With the rapid increase in new fNIRS users employing commercial software, there is a concern that many studies are biased by suboptimal processing methods. The purpose of this study is to provide a visual reference showing the effects of different processing methods, to help inform researchers in setting up and evaluating a processing pipeline. We show the significant impact of pre- and post-processing choices and stress again how important it is to combine data from both hemoglobin species in order to make accurate inferences about the activation site.

Wearable technology and neuroimaging equipment using photoplethysmography (PPG) have become increasingly popularized in recent years. Several investigations deriving pulse rate variability (PRV) from PPG have demonstrated that a slight bias exists compared to concurrent heart rate variability (HRV) estimates. PPG devices commonly sample at ~20–100 Hz, where the minimum sampling frequency to derive valid PRV metrics is unknown. Further, due to different autonomic innervation, it is unknown if PRV metrics are harmonious between the cerebral and peripheral vasculature. Cardiac activity via electrocardiography (ECG) and PPG were obtained concurrently in 54 participants (29 females) in an upright orthostatic position. PPG data were collected at three anatomical locations: left third phalanx, middle cerebral artery, and posterior cerebral artery using a Finapres NOVA device and transcranial Doppler ultrasound. Data were sampled for five minutes at 1000 Hz and downsampled to frequencies ranging from 20 to 500 Hz. HRV (via ECG) and PRV (via PPG) were quantified and compared at 1000 Hz using Bland–Altman plots and coefficient of variation (CoV). A sampling frequency of ~100–200 Hz was required to produce PRV metrics with a bias of less than 2%, while a sampling rate of ~40–50 Hz elicited a bias smaller than 20%. At 1000 Hz, time- and frequency-domain PRV measures were slightly elevated compared to those derived from HRV (mean bias: ~1–8%). In conjunction with previous reports, PRV and HRV were not surrogate biomarkers due to the different nature of the collected waveforms. Nevertheless, PRV estimates displayed greater validity at a lower sampling rate compared to HRV estimates.

Functional near-infrared spectroscopy (fNIRS) is a technology that is increasingly being applied to monitor brain function in healthy, diseased, or injured brains.^{1 – 6} As it is portable and relatively accessible in terms of data collection and processing, and it may rival MRI for assessing brain function in a wide range of neurological conditions including concussion. Concussion is a mild traumatic brain injury (mTBI) that results in altered neurological states leading to symptoms of memory and perception deficits, headaches, and other behavioral changes.^{7 – 10} The functional nature of these symptoms makes fNIRS an ideal method for monitoring the injury. In this paper, we investigate fNIRS as a tool for assessing concussion.

Background: Approximately one-third of all concussions lead to persistent postconcussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has a strong potential to be used as a treatment for patients with PPCS. Functional near-infrared spectroscopy (fNIRS) has already been used as a tool to assess patients with PPCS and may provide insight into the pathophysiology of rTMS treatment in patients with PPCS. Objective: The primary objective of this research is to determine whether rTMS treatment improves symptom burden in patients with PPCS compared to sham treatment using the Rivermead postconcussion symptom questionnaire. The secondary objective is to explore the neuropathophysiological changes that occur following rTMS in participants with PPCS using fNIRS. Exploratory objectives include determining whether rTMS treatment in participants with PPCS will also improve quality of life, anxiety, depressive symptoms, cognition, posttraumatic stress, and function secondary to headaches. Methods: A total of 44 adults (18-65 years old) with PPCS (>3 months to 5 years) will participate in a double-blind, sham-controlled, concealed allocation, randomized clinical trial. The participants will engage in either a 4-week rTMS treatment protocol or sham rTMS protocol (20 treatments). The left dorsolateral prefrontal cortex will be located through Montreal Neurologic Institute coordinates. The intensity of the rTMS treatment over the left dorsolateral prefrontal cortex will be 120% of resting motor threshold, with a frequency of 10 Hz, 10 trains of 60 pulses per train (total of 600 pulses), and intertrain interval of 45 seconds. Prior to starting the rTMS treatment, participant and injury characteristics, questionnaires (symptom burden, quality of life, depression, anxiety, cognition, and headache), and fNIRS assessment will be collected. Repeat questionnaires and fNIRS will occur immediately after rTMS treatment and at 1 month and 3 months post rTMS. Outcome parameters will be analyzed by a 2-way (treatment × time) mixed analysis of variance. Results: As of May 6, 2021, 5 participants have been recruited for the study, and 3 have completed the rTMS protocol. The estimated completion date of the trial is May 2022. Conclusions: This trial will expand our knowledge of how rTMS can be used as a treatment option of PPCS and will explore the neuropathophysiological response of rTMS through fNIRS analysis. Trial Registration: ClinicalTrials.gov NCT04568369; https://clinicaltrials.gov/ct2/show/NCT04568369 International Registered Report Identifier (IRRID): DERR1-10.2196/31308

Accelerometers are being increasingly incorporated into neuroimaging devices to enable real-time filtering of movement artifacts. In this study, we evaluate the reliability of sway metrics derived from these accelerometers in a standard eyes-open balance assessment to determine their utility in multimodal study designs. Ten participants equipped with a head-mounted accelerometer performed an eyes-open standing condition on 7 consecutive days. Sway performance was quantified with 4 standard metrics: root-mean-square (RMS) acceleration, peak-to-peak (P2P) acceleration, jerk, and ellipse area. Intraclass correlation coefficients (ICC) quantified reliability. P2P in both the mediolateral (ICC = 0.65) and anteroposterior (ICC = 0.67) planes yielded the poorest reliability. Both ellipse area and RMS exhibited good reliability, ranging from 0.76 to 0.84 depending on the plane. Finally, jerk displayed the highest reliability with an ICC value of 0.95. Moderate to excellent reliability was observed in all sway metrics. These findings demonstrate that head-mounted accelerometers, commonly found in neuroimaging devices, can be used to reliably assess sway. These data validate the use of head-mounted accelerometers in the assessment of motor control alongside other measures of brain activity such as electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS).

BACKGROUND Approximately one-third of all concussions lead to persistent postconcussion syndrome (PPCS). Repetitive transcranial magnetic stimulation (rTMS) is a form of noninvasive brain stimulation that has been extensively used to treat refractory major depressive disorder and has a strong potential to be used as a treatment for patients with PPCS. Functional near-infrared spectroscopy (fNIRS) has already been used as a tool to assess patients with PPCS and may provide insight into the pathophysiology of rTMS treatment in patients with PPCS. OBJECTIVE The primary objective of this research is to determine whether rTMS treatment improves symptom burden in patients with PPCS compared to sham treatment using the Rivermead postconcussion symptom questionnaire. The secondary objective is to explore the neuropathophysiological changes that occur following rTMS in participants with PPCS using fNIRS. Exploratory objectives include determining whether rTMS treatment in participants with PPCS will also improve quality of life, anxiety, depressive symptoms, cognition, posttraumatic stress, and function secondary to headaches. METHODS A total of 44 adults (18-65 years old) with PPCS (>3 months to 5 years) will participate in a double-blind, sham-controlled, concealed allocation, randomized clinical trial. The participants will engage in either a 4-week rTMS treatment protocol or sham rTMS protocol (20 treatments). The left dorsolateral prefrontal cortex will be located through Montreal Neurologic Institute coordinates. The intensity of the rTMS treatment over the left dorsolateral prefrontal cortex will be 120% of resting motor threshold, with a frequency of 10 Hz, 10 trains of 60 pulses per train (total of 600 pulses), and intertrain interval of 45 seconds. Prior to starting the rTMS treatment, participant and injury characteristics, questionnaires (symptom burden, quality of life, depression, anxiety, cognition, and headache), and fNIRS assessment will be collected. Repeat questionnaires and fNIRS will occur immediately after rTMS treatment and at 1 month and 3 months post rTMS. Outcome parameters will be analyzed by a 2-way (treatment × time) mixed analysis of variance. RESULTS As of May 6, 2021, 5 participants have been recruited for the study, and 3 have completed the rTMS protocol. The estimated completion date of the trial is May 2022. CONCLUSIONS This trial will expand our knowledge of how rTMS can be used as a treatment option of PPCS and will explore the neuropathophysiological response of rTMS through fNIRS analysis. CLINICALTRIAL ClinicalTrials.gov NCT04568369; https://clinicaltrials.gov/ct2/show/NCT04568369 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/31308