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of discovery in brain science. The discrepancy in post-processing algorithms improved visualization
treatment options for conditions above vs. below the of both healthy and pathological brain tissue (11).
neck contributed to a growing population of adults Anatomical detail provided by high field MRI
living longer lifespans, including a growing number opened a new world of brain structure-function rela-
of individuals with age-associated neurodegenerative tionships supported by the demarcation of tissue
diseases (8). The limited treatment options for the classification into cortical gray matter, subcortical
projected expansion of adults with neurodegenera- white matter, and subcortical gray matter. Volumes
tive diseases of the brain such as Alzheimer’s disease, of brain regions (e.g., frontal lobe) and specific nuclei
growing healthcare costs, and increasing numbers of (e.g., caudate nucleus) could be readily quantified
uninsured individuals all pointed towards an emerg- and contrasted between patient groups and healthy
ing health crisis. controls or analyzed within groups to determine the
Political pressure culminated in a Presidential degree of shared variance between brain volumes
proclamation signed in 1989 declaring the period and measures of cognition, personality, or emotion.
from 1990-1999 as the “Decade of the Brain” (5). Landmark studies revealed reduced hippocampal
The initiative targeted 14 areas in the neurological volume in the earliest stages of Alzheimer’s disease (6),
sciences primed for breakthroughs in prevention, microvascular infarcts in subcortical white matter (2),
treatment, and cures for the most vexing and com- as well as numerous other clinically relevant findings.
mon neurological conditions. The Decade ended However, the focus on specific nuclei and regional
with few treatments and no interventions capable lobes belied the anatomical complexity of the brain
of reversing or halting common forms of neuro- previously characterized in histological studies. Work
degenerative diseases, such as Alzheimer’s disease, dating back to Golgi and Cajal (1) brilliantly revealed
Parkinson’s disease, or vascular dementia. However, the multiplex architecture of neural networks using
innovative work in the field of neural bioinformatics relatively crude methods in the 1800s, yet modern
and neuroimaging flourished during this period, and neuroimaging studies restricted analyses to focal
enthusiasm was high that neuroimaging technology brain regions. In effect, the field defaulted to a digi-
seeded during the 1990s would significantly alter the tized version of phrenology, ascribing complex and
cadence of brain science outcomes in the near future diverse human behaviors to isolated brain volumes.
(10). This prediction proved accurate as borne out New technology was needed to measure brain net-
through subsequent research that leveraged a his- work integrity on a larger scale.
torical foundation in magnetic resonance imaging The introduction of diffusion tensor imaging
(MRI). (DTI) opened a new technical portal away from the
Early MRI systems introduced in the 1970s pro- hyper-focused regionalization of volumetric studies.
vided researchers and clinicians with vastly improved DTI measures the rate and direction of water flow (i.e.,
spatial resolution of brain anatomy compared to hydrogen) in the brain, both of which are altered by
radiographic methods of the past. High field MRI neuronal damage (9). Common DTI outputs include
using 1.5 Tesla (15,000 Gauss) became common in scalar metrics of water diffusion, such as fractional
both research and clinical settings, followed by the anisotropy, mean diffusivity, axial diffusivity, and
introduction of 3 Tesla systems. The image resolution radial diffusivity (see Baker et al. in this issue for
of 3 Tesla MRI is approximately 16 times that of 1.5 review). Refinement of DTI pulse sequences during
Tesla systems, allowing for significantly improved the Decade of the Brain allowed researchers to visual-
signal-to-noise ratio and improved anatomical detail. ize network connections by measuring the curvature
Eventually, 4 Tesla and even 7 Tesla systems were of the diffusion metrics along known anatomical fas-
introduced at select research centers, the latter pro- ciculi. For the first time, the structural integrity of the
viding a magnetic field 140,000 times that of earth’s brain (later referred to as the connectome) (12) could
gravitational force. The improvements in image acqui- be defined. Subsequent studies developed methods
sition at higher field strengths combined with robust to quantify the integrity of brain white matter tracts