February 22, 2016
MS Society-funded doctoral student demonstrates the adaptive potential of a child’s brain in pediatric-onset MS
The human brain is a web of nerve cells that are in constant communication with one another. Even when the brain is unconscious, certain networks of nerve cells continue to fire away in a flurry of activity. These so-called resting-state networks are thought to keep the brain primed and alert, ready to respond at a moment’s notice. Some are even considered necessary for higher order cognitive functions, such as processing emotions.
The strength of connection, or functional connectivity, between different regions of a nerve network is altered by a number of neurological disorders, including multiple sclerosis (MS). In adults living with MS, disruption of the myelin-rich regions of the brain leads to reduced connectivity within these resting-state networks, leading to deficits in cognitive ability.
A team led by Dr. Brenda Banwell at Toronto’s Hospital for Sick Children is focused on understanding whether a similar relationship exists between demyelination and resting-state networks in childhood-onset MS. Physical disability appears to progress at a much slower pace in children compared to adults with MS. This may be partly explained by an adaptive response within the child’s brain that promotes the preservation of key functional neural networks such as resting-state.
These questions formed the basis of a study carried out by Dr. Banwell’s team, including Dr. Nadine Akbar, who was supported by a National Bank Financial Group Doctoral Studentship Award from the MS Society of Canada. The findings of the study were published in the journal PLOS ONE.
19 individuals with childhood-onset MS (less than 18 years of age at time of first MS attack), were recruited from the MS program at Toronto’s Hospital for Sick Children. The participants were compared to an age and sex-matched group of 16 individuals without MS.
Magnetic resonance imaging (MRI) scans were carried out on the study participants. MRI is a powerful tool that can assess potential damage to regions of myelin in the brain. A variation of the technology called functional MRI (fMRI) can also measure the strength of connectivity within resting-state networks.
The team focused on resting-state networks that are involved in varying aspects of human cognition, including emotional processing, daydreaming, attention control and working memory. An important network the researchers examined is called the default-mode network, a set of brain regions that are active when the mind is at rest and wandering (including thinking about one’s self and others, thinking about others, reflecting on the past and planning for the future), and not focused on a particular task in the outside world.
Participants with MS unsurprisingly exhibited evidence of widespread damage to myelin-rich areas throughout the brain compared to healthy controls based on MRI scans. In stark contrast, MS participants had overall stronger functional connections within the resting state networks that are related to cognition compared to individuals without MS.
The researchers also noted that, within the MS participant group, specific areas of the brain that had greater myelin damage were linked to improved connectivity within the default-mode network.
Dr. Banwell and her team view the increased neural connectivity that they observed as an adaptation to demyelination – the child’s brain adjusted to the MS-related damage by increasing the underlying strength of important resting-state networks. These networks are thought to govern a variety of critical day-to-day activities, from the child’s capacity for focus and attention, to incorporating past experiences into future plans.
The authors suggest that the brain may prioritize such preferred or essential brain regions over others in response to demyelination. It could help explain why all the children within the MS group maintained a high level of cognitive function despite loss of myelin, which normally leads to cognitive deficits in adults. Similar and larger studies will help pinpoint the degree to which increased neural connectivity is able to both compensate for demyelination in childhood MS, as well as maintain cognitive ability in the face of ongoing MS-related damage.
Akbar N et al. (2016). Alterations in functional and structural connectivity in pediatric-onset multiple sclerosis. PLoS ONE (11)1: e0145906. doi:10.1371/journal.pone.0145906.