Functional involvement of cerebral cortex in human narcolepsy

Abstract

The pathophysiology of human narcolepsy is still poorly understood. The hypoactivity of some neurotransmitter systems has been hypothesised on the basis of the canine model. To determine whether narcolepsy is associated with changes in excitability of the cerebral cortex, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in 13 patients with narcolepsy and in 12 control subjects. We used several TMS paradigms that can provide information on the excitability of the motor cortex. Resting and active motor thresholds were higher in narcoleptic patients than in controls and intracortical inhibition was more pronounced in narcoleptic patients. No changes in the other evaluated measures were detected. These results are consistent with an impaired balance between excitatory and inhibitory intracortical circuits in narcolepsy that leads to cortical hypoexcitability. We hypothesise that the deficiency of the excitatory hypocretin/orexin-neurotransmitter-system in narcolepsy is reflected in changes of cortical excitability since circuits originating in the lateral hypothalamus and in the basal forebrain project widely to the neocortex, including motor cortex. This abnormal excitability of cortical networks could be the physiological correlate of excessive daytime sleepiness and it could be the substrate for allowing dissociated states of wakefulness and sleep to emerge suddenly while patients are awake, which constitute the symptoms of narcolepsy.

Cortical Excitability Changes in Patients with Sleep-Wake Disturbances after Traumatic Brain Injury

“…Both RMT and SICI correlated significantly with the conventional neurophysiological method of MSLT. Interestingly, similar TMS findings have been reported in previous studies on patients with narcolepsy (Oliviero et al, 2005;Nardone et al, 2010;Yoo et al, 2010). Furthermore, Nardone and associates (2010) found in narcoleptic patients a significant correlation between these two TMS measures and the clinically validated measures of daytime sleepiness, the MSLT and the subjective ESS.…”

Central nervous system dysfunction in primary biliary cirrhosis and its relationship to symptoms

“…However, if neurological function is so demonstrably abnormal in these patients, it suggests that the reduced central activation is caused at least in part by organic processes not under voluntary control. Interestingly, impaired ICI is associated with central fatigue in multiple sclerosis [13] and has previously been shown to be similarly deficient in patients with depression, somnambulants, and hepatitis C patients with and without clinically manifest encephalopathy [16][17][18][19].…”

Orexinergic projections to the cat midbrain mediate alternation of emotional behavioural states from locomotion to cataplexy

“…It is therefore critical to consider how forebrain structures contribute to the pathogenesis in narcolepsy. In fact, activity of cerebral cortex was altered in human narcolepsy patients (Oliviero et al 2005). Mesopontine tegmentum receives volitional signals from the cerebral cortex and emotional signals from limbic structures such as the hippocampus and the amygdala (see Takakusaki et al 2004 b ).…”