172 participants formed the study cohort (median age 34, interquartile range [IQR]: 26-45), comprising FUS (n = 44), NDE (n = 53), and DRE (n = 75). Mean QOLIE-31 score was 56 (standard deviation [SD] ± 18) and median EQ-5D-5L score was 0.77 (IQR: 0.56-0.92). QOLIE-31 but not EQ-5D-5L scores were significantly lower in the DRE group compared to FUS and NDE groups (p < 0.001). Overall, 64.5% of participants participated in paid work, with fewer DRE (52.0%) compared with FUS (76.7%) and NDE (72.5%) (p < 0.001). Compared to those not in paid employment, those in paid employment had significantly higher quality of life scores (p < 0.001). Almost 5.8% of participants required formal care (median 20 h/week, IQR: 12-55) and 17.7% required informal care (median 16 h/week, IQR: 7-101). SIGNIFICANCE: Epilepsy is associated with a large burden in terms of quality of life, productivity and care needs. PLAIN LANGUAGE SUMMARY: This is a pilot study from the Australian Epilepsy Project (AEP). It reports health economic data for adults of working age who live with epilepsy. It found that people with focal drug-resistant epilepsy had lower quality of life scores and were less likely to participate in paid employment compared to people with new diagnosis epilepsy. This study provides important local data regarding the burden of epilepsy and will help researchers in the future to measure the impact of the AEP on important personal and societal health economic outcomes.

Mapping brain activity using event-related independent components analysis (eICA): specific advantages for EEG-fMRI.

Event-related analyses of functional MRI (fMRI) typically assume that the onset and offset of neuronal activity match stimuli onset and offset, and that evoked fMRI signal changes follow the canonical haemodynamic response function (HRF). Some event types, however, may be unsuited to this approach: brief stimuli might elicit an extended neuronal response; anticipatory effects might result in activity preceding the event; or altered neurovascular coupling may result in a non-canonical HRF. An example is interictal epileptiform discharges (IEDs), which may show a non-canonical HRF and fMRI signal changes preceding their onset as detected on EEG. In such cases, less constrained analyses - capable of detecting early, non-canonical responses - may be necessary. A consequence of less constrained analyses, however, is that artefactual sources of signal change - motion or physiological noise for example - may also be detected and mixed with the neuronally-generated signals. In this paper, to address this issue, we describe an event-related independent components analysis (eICA) that identifies different sources of event-related signal change that can then be separately assessed to identify likely artefacts and separate primary from propagated activity. We also describe a group analysis that identifies eICA components that are spatially and temporally consistent across subjects and provides an objective approach for selecting group-specific components likely to be of neural origin. We apply eICA to patients with rolandic epilepsy - with stereotypical IEDs arising from a focus in the rolandic fissure - and demonstrate that a single event-related component, concordant with this source location, is detected.

Sample size estimates for well-powered cross-sectional cortical thickness studies.

INTRODUCTION: Cortical thickness mapping is a widely used method for the analysis of neuroanatomical differences between subject groups. We applied power analysis methods over a range of image processing parameters to derive a model that allows researchers to calculate the number of subjects required to ensure a well-powered cross-sectional cortical thickness study. METHODS: 0.9-mm isotropic T1 -weighted 3D MPRAGE MRI scans from 98 controls (53 females, age 29.1 ± 9.7 years) were processed using Freesurfer 5.0. Power analyses were carried out using vertex-wise variance estimates from the coregistered cortical thickness maps, systematically varying processing parameters. A genetic programming approach was used to derive a model describing the relationship between sample size and processing parameters. The model was validated on four Alzheimer's Disease Neuroimaging Initiative control datasets (mean 126.5 subjects/site, age 76.6 ± 5.0 years). RESULTS: Approximately 50 subjects per group are required to detect a 0.25-mm thickness difference; less than 10 subjects per group are required for differences of 1 mm (two-sided test, 10 mm smoothing, α = 0.05). Sample size estimates were heterogeneous over the cortical surface. The model yielded sample size predictions within 2-6% of that determined experimentally using independent data from four other datasets. Fitting parameters of the model to data from each site reduced the estimation error to less than 2%. CONCLUSIONS: The derived model provides a simple tool for researchers to calculate how many subjects should be included in a well-powered cortical thickness analysis.

Absence epilepsy subnetworks revealed by event-related independent components analysis of functional magnetic resonance imaging.

PURPOSE: The aim of this study was to provide better spatiotemporal description of the brain activity observed during generalized spike-and-wave (GSW) discharges. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies of these epileptiform events have shown regional differences in the timing of fMRI signal changes, which suggests activities within multiple interacting networks rather than a single unified network. METHODS: EEG-fMRI recordings from eight patients with childhood absence epilepsy (CAE) were studied using event-related independent components analysis (eICA). This technique separates the fMRI signal changes observed during GSW discharges into different spatial components, each showing different event-related timing. Unlike standard independent components analysis (ICA), which is applied to the entire fMRI time series, the eICA method is applied only to the event-related time courses at each voxel, which means that only a small number of components are generated that are all explicitly related to the event of interest. KEY FINDINGS: Six eICA components were identified, representing distinct GSW-related subnetworks. Activations were detected in a number of brain regions, including the striatum, which have not previously been reported in association with GSW in CAE patients. SIGNIFICANCE: The eICA results support previous findings that the earliest activity associated with GSW may be in posterior cortical regions and provide new evidence that the thalamostriate network may play a more important role in the generation of GSW than suggested by previous studies.

Tonic seizures of Lennox-Gastaut syndrome: periictal single-photon emission computed tomography suggests a corticopontine network.

PURPOSE: Lennox-Gastaut syndrome (LGS) is a severe epileptic disorder with characteristic electroclinical features but diverse etiologies. The shared electroclinical characteristics suggest that common cerebral networks are involved in generating seizures. We sought to reveal these networks by comparing ictal and interictal single-photon emission computed tomography (SPECT). METHODS: We identified 10 ictal-interictal SPECT pairs from seven patients with LGS (median age 11 years; range 1-38) who were studied during video electroencephalography (EEG)-confirmed tonic seizures. We performed a voxel-wise comparison of ictal and interictal SPECT studies across the group. The evolution of blood flow changes was explored by examining early and late injection groups. KEY FINDINGS: Median duration of tonic seizures was 10 s (range 6-29 s), and injection latency from seizure offset was -8 to 48 s. In the early injection group (<10 s; three studies), there was hyperperfusion over pons and cerebellar hemispheres (p < 0.05 cluster corrected family wise error), and hypoperfusion bilaterally over the pericentral region, with a trend toward hyperperfusion over bilateral superior and middle frontal gyri, and lateral parietal cortex. In the late injection group, there was hyperperfusion over midline and lateral cerebellar regions, with hypoperfusion widely over bilateral frontal regions. SIGNIFICANCE: This study suggests that the tonic seizures of LGS result from activity in a network, containing bilateral frontal and parietal association areas and the pons. We postulate that tonic seizures recruit the corticoreticular system, which connects frontal attentional areas to the pontine reticular formation, and is normally responsible for postural tone and orienting behavior.

COMBIT: protocol of a randomised comparison trial of COMbined modified constraint induced movement therapy and bimanual intensive training with distributed model of standard upper limb rehabilitation in children with congenital hemiplegia.

INTRODUCTION: Children with congenital hemiplegia often present with limitations in using their impaired upper limb which impacts on independence in activities of daily living, societal participation and quality of life. Traditional therapy has adopted a bimanual training approach (BIM) and more recently, modified constraint induced movement therapy (mCIMT) has emerged as a promising unimanual approach. Evidence of enhanced neuroplasticity following mCIMT suggests that the sequential application of mCIMT followed by bimanual training may optimise outcomes (Hybrid CIMT). It remains unclear whether more intensely delivered group based interventions (hCIMT) are superior to distributed models of individualised therapy. This study aims to determine the optimal density of upper limb training for children with congenital hemiplegia. METHODS AND ANALYSES: A total of 50 children (25 in each group) with congenital hemiplegia will be recruited to participate in this randomized comparison trial. Children will be matched in pairs at baseline and randomly allocated to receive an intensive block group hybrid model of combined mCIMT followed by intensive bimanual training delivered in a day camp model (COMBiT; total dose 45 hours direct, 10 hours of indirect therapy), or a distributed model of standard occupational therapy and physiotherapy care (SC) over 12 weeks (total 45 hours direct and indirect therapy). Outcomes will be assessed at 13 weeks after commencement, and retention of effects tested at 26 weeks. The primary outcomes will be bimanual coordination and unimanual upper-limb capacity. Secondary outcomes will be participation and quality of life. Advanced brain imaging will assess neurovascular changes in response to treatment. Analysis will follow standard principles for RCTs, using two-group comparisons on all participants on an intention-to-treat basis. Comparisons will be between treatment groups using generalized linear models. TRIAL REGISTRATION: ACTRN12613000181707.

Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging.

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.