The Role of White Matter Connections in Adolescent Mental Health and Cognition

What's the science?

The brain’s white matter pathways connect many different regions of the brain, and these connections undergo immense change during adolescence. Psychiatric disorders or their symptoms (e.g. anxiety, depression, obsessive-compulsive disorder, attention deficit hyperactivity disorder, post-traumatic stress disorder) often develop during this time. This week in JAMA Psychiatry, Alnaes and colleagues report that cognition and psychopathology symptoms are related to the brain’s connections in the frontal lobe.

How did they do it?

6487 adolescents (without a diagnosed mental disorder) completed 1) reports on a wide variety of clinical /psychopathological symptoms, and 2) cognitive tests. Of these adolescents, 748 had MRI scans of the brain’s white matter connections, and 2946 had genetic testing done. They assessed whether psychopathological symptoms and cognitive scores were heritable (ie. genetically inherited) and whether these scores were related to brain connectivity patterns. They then used a robust technique called machine learning to test relationships, meaning they ensured that the proposed model of the relationship between the brain and cognition/psychopathy was accurate in multiple different subgroups of participants.

What did they find?

Weaker connections in two of the brain’s white matter tracts (uncinate fasciculus and inferior fronto-occipital fasciculus) were associated with lower cognitive scores, and a greater number of psychopathological symptoms. Anxiety, antisocial behaviour, and psychosis were correlated with these connections. Genetic variance explained 18% of an individual’s cognitive score and 16% of their general psychopathy score.

William Hirstein. Diagram by Katie Reinecke., White matter fiber tracts, colour by BrainPost, CC BY 3.0

What's the impact?

This study found that psychopathological symptoms in adolescents and lower cognitive scores were predicted by lower connectivity in pathways of the brain’s frontal lobe. These pathways connect the frontal lobe with other regions known to be involved in emotion and cognition. Lower connectivity in frontal white matter pathways could play a role in the development of psychiatric disorders in youth.

D. Alnaes et al., Association of Heritable Cognitive Ability and Psychopathology With White Matter Properties in Children and Adolescents. JAMA Psychiatry. (2018) Access the original scientific publication here.

Reduced Brain Volume in Epilepsy Patients

What’s the science?

Epilepsy is a complex disorder characterized by seizures. The way that brain structure relates to the severity of epilepsy is not well understood. This week in Brain, Whelan and colleagues report structural brain changes in a large sample of epilepsy patients.

How did they do it?

Epilepsy patients were recruited from 24 research centers across 14 different countries. This resulted in 2149 epilepsy patients that were divided into 4 subgroups based on epilepsy type. The patients were scanned using MRI and the brain scans were analyzed to measure brain volumes and cortical thickness (the thickness of the outermost layer of the brain: the cerebral cortex) compared to healthy control participant brains.

What did they find?

They found that in all types of epilepsy, there was reduced brain volume in the right and left thalamus and reduced cortical thickness in the right and left precentral gyrus (motor cortex), which are both important brain regions involved in movement. In the subgroup of medial temporal lobe epilepsy patients, there was reduced brain volume in the hippocampus (a region involved in memory). Lower brain volumes and cortical thickness were associated with a longer duration of epilepsy.

What’s the impact?

This is the largest brain imaging study of epilepsy that has ever been done. Before this study, we didn’t know the extent to which structural brain changes occur in epilepsy. We now know that there are significant structural brain changes in the thalamus and precentral gyrus in epilepsy, which are both very important brain regions for movement and should be investigated further.

C. D. Whelan et al., Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study. Brain. 0, 1–18 (2018). 

Access the original scientific publication here.

The Link Between a High Salt Diet and Impaired Brain Function in Mice

What's the science?

A diet high in salt has been linked to altered brain blood supply, stroke and cognitive impairment. Evidence suggests that the immune system becomes activated in response to salt, and may be involved. Recently in Nature Neuroscience, Faraco and colleagues report a mechanism linking salt in the gut to immune system activation and reduced blood flow in the brain.

How did they do it?

They fed mice high salt diets and measured immune system markers in the blood and the function of cells lining brain blood vessels (endothelial cells which work to allow blood flow) at set time intervals over a 24 week period. They also measured resting brain blood flow using magnetic resonance imaging (MRI) with arterial spin labelling.

What did they find?

Mice fed a high salt diet had lower brain blood flow and dysfunctional endothelial cells. Additionally, they had worsened memory function, and a reduced ability to perform daily activities. Mice fed a high salt diet also had higher levels of immune cells (lymphocytes) in the gut, which resulted in higher inflammatory markers (IL-17) in the blood. Importantly, the lowered brain blood flow and cognitive problems were dependent on this immune system response.

What's the impact?

This study confirms previous theories that the immune system plays a role in linking dietary salt with brain function. Importantly, it reveals a specific immune system pathway linking the gut and the brain. This gut-brain pathway could be targeted with therapies to prevent harmful effects of salt on the brain. 

G. Faraco et al., Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat. Neurosci. (2018)

Access the original scientific publication here.