Baby versus adult brain, the fMRI picture

What’s going on inside a baby’s brain?

If you’re asking whether your baby is currently pondering the immensity of the universe or simply resenting your friend for making a snide comment about its hair (or lack thereof), there’s probably no way to provide you with a definite answer (although I would venture to say it’s probably not doing either of those things). However, if you’re asking whether a baby’s brain works the same way as an adult brain, at its most basic level of functioning, then it’s possible to start answering the question.

For one thing, the basic cellular mechanisms of how neurons in the brain transmit messages is the same. However, when it comes to the changes in blood flow usually associated with brain activity, a recent study published in the scientific journal PNAS suggests that the picture of what happens in newborn brains is actually quite different from the one of adult brains.

Before diving into the good stuff (the actual study), let me sum up what I learned while preparing this post and what you’ll need to know to keep reading the post until the end.

  • Brain activity and hemoglobin

A sensory stimulus (say, someone tingles your right foot) results in the activation of the corresponding area of the sensory cortex in the brain. This increase in local neuronal activity leads to an increase in oxygen consumption. However, in adult brains, a sensory stimulus also leads to an increase in blood flow in the corresponding region of the sensory cortex. As a result, there is an increased delivery of oxygenated blood that outstrips the oxygen consumption by the neurons. The overall picture is therefore that of an increase in local oxygenation and blood volume in the area of the brain that is activated by the stimulus. It can be measured as a local increase in oxygenated hemoglobin (the molecule that carries oxygen in the blood) and in total hemoglobin and a decrease in deoxygenated hemoglobin concentrations.

  • Functional magnetic resonance imaging, or fMRI

A way to record what areas of the brain are activated at any time point is to follow changes in blood flow by using a specialized type of brain scan called functional magnetic resonance imaging (fMRI). fMRI tracks changes in the concentration of paramagnetic deoxygenated hemoglobin and delivers an output signal called a “BOLD signal” (blood oxygen level-dependent signal): a ”positive BOLD” corresponds to a local decrease, and a “negative BOLD” to a local increase, in deoxygenated hemoglobin concentration.

In an adult brain, an area of the cortex that is being activated following a sensory stimulus will therefore appear as a positive BOLD signal in fMRI.

  • fMRI in babies – where issues arise

fMRI has become an important tool for neuroscience over the last two decades, and neuroscientists interested in development have used the technique to study how babies’ brains differ from adults’ and how they develop over time. However, while the hemodynamic response (the change in blood flow) to a sensory stimulus is relatively well defined in adults, it is not so in newborns.

Basically, studies of the neonatal hemodynamic response using fMRI have led to conflicting results: either they report a positive BOLD response (decrease in local deoxygenated hemoglobin) that looks like the response seen in adults’ brains (and that corresponds to an increase in blood flow in the activated brain region), or they show an inverted response (negative BOLD, increase in local deoxygenated hemoglobin, opposite of what is seen in adults).

Figuring out what could underlie such discrepancies is not easy considering the many limitations of these studies. Most of them:
– were performed on human neonates (and therefore have to take into account the large variability stemming from differences between individuals, a limitation that is considerably lessened in animal studies)
– did not follow the same subjects throughout development
– had small numbers of subjects (making it difficult to know whether the observed effects are representative of the general picture or not)
– used different sensory stimulation protocols (making direct comparisons between studies impossible).
In addition, many studies were performed on premature infants or infants with other medical conditions, which may be a confounding factor when trying to understand what the general fMRI neonate response looks like.

That’s where the new study published in PNAS in February comes in. The data presented by the authors not only helps to build a picture of what the baseline hemodynamic response in the brain looks like in a newborn and throughout development, but also offers a possible explanation for the inconsistencies observed in the previous studies.

  • The study findings

The researchers looked at the changes in blood flow in the brain of rat pups aged 12-13 days (which are developmentally equivalent to human newborns) following a sensory stimulus applied to the hind paw. They also looked at older pups and adults for comparison.

1) Possible explanation for previous inconsistencies in babies’ fMRI responses

One of the first observations made by the researchers was that the blood pressure of the rat pups varied depending on the intensity of the sensory stimulation: when a low-intensity stimulus was applied, there was no change in blood pressure, but when the stimulus was stronger, the blood pressure increased. This increase led to more blood flow in the entire brain, which, if looking only at the area of the sensory cortex expected to be activated by the stimulus, could then be mistaken for a positive fMRI BOLD signal like the one seen in adult brains.

Such an observation can explain, at least in part, the conflicting results of studies on infants. In some studies, a stronger stimulus affecting blood pressure may have been used, leading to a positive BOLD signal in fMRI. However, this signal was not specific of the infant’s brain response to the sensory stimulus ; rather, it reflected the limited capacity of the neonatal brain to autoregulate when faced with variations in blood pressure in the circulation.

2) The true fMRI picture in babies?

When the researchers applied a low sensory stimulus that did not affect blood pressure, they observed an inverted response in the rat pups’ brains compared to what was seen in adult rats’ brains: the concentration in deoxygenated hemoglobin increased, corresponding to a negative fMRI BOLD signal.

This negative BOLD signal does not however mean that there was no increase in brain activity following the sensory stimulus. It could be that in young rat pups (and in human newborns) neurons can fire without a concomitant increase in blood flow and oxygenation. In fact, the authors note that this would make sense considering the ability of the fetal brain to tolerate low amounts of oxygen in the womb and during delivery.

3) Changes with age

The researchers then recorded the fMRI response of pups at different ages (between 12 to 23 days of age – to put in context, rat pups open their eyes between 12 to 15 days of age and are weaned when they are 21-28 days old).

They saw that the fMRI response to sensory stimulation gradually changed from a negative BOLD signal to a positive one. In 15 day-old pups there was a small increase in blood flow visible at the beginning of the response to the stimulus in the corresponding area of the brain, although it was not sustained. As the pups grew older, however, the increase in blood flow intensified, to finally lead to a complete positive BOLD signal by 23 days of age.

The authors of the study hypothesize that this might represent the gradual development of a mature vasculature and neurovascular coupling: the brain puts in place a system that compensates the local consumption of oxygen by the activated neurons with a local increase in blood flow and hyperoxygenation.

One consequence of the fMRI response moving from a negative to a positive BOLD signal with age is that neuroscientists should be careful in interpreting fMRI data when studying brain development: changes in the timing, amplitude and localization of positive BOLD fMRI signals in the brain could actually reflect changes in the neurovascular coupling as much as changes in neuronal function and connectivity.

  • To sum up

The findings of this study suggest that a “true” fMRI response to sensory stimulation in neonates would appear as a negative BOLD signal, in contrast to the normal positive signal seen in adults. So, to answer (at least partially) our initial question – Do babies’ brains work as adult brains? -, it seems that the response is “no” when it comes to associating neuronal activity and local variation in blood flow.

Nevertheless, the results of the study do not mean that fMRI is not a useful technique to study brain activity and development in infants. Rather, they give a clue as to why previous studies have led to conflicting data and offer a base for neuroscientists to rethink the way they interpret fMRI data from babies.

Reference
Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain. Kozberg MG, Chen BR, Deleo SE, Bouchard MB, Hillman EM. PNAS February 20, 2013.
doi: 10.1073/pnas.1212785110
PMID: 23426630

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