rTMS treatment of visual hallucinations using a connectivity-based targeting method - A case study

Abstract

Visual hallucinations (VH) are conscious visual perceptions that occur in the absence of an external stimulus. VHs are neuro-ophthalmological dysfunctions that are very disabling and are based on various pathologies, including eye diseases and neurodegenerative disorders [1,2]. VHs are difficult to treat, because pharmacological interventions are only partially effective and related to many adverse effects. One of the alternative nonpharmacological treatments for VHs is repetitive transcranial magnetic stimulation (rTMS). However, the challenge rTMS faces is the identification of the optimal stimulation sites [3]. Usually, the same cortical stimulation site is used for all patients with a particular diagnosis. However, this does not account for possible inter-subject variability, both in functional neuroarchitecture and clinical symptoms. If we could determine individually optimized target sites for rTMS, this would improve its efficacy as treatment. Here, we present a connectivity-based targeting approach, based on resting state (rs) fMRI data, to identify regions of high connectivity (“hubs”) within functional networks. We used these regions as target sites for rTMS treatment of a 67-year-old female patient who was diagnosed with Parkinson s disease (PD) at the age of 62. Her hallucinations started two years after she had been diagnosed with PD, at the time of her first L-dopa treatment. In addition, shewas diagnosedwith retinitis pigmentosa (RP) 30 years previously, whichwas gradually progressive and resulted in Charles Bonnet syndrome. She had severely reduced vision in her right eye and only light perception in her left eye. The VHs were mostly present during daytime, with her eyes open. All conventional pharmacological treatments, including clozapine, rivastigmine, quetiapine and olanzapine, failed to reduce her VH, and were discontinued. Firstly, a baseline fMRI scan served to gain an impression of potential functional neural networks involved in the VH of our subject. Subsequent fMRI data acquisition, rTMS treatment and clinical assessment were organised as follows: pre-treatment fMRI data were acquired in both eyes-open and eyes-closed conditions. Next, the patient was stimulated with 1 Hz rTMS during 5 days, followed by 30 Hz theta-burst stimulation for another 5 days. On the day of the last rTMS stimulation, post-treatment fMRI data were collected using identical experimental conditions. Clinical assessments consisted of brief daily interviews, to obtain qualitative data on the content and intensity of her VHs, both during rTMS treatment and follow-up for 6 months.