A Radical New Model of the Brain Illuminates Its Wiring

As both a clinician and a scientist, Fox is particularly interested in using the network approach not only to better understand particular diseases, but also to treat them. He has spent years working to optimize brain-stimulation treatments for diseases like Parkinson’s and depression. The two primary approaches to brain stimulation—deep brain stimulation (DBS), which involves surgically implanting wires directly into the brain, and transcranial magnetic stimulation (TMS), a noninvasive approach that involves passing a magnet over specific locations on the skull—were both available when Fox began his work in the 2000s, but they were far from being perfected.

Both technologies are based on the idea that some neurological and psychiatric diseases are caused by abnormal brain activity, and stimulation may be able to correct them. In Parkinson’s, stimulating an area called the basal ganglia relieves symptoms like tremor, and a closely related technology called responsive neurostimulation can quell epileptic seizures by targeting where they originate. “As an electrical engineer, the idea that you could stick electrodes in someone’s brain, turn them on, and have almost miracle-like effects on Parkinson’s symptoms—or hold an electromagnet over somebody’s brain and fix their depression—it almost seemed like science fiction,” he says.

But decades of research have proven that, for most other diseases, such regions don’t exist. And even if they did, stimulation to a specific spot is not going to remain confined to that spot, because an activated brain region will send out signals along white matter tracts, and those signals may in turn activate other regions. “If you want to stimulate [a] particular area of the brain to quiet a seizure, your stimulation to that region doesn’t stay in the region—it goes everywhere else,” Bassett says.

Along with giving clinicians a better understanding of the consequences of brain stimulation, network neuroscience may also help scientists design better techniques. In particular, if scientists can determine the circuits that a highly invasive technique like deep brain stimulation is acting upon, they might be able to achieve similar results with a nonsurgical approach like TMS. “Once your target is a circuit, you can target that circuit in different ways,” Fox says. “You could begin to test the therapeutic effect of the circuit noninvasively before you do something invasive.” In particular, this approach could allow clinicians to access regions buried in the brain, like those targeted in DBS treatments for Parkinson’s, through areas closer to the surface. “If those regions are connected to more superficial regions, then perhaps, with this network understanding, you can figure out which region is connected in the best way to the target region so that TMS will be effective,” Vértes says.

And as scientists start thinking of brain diseases as the results of multiple regions acting in concert, as opposed to single regions, they can start trying to target the whole circuit at once. “It might be that the best way to help a symptom that maps to a circuit is actually multiple electrodes, or multiple stimulation sites,” Fox says.

Pharmacological treatments, which dominate psychiatric practice, don’t only affect specific brain areas. Just like a painkiller will lessen pain throughout the body, so too will a psychiatric medication spread throughout the brain. Nevertheless, network neuroscience could still prove useful for optimizing drug regimens: It could help clinicians target their choice of drug to the individual, not the disease. If scientists better understand what makes each brain different, they may be able to leverage those differences to predict who will respond best to which drug.

“For some people, drug X works, and for some other people, drug Y works, and you don’t know until you try them both,” Bassett says. “And I feel like it’s medieval science. But hopefully, with an understanding of the individual differences in the brain, we will have a better lever on how to predict human responses to a particular intervention—and then not have to have people go for a year through different kinds of medication before we find one that works for them.”

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