Alterations of Excitation-Inhibition Balance and Brain Network Dynamics Support Sensory Deprivation Theory in Presbycusis

Abstract

Sensory deprivation theory is an important hypothesis involving potential pathways between hearing loss and cognitive impairment in patients with presbycusis. The theory suggests that prolonged auditory deprivation in presbycusis, including neural deafferentation, cortical reallocation, and atrophy, causes long-lasting changes and reorganization in brain structure and function. However, neurophysiological changes underlying the cognition-ear link have not been explored. In this study, we recruited 98 presbycusis patients and 60 healthy controls and examined the differences between the two groups in gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in bilateral auditory cortex, excitation-inhibition (E/I) balance (Glu/GABA ratio), dynamic functional network connectivity (dFNC), hearing ability and cognitive performance. Then, correlations with each other were investigated and variables with statistical significance were further analyzed using the PROCESS Macro in SPSS. GABA levels in right auditory cortex and Glu levels in bilateral auditory cortex were lower but E/I balance in right auditory cortex were higher in presbycusis patients compared to healthy controls. Hearing assessments and cognitive performance were worse in presbycusis patients. Three recurring connectivity states were identified after dFNC analysis: State 1 (least frequent, middle-high dFNC strength with negative functional connectivity), State 2 (high dFNC strength), and State 3 (most frequent, low dFNC strength). The occurrence and dwell time of State 3 were higher, on the other hand, the dwell time of State 2 decreased in patients with presbycusis compared to healthy controls. In patients with presbycusis, worse hearing assessments and cognition were correlated with decreased GABA levels, increased E/I balance, and aberrant dFNC, decreased GABA levels and increased E/I balance were correlated with decreased occurrence and dwell time in State 3. In the mediation model, the fractional windows, as well as dwell time in State 3, mediated the relationship between the E/I balance in right auditory cortex and episodic memory (Auditory Verbal Learning Test, AVLT) in presbycusis. Moreover, in patients with presbycusis, we found that worse hearing loss contribute to lower GABA levels, higher E/I balance, and further impact aberrant dFNC, which caused lower AVLT scores. Overall, the results suggest that a shift in E/I balance in right auditory cortex plays an important role in cognition-ear link reorganization and provide evidence for sensory deprivation theory, enhancing our understanding the connection between neurophysiological changes and cognitive impairment in presbycusis. In presbycusis patients, E/I balance may serve as a potential neuroimaging marker for exploring and predicting cognitive impairment.

Keywords: GABA; cognitive impairment; dynamic functional network connectivity; excitation–inhibition balance; presbycusis; sensory deprivation theory.

FIGURE 1

Average MM‐suppressed MEGA‐PRESS and PRESS spectra and VOI in both right (A) and left (B) auditory region are depicted. MEGA‐PRESS: Mescher–Garwood point‐resolved spectroscopy sequence, MM: macromolecules.

FIGURE 2

The 26 independent components identified by a group ICA. (A) The 26 independent components and their spatial distribution. (B) 26 independent components were rearranged into seven functional networks. Pearson correlation coefficient were transformed to z‐score (the correlation value) using Fisher's z‐transformation. The color‐coded legend under the matrix was matched with the overlaid colors of the spatial maps in (A). AN: auditory network, CB: cerebellar, CEN: cognitive executive network, DMN: default mode network, SMN: sensorimotor network, SN: subcortical, VN: visual network.

FIGURE 3

Cluster centroids for each state in the upper row and temporal properties of FNC state analysis in the lower row. (A) The total number of subjects, the percentage of occurrence in each state were above the picture. The fractional windows (B) (the percentage of windows belonging to one state), dwell time (C) (the average number of consecutive windows belonging to one state before switching to another), and the number of transitions (D) (the count of transitions between different states) is depicted for healthy controls (HC) and patients with presbycusis (PC). AN: auditory network, CB: cerebellar, CEN: cognitive executive network, DMN: default mode network, SMN: sensorimotor network, SN: subcortical, VN: visual network. ***p < 0.001, *p < 0.05.

FIGURE 4

Heatmap showing the correlation of among hearing assessment, E/I‐R, dFNC, and cognition. DT: dwell time, E/I‐R: E/I balance in the right auditory region, FW: fractional windows, GABA‐R: GABA level in the right auditory region, GLU‐L: GLU level in the left auditory region, GLU‐R: GLU level in the right auditory region. *p < 0.05.

FIGURE 5

Simple mediation models show the correlation between E/I balance in right auditory cortex and AVLT with fractional windows or dwell time as mediator. AVLT: Auditory Verbal Learning Test, E/I: excitation–inhibition. ***p < 0.001, **p < 0.01, *p < 0.05.

FIGURE 6

Serial mediation models show the correlation among PTA, E/I balance in right auditory cortex, fractional windows/dwell time, and AVLT. AVLT: Auditory Verbal Learning Test, EI: excitation–inhibition, PTA: pure tone average. ***p < 0.001, **p < 0.01, *p < 0.05.