Neural correlates of lexical decisions in Parkinson's disease revealed with multivariate extraction of cortico-subthalamic interactions.

OBJECTIVE: Neural interactions between cortex and basal ganglia are pivotal for sensorimotor processing. Specifically, coherency between cortex and subthalamic structures is a frequently studied phenomenon in patients with Parkinson's disease. However, it is unknown whether cortico-subthalamic coherency might also relate to cognitive aspects of task performance, e.g., language processing. Furthermore, standard coherency studies are challenged by how to efficiently handle multi-channel recordings. METHODS: In eight patients with Parkinson's disease treated with deep brain stimulation, simultaneous recordings of surface electroencephalography and deep local field potentials were obtained from bilateral subthalamic nuclei, during performing a lexical decision task. A recent multivariate coherency measure (maximized imaginary part of coherency, MIC) was applied, simultaneously accounting for multi-channel recordings. RESULTS: Cortico-subthalamic synchronization (MIC) in 14-35Hz oscillations positively correlated with accuracy in lexical decisions across patients, but not in 7-13Hz oscillations. In contrast to multivariate MIC, no significant correlation was obtained when extracting cortico-subthalamic synchronization by "standard" bivariate coherency. CONCLUSIONS: Cortico-subthalamic synchronization may relate to non-motor aspects of task performance, here reflected in lexical accuracy. SIGNIFICANCE: The results tentatively suggest the relevance of cortico-subthalamic interactions for lexical decisions. Multivariate coherency might be effective to extract neural synchronization from multi-channel recordings.

Correlation between cortical and subcortical neural dynamics on multiple time scales in Parkinson's disease.

Complex amplitude dynamics of dominant alpha oscillations (8-13 Hz) in the cortex can be captured with long-range temporal correlations (LRTC) in healthy subjects and in various diseases. In patients with Parkinson's disease (PD), intra-nuclear coherence was demonstrated in dominant beta rhythms (10-30 Hz) in the basal ganglia. However, so far the relation between cortical LRTC (across tens of seconds) and subcortical coherence (millisecond scale) is unknown. We addressed these "multiscale interactions" by simultaneous recordings of surface electroencephalography (EEG) and deep local field potentials (LFP) from the bilateral subthalamic nucleus (STN) in eight patients with severe PD eligible for deep brain stimulation, who performed a lexical decision task on medication. In the continuous data set LRTC up to 20s were calculated in the amplitude envelope of 8-13-Hz EEG oscillations (across whole scalp), and subcortical coherence was assessed with measures being insensitive to volume conduction artifacts (imaginary part of coherency; iCOH) in 10-20 and 21-30-Hz oscillations in STN-LFP. We showed a significant positive correlation across patients between cortical LRTC (8-13Hz) and subcortical iCOH selectively in 10-20-Hz oscillations in the left STN. Our results suggest a relation between neural dynamics in the most dominant rhythms in the cortex and basal ganglia in PD, extending across multiple time scales (milliseconds vs. tens of seconds). Furthermore, the investigation of multiscale interactions might contribute to our understanding of cortical-subcortical neural coupling in PD.

Previously not recognized deletion in presenilin-1 (p.Leu174del.) in a patient with early-onset familial Alzheimer's disease.

We report on a previously not recognized mutation in exon 6 of presenilin-1 (PSEN1) (c.520_522delCTG) in a male patient with early onset familial Alzheimer disease. The mutation results in the deletion of a leucine at amino acid position 174 of the protein. The index patient presented with progressive memory loss at 50 years of age. Initially, depression was the only ancillary symptom. At age 53 clinical diagnosis of early Alzheimer disease was made based on neuropsychological, neuroimaging, and CSF findings. The patient's father and his paternal grandmother also suffered from memory loss and cognitive decline. The clinical findings in the patient are similar to signs and symptoms in previously reported patients with missense mutations at codon 174 of PSEN1.