Evidence for cognitive resource imbalance in adolescents with narcolepsy

Abstract

The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

Keywords: EEG; GABA; MRS; Narcolepsy; Working memory; fMRI.

Fig. 1

Representative axial slices of group-level fMRI activation during the working memory task across all subjects. a Encoding of sentences. b Recognition of words. All activation maps thresholded at p < 0.05, using Family Wise Error correction for comparing across all voxels in the brain. Color bars are scaled in terms of t-statistic. Slices were created using Mango (http://ric.uthscsa.edu/mango/; Jack L. Lancaster and Michael J. Martinez)

Fig. 2

Results from between-group comparisons of activation within the default mode network (DMN) region-of-interest. a Encoding of sentences. b Recognition of words. C. Parametric effect of load during recognition of words. Activation displayed as estimated marginal means (corrected for age, gender, and number of missed trials) of beta values, with healthy controls shown in dark gray and narcolepsy patients in light gray. Error bars are given in terms of standard error

Fig. 3

Results from the correlation analysis comparing activation levels in left middle frontal gyrus (LMFG) and DMN. a Encoding of sentences. b Recognition of words. c Parametric effect of load during encoding of sentences. d Parametric effect of load during recognition of words. Dashed lines indicate best linear fit of all data across both groups. For illustrative purposes, narcolepsy data points are indicated by light gray diamonds and healthy controls by dark gray squares

Fig. 4

Results from correlation analysis comparing activation levels in LMFG to working memory task accuracy. a Encoding of sentences. b Recognition of words. Dashed lines indicate best linear fit of all data across both groups. For illustrative purposes, narcolepsy data points are indicated by light gray diamonds and healthy controls by dark gray squares

Fig. 5

Results from the EEG neuroimaging analysis. The figure represents the results of the microstate segmentation done on the grand means of each group over the 1000 ms EEG epoch, reflecting the total time of the word presentation, where 0 ms indicates the stimulus presentation. The figure shows the three microstates that occurred in both the patient (top line) and the control (bottom line) group. We did not consider segments with an average duration of less than 10 time frames (80 ms) as physiological, they represent transitional microstates and were also not found to be significant after fitting back on the individual EEG data

Fig. 6

Results from correlation analysis comparing GABA+ and Glutamate concentrations to BOLD activity levels in medial prefrontal cortex during the encoding of sentences. a GABA+ with deactivation in medial prefrontal cortex (mPFC). b Glutamate with deactivation in mPFC. Dashed lines indicate best linear fit, and narcolepsy data points are indicated by light gray diamonds and healthy controls by dark gray squares