The Basal Forebrain Influences the Brain’s Default Mode

What's the science?

The ‘default mode network’ is a unique network of brain regions that is dysregulated in many clinical conditions, like epilepsy and depression. Typically, these regions are most active while a person is resting or reflecting internally. Brain activity in the default mode network at a particular frequency (gamma frequency) is high during rest.The basal forebrain is a brain region thought to contribute to arousal and attention - for example, it accelerates learning and boosts neural signals in response to sensory stimulation. This week in PNAS, Nair and colleagues assessed the relationship between gamma frequency power (strength) in the basal forebrain and the default mode network, to understand how these regions might influence one another. 

How did they do it?

They studied the basal forebrain and default mode network in rats using recordings from electrodes in these regions, specifically measuring the gamma power. During the recordings, the rats were placed in their home cages where they groomed themselves and were quiet but awake, or they were placed in a large new area, where they tend to engage in active, exploratory behaviour. Next, they recorded the firing (activity) of basal forebrain neurons and tested whether it was correlated with fluctuations in gamma power, in order to understand whether the gamma frequency was generated locally. Finally, they tested whether patterns of gamma frequency activity in the basal forebrain predicted activity in the default mode network or vice versa.

What did they find?

They found that gamma power was high while the mice were in their home cages, and low while the mice explored an area. This change in gamma power was not due to movement. They also found that the neuronal firing of basal forebrain neurons was related to gamma power, indicating that these neurons were responsible for generating the signal. Finally, they found that gamma power in the basal forebrain predicted gamma power in the default mode network.

Hugo Gambo, Eeg gamma, image by BrainPost, CC BY-SA 3.0

What's the impact?

This is the first study to observe a link between the the default mode network, active during rest, and the basal forebrain, traditionally understood to increase arousal. Basal forebrain neurons are also activated during rest along with the default mode network. This study suggests that the default mode network is influenced by the basal forebrain, which could be a new clinical target for disorders in which the default mode network is affected.

Nair et al., Basal forebrain contributes to default mode network regulation. PNAS. (2018). Access the original scientific publication here.

Hunger Affects Brain Activation in Response to Food Across the Lifespan

What's the science?

In adults, brain activity in response to food cues has been shown to predict overeating and weight gain. We do not yet understand the relationship between the brain’s response to food and overeating across the lifespan, including in children, who are especially vulnerable to food cues. Recently in Neuroimage, Charbonnier and colleagues show how certain brain regions activate in response to food depending on hunger level in different age groups.

How did they do it?

They recruited children, teens, adults and elderly participants who were scanned twice using functional MRI, once in a hungry state after fasting all night and once in a full (‘sated’) state after being fed.  Before the scan, participants rated how much they liked various foods. In the scanner, participants performed a food-viewing task where they viewed images of high and low calorie foods. The viewing of non-food images was a control task. Brain activity was compared while participants viewed high versus low calorie foods, in the hungry or full state, across different age groups.

What did they find?

Brain activation in the hungry state was greater across the lifespan when viewing high calorie foods (compared to low calorie foods) in two regions of the prefrontal cortex: the dorsolateral prefrontal cortex (involved in controlling actions) and the dorsomedial prefrontal cortex (involved in processing reward and value). Hunger state alone did not affect brain activation when viewing food. Age also did not affect brain activation for high compared to low calorie foods, even though younger participants rated liking high calorie food more.

What's the impact?

This is the first study to look at the effects of hunger and different food cues on brain activation in different age groups. The activation of the dorsolateral prefrontal cortex could reflect inhibition of eating, whereas the dorsomedial prefrontal cortex could be activating to process the reward value of the food, however this needs to be investigated further. It is important to understand brain mechanisms for eating behaviors across the lifespan in order to develop strategies to prevent obesity.

Reach out to study author Dr. Daniel Crabtree on Twitter @DanielCrabtree9

L. Charbonnier et al., Effects of hunger state on the brain responses to food cues across the life span. Neuroimage. 171, 246–255 (2018). Access the original scientific publication here.

Dyskinesias in Parkinson’s disease are Caused by a Subgroup of Neurons

What's the science?

In Parkinson’s disease, dopamine neurons in the midbrain degenerate resulting in problems with body movement. A dopamine medication called levodopa can be very effective for improving symptoms, however, in some cases it causes involuntary movements called dyskinesias. We know that unwanted neural activity in brain regions such as the striatum, motor cortex and sensorimotor cortex may be involved, but the specific brain region and cells causing dyskinesias are not known. Recently in Neuron, Girasole and colleagues identify a subgroup of neurons responsible for dyskinesias.

How did they do it?

They first used a method called Targeted Recombination in Active Populations (TRAP) in transgenic (genetically modified) mice. TRAP allows certain proteins (acting as labels) to be expressed in active neurons (as opposed to inactive neurons). In mice with levodopa-induced dyskinesias, they identified neurons that were active during the dyskinesias compared to control mice. Second, they then used optogenetics: Controlling neuron activation by shining light on genetically modified neurons of interest. This allowed them to inhibit and activate these specific neurons in the mice to see if they played a causal role in dyskinesias.

What did they find?

Only neurons in the striatum were significantly more active during dyskinesias compared to control mice. When examining these neurons more closely, they found that most of the active neurons were medium spiny neurons (a specific cell type of neuron found in the striatum) that were part of the 'direct pathway', an inhibitory pathway involved in motor function that is defective in Parkinson’s disease. When these neurons were inhibited with optogenetics, the dyskinesias were reduced. Inhibiting the activity of neurons in the motor or sensorimotor cortices did not reduce dyskinesias, demonstrating a causal role for striatal neurons in producing medication-induced dyskinesias.

Images are generated by Life Science Databases(LSDB)., Striatum, colour by BrainPost, CC BY-SA 1.0

What's the impact?

This is the first study to identify the neurons within the striatum that cause dyskinesias in mice. Dyskinesias are a detrimental side effect of levodopa in Parkinson’s disease and can be debilitating to patients who experience them. Understanding which neurons cause dyskinesias brings us one step closer to finding a way to treat them.

Reach out to study author Ally Girasole on Twitter @AllyGirasole

A. E. Girasole et al., A Subpopulation of Striatal Neurons Mediates Levodopa-Induced Dyskinesia. Neuron. 97, 1–9 (2018). Access the original scientific publication here.