MRI-negative temporal lobe epilepsy: A network disorder of neocortical connectivity.
OBJECTIVE
To define the functional network changes that characterize MRI-negative temporal lobe epilepsy (TLE) and TLE with hippocampal sclerosis (HS-TLE).


METHODS
We studied 36 patients with medically refractory unilateral TLE, having either a normal clinical MRI (n = 18) or unilateral hippocampal sclerosis (n = 18). Patients were compared to healthy controls of equivalent age and sex (n = 27). Functional connectivity in 10 minutes of task-free functional MRI was assessed using a voxel-resolution graph theoretic analysis, using the metrics of degree, clustering coefficient, eigenvector, and betweenness centrality. Significant clusters were further explored with a seed-based analysis.


RESULTS
MRI-negative TLE showed decreased connectivity at the ipsilateral superior and middle temporal gyri compared to controls (decreased eigenvector centrality). No functional abnormality was detected within mesial temporal structures. In contrast, HS-TLE showed increased connectivity within the affected hippocampus and anterior thalamus (increased clustering coefficient) and decreased connectivity of the ventromesial prefrontal cortex (decreased betweenness centrality). Using the detected clusters as seed regions revealed decreased connectivity from the sclerotic hippocampus to both the contralateral temporal lobe and regions of the default mode network.


CONCLUSIONS
MRI-negative TLE is associated with impaired interictal connectivity of the temporal neocortex, lateralized to the epileptic side. HS-TLE shows a different pattern, with functional segregation of the sclerotic hippocampus and impairment of its long-range connectivity. This suggests that MRI-negative TLE is not merely a subtle version of hippocampal sclerosis, but is rather a separate condition that involves distinct brain networks.
From the Florey Institute of Neuroscience and Mental Health (D.N.V., G.R., C.T., G.D.J.); Department of Neurology (D.N.V., G.D.J.), Austin Health; and Melbourne School of Psychological Sciences (G.R., C.T.) and Department of Medicine (G.D.J.), University of Melbourne, Australia. david.vaughan@florey.edu.au.
David N
DN
Vaughan
From the Florey Institute of Neuroscience and Mental Health (D.N.V., G.R., C.T., G.D.J.); Department of Neurology (D.N.V., G.D.J.), Austin Health; and Melbourne School of Psychological Sciences (G.R., C.T.) and Department of Medicine (G.D.J.), University of Melbourne, Australia.
Genevieve
G
Rayner
From the Florey Institute of Neuroscience and Mental Health (D.N.V., G.R., C.T., G.D.J.); Department of Neurology (D.N.V., G.D.J.), Austin Health; and Melbourne School of Psychological Sciences (G.R., C.T.) and Department of Medicine (G.D.J.), University of Melbourne, Australia.
Chris
C
Tailby
From the Florey Institute of Neuroscience and Mental Health (D.N.V., G.R., C.T., G.D.J.); Department of Neurology (D.N.V., G.D.J.), Austin Health; and Melbourne School of Psychological Sciences (G.R., C.T.) and Department of Medicine (G.D.J.), University of Melbourne, Australia.
Graeme D
GD
Jackson
D000293:Adolescent; D000328:Adult; D000368:Aged; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000000981:diagnostic imaging / Q000473:pathology*; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology*; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D015422:Scleral Diseases / Q000150:complications / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon; D014741:Video Recording; D055815:Young Adult