Sleep is a fundamental homeostatic process, and disorders of sleep can greatly affect quality of life. Parkinson's disease (PD) is highly comorbid for a spectrum of sleep disorders and deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been reported to improve sleep architecture in PD. We studied local field potential (LFP) recordings in PD subjects undergoing STN-DBS over the course of a full-night's sleep. We examined the changes in oscillatory activity recorded from STN between ultradian sleep states to determine whether sleep-stage dependent spectral patterns might reflect underlying dysfunction. For this study, PD (n=10) subjects were assessed with concurrent polysomnography and LFP recordings from the DBS electrodes, for an average of 7.5 hours in 'off' dopaminergic medication state. Across subjects, we found conserved spectral patterns among the canonical frequency bands (delta 0-3 Hz, theta 3-7 Hz, alpha 7-13 Hz, beta 13-30 Hz, gamma 30-90 Hz and high frequency 90-350 Hz) that were associated with specific sleep cycles: delta (0-3 Hz) activity during non-rapid eye movement (NREM) associated stages was greater than during Awake, whereas beta (13-30 Hz) activity during NREM states was lower than Awake and rapid eye movement (REM). In addition, all frequency bands were significantly different between NREM states and REM. However, each individual subject exhibited a unique mosaic of spectral interrelationships between frequency bands. Our work suggests that LFP recordings from human STN differentiate between sleep cycle states, and sleep-state specific spectral mosaics may provide insight into mechanisms underlying sleep pathophysiology.

Although motor subtypes of Parkinson's disease (PD), such as tremor dominant (TD) and postural instability and gait difficulty (PIGD), have been defined based on symptoms since the mid-1990s, no underlying neural correlates of these clinical subtypes have yet been identified. Very limited data exist regarding the electrophysiological abnormalities within the subthalamic nucleus (STN) that likely accompany the symptom severity or the phenotype of PD. Here, we show that activity in subbands of local field potentials (LFPs) recorded with multiple microelectrodes from subterritories of STN provide distinguishing neurophysiological information about the motor subtypes of PD. We studied 24 patients with PD and found distinct patterns between TD ( = 13) and PIGD ( = 11) groups in high-frequency oscillations (HFOs) and their nonlinear interactions with beta band in the superior and inferior regions of the STN. Particularly, in the superior region of STN, the power of the slow HFO (sHFO) (200-260 Hz) and the coupling of its amplitude with beta-band phase were significantly stronger in the TD group. The inferior region of STN exhibited fast HFOs (fHFOs) (260-450 Hz), which have a significantly higher center frequency in the PIGD group. The cross-frequency coupling between fHFOs and beta band in the inferior region of STN was significantly stronger in the PIGD group. Our results indicate that the spatiospectral dynamics of STN-LFPs can be used as an objective method to distinguish these two motor subtypes of PD. These observations might lead to the development of sensing and stimulation strategies targeting the subterritories of STN for the personalization of deep-brain stimulation (DBS).

Optimal electrophysiological placement of the DBS electrode may lead to better long term clinical outcomes. Inter-subject anatomical variability and limitations in stereotaxic neuroimaging increase the complexity of physiological mapping performed in the operating room. Microelectrode single unit neuronal recording remains the most common intraoperative mapping technique, but requires significant expertise and is fraught by potential technical difficulties including robust measurement of the signal. In contrast, local field potentials (LFPs), owing to their oscillatory and robust nature and being more correlated with the disease symptoms, can overcome these technical issues. Therefore, we hypothesized that multiple spectral features extracted from microelectrode-recorded LFPs could be used to automate the identification of the optimal track and the STN localization. In this regard, we recorded LFPs from microelectrodes in three tracks from 22 patients during DBS electrode implantation surgery at different depths and aimed to predict the track selected by the neurosurgeon based on the interpretation of single unit recordings. A least mean square (LMS) algorithm was used to de-correlate LFPs in each track, in order to remove common activity between channels and increase their spatial specificity. Subband power in the beta band (11–32 Hz) and high frequency range (200–450 Hz) were extracted from the de-correlated LFP data and used as features. A linear discriminant analysis (LDA) method was applied both for the localization of the dorsal border of STN and the prediction of the optimal track. By fusing the information from these low and high frequency bands, the dorsal border of STN was localized with a root mean square (RMS) error of 1.22 mm. The prediction accuracy for the optimal track was 80%. Individual beta band (11–32 Hz) and the range of high frequency oscillations (200–450 Hz) provided prediction accuracies of 72 and 68% respectively. The best prediction result obtained with monopolar LFP data was 68%. These results establish the initial evidence that LFPs can be strategically fused with computational intelligence in the operating room for STN localization and the selection of the track for chronic DBS electrode implantation.

Ethanol is known as a potent teratogen having adverse effects on brain and behavior. However, some of the behavioral deficits caused by fetal alcohol exposure and well expressed in juveniles ameliorate with maturation may suggest some kind of functional recovery occurring during postnatal development. The aim of this study was to reexamine age-dependent behavioral impairments in fetal-alcohol rats and to investigate the changes in neurogenesis and gross morphology of the hippocampus during a protracted postnatal period searching for developmental deficits and/or delays that would correlate with behavioral impairments in juveniles and for potential compensatory processes responsible for their amelioration in adults. Ethanol was delivered to the pregnant dams by intragastric intubation throughout 7-21 gestation days at daily dose of 6 g/kg. Isocaloric intubation and intact control groups were included. Locomotor activity, anxiety, and spatial learning tasks were applied to juvenile and young-adult rats from all groups. Unbiased stereological estimates of hippocampal volumes, the total number of pyramidal and granular cells, and double cortin expressing neurons were carried out for postnatal days (PDs) PD1, PD10, PD30, and PD60. Alcohol insult during second trimester equivalent caused significant deficits in the spatial learning in juvenile rats; however, its effect on hippocampal morphology was limited to a marginally lower number of granular cells in dentate gyrus (DG) on PD30. Thus, initial behavioral deficits and the following functional recovery in fetal-alcohol subjects may be due to more subtle plastic changes within the hippocampal formation but also in other structures of the extended hippocampal circuit. Further investigation is required.

Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic.Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest.Results: In all PD patients, we noted excessive beta band activity (13–30 Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200 and 400 Hz, indicating the presence of beta-HFO CFC. In all 3TS patients at rest, we observed theta band activity (4–7 Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200–400 Hz) and gamma band (35–200 Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5–10 Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects.Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting state 5–10 Hz-HFO CFC shifts to beta-HFO CFC which can be used to trigger stimulation in a closed loop system when tics are present.