Felicitas Ehlen

Effects of subthalamic deep brain stimulation on dysarthrophonia in Parkinson’s disease

Background: Motor deficits in Parkinson’s disease (PD) are reduced by deep brain stimulation (DBS) of the subthalamic nucleus (STN), but the impact of this therapy on dysarthrophonic problems in PD remains controversial. We therefore aimed to disentangle the effects of STN DBS on the speech skills of long-term treated patients. Methods: Under continued medication, speech and motor functions of 19 patients with PD with bilateral STN DBS were studied when their therapeutic stimulation was active (STIM-ON) versus switched off (STIM-OFF). Per condition, perceptual speech ratings were given by: (i) the patients themselves, (ii) the treating physician, and (iii) professional speech therapists. Furthermore, single speech parameters were measured with a battery of technical exams in both STIM-ON and STIM-OFF. Results: STN DBS significantly worsened speech performance according to all perceptual rating methods applied. In contrast, technical measures showed DBS-induced improvements of single speech dimensions affected by the PD-specific motor disorder. These changes occurred independently of the reduction of motor impairment, which was consistently effectuated by STN DBS. Conclusion: In parallel to the beneficial effects on the motor symptoms of PD, STN DBS reduces designated disease-inherent dysarthrophonic symptoms, such as glottic tremor. However, these actions on speech are predominantly outweighed by the general dysarthrogenic effects of STN DBS, probably based on a decline of complex (eg, prosodic) functions. Thus, stimulation-induced speech impairment should be considered a likely problem in the course of this treatment.

Neuropathy in Parkinson’s Disease Patients with Intestinal Levodopa Infusion versus Oral Drugs

Background Severe polyneuropathy has been observed in a number of patients treated for Parkinson’s disease with Levodopa/Carbidopa intestinal gel infusion. This may reflect a rare individual complication or a systematic side effect. Objective To investigate whether peripheral nerve function differed between patients with oral treatment versus Levodopa/Carbidopa intestinal gel infusion. Methods In an observational design, data from median, tibial, and peroneal neurography were prospectively assessed and compared between patients with conventional drug treatment (n = 15) and with Levodopa/Carbidopa intestinal gel infusion (n = 15). The groups were matched for age and disease duration. In view of the medical risk profile for polyneuropathy, comorbidity and basic serological parameters were assessed. Results Axonal neuropathy was common in both patient groups. However, although group differences in risk factors for polyneuropathy were not evident, neurographic abnormalities were more severe in the patients treated with Levodopa/Carbidopa intestinal gel infusion than in the orally treated patients. In the group with Levodopa/Carbidopa intestinal gel infusion, the degree of neuropathic change correlated with weight lost since therapy initiation and with the drug dose. In contrast to the axonal abnormalities, conduction velocity was found normal in both groups. Conclusion The results are compatible with the promotion of axonal neuropathy by Levodopa/Carbidopa intestinal gel infusion. This could be due to the intrinsically high levodopa doses associated with the therapy and/or malnutritional effects from intestinal drug application. The results should be corroborated by a larger longitudinal and controlled trial.

Functional roles of the thalamus for language capacities

Early biological concepts of language were predominantly corticocentric, but over the last decades biolinguistic research, equipped with new technical possibilities, has drastically changed this view. To date, connectionist models, conceiving linguistic skills as corticobasal network activities, dominate our understanding of the neural basis of language. However, beyond the notion of an involvement of the thalamus and, in most cases also, the basal ganglia (BG) in linguistic operations, specific functions of the respective depth structures mostly remain rather controversial. In this review, some of these issues shall be discussed, particularly the functional configuration of basal network components and the language specificity of subcortical supporting activity. Arguments will be provided for a primarily cortico-thalamic language network. In this view, the thalamus does not engage in proper linguistic operations, but rather acts as a central monitor for language-specific cortical activities, supported by the BG in both perceptual and productive language execution.

Intact lexicon running slowly--prolonged response latencies in patients with subthalamic DBS and verbal fluency deficits.

Background Verbal Fluency is reduced in patients with Parkinson’s disease, particularly if treated with deep brain stimulation. This deficit could arise from general factors, such as reduced working speed or from dysfunctions in specific lexical domains. Objective To test whether DBS-associated Verbal Fluency deficits are accompanied by changed dynamics of word processing. Methods 21 Parkinson’s disease patients with and 26 without deep brain stimulation of the subthalamic nucleus as well as 19 healthy controls participated in the study. They engaged in Verbal Fluency and (primed) Lexical Decision Tasks, testing phonemic and semantic word production and processing time. Most patients performed the experiments twice, ON and OFF stimulation or, respectively, dopaminergic drugs. Results Patients generally produced abnormally few words in the Verbal Fluency Task. This deficit was more severe in patients with deep brain stimulation who additionally showed prolonged response latencies in the Lexical Decision Task. Slowing was independent of semantic and phonemic word priming. No significant changes of performance accuracy were obtained. The results were independent from the treatment ON or OFF conditions. Conclusion Low word production in patients with deep brain stimulation was accompanied by prolonged latencies for lexical decisions. No indication was found that the latter slowing was due to specific lexical dysfunctions, so that it probably reflects a general reduction of cognitive working speed, also evident on the level of Verbal Fluency. The described abnormalities seem to reflect subtle sequelae of the surgical procedure for deep brain stimulation rather than of the proper neurostimulation.

Modulation of cortical neural dynamics during thalamic deep brain stimulation in patients with essential tremor.

Although thalamic deep brain stimulation is an effective treatment for patients with essential tremor, little is known about its effect on cortical neural dynamics. Therefore, we investigated long-range temporal correlations and spectral power in electroencephalographic recordings of patients during OFF versus ON bilateral thalamic deep brain stimulation in comparison with healthy controls. Cortical dynamics were analyzed in the range of 6–30 Hz. We found the presence of long-range temporal correlations up to 20 s in patients and controls. Thalamic deep brain stimulation was associated with increased long-range temporal correlations in the high beta band (21–30 Hz) and decreased power in the low beta band (13–20 Hz) compared with OFF stimulation and healthy controls. Long-range temporal correlations in the 6–10 Hz range were increased with OFF stimulation compared with the controls. Importantly, deep brain stimulation-induced changes in long-range temporal correlations within 6–10 Hz and in the beta ranges (13–20, 21–30 Hz) were correlated with OFF–ON changes in the tremor severity and with the disease duration, respectively. The differential reactivity of long-range temporal correlations and spectral power to deep brain stimulation might suggest that both measures reflect distinct aspects of cortical dynamics and might represent biomarkers for stimulation-induced modulations of neural dynamics in electroencephalography. The fact that long-range temporal correlations, but not spectral power, were correlated with clinical information might suggest long-range temporal correlations as a potential marker for disease severity in essential tremor.

The Absoluteness of Semantic Processing: Lessons from the Analysis of Temporal Clusters in Phonemic Verbal Fluency

Background For word production, we may consciously pursue semantic or phonological search strategies, but it is uncertain whether we can retrieve the different aspects of lexical information independently from each other. We therefore studied the spread of semantic information into words produced under exclusively phonemic task demands. Methods 42 subjects participated in a letter verbal fluency task, demanding the production of as many s-words as possible in two minutes. Based on curve fittings for the time courses of word production, output spurts (temporal clusters) considered to reflect rapid lexical retrieval based on automatic activation spread, were identified. Semantic and phonemic word relatedness within versus between these clusters was assessed by respective scores (0 meaning no relation, 4 maximum relation). Results Subjects produced 27.5 (±9.4) words belonging to 6.7 (±2.4) clusters. Both phonemically and semantically words were more related within clusters than between clusters (phon: 0.33±0.22 vs. 0.19±0.17, p<.01; sem: 0.65±0.29 vs. 0.37±0.29, p<.01). Whereas the extent of phonemic relatedness correlated with high task performance, the contrary was the case for the extent of semantic relatedness. Conclusion The results indicate that semantic information spread occurs, even if the consciously pursued word search strategy is purely phonological. This, together with the negative correlation between semantic relatedness and verbal output suits the idea of a semantic default mode of lexical search, acting against rapid task performance in the given scenario of phonemic verbal fluency. The simultaneity of enhanced semantic and phonemic word relatedness within the same temporal cluster boundaries suggests an interaction between content and sound-related information whenever a new semantic field has been opened.

Subcortical roles in lexical task processing: Inferences from thalamic and subthalamic event-related potentials.

Subcortical functions for language capacities are poorly defined, but may be investigated in the context of deep brain stimulation. Here, we studied event‐related potentials recorded from electrodes in the subthalamic nucleus (STN) and the thalamic ventral intermediate nucleus (VIM) together with surface‐EEG. Participants completed a lexical decision task (LDT), which required the differentiation of acoustically presented words from pseudo‐words by button press. Target stimuli were preceded by prime‐words. In recordings from VIM, a slow potential shift apparent at the lower electrode contacts persisted during target stimulus presentation (equally for words and pseudo‐words). In contrast, recordings from STN electrodes showed a short local activation on prime‐words but not target‐stimuli. In both depth‐recording regions, further components related to contralateral motor responses to target words were evident. On scalp level, mid‐central activations on (pseudo)lexical stimuli were obtained, in line with the expression of N400 potentials. The prolonged activity recorded from VIM, exclusively accompanying the relevant LDT phase, is in line with the idea of thalamic “selective engagement” for supporting the realization of the behavioral focus demanded by the task. In contrast, the phasic prime related activity rather indicates “procedural” STN functions, for example, for trial sequencing or readiness inhibition of prepared target reactions. Hum Brain Mapp 38:370–383, 2017.

Disturbance of verticality perception and postural dysfunction in Parkinson's disease

Verticality perception is known to be abnormal in Parkinsons disease (PD), but in which stage respective dysfunctions arise and how they relate to postural disorders remains to be settled. These issues were studied with respect to different dimensions of the subjective visual vertical (SVV) in relation to clinical parameters of postural control.

Theory of mind performance in Parkinson’s disease is associated with motor and cognitive functions, but not with symptom lateralization

Abstract Next to the typical motor signs, Parkinson’s disease (PD) goes along with neuropsychiatric symptoms, amongst others affecting social cognition. Particularly, Theory of Mind (ToM) impairments have mostly been associated with right hemispherical brain dysfunction, so that it might prevail in patients with left dominant PD. Fourty-four PD patients, twenty-four with left and twenty with right dominant motor symptoms, engaged in the Reading the Mind in the Eyes (RME) and the Faux Pas Detection Test (FPD) to assess affective and cognitive ToM. The results were correlated with performance in further cognitive tests, and analyzed with respect to associations with the side of motor symptom dominance and severity of motor symptoms. No association of ToM performance with right hemispheric dysfunction was found. RME results were inversely correlated with motor symptom severity, while FPD performance was found to correlate with the performance in verbal fluency tasks and the overall cognitive evaluation. Affective ToM was found associated with motor symptom severity and cognitive ToM predominantly with executive function, but no effect of PD lateralization on this was identified. The results suggest that deficits in social cognition occur as a sequel of the general corticobasal pathology in PD, rather than as a result of hemisphere-specific dysfunction.

Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients

Objective Reduced verbal fluency (VF) has been reported in patients with Parkinson’s disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Method Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., ‘clusters’ as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., ‘switches’ reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. Results PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Discussion Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.