Altered neural oscillations in classical galactosaemia during sentence production.

Classical galactosaemia (CG) is a hereditary disease in galactose metabolism that despite dietary treatment is characterized by a wide range of cognitive deficits, among which is language production. CG brain functioning has been studied with several neuroimaging techniques, which revealed both structural and functional atypicalities. In the present study, for the first time, we compared the oscillatory dynamics, especially the power spectrum and time-frequency representations (TFR), in the electroencephalography (EEG) of CG patients and healthy controls while they were performing a language production task. Twenty-one CG patients and 19 healthy controls described animated scenes, either in full sentences or in words, indicating two levels of complexity in syntactic planning. Based on previous work on the P300 event related potential (ERP) and its relation with theta frequency, we hypothesized that the oscillatory activity of patients and controls would differ in theta power and TFR. With regard to behavior, reaction times showed that patients are slower, reflecting the language deficit. In the power spectrum, we observed significant higher power in patients in delta (1-3 Hz), theta (4-7 Hz), beta (15-30 Hz) and gamma (30-70 Hz) frequencies, but not in alpha (8-12 Hz), suggesting an atypical oscillatory profile. The time-frequency analysis revealed significantly weaker event-related theta synchronization (ERS) and alpha desynchronization (ERD) in patients in the sentence condition. The data support the hypothesis that CG language difficulties relate to theta-alpha brain oscillations.

Impact of theta transcranial alternating current stimulation on language production in adult classic galactosemia patients.

Patients with classic galactosemia (CG), an inborn error of galactose metabolism, suffer from impairments in cognition, including language processing. Potential causes are atypical brain oscillations. Recent electroencephalogram (EEG) showed differences in the P300 event-related-potential (ERP) and alterations in the alpha/theta-range during speech planning. This study investigated whether transcranial alternating current stimulation (tACS) at theta-frequency compared to sham can cause a normalization of the ERP post stimulation and improves language performance. Eleven CG patients and fourteen healthy controls participated in two tACS-sessions (theta 6.5 Hz/sham). They were engaged in an active language task, describing animated scenes at three moments, that is, pre/during/post stimulation. Pre and post stimulation, behavior (naming accuracy, voice-onset-times; VOT) and mean-amplitudes of ERP were compared, by means of a P300 time-window analysis and cluster-based-permutation testing during speech planning. The results showed that theta stimulation, not sham, significantly reduced naming error-percentage in patients, not in controls. Theta did not systematically speed up naming beyond a general learning effect, which was larger for the patients. The EEG analysis revealed a significant pre-post stimulation effect (P300/late positivity), in patients and during theta stimulation only. In conclusion, theta-tACS improved accuracy in language performance in CG patients compared to controls and altered the P300 and late positive ERP-amplitude, suggesting a lasting effect on neural oscillation and behavior.