Encoding of sequence boundaries in the subthalamic nucleus of patients with Parkinson's disease

Sequential behaviour is widespread not only in humans but also in animals, ranging in different degrees of complexity from locomotion to birdsong or music performance. The capacity to learn new motor sequences relies on the integrity of basal ganglia-cortical loops. In Parkinson's disease the execution of habitual action sequences as well as the acquisition of novel sequences is impaired partly due to a deficiency in being able to generate internal cues to trigger movement sequences. In addition, patients suffering from Parkinson's disease have difficulty initiating or terminating a self-paced sequence of actions. Direct recordings from the basal ganglia in these patients show an increased level of beta (14-30 Hz) band oscillatory activity associated with impairment in movement initiation. In this framework, the current study aims to evaluate in patients with Parkinson's disease the neuronal activity in the subthalamic nucleus related to the encoding of sequence boundaries during the explicit learning of sensorimotor sequences. We recorded local field potential activity from the subthalamic nucleus of 12 patients who underwent deep brain stimulation for the treatment of advanced Parkinson's disease, while the patients in their usual medicated state practiced sequences of finger movements on a digital piano with corresponding auditory feedback. Our results demonstrate that variability in performance during an early phase of sequence acquisition correlates across patients with changes in the pattern of subthalamic beta-band oscillations; specifically, an anticipatory suppression of beta-band activity at sequence boundaries is linked to better performance. By contrast, a more compromised performance is related to attenuation of beta-band activity before within-sequence elements. Moreover, multivariate pattern classification analysis reveals that differential information about boundaries and within-sequence elements can be decoded at least 100 ms before the keystroke from the amplitude of oscillations of subthalamic nucleus activity across different frequency bands, not just from the beta-band. Additional analysis was performed to assess the strength of how much the putative signal encoding class of ordinal position (boundaries, within-sequence elements) is reflected in each frequency band. This analysis demonstrates that suppression of power in the beta-band contains the most class-related information, whereas enhancement of gamma band (31-100 Hz) activity is the second main contributor to the encoding. Our findings support the hypothesis that subthalamic nucleus-mediated gating of salient boundary elements during sequence encoding may be a prerequisite for the adequate acquisition of action sequences and the transition to habitual behaviour.