2018 was when neuroscience made the impossible possible.

There was the dazzling array of crazy neurotech: paralyzed patients shopped and texted using an Android tablet with just their brain waves; BrainNet let three people collaboratively play a Tetris-like game using their thoughts; a first memory prosthesis boosted recall in humans; and brain-controlled robotic limbs could know their location in space or even add a “third arm” in able-bodied people.

There was the new lineup of exquisitely detailed brain maps that further unveiled the brain’s nooks and crannies: a digital museum, constructed with the help of a quarter million gamers, that showcases every bend and turn of neurons in the mouse’s retina, or a map in which billions of synapses in the mouse brain light up like the starry night.

It was the year that human brain organoids—“mini-brains” that loosely resemble the real thing during fetal development—grew their own blood supply, thrived for months inside mouse brains, and shocked the world by producing electrical patterns that resemble those seen in premature babies, launching a debate on their ethical use.

But that’s not all. Here are five neuroscience findings from 2018 that still blow our minds as we kick off the new year.

1. An infectious side to Alzheimer’s disease

Potential new drugs for Alzheimer’s have all ended up in its notorious graveyard of dreams. Despite best efforts, drugs that target two proteins that build up in Alzheimer’s disease—beta-amyloid and mutant tau—have consistently failed human drug trails.

This year, scientists are beginning to think outside the box, and new theories of how the disease is triggered and progresses are gaining steam.

In October, several studies presented some of the strongest evidence yet that herpes simplex virus type I (HSV1)—the annoying virus responsible for cold sores—may be a potential trigger. Scientists have known since the 1990s that HSV1 confers a large risk for Alzheimer’s in people who carry a specific variant of a gene called APOE4.

Most people get infected with HSV1 as children, and the virus then remains dormant until external cues such as stress reactivate it. The new theory suggests that repeated activation of the virus in adulthood in the brain could cause cumulative damage, particularly in the elderly with declined immune function. If the theory holds water, it means that anti-viral drugs may be a new avenue of treatment.

What’s more, beta-amyloid itself may be transmissible. Using cadaver-derived growth hormones (eww) prepared in the 1980s, a team in Britain injected the sample into mice and found extensive beta-amyloid clumps in their brains. While this doesn’t mean that Alzheimer’s itself is contagious, it does raise concern that medical procedures such as brain surgery could pose a risk for shuttling toxic forms of the protein from one brain to another.

2. Electrical implant restores walking in paralyzed patients

2018 was, without doubt, a breakthrough year for restoring mobility in paralyzed patients.

The technology is several years in the making, with initial positive results in monkeys. It works by implanting a neuroprosthesis into the spinal cord to bypass the site of injury by artificially stimulating remaining nerves.

In September, the Mayo Clinic reported the extraordinary case of Jered Chinnock, who was paralyzed at the waist in 2013. After getting the implant, he walked half the length of a football field. Another report showed that electrical stimulation in four cases was able to help some paralyzed patients go home and get around with only a walker.

Less than a month later, yet another team reported that electrical stimulation using a wireless implant helped three paralyzed patients walk with the aid of crutches or a walker. After a few months of training, the patients could more easily move around even when the stimulation was off, suggesting that the regime had helped remaining healthy nerves rework their connections to adapt and heal.

Electrical stimulation isn’t the only treatment in the works. Another study found that human stem cells, when implanted into monkeys, could synapse with the recipient’s own neurons and restore natural movement after spinal cord injury. These therapies—although expensive and in their infancy—lay a promising road ahead for returning mobility to paralyzed patients.

3. CRISPR barcodes map brain development in exquisite detail

The developing mammalian brain consists of an intricately-choreographed dance of newborn neurons, with each adopting its specific identity and migrating to its home base in the brain. Scientists have long hoped to examine the process in detail, which could help uncover secrets of brain development—and how it goes wrong.

Perhaps unsurprisingly, tracing the history of every single one of the billions of developing cells in the brain has been impossible—until CRISPR came along.

Last August, a team used CRISPR to generate a unique genetic barcode for every single cell in the mouse brain. By reading the barcodes, scientists were able to retrace a cell’s entire history in the developing brain. Like genetic sleuths, the scientists reconstructed entire cellular family trees to show how cells relate to one another.

It’s a technical tour-de-force, and a “holy grail” for developmental biology, earning Science’s Breakthrough of the Year title. The trove of technologies and data are poised to uncover how human cells mature with age, how tissues regenerate, and how the processes go wrong in disease.

4. A new type of neuron in the cortex that’s potentially uniquely human

Perhaps shockingly, even today neuroscientists are still uncovering new cellular components that make up our mighty brains. Last year saw the discovery of giant neurons within the claustrum, a thin sheet of cells that some believe is the seat of consciousness.

This year, the Allen Institute in Seattle is back at it with another finding: rosehip neurons, each containing dense bundles of processes around the cell’s center that make it look like a rose after shedding its petals.

These neurons make up nearly 15 percent of neurons in the outermost layer of the brain that supports high-level cognitive functions. Remarkably, rosehip neurons have never before been seen in mice or other well-studied lab animals. Although the team can’t yet fully conclude that they’re specific to humans, their scarcity within the animal kingdom is intriguing.

The next step is figuring out the functions of these rose-like neurons—in particular, are they partly why our brains are special?—and whether they are linked to neuropsychiatric disorders.

5. Gut-brain connection grows stronger with direct anatomical link

One of the hottest research trends in neuroscience is the link between the brain and the gut—often dubbed the “little brain.”

The human gut is lined with over 100 million nerve cells that allow it to talk to the brain, letting us know when we’re hungry or when we’ve over-indulged. But it’s not all digestion: scientists are increasingly realizing that the gut could contribute to anxiety, depression, or more controversially, cognition.

Last year scientists found a new set of informational highways that directly link the gut to the brain. Within the gut, enteroendocrine cells pump out hormones that kick off digestion and suppress hunger. These cells have little foot-like protrusions that look remarkably like synapses—the structure that neurons use to talk to each other using chemicals.

With the help of a glow-in-the-dark rabies virus, which can jump from synapse to synapse, the team found that enteroendocrine cells directly link to neurons in the vagus nerve—a giant nerve that runs from the brain to vital organs such as the heart and lungs. What’s more, they chat with their partners using classical neurotransmitters including glutamate and serotonin, which work much faster than hormones.

Another study found that the gut directly links to the brain’s reward centers through the vagus nerve. Using lasers to zap sensory neurons in the gut of mice, the scientists found increased levels of mood-boosting dopamine in their brains.

These new connections could explain why vagus nerve stimulation is potentially helpful for those with severe depression. More relevant to the holiday season, it also could explain why eating makes us feel warm and fuzzy.

Uncovering the gut-brain connection is gaining steam as a research field. Eventually, the findings could lead to new treatments for disorders linked to a malfunctioning gut—for example, obesity, eating disorders, depression, or even autism.

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