Allometric constraints on brain tissue configuration

Poster No:


Submission Type:

Abstract Submission 


Jakob Seidlitz1, Margaret Gardner1, Lena Dorfschmidt2, Gabriel Devenyi3, Mallar Chakravarty4, Chet Sherwood5, William Hopkins6, Yaniv Assaf7, Yossi Youvel7, Ting Xu8, Samuel Alldritt8, Julian Ramirez8, Gareth Ball9, Jacob Vogel10, Edward Bullmore11, Richard Bethlehem12, Aaron Alexander-Bloch1


1University of Pennsylvania, Philadelphia, PA, 2The Children’s Hospital of Philadelphia, Philadelphia, PA, 3McGill University, Montreal, Quebec, 4Brain Imaging Centre, Douglas Research Centre, Montreal, Quebec, 5The George Washington University, Washington, DC, 6MD Anderson Cancer Center Texas, Houston, TX, 7Tel Aviv University, Tel Aviv, Israel, 8Child Mind Institute, New York, NY, 9Murdoch Children's Research Institute, Melbourne, VIC, 10Lund University, Lund, n/a, 11University of Cambridge, Cambridge, United Kingdom, 12Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom

First Author:

Jakob Seidlitz  
University of Pennsylvania
Philadelphia, PA


Margaret Gardner  
University of Pennsylvania
Philadelphia, PA
Lena Dorfschmidt  
The Children’s Hospital of Philadelphia
Philadelphia, PA
Gabriel Devenyi  
McGill University
Montreal, Quebec
Mallar Chakravarty, PhD  
Brain Imaging Centre, Douglas Research Centre
Montreal, Quebec
Chet Sherwood  
The George Washington University
Washington, DC
William Hopkins  
MD Anderson Cancer Center Texas
Houston, TX
Yaniv Assaf  
Tel Aviv University
Tel Aviv, Israel
Yossi Youvel  
Tel Aviv University
Tel Aviv, Israel
Ting Xu  
Child Mind Institute
New York, NY
Samuel Alldritt  
Child Mind Institute
New York, NY
Julian Ramirez  
Child Mind Institute
New York, NY
Gareth Ball  
Murdoch Children's Research Institute
Melbourne, VIC
Jacob Vogel, PhD  
Lund University
Lund, n/a
Edward Bullmore  
University of Cambridge
Cambridge, United Kingdom
Richard Bethlehem  
Autism Research Centre, Department of Psychiatry, University of Cambridge
Cambridge, United Kingdom
Aaron Alexander-Bloch  
University of Pennsylvania
Philadelphia, PA


A critical event in human evolution was the emergence of increased brain size variation relative to other species1,2. Total brain size can vary ~700-fold across primate species3, as much as 2-fold in adult humans4, and dynamically changes across the lifespan5. In humans, scaling of brain regions with total brain size is largely non-linear (allometric)4, with areas of extreme allometric scaling subserving highly specialized functions, greater interindividual variability, and elevated disease vulnerability4. However, the comparative allometric relationships within (static) and between (evolutionary) species of brain tissue compartments remains unknown.


We assessed brain scaling across multiple structural magnetic resonance imaging datasets comprising 101,457 humans aged 115 days post conception to 100 years5, 210 chimpanzees aged 6 years to 56 years, 87 macaques aged 85 days post conception to 23 years, and 226 mammals across 123 species (MaMI)6. Tissue segmentation for whole-brain gray matter volume (GMV), white matter volume (WMV), and cerebrospinal fluid (CSF) was performed using FreeSurfer (v5.3, v6.1, or infant), CIVET (v.1.1.10 or v2.1.0), or custom pipelines in the human datasets (and harmonized across studies5); and custom pipelines for the chimpanzee7 and macaque8 datasets. Brain size was indexed as total cerebrum volume (TCV) for human data or total brain volume (TBV) for the chimpanzee and macaque datasets, after observing high correlations (r>0.98) of TCV and TBV in the largest studies within the human dataset (ABCD, UK Biobank). To evaluate allometric tissue volume relationships with total brain size, log-log regressions were performed in R using linear mixed-effects models (multi-species) and generalized additive models for within-species tests4. As such, a coefficient of one represents linear scaling (isometric) and values less than (hypo-allometric) or greater than (hyper-allometric) one represent non-linear scaling.


Within-species (static) allometric scaling coefficients were similar for humans (GMV=0.89, WMV=1.14, CSF=0.95), chimpanzees (GMV=0.89, WMV=1.15, CSF=0.86), and macaques (GMV=0.88, WMV=1.19, CSF=1.01). Across-species compartmental allometric scaling coefficients were similar to previously reported estimates (MaMi: GMV=0.98, WMV=1.16; Previous9: GMV=0.96, WMV=1.17), with notable static (relative to evolutionary) hypo-allometry of GMV. A sliding-window approach revealed highly dynamic scaling relationships for each tissue class across the human lifespan (Fig. 1A). Interestingly, despite static isometry, CSF volume shifted from being hypo-allometric in the perinatal and childhood periods to hyper-allometric for adolescence and adulthood. GMV showed a similar but opposing pattern, decreasing at a faster rate than TBV (increased hypo-allometry) in adulthood. Cortical regional analyses using age epochs defined by scaling inflection points showed that while higher-order association areas changed from hyper- to hypo-allometric scaling, primary sensory and insular areas remained consistently hypo-allometric relative to TBV (Fig. 1A). Comparing the variance of total brain size (vT) to the summed variances of the constituent tissues (vC), we observed a marked shift from a period of compensation in the first two years of life (vT < vC) to a period of increased coordination (vT > vC), peaking in mid-adolescence and declining thereafter, demonstrating the dynamics of human brain compartmentalization10 (Fig. 1B).
Supporting Image: Screenshot2023-11-29at94227PM.png


Despite marked evolutionary changes in brain size and variation, patterns of allometric scaling were similar across species. However, the flexibility of developmental scaling across the human lifespan highlighted strong hyper-allometric scaling of association cortical regions during the greatest period of brain growth in infancy and early childhood.

Lifespan Development:

Early life, Adolescence, Aging 1

Neuroanatomy, Physiology, Metabolism and Neurotransmission:

Cortical Anatomy and Brain Mapping 2
Normal Development


Cross-Species Homologues

1|2Indicates the priority used for review

Provide references using author date format

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