2026 American Academy of Neurology Abstract Website

Salvatore Citro¹, Matt Dawson², Ahmad Beyh³, Flavio Dell’Acqua², Carlo Cavaliere⁴, Tim B. Dyrby⁵, Kristine Krug⁶, Maurice Ptito⁷, Lorenzo Carnevale⁸, Sergio Della Sala⁹, William D. Hopkins¹⁰, Marsel M. Mesulam¹¹, Marco Catani¹
¹Department of Neuroscience, Imaging, and Clinical Sciences (DNISC) e Istituto Tecnologie Biomediche Avanzate (ITAB), University G. d’Annunzio of Chieti-Pescara, ²NatBrainLab, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, ³Department of Psychiatry, Brain Health Institute, Rutgers University, ⁴IRCCS SYNLAB SDN, ⁵Danish Research Centre for Magnetic Resonance (DRCMR), Department of Radiology and Nuclear Medicine, Copenhagen University Hospital, ⁶Department of Physiology, Anatomy, and Genetics, Oxford University, ⁷Department of Neurology and Neurosurgery, Montréal Neurological Institute, Université de Montréal, ⁸Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, ⁹Human Cognitive Neuroscience, Psychology Department, University of Edinburgh, ¹⁰Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center, ¹¹Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Northwestern University

Objective:

By investigating the frontal aslant tract (FAT) and its extended networks across non-human and human primates, we aim to establish how the possible inter-species variances may explain the emergence of human speech, and in turn to predict specific language deficits following lesions/degeneration in different FAT portions.

Background:

Vocalization and speech rely on dorsomedial and ventrolateral frontal regions connected by the FAT. The involvement of the FAT in different aspects of speech is not completely understood.

Design/Methods:

We used spherical deconvolution tractography to dissect the FAT, its subsegments and its extended networks in 9 monkeys, 43 chimpanzees and 43 humans. We also dissect the dorsomedial/limbic (cingulum) and ventrolateral/auditory (arcuate fasciculus) FAT extended networks and compared the volumes of those tracts among the three species. We then correlated FAT subsegments degeneration and different language deficits in 98 PPA patients.

Results:

The FAT is different among the three species (W=88.7; p<0.001), enlarged in humans compared to non-human primates. Differences among the three species are present for both posterior (W=116.2; p<0.001) and anterior (W=479.5; p<0.001) FAT segments. The posterior FAT is reduced in chimpanzees and humans compared to monkeys, whereas the anterior FAT is enlarged in chimpanzees and even more so in humans.
In PPA, we found a posterior-to-anterior gradient for verbal fluency (Words Per Minute-WPM) and syntax (Northwestern Anagram Test-NAT). WPM showed a progressively weaker correlation from the posterior (r=0.397; p<0.001) to the anterior FAT (r=0.042; p=0.707). Conversely, NAT showed stronger correlation from the posterior (r=0.177; p=0.104) to the anterior FAT (r=0.318; p=0.004).

Conclusions:

Unique aspects of human speech, including syntax, evolved from exaptation/remodeling of the FAT and its ventrolateral extended network. We can predict a spectrum of aphasia syndromes resulting from lesions in the motor FAT/FAT opercularis (aphemia spectrum); in the FAT opercularis/triangularis (posterior transcortical motor aphasia); in the FAT triangularis/orbitalis (agrammatic-anterior transcortical motor aphasia).