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Francesca Benuzzi

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YNIMG Journal 2021 Journal Article

Cortical and subcortical hemodynamic changes during sleep slow waves in human light sleep

  • Monica Betta
  • Giacomo Handjaras
  • Andrea Leo
  • Alessandra Federici
  • Valentina Farinelli
  • Emiliano Ricciardi
  • Francesca Siclari
  • Stefano Meletti

EEG slow waves, the hallmarks of NREM sleep are thought to be crucial for the regulation of several important processes, including learning, sensory disconnection and the removal of brain metabolic wastes. Animal research indicates that slow waves may involve complex interactions within and between cortical and subcortical structures. Conventional EEG in humans, however, has a low spatial resolution and is unable to accurately describe changes in the activity of subcortical and deep cortical structures. To overcome these limitations, here we took advantage of simultaneous EEG-fMRI recordings to map cortical and subcortical hemodynamic (BOLD) fluctuations time-locked to slow waves of light sleep. Recordings were performed in twenty healthy adults during an afternoon nap. Slow waves were associated with BOLD-signal increases in the posterior brainstem and in portions of thalamus and cerebellum characterized by preferential functional connectivity with limbic and somatomotor areas, respectively. At the cortical level, significant BOLD-signal decreases were instead found in several areas, including insula and somatomotor cortex. Specifically, a slow signal increase preceded slow-wave onset and was followed by a delayed, stronger signal decrease. Similar hemodynamic changes were found to occur at different delays across most cortical brain areas, mirroring the propagation of electrophysiological slow waves, from centro-frontal to inferior temporo-occipital cortices. Finally, we found that the amplitude of electrophysiological slow waves was positively related to the magnitude and inversely related to the delay of cortical and subcortical BOLD-signal changes. These regional patterns of brain activity are consistent with theoretical accounts of the functions of sleep slow waves.

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YNICL Journal 2021 Journal Article

Hypothalamus and amygdala functional connectivity at rest in narcolepsy type 1

  • Daniela Ballotta
  • Francesca Talami
  • Fabio Pizza
  • Anna Elisabetta Vaudano
  • Francesca Benuzzi
  • Giuseppe Plazzi
  • Stefano Meletti

INTRODUCTION: functional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcoleptic patients would influence both brain metabolism and perfusion and would cause reduction in cortical grey matter. Previous fMRI studies have mainly focused on cerebral functioning during emotional processing. The aim of the present study was to explore the hemodynamic behaviour of spontaneous BOLD fluctuation at rest in patients with Narcolepsy type 1 (NT1) close to disease onset. METHODS: Fifteen drug naïve children/adolescents with NT1 (9 males; mean age 11.7 ± 3 years) and fifteen healthy children/adolescents (9 males; mean age 12.4 ± 2.8 years) participated in an EEG-fMRI study in order to investigate the resting-state functional connectivity of hypothalamus and amygdala. Functional images were acquired on a 3 T system. Seed-based functional connectivity analyses were performed using SPM12. Regions of Interest were the lateral hypothalamus and the amygdala. RESULTS: compared to controls, NT1 patients showed decreased functional connectivity between the lateral hypothalamus and the left superior parietal lobule, the hippocampus and the parahippocampal gyrus. Decreased functional connectivity was detected between the amygdala and the post-central gyrus and several occipital regions, whereas it was increased between the amygdala and the inferior frontal gyrus, claustrum, insula, and putamen. CONCLUSION: in NT1 patients the abnormal connectivity between the hypothalamus and brain regions involved in memory consolidation during sleep, such as the hippocampus, may be linked to the loss of orexin containing neurons in the dorsolateral hypothalamus. Moreover, also functional connectivity of the amygdala seems to be influenced by the loss of orexin-containing neurons. Therefore, we can hypothesize that dysfunctional interactions between regions subserving the maintenance of arousal, memory and emotional processing may contribute to the main symptom of narcolepsy.

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