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The brain’s ebb and flow cares not for distance

Over the past decade, functional neuroimaging has revealed that our brains go through ever-changing patterns of activity, whether we are active or at rest, healthy or sick, under legal medication or high on illegal drugs. Yet this dynamic activity takes place over the comparatively fixed anatomical grid of neuronal connections; the functional weights of those connections therefore must be changing over time. Two competing hypotheses have been put forth regarding the strength and malleability of neuronal connections: on the one hand, local neuronal connections could be more stable than long-distance ones, because neighboring regions of the cerebral cortex tend to take part in the same functions. On the other one, the flexibility of connections might not depend on their length, thus promoting equilibrium between local specialization and widespread integration. Bratislav Misic, Marc G. Berman and their colleagues, from the Rotman Research Institute in Toronto and the University of Chicago, among others, set out to find evidence for either of these hypotheses by analyzing an extremely diverse bunch of data, lumping together different functional neuroimaging modalities (what the participants were tested with), clinical populations (who the participants were) and task parameters (what they were asked to do). Notwithstanding this immense heterogeneity, they were able to show that the spatial distance between regions does not impact the stability of their functional connections. Their results, published in PLOS ONE, support the notion that the brain’s functional connectivity transits seamlessly between local specialized processing and global integration.

A cocktail of studies

The authors re-analyzed the data from six studies: four used functional MRI, one magnetoencephalography and one positron emission tomography. The participants were either healthy volunteers or patients suffering from depression or breast cancer. Finally, the experimental conditions consisted of either just resting in the scanner on 2 separate occasions, ruminating autobiographical memories versus rest, or performing various tasks of sensory perception or learning and memory. The authors selected such a diverse group of studies precisely so that they would be able to assess connectivity changes across a wide spectrum of situations, regardless of the methodological details of each study.

In each study and for each participant, the authors first grouped measurements of brain activity into regions of interest and then correlated cerebral activity in each region of interest to that of all the others, yielding matrices of functional connectivity within each experimental condition. They then measured the distance between all the regions of interest and computed the correlation between distance and functional connectivity. Others had previously found that regions of the brain that were closer to each other tended to have higher functional connectivity, and that is also what the authors observed here. This probably reflects the fact that neighboring brain regions tend to carry out the same functions.

No correlation between anatomical distance and changes in functional connectivity

The authors then undertook to compare how distance between brain regions correlated with changes in functional connectivity across experimental conditions. They computed two indexes of connectivity changes: salience values derived from a partial least-squares analysis, as well as simply subtracting the connectivity values from different experimental conditions. Overall, they found no correlation between the distance between two brain regions and changes in their connectivity across experimental conditions.

This held true regardless of whether the connectivity increased or decreased as a result of the experimental condition, whether only those brain regions that displayed strong connectivity changes were taken into account, whether the regions were part of the same functional brain networks, or even whether they were in the same or the opposite cerebral hemisphere. These results thus argue against the notion that there is a relationship between anatomical distance and changes in functional connectivity. Importantly, it made no difference which neuroimaging technique was used to look at brain function, since the magnetoencephalography and positron emission studies yielded essentially the same observations as the ones that used functional MRI.

Intriguingly, homotopic regions (i.e. the same region on both cerebral hemispheres) had the lowest tendency to see their functional connectivity change across experimental conditions, suggesting that interhemispheric connections between homotopic regions are among the most stable.

When negative evidence yields positive results

In this study, the authors provide mostly negative evidence, which means that they looked for a systematic tendency of functional connectivity changes as a function of anatomical distance and failed to find it. Because absence of evidence is not the same as evidence of absence, does that mean that the conclusions of the article are unwarranted? Most likely not: the fact that there was no correlation across such a diverse group of participant populations, task parameters, and even neuroimaging modalities argues strongly for the hypothesis that, indeed, anatomical distance plays no role in determining the stability or flexibility of functional connections.

What is the functional consequence of this? According to the authors, the fact that short- and long-distance connections have an equal propensity to change might favor a subtle balance between local, presumably specialized processing of information by the brain and the integration of this processing with that of distant modules within distributed networks. The authors suggest that the stable interhemispheric connections between homotopic regions might serve as anchors within this dynamic connectivity landscape.


Mišić B, Fatima Z, Askren MK, Buschkuehl M, Churchill N, Cimprich B, Deldin PJ, Jaeggi S, Jung M, Korostil M, Kross E, Krpan KM, Peltier S, Reuter-Lorenz PA, Strother SC, Jonides J, McIntosh AR, Berman MG (2014) The Functional Connectivity Landscape of the Human Brain. PLoS ONE 9(10): e111007. doi: 10.1371/journal.pone.0111007

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