Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography (ECoG) and subthalamic local field potential (LFP) recordings were performed OFF therapy (N = 22), ON dopaminergic medication (N = 18) and ON subthalamic deep brain stimulation (N = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography (EMG). In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Optic chiasm measurements may be useful markers of anterior optic pathway degeneration in neuromyelitis optica spectrum disorders.

OBJECTIVES: We aimed to evaluate optic chiasm (OC) measures as potential imaging marker for anterior optic pathway damage assessment in the context of neuromyelitis optica spectrum disorders (NMOSD). MATERIALS AND METHOD: This cross-sectional study included 39 patients exclusively with aquaporin 4-IgG seropositive NMOSD of which 25 patients had a history of optic neuritis (NMOSD-ON) and 37 age- and sex-matched healthy controls (HC). OC heights, width, and area were measured using standard 3D T1-weighted MRI. Sensitivity of these measures to detect neurodegeneration in the anterior optic pathway was assessed in receiver operating characteristics analyses. Correlation coefficients were used to assess associations with structural measures of the anterior optic pathway (optic nerve dimensions, retinal ganglion cell loss) and clinical measures (visual function and disease duration). RESULTS: OC heights and area were significantly smaller in NMOSD-ON compared to HC (NMOSD-ON vs. HC p < 0.0001). An OC area smaller than 22.5 mm2 yielded a sensitivity of 0.92 and a specificity of 0.92 in separating chiasms of NMOSD-ON from HC. OC area correlated well with structural and clinical measures in NMOSD-ON: optic nerve diameter (r = 0.4, p = 0.047), peripapillary retinal nerve fiber layer thickness (r = 0.59, p = 0.003), global visual acuity (r = - 0.57, p = 0.013), and diseases duration (r = - 0.5, p = 0.012). CONCLUSION: Our results suggest that OC measures are promising and easily accessible imaging markers for the assessment of anterior optic pathway damage. KEY POINTS: • Optic chiasm dimensions were smaller in neuromyelitis optica spectrum disorder patients compared to healthy controls. • Optic chiasm dimensions are associated with retinal measures and visual dysfunction. • The optic chiasm might be used as an easily accessible imaging marker of neurodegeneration in the anterior optic pathway with potential functional relevance.

Invasive neurophysiology and whole brain connectomics for neural decoding in patients with brain implants.

Brain computer interfaces (BCI) provide unprecedented spatiotemporal precision that will enable significant expansion in how numerous brain disorders are treated. Decoding dynamic patient states from brain signals with machine learning is required to leverage this precision, but a standardized framework for identifying and advancing novel clinical BCI approaches does not exist. Here, we developed a platform that integrates brain signal decoding with connectomics and demonstrate its utility across 123 hours of invasively recorded brain data from 73 neurosurgical patients treated for movement disorders, depression and epilepsy. First, we introduce connectomics-informed movement decoders that generalize across cohorts with Parkinson's disease and epilepsy from the US, Europe and China. Next, we reveal network targets for emotion decoding in left prefrontal and cingulate circuits in DBS patients with major depression. Finally, we showcase opportunities to improve seizure detection in responsive neurostimulation for epilepsy. Our platform provides rapid, high-accuracy decoding for precision medicine approaches that can dynamically adapt neuromodulation therapies in response to the individual needs of patients.

Bistable perception alternates between internal and external modes of sensory processing.

Perceptual history can exert pronounced effects on the contents of conscious experience: when confronted with completely ambiguous stimuli, perception does not waver at random between diverging stimulus interpretations but sticks with recent percepts for prolonged intervals. Here, we investigated the relevance of perceptual history in situations more similar to everyday experience, where sensory stimuli are usually not completely ambiguous. Using partially ambiguous visual stimuli, we found that the balance between past and present is not stable over time but slowly fluctuates between two opposing modes. For time periods of up to several minutes, perception was either largely determined by perceptual history or driven predominantly by disambiguating sensory evidence. Computational modeling suggested that the construction of unambiguous conscious experiences is modulated by slow fluctuations between internally and externally oriented modes of sensory processing.

An active role of inferior frontal cortex in conscious experience.

In the search for the neural correlates of consciousness, it has remained controversial whether prefrontal cortex determines what is consciously experienced or, alternatively, serves only complementary functions, such as introspection or action. Here, we provide converging evidence from computational modeling and two functional magnetic resonance imaging experiments that indicated a key role of inferior frontal cortex in detecting perceptual conflicts caused by ambiguous sensory information. Crucially, the detection of perceptual conflicts by prefrontal cortex turned out to be critical in the process of transforming ambiguous sensory information into unambiguous conscious experiences: in a third experiment, disruption of neural activity in inferior frontal cortex through transcranial magnetic stimulation slowed down the updating of conscious experience that occurs in response to perceptual conflicts. These findings show that inferior frontal cortex actively contributes to the resolution of perceptual ambiguities. Prefrontal cortex is thus causally involved in determining the contents of conscious experience.