Low Prefrontal GABA Levels Are Associated With Poor Cognitive Functions in Professional Boxers

Abstract

Cognitive dysfunction has long been recognized as a frequently observed symptom in individuals with repetitive mild traumatic brain injury (rmTBI) such as professional boxers. The exact neurobiological mechanisms underlying this cognitive deficit have not yet been identified, but it is agreed upon that the prefrontal cortex (PFC) is one of the most commonly affected brain regions in professional boxers. Noting the pivotal role of the two major brain metabolites in human cognitive functions, γ-aminobutyric acid (GABA) and glutamate/glutamine (Glx), we hypothesized that alterations in levels of GABA and Glx in the PFC would be prominent and may correlate with cognitive deficits in professional boxers. Twenty male professional boxers (Boxers) and 14 age-matched healthy males who had never experienced any TBI (CON) were recruited. Using a 3T magnetic resonance imaging (MRI) scanner, single-voxel proton magnetic resonance spectroscopy with Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence was performed to evaluate the levels of GABA and Glx in the PFC. Cognitive function was assessed using the memory and attention domains from the Cambridge Neuropsychological Test Automated Battery. The Boxers showed lower GABA level in the PFC compared to the CON, while also showing lower performance in the attention and memory domains. There were no significant between-group differences in Glx levels. Furthermore, the GABA level correlated with memory performance in the Boxers, but not in attention performance. The current findings may suggest that alterations in GABA levels in the PFC may be a potential neurochemical correlate underlying memory dysfunction related to rmTBI.

Understanding the Consequences of Repetitive Subconcussive Head Impacts in Sport: Brain Changes and Dampened Motor Control Are Seen After Boxing Practice

“…Animal studies confirmed the acute metabolic response to impact, showing that 1 h after actual traumatic brain injury the balance between excitatory and inhibitory neurotransmitters is altered (Harris et al, 2012). The chronic GABAergic response in sport was confirmed using spectroscopy in boxers in this issue (Kim et al, 2019), and previously in American football players by Tremblay et al (2014) assessed through spectroscopy as well as TMS assessed cortical silent period. They found a complex but interesting pattern of results suggesting that indeed the normal balance between GABA mediated inhibition and excitation was altered in the players who sustained a concussion on average 3 years prior.…”

Approaches to Monitor Circuit Disruption after Traumatic Brain Injury: Frontiers in Preclinical Research

“…Experimental data have indicated that TBI can cause reduced expression of GAT at 24 h post-injury [68]. Magnetic resonance spectroscopy (MRI) has shown lower GABA levels in the prefrontal cortex associated with memory deficits in professional boxers repetitive mild TBI [69]. Utilizing this technique, recent work has indicated region and time-specific changes in the GABA showing reduced levels in the cerebral cortex at 72 h and two-week post-mild TBI [70].…”

GABA Measurement in a Neonatal Fragile X Syndrome Mouse Model Using 1H-Magnetic Resonance Spectroscopy and Mass Spectrometry

“…Recent studies have also found that inhibitory deficits in the medial prefrontal cortex in a prepubescent FXS mouse model (Kramvis et al, 2020). Multiple clinical 1 H-MRS studies measuring GABA in various adult populations have found that decreased GABA concentrations in the prefrontal cortex, dorsolateral prefrontal cortex, or frontal cerebrum are correlated with decreased cognitive function and working memory task performance (Yoon et al, 2016;Porges et al, 2017;Kim et al, 2019). Another 1 H-MRS clinical study found a positive correlation between visual intelligence and GABA concentration in the primary visual cortex (Cook et al, 2016).…”