For more than a century, neuroscientists have studied the human brain much as early cartographers mapped unknown lands: piecing together a vast landscape from scattered observations.
Even today, pathologists diagnosing disorders such as Alzheimer's disease typically inspect a handful of tissue samples from an organ containing some 86 billion neurons. Much of the landscape remains unseen.
That is why scientists at the Sudha Gopalakrishnan Brain Centre (SGBC) at the Indian Institute of Technology, Madras (IIT-M) believe they have taken an important step towards filling one of neuroscience's biggest gaps.
They have produced what they describe as the world's most detailed three-dimensional atlas of the human brainstem at cellular resolution - a digital map that lets scientists travel seamlessly from MRI scans of the whole brain to individual nerve cells.
Called Anchor (Atlas of Neurochemical Characterisation of the Human Brainstem with 3D Reconstruction), it combines more than 500 tissue sections from foetal, childhood and adult brains.
Built from high-resolution microscope images rather than costlier molecular techniques, it creates a detailed three-dimensional map of the brainstem, identifying more than 200 clusters of brain cells and nerve pathways.
Eight chemical markers help distinguish different cell types, producing one of the clearest pictures yet of this vital, but poorly, understood part of the brain.
The brainstem occupies only a sliver of the brain, yet it keeps people alive. It links the brain to the spinal cord and controls breathing, heartbeat, sleep, wakefulness and movement.
Damage to tiny clusters of cells within it can prove catastrophic, but the region's densely packed architecture has long frustrated efforts to map it in detail.
Anchor's importance lies not simply in producing another anatomical map, but in linking two worlds that have largely remained separate: medical imaging, which shows the brain as a whole, and cellular pathology, which reveals it one cell at a time.
"We are seeing a visionary programme that puts India at the international table," says Shubha Tole, an Indian neuroscientist at the Tata Institute of Fundamental Research, describing the project as an "unprecedented integration" of engineering, neuroscience and medicine.
Doctors typically begin by examining the whole brain at autopsy or tissue removed during neurosurgery. An adult brain weighs about 1.2-1.5kg, and its folds and major structures can reveal important clues before microscopic examination begins.
"As a neuropathologist, I begin by examining an entire brain with the naked eye before looking at small pieces under the microscope," says Rebecca Folkerth, who is affiliated with Harvard Medical School and New York University and collaborated with the SGBC team.
"For Alzheimer's disease, we may examine only 15 to 20 sections - just a fraction of a percent of the whole organ."
That has been the practice since the pioneering work of Spanish neuroscientist Santiago Ramón y Cajal more than a century ago. Modern MRI reveals the whole brain but lacks cellular detail; microscopes reveal individual cells but only in isolated slices.
"What the Indian centre has created is essentially what I dreamed of early in my career - to have brain scans match the brain's microscopic anatomy," Folkerth, who has examined thousands of brains over more than three decades, told the BBC.
