Longitudinal EEG and fMRI Measures of Excitation:Inhibition Ratio after Traumatic Brain Injury

1683 

Abstract Submission 

Ana Radanovic¹, Samuel Louviot², Keith Jamison³, Sudhin Shah², Amy Kuceyeski³

¹Weill Cornell Graduate School of Medical Sciences, New York, NY, ²Department of Radiology, Weill Cornell Medicine, New York, NY, ³Weill Cornell Medicine, New York City, NY

Ana Radanovic  
Weill Cornell Graduate School of Medical Sciences
New York, NY

Samuel Louviot  
Department of Radiology, Weill Cornell Medicine
New York, NY

Keith Jamison  
Weill Cornell Medicine
New York City, NY

Sudhin Shah  
Department of Radiology, Weill Cornell Medicine
New York, NY

Amy Kuceyeski  
Weill Cornell Medicine
New York City, NY

Traumatic brain injury (TBI) is associated with persistent symptoms and incomplete recovery, and is a leading cause of long-term disability worldwide (Ahsman et al., 2006). Acute TBI is known to begin with a period of high excitotoxicity, however, the mechanisms of injury and recovery long-term remain unknown. Examining neurobiological mechanisms via neuroimaging is crucial for gaining insights into the processes of recovery, prognostic assessment, and potential treatment targets. The excitation to inhibition (E:I ratio) is thought to play an important role in pathophysiological mechanisms of autism, schizophrenia, and other intellectual disabilities (eg. Molina et. al, 2020). In addition, alterations in connectivity that occur after TBI are associated with changes in excitatory targets (dopamingergic and nornoradrenergic; Woodrow et. al, 2023). Thus, investigating the E:I ratio after TBI could reveal important information regarding injury and recovery mechanisms after TBI. There are noninvasive proxy markers of E:I in both electrophysiological (electroencephalography, EEG) and functional neuroimaging (functional Magnetic Resonance Imaging, fMRI). A measure of E:I in EEG, namely the aperiodic signal of the power spectral density (PSD) known as 1/f, has gained much interest. A proxy marker for E:I ratio identified in fMRI is the Hurst exponent (H) or, similarly, fALFF (fractional amplitude of low-frequency fluctuations). Both 1/f and fALFF have been independently validated, correlated, and shown to be clinically relevant (Gao et. al, 2017; Maschke et. al, 2023; Molina et. al, 2020; Trakoshis et al., 2020).

Longitudinal resting state fMRI and EEG data were collected from TBI patients and non-injured healthy controls (HC). TBI patients were measured at 2 timepoints: 4-6 months and 1 year after injury. EEG analyses were conducted on 29 TBI subjects (6 females, aged 18-82 mean 43 years) and 45 HC (13 females, aged 18-76 mean 41 years). EEG signals at rest were preprocessed using standard pipelines and aperiodic exponents were extracted using the specparam toolbox (Donoghue et al, 2020). fMRI analyses were conducted on 32 TBI subjects (8 females, aged 24-83 mean 53 years) and 14 HC (6 females, aged 23-86 mean 56 years). fMRI resting state data was processed using standard pipelines and fALFF was calculated for each of the FreeSurfer atlas's 86 regions. Between session analysis was conducted using a paired t-test. Analysis of differences between TBI and HC measurements were conducted using an ANCOVA, considering age and sex. The number of subjects used for each analysis is mentioned per figure.

The TBI subjects' average exponent values decreased on frontal channels over time (p=0.05) (Fig 1c). Frontal regions of the scalp show the most change over time in exponent values in TBI subjects, and these same channels tend to differ when compared with healthy controls (Fig1a), indicating a change in the TBI subjects over time that brought them closer to controls. Frontal fALFF values do not show the same significant trend over time (Fig 2b). Average frontal fALFF values seem to be higher in TBI subjects compared to healthy controls (Fig 2a., controlled for Age, Sex; p<0.1) but decrease over time to be closer to control values (although this was not significant).

With the aperiodic exponent as a proxy measure of E:I ratio, TBI subjects have a decreased aperiodic exponent (increased excitation) through recovery. This change is significant in the frontal and frontal midline regions, which are known to be important for executive attention (Kim et al, 2023). fALFF in the frontal regions seems to be higher (decreased excitation) compared to healthy controls at the first time point, and trends towards decreasing over time toward healthy control levels. This work suggests E:I ratio changes over time during TBI recovery, and understanding this progression could hint towards biomarkers of chronic pathology or recovery.

Psychiatric (eg. Depression, Anxiety, Schizophrenia)

EEG/MEG Modeling and Analysis ¹

Task-Independent and Resting-State Analysis ²

BOLD fMRI

EEG

ADULTS

ELECTROCORTICOGRAPHY

Electroencephaolography (EEG)

FUNCTIONAL MRI

Other - Brain Injury, Resting State