Cortico-Subthalamic Field Potentials Support Classification of the Natural Gait Cycle in Parkinson's Disease and Reveal Individualized Spectral Signatures.

The ability of humans to coordinate stereotyped, alternating movements between the two legs during bipedal walking is a complex motor behavior that requires precisely timed activities across multiple nodes of the supraspinal network. Understanding of the neural network dynamics that underlie natural walking in humans is limited. We investigated cortical and subthalamic neural activities during overground walking and evaluated spectral biomarkers to decode the gait cycle in three patients with Parkinson's disease without gait disturbances. Patients were implanted with chronic bilateral deep brain stimulation (DBS) leads in the subthalamic nucleus (STN) and electrocorticography paddles overlaying the primary motor and somatosensory cortices. Local field potentials were recorded from these areas while the participants performed overground walking and synchronized to external gait kinematic sensors. We found that the STN displays increased low-frequency (4-12 Hz) spectral power during the period before contralateral leg swing. Furthermore, STN shows increased theta frequency (4-8 Hz) coherence with the primary motor through the initiation and early phase of contralateral leg swing. Additional analysis revealed that each patient had specific frequency bands that could detect a significant difference between left and right initial leg swing. Our findings indicate that there are alternating spectral changes between the two hemispheres in accordance with the gait cycle. In addition, we identified patient-specific, gait-related biomarkers in both the STN and cortical areas at discrete frequency bands that may be used to drive adaptive DBS to improve gait dysfunction in patients with Parkinson's disease.

Epidural Spinal Electrogram Provides Direct Spinal Recordings in Awake Human Participants.

Little is known about the electrophysiological activity of the spinal cord during voluntary movement control in humans. We present a novel method for recording electrophysiological activity from the human spinal cord using implanted epidural electrodes during naturalistic movements including overground walking. Spinal electrograms (SEGs) were recorded from epidural electrodes implanted as part of a test trial for patients with chronic pain undergoing evaluation for spinal cord stimulation. Externalized ends of the epidural leads were connected to an external amplifier to capture SEGs. Electromyographic and accelerometry data from the upper and lower extremities were collected using wireless sensors and synchronized to the SEG data. Patients were instructed to perform various arm and leg movements while SEG and kinematic data were collected. This study proves the safety and feasibility of performing epidural spinal recordings from human subjects performing movement tasks.

Prefrontal Physiomarkers of Anxiety and Depression in Parkinson's Disease.

Objective: Anxiety and depression are prominent non-motor symptoms of Parkinson's disease (PD), but their pathophysiology remains unclear. We sought to understand their neurophysiological correlates from chronic invasive recordings of the prefrontal cortex (PFC). Methods: We studied four patients undergoing deep brain stimulation (DBS) for their motor signs, who had comorbid mild to moderate anxiety and/or depressive symptoms. In addition to their basal ganglia leads, we placed a permanent prefrontal subdural 4-contact lead. These electrodes were attached to an investigational pulse generator with the capability to sense and store field potential signals, as well as deliver therapeutic neurostimulation. At regular intervals over 3-5 months, participants paired brief invasive neural recordings with self-ratings of symptoms related to depression and anxiety. Results: Mean age was 61 ± 7 years, mean disease duration was 11 ± 8 years and a mean Unified Parkinson's Disease Rating Scale, with part III (UPDRS-III) off medication score of 37 ± 13. Mean Beck Depression Inventory (BDI) score was 14 ± 5 and Beck Anxiety Index was 16.5 ± 5. Prefrontal cortex spectral power in the beta band correlated with patient self-ratings of symptoms of depression and anxiety, with r-values between 0.31 and 0.48. Mood scores showed negative correlation with beta spectral power in lateral locations, and positive correlation with beta spectral power in a mesial recording location, consistent with the dichotomous organization of reward networks in PFC. Interpretation: These findings suggest a physiological basis for anxiety and depression in PD, which may be useful in the development of neurostimulation paradigms for these non-motor disease features.

Long-term wireless streaming of neural recordings for circuit discovery and adaptive stimulation in individuals with Parkinson's disease.

Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.