Letter to the Editor

A neuromodulation experience registry for deep brain stimulation studies in psychiatric research: Rationale and recommendations for implementation

At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders. At the single-patient level, however, symptoms may sometimes persist despite “optimal” electrode placement at established treatment coordinates. This may be partly explained by limitations of disease-centric strategies that are unable to account for heterogeneous phenotypes and comorbidities observed in clinical practice. Instead, tailoring electrode placement and programming to individual patients’ symptom profiles may increase the fraction of top-responding patients. Here, we propose a three-step, circuit-based framework with the aim of developing patient-specific treatment targets that address the unique symptom constellation prevalent in each patient. First, we describe how a symptom network target library could be established by mapping beneficial or undesirable DBS effects to distinct circuits based on (retrospective) group-level data. Second, we suggest ways of matching the resulting symptom networks to circuits defined in the individual patient (template matching). Third, we introduce network blending as a strategy to calculate optimal stimulation targets and parameters by selecting and weighting a set of symptom-specific networks based on the symptom profile and subjective priorities of the individual patient. We integrate the approach with published literature and conclude by discussing limitations and future challenges.

The number of molecularly defined degenerative ataxia diseases is rapidly increasing, many of them involving complex multisystemic presentations including parkinsonism. The increasing number of novel ataxia genes –with most of them being ultra-rare – often makes it difficult for clinicians and scientists to identify the molecular diagnosis underlying these ataxia-parkinsonism syndromes. Here we aim to provide an overview on the most frequent diseases and molecular causes underlying ataxia-parkinsonism, focusing both on novel aspects of well-known causes of ataxia-parkinsonism (MSA-C, PSP-C, FXTAS, repeat-expansion spinocerebellar ataxias [SCAs], conventional mutation SCAs) as well as on more recently identified rare genetic causes of ataxia-parkinsonism (AT, POLG, SPG7). We demonstrate that frequency data and phenotype characteristics help to guide diagnostics in patients with unexplained ataxia-parkinsonism, while the newly identified rare genetic causes of ataxia-parkinsonism provide novel insights into molecular key pathways underlying the shared vulnerability of cerebellar and basal ganglia neurons.

Recent advances in deep brain stimulators and brain-machine interfaces have greatly expanded the possibilities of neuroprosthetics and neuromodulation. Together with advances in neuroengineering, nanotechnology, molecular biology and material sciences, it is now possible to address fundamental questions in neuroscience in new, more powerful ways. It is now possible to apply these new technologies in ways that range from augmenting and restoring function to neuromodulation modalities that treat neuropsychiatric disorders. Recent developments in neuromodulation methods offer significant advantages and potential clinical benefits for a variety of disorders. Here we describe the current state of the art in neuromodulation methods, and some advances in brain-machine interfaces, describing the advantages and limitations of the clinical applications of each method. The future applications of these new methods and how they will shape the future of psychiatry and medicine, along with safety and ethical implications, are also discussed.