Working memory in 8 Kleine-Levin syndrome patients: an fMRI study

Abstract

Study objectives: The objectives of this study were to investigate possible neuropathology behind the Kleine-Levin Syndrome (KLS), a severe form of hypersomnia with onset during adolescence.

Design: Functional magnetic resonance imaging (fMRI) applying a verbal working memory task was used in conjunction with a paper-and-pencil version of the task.

Participants: Eight patients with KLS and 12 healthy volunteers participated in the study.

Results: The results revealed a pattern of increased thalamic activity and reduced frontal activity (involving the anterior cingulate and adjacent prefrontal cortex) while performing a reading span task.

Discussion: This finding may explain the clinical symptoms observed in KLS, in that the thalamus is known to be involved in the control of sleep. Given the increasing access to fMRI, this investigation may aid clinicians in the diagnosis of patients suffering from severe forms of hypersomnia.

Figure 1

Illustration of the fMRI paradigm used for the working memory task. Difficulty levels were based on the recollection of the last word in each sentence after presentation of 1, 2, 3, or 4 sentences in a block. After sentence reading the participants were presented 4 words for 5 s each. The task was to indicate if the word was a lure or a target. Each difficulty level contained 5 Sentence/Word blocks. S = Sentences, W = Words.

Figure 2

Results from the reading span working memory task show performance accuracy (left panel) and response latency (right panel) for KLS and controls as a function of difficulty (number of words to retain).

Figure 3

Activation in healthy controls during working memory performance assessed by random effects analysis (one-sample t-test).

Figure 4

Cerebral activation in patients with Kleine-Levin syndrome during working memory performance using fMRI assessed by random effects analysis (one-sample t-test).

Figure 5

Results showing regions that are more activated by one group compared to the other. The healthy subjects (Controls) activated the cingulate gyrus and adjacent dorsomedial prefrontal cortex (a) more than patients with Kleine-Levin syndrome (KLS). Patients activated the inferior frontal gyrus, pars triangularis (b) and thalamus (d) more than controls. A significant negative correlation with task difficulty was observed in the control group (b).