The default-mode network encompasses a set of far-flung brain areas that hum in unison when the mind is at rest, but how ingrained is the “default”? While structural anatomy determines in large part which brain areas fire in parallel, networks are, in fact, more nuanced, with some regions able to reconfigure their connections on the fly. What’s more, a study posted online December 12 in the Proceedings of the National Academy of Sciences shows that scientists can adjust network connectivity in healthy adults using low- or high-frequency magnetic stimulation. Led by Alvaro Pascual-Leone of Beth Israel Deaconess Medical Center in Boston, the research hints that the brain may reorganize its connections according to the demands of a given task. It also raises the possibility that neurological disorders could stem from loss of this capability, and that transcranial magnetic stimulation (TMS) might restore it. While the paper supports these speculations, much additional work is needed to establish the therapeutic potential of TMS in treating cognitive disorders.

The default-mode network intrigues scientists who study neurodegenerative disease. Components of this network overlap heavily with brain regions that atrophy and accumulate β-amyloid plaques in Alzheimer’s disease (see ARF related news story), and early AD patients have disrupted default-mode activity (see ARF related news story). First author Mark Eldaief and colleagues wondered about the plasticity of this network. Are regions within the default-mode network “fixed in terms of their communication with each other, or do they have the ability to break off communication with one region and form a little bit stronger connection with another one?” Eldaief asked.

Specific cognitive tasks have been shown to tap parts, but not all, of the default-mode network (see Andrews-Hanna et al., 2010). In the current study, the scientists wanted to identify such subsystems by tweaking the network’s connectivity. They did this with repetitive transcranial magnetic stimulation (rTMS). This is a non-invasive technique that uses magnetic fields to create weak currents that excite or suppress neuronal activity in the targeted tissue. They measured these changes across the network using functional magnetic resonance imaging (fMRI).

Twenty-five young adults took part in the study. After an initial fMRI scan to map out their default-mode network, each participant returned for low-frequency (1-Hz) and high-frequency (20-Hz) rTMS. These were applied to the same default-mode region (left posterior inferior parietal lobule, or lpIPL) in two separate sessions at least a week apart, with fMRI just before and after. The researchers analyzed rTMS-induced changes in functional connectivity between the stimulation site and five additional default-mode network regions.

Consistent with prior work on rTMS in the motor cortex (Rounis et al., 2005), the two frequencies induced opposite effects—1 Hz increased whereas 20 Hz decreased functional connectivity in the default-mode network. Surprisingly, though, these effects did not pervade the total network, but were confined to specific connections, Eldaief said. High-frequency stimulation decreased connectivity between several cortical nodes, but not between these nodes and the hippocampal formation. Low-frequency stimulation, on the other hand, left most of the network unaltered but strengthened connectivity between the stimulation site and the hippocampus.

“The default-mode network is not a homogeneous entity. It has the ability to, perhaps very slightly, change the relationships between its network nodes. That’s the take-home message,” Eldaief told ARF.

Keith Johnson of Massachusetts General Hospital, Boston, sees the analysis as “really interesting work, helping to tease apart the anatomy and functional significance of the default-mode network.”

In an ARF phone interview, Martijn van den Heuvel of University Medical Center Utrecht, The Netherlands, said, “It’s pretty cool to see that one can modulate brain connectivity. It could open new doors for treatment of brain disease.” Currently, rTMS is approved by the U.S. Food and Drug Administration to treat major depressive disorder. It has been used for other neuropsychiatric disorders as well, but not as effectively as in treatment-refractory depression.

Van den Heuvel and others, including the authors, agree that the current research is quite a way from demonstrating the therapeutic utility of rTMS. For starters, the finding needs confirmation in a different cohort. Another issue is the durability of the rTMS effects. “If they can last for a long period, then one can modulate, for example, connectivity between the hippocampus and cortex, and this could perhaps lead to better formation or storage of memory,” van den Heuvel suggested. Using diffusion tensor imaging, van den Heuvel and colleagues recently identified a set of unusually interconnected regions, dubbed a “rich club,” within the cortex of healthy adults (ARF related news story on van den Heuvel and Sporns, 2011).

More fundamentally, clinical use of rTMS “is based on the supposition that functional correlations between brain regions are important to someone’s cognition and emotional health,” Eldaief said. “If that is true, and TMS can actually change those things, would this translate in a causal way to changes in behavior or symptoms? If we can show these things, it has a lot of potential. But we have a long way to go.” In addition to replicating the current findings, Eldaief and colleagues plan to see whether rTMS can induce similar changes in other networks, and whether connectivity changes in one network can ripple across to influence other networks. “We need a better sense of what exactly is happening at the site of stimulation,” Eldaief said. “Is it being activated or suppressed?” As for the potential of treating diseases like AD, there is concern that the integrity of the connections themselves may be too damaged. “The wires might be frayed,” Eldaief said.—Esther Landhuis

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References

News Citations

  1. Cortical Hubs Found Capped With Amyloid
  2. Network Diagnostics: "Default-Mode" Brain Areas Identify Early AD
  3. Cortical Hubs Form "Rich Club" in Human Brain

Paper Citations

  1. . Functional-anatomic fractionation of the brain's default network. Neuron. 2010 Feb 25;65(4):550-62. PubMed.
  2. . Frequency specific changes in regional cerebral blood flow and motor system connectivity following rTMS to the primary motor cortex. Neuroimage. 2005 May 15;26(1):164-76. PubMed.
  3. . Rich-club organization of the human connectome. J Neurosci. 2011 Nov 2;31(44):15775-86. PubMed.

Further Reading

Papers

  1. . Emergence of persistent networks in long-term intracranial EEG recordings. J Neurosci. 2011 Nov 2;31(44):15757-67. PubMed.

Primary Papers

  1. . Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. PubMed.