Diana Cunha-Reis, researcher at the Molecular Biodiscovery and Functional Bioanalysis Lab, at Ciências ULisboa, published a new paper, in the journal Biomedicines, on which she establishes, for the first in this field, a correlation between the cognitive decline (substantiated by attention deficit and lack of novelty detection) and the dysfunction of the brain circuits compromised in patients with Mesial temporal lobe epilepsy (MTLE).

What was the starting point that led to the current research?

Mesial temporal lobe epilepsy (MTLE) patients, display a marked cognitive decline with disease progression. This is reproduced in animal models of the disease that also display an attention-deficit hyperactivity disorder (ADHD) -like phenotype. This suggested us that attention and novelty detection may be the main learning trait affected in MTLE, subsequently leading to cognitive decline, and that dysfunction of brain circuits implicated in arousal and vigilance could be particularly compromised in MTLE, especially in the hippocampus. This was not comprehensively explored so far in MTLE research.

What is the main finding reported in this paper?

We found that among distinct novelty traits mismatch novelty detection, as occurring during detection of a particular event in a distinct physical or temporal context is particularly compromised in a rat model of MTLE. In addition, this was associated with an enhancement in noradrenergic inputs to the hippocampus, the main brain structure involved in mismatch novelty detection. This is the opposite from what is observed in ADHD yet leads to the same behavioral manifestation. Furthermore, a decline in dopaminergic and serotonergic inputs to the hippocampus is observed, likely contributing to co-morbid depression often observed in MTLE.

If you had to explain the main finding to a 5-year-old child, how would you do it? 

In epilepsy seizures destroy your capacity to learn by making you less capable to pay attention to changes in your surroundings, and for this it makes it harder to learn. Our study may help discover new medicines and treatments for people with epilepsy, so they can keep attention and learn.

Why is it important for the scientific community and for society at large?

This discovery is important to the scientific community in that it reveals alterations in neurotransmitter systems not fully explored in the context of MTLE and suggests their contribution to altered cognitive ability in this disease Given the burden of MTLE to healthcare systems worldwide, this is also important to the society at large in that it may lead to the development of new therapies for MTLE. In addition, it also brings valuable knowledge when considering the choice drugs for treating MTLE comorbidities like depression or anxiety.

What are the next steps?

The next steps would be to confirm these observations in hippocampal tissue from MTLE patients, to get an insight on the clinical relevance of this discovery. Also, to try to target the hippocampal noradrenergic system in rodent models of MTLE with pharmacological and behavioral approaches to try to reverse such alterations and understand if this could be beneficial in MTLE treatment.

Figure: Paper’s graphical abstract

Read the full paper here.