Reiko Ohdake

Distinct phenotypes of speech and voice disorders in Parkinson's disease after subthalamic nucleus deep brain stimulation

Objectives To elucidate the phenotypes and pathophysiology of speech and voice disorders in Parkinsons disease (PD) with subthalamic nucleus deep brain stimulation (STN-DBS). Methods We conducted a cross-sectional study on 76 PD patients treated with bilateral STN-DBS (PD-DBS) and 33 medically treated PD patients (PD-Med). Speech and voice functions, electrode positions, motor function and cognitive function were comprehensively assessed. Moreover, speech and voice functions were compared between the on-stimulation and off-stimulation conditions in 42 PD-DBS patients. Results Speech and voice disorders in PD-DBS patients were significantly worse than those in PD-Med patients. Factor analysis and subsequent cluster analysis classified PD-DBS patients into five clusters: relatively good speech and voice function type, 25%; stuttering type, 24%; breathy voice type, 16%; strained voice type, 18%; and spastic dysarthria type, 17%. STN-DBS ameliorated voice tremor or low volume; however, it deteriorated the overall speech intelligibility in most patients. Breathy voice did not show significant changes and stuttering exhibited slight improvement after stopping stimulation. In contrast, patients with strained voice type or spastic dysarthria type showed a greater improvement after stopping stimulation. Spastic dysarthria type patients showed speech disorders similar to spastic dysarthria, which is associated with bilateral upper motor neuron involvement. Strained voice type and spastic dysarthria type appeared to be related to current diffusion to the corticobulbar fibres. Conclusions Stuttering and breathy voice can be aggravated by STN-DBS, but are mainly due to aging or PD itself. Strained voice and spastic dysarthria are considered corticobulbar side effects.

Voice features of Parkinson’s disease patients with subthalamic nucleus deep brain stimulation

Voice and speech disorders are one of the most important issues after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease patients; however, their characteristics remain unclear. We performed a comprehensive voice evaluation including the multi-dimensional voice program for acoustic analysis, the GRBAS scale for perceptual analysis, and the evaluation of the voice handicap index (VHI) for psychosocial analysis. In total, 68 patients who had undergone STN-DBS (37 assessed in the on- and off-stimulation conditions) and 40 who had been treated with medical therapy alone were evaluated. Further, we performed laryngoscopic examinations in 13 STN-DBS and 19 medical-therapy-alone patients. The STN-DBS group, especially females, showed widespread impairment of voice parameters and significantly poorer VHI scores than the medical-therapy-alone group. The degree of voiceless (DUV) and strained voice were the most impaired factors in the STN-DBS group; and DUV significantly improved after stopping stimulation. Furthermore strained voice, breathiness, and asthenia improved after stopping stimulation. Laryngoscopic examination showed that abnormal laryngeal muscle contraction and incomplete glottal closure were more prominent in the STN-DBS group than in the medical-therapy-alone group. We demonstrated that (1) more widespread voice impairment in females, (2) poorer voice-related QOL, (3) worse DUV and strained voice, and (4) abnormal laryngeal muscle contraction were the characteristic voice and laryngeal findings in the STN-DBS group compared with those in the medical-therapy-alone group.

Characteristic laryngoscopic findings in Parkinson's disease patients after subthalamic nucleus deep brain stimulation and its correlation with voice disorder.

Speech and voice disorders are one of the most common adverse effects in Parkinson’s disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). However, the pathophysiology of voice and laryngeal dysfunction after STN-DBS remains unclear. We assessed 47 PD patients (22 treated with bilateral STN-DBS (PD-DBS) and 25 treated medically (PD-Med); all patients in both groups matched by age, sex, disease duration, and motor and cognitive function) using the objective and subjective voice assessment batteries (GRBAS scale and Voice Handicap Index), and laryngoscopy. Laryngoscopic examinations revealed that PD-DBS patients showed a significantly higher incidence of incomplete glottal closure (77 vs 48xa0%; pxa0=xa00.039), hyperadduction of the false vocal folds (73 vs 44xa0%; pxa0=xa00.047), anteroposterior hypercompression (50 vs 20xa0%; pxa0=xa00.030) and asymmetrical glottal movement (50 vs 16xa0%; pxa0=xa00.002) than PD-Med patients. On- and off-stimulation assessment revealed that STN-DBS could induce or aggravate incomplete glottal closure, hyperadduction of the false vocal folds, anteroposterior hypercompression, and asymmetrical glottal movement. Incomplete glottal closure and hyperadduction of the false vocal folds significantly correlated with breathiness and strained voice, respectively (rxa0=xa00.590 and 0.539). We should adjust patients’ DBS settings in consideration of voice and laryngeal functions as well as motor function.

Articulation Features of Parkinson’s Disease Patients with Subthalamic Nucleus Deep Brain Stimulation

BACKGROUNDnVoice and speech disorders are one of the most important issues after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinsons disease (PD) patients. However, articulation features in this patient population remain unclear.nnnOBJECTIVEnWe studied the articulation features of PD patients with STN-DBS.nnnMETHODSnParticipants were 56 PD patients treated with STN-DBS (STN-DBS group) and 41 patients treated only with medical therapy (medical-therapy-alone group). Articulation function was evaluated with acoustic and auditory-perceptual analyses. The vowel space area (VSA) was calculated using the formant frequency data of three vowels (/a/, /i/, and /u/) from sustained phonation task. The VSA reportedly reflects the distance of mouth/jaw and tongue movements during speech and phonation. Correlations between acoustic and auditory-perceptual measurements were also assessed.nnnRESULTSnThe VSA did not significantly differ between the medical-therapy-alone group and the STN-DBS group in the off-stimulation condition. In the STN-DBS group, the VSA was larger in the on-stimulation condition than in the off-stimulation condition. However, individual analysis showed the VSA changes after stopping stimulation were heterogeneous. In total, 89.8% of the STN-DBS group showed axa0large VSA size in the on- than in the off-stimulation condition. In contrast, the VSA of the remaining patients in that group was smaller in the on- than the off-stimulation condition.nnnCONCLUSIONSnSTN-DBS may resolve hypokinesia of the articulation structures, including the mouth/jaw and tongue, and improve maximal vowel articulation. However, in the on-stimulation condition, the VSA was not significantly correlated with speech intelligibility. This may be because STN-DBS potentially affects other speech processes such as voice and/or respiratory process.

Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson’s disease

Objective Severe hyposmia is a risk factor of dementia in Parkinson’s disease (PD), while the underlying functional connectivity (FC) and brain volume alterations in PD patients with severe hyposmia (PD-SH) are unclear. Methods We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH), and 15 healthy controls (HCs). Results Decreased gray matter volume (GMV) was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke’s Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH. Conclusion PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

Early detection of speech and voice disorders in Parkinson’s disease patients treated with subthalamic nucleus deep brain stimulation: a 1-year follow-up study

We previously reported that Parkinson’s disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) had distinct phenotypes of speech and voice disorders: hypokinetic dysarthria, stuttering, breathy voice, strained voice, and spastic dysarthria. However, changes over time remain unclear. In the present study, 32 consecutive PD patients were assessed before and up to 1xa0year after surgery (PD-DBS). Eleven medically treated PD patients were also assessed (PD-Med). Speech, voice, motor, and cognitive functions were evaluated. At baseline, the incidence of hypokinetic dysarthria (63% of PD-DBS vs. 82% of PD-Med), stuttering (50% vs. 45%), breathy voice (66% vs. 73%), and strained voice (3% vs. 9%) was similar between groups. At 1xa0year, a slight but significant deterioration in speech intelligibility (pxa0<xa00.001) and grade of dysphonia (pxa0=xa00.001) were observed only in PD-DBS group compared with baseline. During the follow-up, stuttering (9% vs. 18%) and breathy voice (13% vs. 9%) emerged in PD-DBS and PD-Med, but strained voice (28%) and spastic dysarthria (44%) emerged only in PD-DBS. After the stimulation was stopped, strained voice and spastic dysarthria improved in most patients, while stuttering and breathy voice improved in a minority of patients. These findings indicate that the most common DBS-induced speech and voice disorders are strained voice and spastic dysarthria and that STN-DBS potentially aggravates stuttering and breathy voice. An improved understanding of these types of disorders may help detect speech and voice deteriorations during the early phase and lead to appropriate treatments.

An unbiased data-driven age-related structural brain parcellation for the identification of intrinsic brain volume changes over the adult lifespan

ABSTRACT This study aims to elucidate age‐related intrinsic brain volume changes over the adult lifespan using an unbiased data‐driven structural brain parcellation. Anatomical brain images from a cohort of 293 healthy volunteers ranging in age from 21 to 86 years were analyzed using independent component analysis (ICA). ICA‐based parcellation identified 192 component images, of which 174 (90.6%) showed a significant negative correlation with age and with some components being more vulnerable to aging effects than others. Seven components demonstrated a convex slope with aging; 3 components had an inverted U‐shaped trajectory, and 4 had a U‐shaped trajectory. Linear combination of 86 components provided reliable prediction of chronological age with a mean absolute prediction error of approximately 7.2 years. Structural co‐variation analysis showed strong interhemispheric, short‐distance positive correlations and long‐distance, inter‐lobar negative correlations. Estimated network measures either exhibited a U‐ or an inverted U‐shaped relationship with age, with the vertex occurring at approximately 45–50 years. Overall, these findings could contribute to our knowledge about healthy brain aging and could help provide a framework to distinguish the normal aging processes from that associated with age‐related neurodegenerative diseases. HighlightsAn unbiased, data‐driven brain parcellation was generated using anatomical images and ICA.Most parcels showed strong negative correlation with age with significant regional variations.Linear combination of parcels reliably predicted chronological age with mean error of 7.2 years.Structural co‐variation analysis showed positive and negative inter‐regional GM correlations.Structural network measures exhibited U‐ or inverted U‐shaped relation with age.

Corpus callosal involvement is correlated with cognitive impairment in multiple system atrophy

ObjectiveWe examined the anatomical involvement related to cognitive impairment in patients with multiple system atrophy (MSA).MethodsWe examined 30 patients with probable MSA and 15 healthy controls. All MSA patients were assessed by the Unified MSA-Rating scale and Addenbrooke’s Cognitive Examination-Revised (ACE-R). We classified 15 MSA patients with ACE-R scoresu2009>u200988 as having normal cognition (MSA–NC) and 15 with scoresu2009≤u200988 as having cognitive impairment (MSA–CI). All subjects underwent 3xa0T MRI scanning and were investigated using voxel-based morphometry and diffusion tensor imaging.ResultsBoth the MSA–NC and MSA–CI patients exhibited cerebellar but not cerebral atrophy in voxel-based morphometry compared to controls. In contrast, tract-based spatial statistics revealed widespread and significantly decreased fractional anisotropy (FA) values, as well as increased mean diffusivity, radial diffusivity, and axial diffusivity in both the cerebrum and cerebellum in MSA–CI patients compared to controls. MSA–NC patients also exhibited similar involvement of the cerebellum but less extensive involvement of the cerebrum compared with the MSA–CI patients. In particular, FA values in MSA–CI patients were significantly decreased in the anterior part of the left corpus callosum compared with those in MSA–NC patients. The mean FA values in the left anterior part of the corpus callosum were significantly correlated with total ACE-R scores and subscores (memory, fluency, and language) in MSA patients.ConclusionsDecreased FA values in the anterior corpus callosum showed a significant correlation with cognitive impairment in MSA.

Distinct manifestation of cognitive deficits associate with different resting-state network disruptions in non-demented patients with Parkinson’s disease

Cognitive deficits in Parkinson’s disease (PD) are heterogeneous entities, but a relationship between the heterogeneity of cognitive deficits and resting-state network (RSN) changes remains elusive. In this study, we examined five sub-domain scores according to Addenbrooke’s Cognitive Examination-Revised (ACE-R) for the cognitive evaluation and classification of 72 non-demented patients with PD. Twenty-eight patients were classified as PD with normal cognition (PD-NC). The remaining 44 were subdivided into the following 2 groups using a hierarchical cluster analysis: 20 with a predominant decrease in memory (PD with amnestic cognitive deficits: PD-A) and 24 with good memory who exhibited a decrease in other sub-domains (PD with non-amnestic cognitive deficits: PD-NA). We used an independent component analysis of RS-fMRI data to investigate the inter-group differences of RSN. Compared to the controls, the PD-A showed lower FC within the ventral default mode network (vDMN) and the visuospatial network. On the other hand, the PD-NA showed lower FC within the visual networks and the cerebellum–brainstem network. Significant differences in the FC within the vDMN and cerebellum–brainstem network were observed between the PD-A and PD-NA, which provided a good discrimination between PD-A and PD-NA using a support vector machine. Distinct patterns of cognitive deficits correspond to different RSN changes.

Involvement of the Precuneus/Posterior Cingulate Cortex Is Significant for the Development of Alzheimer’s Disease: A PET (THK5351, PiB) and Resting fMRI Study

Background: Imaging studies in Alzheimer’s disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.