Functional connectivity between motor cortex and globus pallidus in human non-REM sleep.

Recent evidence suggests that the motor system undergoes very specific modulation in its functional state during the different sleep stages. Here we test the hypothesis that changes in the functional organization of the motor system involve both cortical and subcortical levels and that these distributed changes are interrelated in defined frequency bands. To this end we evaluated functional connectivity between motor and non-motor cortical sites (fronto-central, parieto-occipital) and the globus pallidus (GP) in human non-REM sleep in seven patients undergoing deep brain stimulation (DBS) for dystonia using a variety of spectral measures (power, coherence, partial coherence and directed transfer function (DTF)). We found significant coherence between GP and fronto-central cortex as well as between GP and parieto-occipital cortex in circumscribed frequency bands that correlated with sleep specific oscillations in 'light sleep' (N2) and 'slow-wave sleep' (N3). These sleep specific oscillations were also reflected in significant coherence between the two cortical sites corroborating previous studies. Importantly, we found two different physiological activities represented within the broad band of significant coherence between 9.5 and 17 Hz. One component occurred in the frequency range of sleep spindles (12.5-17 Hz) and was maximal in the coherence between fronto-central and parieto-occipital cortex as well as between GP and both cortical sites during N2. This component was still present between fronto-central and parieto-occipital cortex in N3. Functional connectivity in this frequency band may be due to a common input to both GP and cortex. The second component consisted of a spectral peak over 9.5-12.5 Hz. Coherence was elevated in this band for all topographical constellations in both N2 and N3, but especially between GP and fronto-central cortex. The DTF suggested that the 9.5-12.5 Hz activity consisted of a preferential drive from GP to the fronto-central cortex in N2, whereas in N3 the DTF between GP and fronto-central cortex was symmetrical. Partial coherence supported distinctive patterns for the 9.5-12.5 and 12.5 and 17 Hz component, so that only coherence in the 9.5-12.5 Hz band was reduced when the effects of GP were removed from the coherence between the two cortical sites. The data suggest that activities in the GP and fronto-central cortex are functionally connected over 9.5-12.5 Hz, possibly as a specific signature of the motor system in human non-REM sleep. This finding is pertinent to the longstanding debate about the nature of alpha-delta sleep as a physiological or pathological feature of non-REM sleep.

Coherent spike-wave oscillations in the cortex and subthalamic nucleus of the freely moving rat.

The basal ganglia play a critical role in controlling seizures in animal models of idiopathic non-convulsive (absence) epilepsy. Inappropriate output from the substantia nigra pars reticulata (SNr) is known to exacerbate seizures, but the precise neuronal mechanisms underlying abnormal activity in SNr remain unclear. To test the hypothesis that cortical spike-wave oscillations, often considered indicative of absence seizures, propagate to the subthalamic nucleus, an important afferent of SNr, we simultaneously recorded local field potentials from the frontal cortex and subthalamic nucleus of freely moving rats. Spontaneous spike-wave oscillations in cortex (mean dominant frequency of 7.4 Hz) were associated with similar oscillations in the subthalamic nucleus (mean of 7.9 Hz). The power of oscillations at 5-9 Hz was significantly higher during spike-wave activity as compared with rest periods without this activity. Importantly, spike-wave oscillations in cortex and subthalamic nucleus were significantly coherent across a range of frequencies (3-40 Hz), and the dominant (7-8 Hz) oscillatory activity in the subthalamic nucleus typically followed that in cortex with a small time lag (mean of 2.7 ms). In conclusion, these data suggest that ensembles of subthalamic nucleus neurons are rapidly recruited into oscillations during cortical spike-wave activity, thus adding further weight to the importance of the subthalamic nucleus in absence epilepsy. An increase in synchronous oscillatory input from the subthalamic nucleus could thus partly underlie the expression of pathological activity in SNr that could, in turn, aggravate seizures. Finally, these findings also reiterate the importance of oscillations in these circuits in normal behaviour.

Effects of combined cortical and acoustic stimuli on muscle activity.

Hitherto, it has proven difficult to investigate interactions between cerebral and brainstem motor systems in the human. We hypothesised that transcranial magnetic stimulation (TMS) centred over the dorsal premotor and primary motor cortices might elicit net facilitatory cortico-reticular effects that could interact at the level of the brainstem with a habituated startle to give a reticulospinal discharge and electromyographic (EMG) response with a longer latency than the direct corticospinal response. Conversely, any reticulo-cortical activity evoked by a habituated startle should influence the size of the direct response to cortical TMS. EMG was recorded from active left deltoid muscle in nine healthy volunteers. Acoustic stimulation was delivered binaurally through headphones and repeated until the startle response was habituated. When TMS was centred over the right dorsal premotor or primary motor cortices and delivered 50 ms after the habituated acoustic stimulus, the contralateral direct motor evoked potential was inhibited, compared with the response elicited by TMS alone. The contralateral silent period was shortened and associated with less of a decrease in EMG levels relative to TMS alone. Indeed, an actual increase in EMG over baseline levels occurred in the later half of the silent period in all subjects. We conclude that both cortico-reticular and reticular-cortical effects could be elicited in deltoid through the combination of acoustic stimulation and TMS at short interstimulus intervals. Effects were similar with TMS over premotor and primary motor cortex.