Daniela Ballotta1, Francesca Talami1, Fabio Pizza2, Anna Elisabetta Vaudano3, Francesca Benuzzi1, Giuseppe Plazzi4, Stefano Meletti5. 1. Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Italy; Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Italy. 2. Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche, AUSL of Bologna, Italy. 3. Neurology Unit, OCB Hospital, AOU Modena, Italy. 4. Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Italy; IRCCS Istituto delle Scienze Neurologiche, AUSL of Bologna, Italy. 5. Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, Italy; Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Italy; Neurology Unit, OCB Hospital, AOU Modena, Italy. Electronic address: stefano.meletti@unimore.it.
Abstract
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.
INTRODUCTION: functional and structural MRI studies suggest that the orexin (hypocretin) deficiency in the dorso-lateral hypothalamus of narcolepticpatients 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.