Researchers at the University of Birmingham’s Centre for Human Brain Health in collaboration with the University of Amsterdam say they have uncovered a possible explanation for the mental sluggishness that often accompanies illness. The team investigated the link between “mental fog” and inflammation, the body’s response to illness. In a study (“Selective effects of acute low-grade inflammation on human visual attention”) published in Neuroimage, they showed that inflammation appears to have a particularly negative impact on the brain’s readiness to reach and maintain an alert state.

“Illness is often accompanied by perceived cognitive sluggishness, a symptom that may stem from immune system activation. The current study used electroencephalography (EEG) to assess how inflammation affected three different distinct attentional processes: alerting, orienting, and executive control. In a double-blinded, placebo-controlled within-subjects design (20 healthy males, mean age = 24.5, SD = 3.4), Salmonella typhoid vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur) was used to induce transient mild inflammation, while a saline injection served as a placebo-control. Participants completed the Attention Network Test with concurrent EEG recorded 6 h post-injection. Analyses focused on behavioral task performance and on modulation of oscillatory EEG activity in the alpha band (9–12 Hz) for alerting as well as orienting attention and frontal theta band (4–8 Hz) for executive control. Vaccination induced mild systemic inflammation, as assessed by interleukin-6 (IL-6) levels,” the investigators wrote.

“While no behavioral task performance differences between the inflammation and placebo condition were evident, inflammation caused significant alterations to task-related brain activity. Specifically, inflammation produced greater cue-induced suppression of alpha power in the alerting aspect of attention and individual variation in the inflammatory response was significantly correlated with the degree of alpha power suppression. Notably, inflammation did not affect orienting (i.e., alpha lateralization) or executive control (i.e., frontal theta activity). These results reveal a unique neurophysiological sensitivity to acute mild inflammation of the neural network that underpins attentional alerting functions.

“Observed in the absence of performance decrements, these novel findings suggest that acute inflammation requires individuals to exert greater cognitive effort when preparing for a task in order to maintain adequate behavioral performance.

Ali Mazaheri, PhD, associate professor and Jane Raymond, PhD, professor, of the University’s Centre for Human Brain Health, are the senior authors of the study.

“Scientists have long suspected a link between inflammation and cognition, but it is very difficult to be clear about the cause and effect. For example, people living with a medical condition or being very overweight might complain of cognitive impairment, but it’s hard to tell if that’s due to the inflammation associated with these conditions or if there are other reasons,” said Mazaheri. “Our research has identified a specific critical process within the brain that is clearly affected when inflammation is present.”

The study focused specifically on an area of the brain which is responsible for visual attention. A group of 20 young male volunteers took part and received a salmonella typhoid vaccine that causes temporary inflammation but has few other side effects. They were tested for cognitive responses to simple images on a computer screen a few hours after the injection so that their ability to control attention could be measured. Brain activity was measured while they performed the attention tests.

On a different day, either before or after, they received an injection with water (a placebo) and did the same attention tests. On each test day they were unaware of which injection they had received. Their inflammation state was measured by analyzing blood taken on each day.

The tests used in the study assessed three separate attention processes, each involving distinct parts of the brain. These processes are: “alerting” which involves reaching and maintaining an alert state; “orienting” which involves selecting and prioritizing useful sensory information; and “executive control” used to resolving what to pay attention to when available information is conflicting.

The results showed that inflammation specifically affected brain activity related to staying alert, while the other attention processes appeared unaffected by inflammation.

“These results show quite clearly that there’s a very specific part of the brain network that’s affected by inflammation,” noted Mazaheri. “This could explain ‘brain fog’.”

Raymond added that “this research finding is a major step forward in understanding the links between physical, cognitive, and mental health and tells us that even the mildest of illnesses may reduce alertness.”

“Getting a better understanding of the relationships between inflammation and brain function will help us investigate other ways to treat some of these conditions,” explained Leonie Balter, PhD, of the University of Amsterdam. “For example, further research might show that patients with conditions associated with chronic inflammation, such as obesity, kidney disease, or Alzheimer’s, could benefit from taking anti-inflammatory drugs to help preserve or improve cognitive function. Furthermore, subtle changes in brain function may be used as an early marker cognitive deterioration in patients with inflammatory diseases.”

The next step for the team will be to test the effects of inflammation on other areas of brain function such as memory.

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