Network localization of neurological symptoms from focal brain lesions.
A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P < 10(-5)) and relative to other cortical regions (P < 0.01). Next, we tested for generalizability of our technique by applying it to three additional lesion syndromes: central post-stroke pain, auditory hallucinosis, and subcortical aphasia. In each syndrome, heterogeneous lesions that themselves had little overlap showed significant network overlap in cortical areas previously implicated in symptom expression (P < 10(-4)). These results suggest that (i) heterogeneous lesions producing similar symptoms share functional connectivity to specific brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique requires no specialized imaging of patients it may prove a versatile and broadly applicable approach for localizing neurological symptoms in the setting of brain lesions.
1 Berenson-Allen Centre for Non-invasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Centre, 330 Brookline Ave, Boston, MA, 02215, USA 2 Department of Paediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Mailcode: WACC 8-835, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA aboes@partners.org foxmdphd@gmail.com.
Aaron D
AD
Boes
3 Department of Neurology, Division of Neuro-Ophthalmology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston MA 02115, USA.
Sashank
S
Prasad
4 Athinoula A. Martinos Centre for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA.
Hesheng
H
Liu
4 Athinoula A. Martinos Centre for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA 5 National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, 100875, P. R. China.
Qi
Q
Liu
1 Berenson-Allen Centre for Non-invasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Centre, 330 Brookline Ave, Boston, MA, 02215, USA.
Alvaro
A
Pascual-Leone
2 Department of Paediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Mailcode: WACC 8-835, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Verne S
VS
Caviness
1 Berenson-Allen Centre for Non-invasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Centre, 330 Brookline Ave, Boston, MA, 02215, USA 4 Athinoula A. Martinos Centre for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA 6 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Mailcode: WACC 8-835, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Michael D
MD
Fox
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000150:complications*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology* / Q000473:pathology*; D009434:Neural Pathways / Q000473:pathology*; D055815:Young Adult
central post-stroke pain; hallucination; lesion network mapping; lesion networks; subcortical aphasia