EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients

Abstract

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or "CSF tapping" is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (∆alpha-F3-NPV) and the medial FC (∆alpha-Fz-NPV) induced by CSF tapping (cut-off value of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0), could correctly identified "shunt responders" and "shunt nonresponders" with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH.

Keywords: Cerebrospinal fluid tapping; Electroencephalography; Idiopathic normal pressure hydrocephalus; Neuronal Activity Topography; Normalized power variance; Tap test.

Fig. 1

Moving average filter method was used to calculate the NPV. The NPVs of 2.56-s EEG segments were calculated advancing at 0.64-s steps for 500 s EEG segment. Then, all NPVs were averaged. Top line represents EEG time course, while lower lines represent 2.56-s EEG segments.

Fig. 2

Alpha band NPV in responders (upper row) and nonresponders (lower row) before CSF tapping (left), after CSF tapping (center) and the statistical difference that is t-value between them (right). Responders have medial frontal (Fz)-alpha NPV decrease after CSF tapping, while nonresponders have right-dorsolateral prefrontal (F8)-alpha NPV increase.

Fig. 3

Scatterplots of significant correlations between difference of alpha-F3-NPV and difference of Gait Status Scale (GSS) before and after CSF Tapping (r = 0.55, p = 0.005). Decrease/increase of the alpha NPV at left-dorsal prefrontal cortex (F3) indicates improvement/worsening in gait status by CSF tapping.

Fig. 4

Scatterplots of significant correlations between difference of alpha-Fz-NPV and difference of 10-meter reciprocating walking test (WT) before and after CSF Tapping (r = 0.55, p = 0.004). Decrease/increase of the alpha NPV at medial frontal cortex (Fz) indicates improvement/worsening in gait velocity by CSF tapping.

Fig. 5

Scatterplots of significant correlations between difference of alpha-F8-NPV and difference of WMS-R_Mental Control before and after CSF Tapping (r = − 0.52, p = 0.008). Decrease/increase of the alpha NPV at right-dorsolateral-prefrontal cortex (F8) indicates improvement/worsening in response suppression by CSF tapping.

Fig. 6

Scatterplots of differences in alpha-Fz-NPV (∆alpha-Fz-NPV) and differences in alpha-F3-NPV (∆alpha-F3-NPV) before and after CSF tapping. We could correctly identify “shunt responders (red circle and yellow circle)” and “shunt nonresponders (dark blue cross)” with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3) with the threshold of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0.