Publications by authors named "Fatemeh Fadaie"

8 Publications

  • Page 1 of 1

Altered communication dynamics reflect cognitive deficits in temporal lobe epilepsy.

Epilepsia 2021 Apr 11;62(4):1022-1033. Epub 2021 Mar 11.

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.

Objective: Although temporal lobe epilepsy (TLE) is recognized as a system-level disorder, little work has investigated pathoconnectomics from a dynamic perspective. By leveraging computational simulations that quantify patterns of information flow across the connectome, we tested the hypothesis that network communication is abnormal in this condition, studied the interplay between hippocampal- and network-level disease effects, and assessed associations with cognition.

Methods: We simulated signal spreading via a linear threshold model that temporally evolves on a structural graph derived from diffusion-weighted magnetic resonance imaging (MRI), comparing a homogeneous group of 31 patients with histologically proven hippocampal sclerosis to 31 age- and sex-matched healthy controls. We evaluated the modulatory effects of structural alterations of the neocortex and hippocampus on network dynamics. Furthermore, multivariate statistics addressed the relationship with cognitive parameters.

Results: We observed a slowing of in- and out-spreading times across multiple areas bilaterally, indexing delayed information flow, with the strongest effects in ipsilateral frontotemporal regions, thalamus, and hippocampus. Effects were markedly reduced when controlling for hippocampal volume but not cortical thickness, underscoring the central role of the hippocampus in whole-brain disease expression. Multivariate analysis associated slower spreading time in frontoparietal, limbic, default mode, and subcortical networks with impairment across tasks tapping into sensorimotor, executive, memory, and verbal abilities.

Significance: Moving beyond descriptions of static topology toward the formulation of brain dynamics, our work provides novel insight into structurally mediated network dysfunction and demonstrates that altered whole-brain communication dynamics contribute to common cognitive difficulties in TLE.
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April 2021

Unsupervised machine learning reveals lesional variability in focal cortical dysplasia at mesoscopic scale.

Neuroimage Clin 2020 18;28:102438. Epub 2020 Sep 18.

Neuroimaging of Epilepsy Laboratory, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada. Electronic address:

Objective: Focal cortical dysplasia (FCD) is the most common epileptogenic developmental malformation and a prevalent cause of surgically amenable epilepsy. While cellular and molecular biology data suggest that FCD lesional characteristics lie along a spectrum, this notion remains to be verified in vivo. We tested the hypothesis that machine learning applied to MRI captures FCD lesional variability at a mesoscopic scale.

Methods: We studied 46 patients with histologically verified FCD Type II and 35 age- and sex-matched healthy controls. We applied consensus clustering, an unsupervised learning technique that identifies stable clusters based on bootstrap-aggregation, to 3 T multicontrast MRI (T1-weighted MRI and FLAIR) features of FCD normalized with respect to distributions in controls.

Results: Lesions were parcellated into four classes with distinct structural profiles variably expressed within and across patients: Class-1 with isolated white matter (WM) damage; Class-2 combining grey matter (GM) and WM alterations; Class-3 with isolated GM damage; Class-4 with GM-WM interface anomalies. Class membership was replicated in two independent datasets. Classes with GM anomalies impacted local function (resting-state fMRI derived ALFF), while those with abnormal WM affected large-scale connectivity (assessed by degree centrality). Overall, MRI classes reflected typical histopathological FCD characteristics: Class-1 was associated with severe WM gliosis and interface blurring, Class-2 with severe GM dyslamination and moderate WM gliosis, Class-3 with moderate GM gliosis, Class-4 with mild interface blurring. A detection algorithm trained on class-informed data outperformed a class-naïve paradigm.

Significance: Machine learning applied to widely available MRI contrasts uncovers FCD Type II variability at a mesoscopic scale and identifies tissue classes with distinct structural dimensions, functional and histopathological profiles. Integrating in vivo staging of FCD traits with automated lesion detection is likely to inform the development of novel personalized treatments.
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September 2020

Whole-brain multimodal MRI phenotyping of periventricular nodular heterotopia.

Neurology 2020 10 14;95(17):e2418-e2426. Epub 2020 Aug 14.

From the Neuroimaging of Epilepsy Laboratory (F.D., S.-J.H., F.F., B.C., S.K., N.B., A.B.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada; and Epilepsy Unit (F.D.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Objective: To test the hypothesis that in periventricular nodular heterotopia (PVNH) structure and function of cortical areas overlying the heterotopic gray matter are preferentially affected.

Methods: We studied a group of 40 patients with PVNH and normal-appearing cortex and compared their quantitative MRI markers of brain development, structure, and function to those of 43 age- and sex-matched healthy controls. Inspired by models of neocortical development suggesting that neuronal migration follows a curvilinear path to preserve topologic correspondence between the outer ventricular zone and the cortical surface, we computationally defined the overlying cortex using the Laplace equation and generated synthetic streamlines that link the ventricles, where nodules are located, and the neocortex.

Results: We found multilobar cortical thickening encompassing prefrontal, latero-basal temporal, and temporoparietal cortices largely corresponding with the PVNH group-averaged map of the overlying cortex, the latter colocalized with areas of abnormal function, as defined by resting-state fMRI. Patients also presented hippocampal functional hyperconnectivity and malrotation, the latter positively correlating with neocortical maldevelopment indexed by increased folding complexity of the parahippocampus. In clusters of thickness and curvature findings, there were no significant differences between unilateral and bilateral PVNH; contrasting brain-wide metrics between cohorts was also unrevealing. There was no relationship between imaging markers and disease duration except for positive correlation with functional anomalies.

Conclusion: Our quantitative image analysis demonstrates widespread structural and functional alterations in PVNH with differential interaction with the overlying cortex and the hippocampus. Right hemispheric predominance may be explained by an early insult, likely genetically determined, on brain morphogenesis.
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October 2020

Developmental MRI markers cosegregate juvenile patients with myoclonic epilepsy and their healthy siblings.

Neurology 2019 09 29;93(13):e1272-e1280. Epub 2019 Aug 29.

From the Neuroimaging of Epilepsy Laboratory (B.W., S.-J.H., B.C.B., F.F., N.B., A.B.), McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal; Department of Clinical and Experimental Epilepsy (B.W., C.V., M.J.K.), UCL Institute of Neurology, London, UK; Epilepsy Center, Department of Neurology (C.V.), Klinikum Großhadern, University of Munich, Germany; and Multimodal Imaging and Connectome Analysis Lab (B.C.B.), Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada.

Objective: MRI studies of genetic generalized epilepsies have mainly described group-level changes between patients and healthy controls. To determine the endophenotypic potential of structural MRI in juvenile myoclonic epilepsy (JME), we examined MRI-based cortical morphologic markers in patients and their healthy siblings.

Methods: In this prospective, cross-sectional study, we obtained 3T MRI in patients with JME, siblings, and controls. We mapped sulco-gyral complexity and surface area, morphologic markers of brain development, and cortical thickness. Furthermore, we calculated mean geodesic distance, a surrogate marker of cortico-cortical connectivity.

Results: Compared to controls, patients and siblings showed increased folding complexity and surface area in prefrontal and cingulate cortices. In these regions, they also displayed abnormally increased geodesic distance, suggesting network isolation and decreased efficiency, with strongest effects for limbic, fronto-parietal, and dorsal-attention networks. In areas of findings overlap, we observed strong patient-sibling correlations. Conversely, neocortical thinning was present in patients only and related to disease duration. Patients showed subtle impairment in mental flexibility, a frontal lobe function test, as well as deficits in naming and design learning. Siblings' performance fell between patients and controls.

Conclusion: MRI markers of brain development and connectivity are likely heritable and may thus serve as endophenotypes. The topography of morphologic anomalies and their abnormal structural network integration likely explains cognitive impairments in patients with JME and their siblings. By contrast, cortical atrophy likely represents a marker of disease.
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September 2019

Temporal lobe epilepsy: Hippocampal pathology modulates connectome topology and controllability.

Neurology 2019 05 19;92(19):e2209-e2220. Epub 2019 Apr 19.

From the Neuroimaging of Epilepsy Laboratory (B.C.B., F.F., M.L., B.C., A.B., N.B.) and Multimodal Imaging and Connectome Analysis Laboratory (B.C.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Canada; Department of Bioengineering and Electrical and Systems Engineering (S.G., D.S.B.), University of Pennsylvania, Philadelphia; and York Neuroimaging Center (E.J., J.S.), University of York, UK.

Objective: To assess whether hippocampal sclerosis (HS) severity is mirrored at the level of large-scale networks.

Methods: We studied preoperative high-resolution anatomical and diffusion-weighted MRI of 44 temporal lobe epilepsy (TLE) patients with histopathologic diagnosis of HS (n = 25; TLE-HS) and isolated gliosis (n = 19; TLE-G) and 25 healthy controls. Hippocampal measurements included surface-based subfield mapping of atrophy and T2 hyperintensity indexing cell loss and gliosis, respectively. Whole-brain connectomes were generated via diffusion tractography and examined using graph theory along with a novel network control theory paradigm that simulates functional dynamics from structural network data.

Results: Compared to controls, we observed markedly increased path length and decreased clustering in TLE-HS compared to controls, indicating lower global and local network efficiency, while TLE-G showed only subtle alterations. Similarly, network controllability was lower in TLE-HS only, suggesting limited range of functional dynamics. Hippocampal imaging markers were positively associated with macroscale network alterations, particularly in ipsilateral CA1-3. Systematic assessment across several networks revealed maximal changes in the hippocampal circuity. Findings were consistent when correcting for cortical thickness, suggesting independence from gray matter atrophy.

Conclusions: Severe HS is associated with marked remodeling of connectome topology and structurally governed functional dynamics in TLE, as opposed to isolated gliosis, which has negligible effects. Cell loss, particularly in CA1-3, may exert a cascading effect on brain-wide connectomes, underlining coupled disease processes across multiple scales.
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May 2019

Preferential susceptibility of limbic cortices to microstructural damage in temporal lobe epilepsy: A quantitative T1 mapping study.

Neuroimage 2018 11 3;182:294-303. Epub 2017 Jun 3.

Neuroimaging of Epilepsy Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada. Electronic address:

The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks.
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November 2018

1H-MRS metabolite's ratios show temporal alternation in temporal lobe seizure: Comparison between interictal and postictal phases.

Epilepsy Res 2016 12 9;128:158-162. Epub 2016 Sep 9.

Isfahan Neurosciences Research Center, Neurology Department, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

Purposes: To determine H-MRSI metabolites changes in interictal and postictal phases of patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis and lateralization of seizure foci.

Materials And Methods: MR spectroscopic imaging was performed in 5 adult patients with refractory temporal lobe epilepsy interictally and immediately after the seizure and in 4 adult control subjects. All patients underwent MR imaging and VideoEEG Monitoring.

Results: The results showed statistically significant decreases in N-acetylaspartate/Creatine, N-acetylaspartate/Choline and N-acetylaspartate/(creatine+choline) immediately after ictus in ipsilateral hippocampus as compared with control data and contralateral hippocampus of patients while no statistically significant difference was presented in interictal phase.

Conclusion: The present study clearly indicates H-MRS abnormalities following an ictus of temporal lobe epilepsy with metabolite recovery in interictal phase. This finding suggests postictal H-MRS as a possible useful tool to assist in lateralizing and localizing of seizure foci in epileptic patients with structural lesions.
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December 2016

Cardiac arrest associated with epileptic seizures: A case report with simultaneous EEG and ECG.

Epilepsy Behav Case Rep 2014 29;2:145-51. Epub 2014 Aug 29.

Shefa Neuroscience Research Center, Khatamolanbia Hospital, Tehran, Iran ; Pars Advanced Medical Research Center, Pars Hospital, Tehran, Iran.

Ictal asystole is a rare, probably underestimated manifestation of epileptic seizures whose pathophysiology is still debated. This report describes two patients who had cardiac asystole at the end of their seizure. The first patient was a 13-year-old boy with complex partial seizures.. His MRI showed symmetrical signal abnormality in the bilateral parietooccipital lobe accompanied by mild gliosis and volume loss. During a 3-day long-term video-EEG monitoring, he had cardiac arrest at the end of one of his seizures that was secondarily generalized. The second one was a 42-year-old veteran with penetrating head trauma in the left frontal lobe due to shell injury. During long-term video-EEG monitoring, he had one generalized tonic-clonic seizure accompanied by bradycardia and cardiac asystole. Asystoles could have a role in the incidence of sudden unexpected death in epilepsy (SUDEP), meaning that the presence of ictal bradycardia is a risk factor for SUDEP. In cases of epileptic cardiac dysrhythmia, prolonged simultaneous EEG/ECG monitoring may be required. Cardiological investigation should be included in epilepsy management.
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February 2015