In search of imaging markers in frontotemporal dementia

Neurodegenerative dementias are a group of diseases in which the progressive death of neurons is observed, associated with a profound modification of cognitive functions. Among them, frontotemporal dementia (FTD): it affects approximately 1 to 10 people in 100,000 and is marked by degeneration of the frontal and sometimes temporal lobe, associated with personality, behavioral and language disorders.

To the extent that patients are unaware of their condition and do not seek care, the disease is difficult to detect. It is now necessary to better understand the degenerative processes that underlie the wide variety of cognitive and behavioral symptoms observed in these patients, with the aim of diagnosing as early as possible and avoiding confusing FTD with psychiatric illnesses (depression, bipolar disorder, OCD, etc.) or other dementias.

The organization of brain networks

“The emergence of cognitive and behavioral functions – such as decision-making, language or responding to sensory stimuli – is not simply due to the activation of certain brain networks, but to their synergies,” explains Arabella Bouziguesdoctoral student. “However, these interactions are modified in neurodegeneration, and in particular in FTD. We wanted to understand how. »

At the Brain Institute, Arabella Bouzigues, Lara Migliaccio and their colleagues set out to explore the organization of these networks in 77 patients and 52 healthy subjects, using functional MRI methods which make it possible to study “gradients”. » – that is to say the spatial transitions between different brain networks – and their hierarchy within brain functioning.

The researchers thus observed that, in healthy individuals, a first gradient clearly distinguishes the sensorimotor network, which is responsible for optimizing movements and interpreting sensations, from the so-called “default mode” network, which occurs when an individual is at rest. Then, a second gradient separates the visual network and the so-called “saliency” network, which prioritizes the information to select those which are relevant in order to carry out an action.

Conversely, in patients with frontotemporal dementia, this organization is strongly disrupted, with different dynamics depending on the form of the disease. In the so-called “language” variants of FTD, the functional alterations were focal, and mainly localized at the level of the limbic and sensorimotor gradients. In the so-called “behavioral” variant, on the other hand, the entire hierarchy of gradients was affected. Finally, in all forms of the disease, the visual network seemed to compensate for cognitive and behavioral deficits.

New biomarkers of the disease?

“One of the most surprising aspects of these results is that the distribution of altered networks does not overlap with that of brain degeneration,” explains Arabella Bouzigues. “In other words, it is the inability of different networks to collaborate that determines the severity of symptoms, and not just the death of neurons causing brain atrophy. »

Ultimately, we can hope that these functional markers of frontotemporal dementia will help us detect the disease early, monitor its progression, and even define new therapeutic targets.

“This perspective is very exciting to the extent that things are progressing on the therapeutic level in various neurodegenerative diseases: gene therapy for amyotrophic lateral sclerosis, new anti-amyloid treatments recently approved in Europe for Alzheimer’s disease… early diagnosis takes finally all its meaning,” concludes Lara Migliaccio. “Understanding the organization of the brain now goes beyond simple theoretical knowledge: it can directly guide the development of new treatments, and serve as a marker to evaluate their effectiveness. »