Neuroimaging of depression with diffuse optical tomography during repetitive transcranial magnetic stimulation

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for depression; however, its potential has likely been hindered due to non-optimized targeting, unclear ideal stimulation parameters, and lack of information regarding how the brain is physiologically responding during and after stimulation. While neuroimaging is ideal for obtaining such critical information, existing modalities have been limited due to poor resolutions, along with significant noise interference from the electromagnetic spectrum. In this study, we used a novel diffuse optical tomography (DOT) device in order to advance our understanding of the neurophysiological effects of rTMS in depression. Healthy and depressed subjects aged 18–70 were recruited. Treatment parameters were standardized with targeting of the left dorsolateral prefrontal cortex with a magnetic field intensity of 100% of motor threshold, pulse frequency of 10 per second, a 4 s stimulation time and a 26 s rest time. DOT imaging was simultaneously acquired from the contralateral dorsolateral prefrontal cortex. Six healthy and seven depressed subjects were included for final analysis. Hemoglobin changes and volumetric three-dimensional activation patterns were successfully captured. Depressed subjects were observed to have a delayed and less robust response to rTMS with a decreased volume of activation compared to healthy subjects. In this first-in-human study, we demonstrated the ability of DOT to safely and reliably capture and compare cortical response patterns to rTMS in depressed and healthy subjects. We introduced this emerging optical functional imaging modality as a novel approach to investigating targeting, new treatment parameters, and physiological effects of rTMS in depression.

Optical neuroimaging: advancing transcranial magnetic stimulation treatments of psychiatric disorders

“…In 2021, our group applied DOT imaging concurrent with stimulation for the first time to demonstrate that depressed patients, in comparison with healthy subjects, had abnormal neurovascular responses to TMS, as evidenced by a decreased volume and magnitude of DLPFC activation during TMS treatments (Figs. 1 and 2 ) [ 38 ]. TMS-evoked hemodynamics were immediately blunted in depressed patients and remained diminished during the entire stimulation and inter-training periods of a treatment session.…”

“…1 a Transverse view of the three-dimensional [HbT] images collected by DOT in a healthy subject during a 30-s epoch of TMS; b Sagittal view of the three-dimensional [HbT] images collected by DOT in a healthy subject during a 30-s epoch of TMS. The bronze colored coil symbol represents stimulation of the left dorsolateral prefrontal cortex [ 38 ]

Fig. 2 a Transverse view of the three-dimensional [HbT] images collected by DOT in a depressed subject during a 30-s epoch of TMS; b Sagittal view of the three-dimensional [HbT] images collected by DOT in a depressed subject during a 30-s epoch of TMS.

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“…2 a Transverse view of the three-dimensional [HbT] images collected by DOT in a depressed subject during a 30-s epoch of TMS; b Sagittal view of the three-dimensional [HbT] images collected by DOT in a depressed subject during a 30-s epoch of TMS. The bronze colored coil symbol represents stimulation of the left dorsolateral prefrontal cortex [ 38 ] …”

“…New techniques involving multivariate superficial signal regressions have been developed to attempt to isolate neural signals from any surrounding confounders [ 63 , 64 ]. Relative to other brain imaging methods, DOT also suffers from this problem less because of its inherent imaging reconstruction algorithm that separates the scalp layers from the brain [ 38 , 64 ]. Other proposed approaches for minimizing these obstacles include positioning the TMS coil further from the source detectors (i.e., measuring the signal at a location more distant from the coil), designing a custom interface with carefully separated optodes, or placing the coil above the optical interface and increasing the baseline power to overcome the weakened and more distant resultant magnetic field [ 65 ].…”

“…Given their localization capabilities and the real-time quantification of image analysis, optical modalities are perfectly suited for capturing such data, even in a naturalistic treatment setting. In addition, Shinba et al [ 36 ] and Jiang et al [ 38 ] demonstrated the feasibility of this paradigm, as immediate changes in hemoglobin concentrations during stimulation trains, as well as evoked changes observed during a single TMS treatment session, were reliably obtained and correlated with TMS response. Monitoring hemodynamic biomarkers such as those elicited by DOT during a typical 6-week course of daily TMS treatment sessions could theoretically inform the need for adjustments to various stimulation parameters in order to personalize the TMS protocol and optimize the effects of stimulation for the reduction of specific symptom clusters.…”