Awake Craniotomy for Subcortical Brain Metastasis Beneath the Speech Center: A Technical Case Report.

BACKGROUND: To preserve language function, intraoperative functional brain mapping (IFBM) in and near the speech center is essential. CASE REPORT: We present a case of a 73-year-old right-handed woman with colon cancer. She presented with mild speech disturbance. Magnetic resonance imaging revealed a ringed enhancing lesion in the frontal operculum. The preservation of language function was critical; therefore, she underwent awake craniotomy using IFBM. Thus, the speech site was elicited by cortical electrical stimulation at the surface, near the location of the tumor. We made a safe corticotomy on the surface of the lesion and performed the resection of brain metastasis (BM) via a safety corridor. We achieved gross total resection of the BM while preserving the language function. After surgery, she recovered from speech disturbance. She returned to her normal life with improved language function. CONCLUSION: IFBM is a useful tool to undertake a safe approach via the speech center, avoiding permanent language deficits.

Instability of speech in Parkinson disease patients with subthalamic nucleus deep brain stimulation.

INTRODUCTION: The impact of deep brain stimulation (DBS) on speech rhythm and its mechanism remains unclear. We investigated speech rhythm characteristics of patients with Parkinson's disease (PD) treated with subthalamic nucleus (STN) DBS to understand the underlying pathophysiology better. METHODS: We enrolled a total of 105 participants and evaluated speech rhythm performances among patients with PD who had undergone STN-DBS (the PD-DBS group), patients with PD treated only with medication (the PD-Med group), patients with cerebellar ataxia (the CA group), and healthy controls (the HC group). Each participant was asked to repeat the syllable/pa/at a comfortable self-chosen steady pace. A widely-used software (the Motor Speech Profile) program performed an acoustic analysis. RESULTS: Compared to the PD-Med and HC groups, speech rate instability (DDKjit) was significantly higher in the PD-DBS and CA groups (p < 0.01). However, after DBS was turned off, the DDKjit of the PD-DBS group improved to a level comparable to that of the PD-Med and HC groups. In contrast to the significantly higher variability of speech volume (DDKcvi) in the CA group, the PD-DBS group showed similar DDKcvi to the PD-Med and HC groups. CONCLUSIONS: STN-DBS affects the speech rate stability of patients with PD. Speech rhythm disorders caused by STN-DBS were phenotypically similar to that in CA in terms of interval variability but different regarding amplitude variability. Further studies are warranted to elucidate the underlying pathophysiology of speech rhythm disorders in PD patients treated with DBS.

Sleep disturbances in the speech-language variant of progressive supranuclear palsy.

INTRODUCTION: Progressive supranuclear palsy (PSP) variants other than PSP-Richardson Syndrome (PSP-RS) have been recognized, including PSP with speech and language problems (PSP-SL). Given the reported sleep disruptions in PSP-RS, we investigated sleep abnormalities in PSP-SL. METHODS: Four sleep-related screening questions were given to the caregivers of 90 patients with PSP-SL (59 suggestive of PSP-SL and 31 possible PSP-SL) and 71 probable PSP-RS (prob. PSP-RS) patients. RESULTS: At least one sleep-related disturbance was observed in 35.6% of suggestive of PSP-SL, 38.7% of possible PSP-SL, and 67.6% of prob. PSP-RS, the most common being "unable to fall or stay asleep". Prob. PSP-RS showed higher frequency of "screaming or talking in sleep", "acting out dreams", and "unable to fall or stay asleep" compared to both PSP-SL groups, but did not differ from possible PSP-SL in "excessive daytime sleepiness". CONCLUSION: Sleep abnormalities are common in PSP-SL, but less frequent than prob.PSP-RS.

Quantification of brainstem norepinephrine relative to vocal impairment and anxiety in the Pink1-/- rat model of Parkinson disease.

Vocal communication impairment and anxiety are co-occurring and interacting signs of Parkinson Disease (PD) that are common, poorly understood, and under-treated. Both vocal communication and anxiety are influenced by the noradrenergic system. In light of this shared neural substrate and considering that noradrenergic dysfunction is a defining characteristic of PD, tandem investigation of vocal impairment and anxiety in PD relative to noradrenergic mechanisms is likely to yield insights into the underlying disease-specific causes of these impairments. In order to address this gap in knowledge, we assessed vocal impairment and anxiety behavior relative to brainstem noradrenergic markers in a genetic rat model of early-onset PD (Pink1-/-) and wild type controls (WT). We hypothesized that 1) brainstem noradrenergic markers would be disrupted in Pink1-/-, and 2) brainstem noradrenergic markers would be associated with vocal acoustic changes and anxiety level. Rats underwent testing of ultrasonic vocalization and anxiety (elevated plus maze) at 4, 8, and 12 months of age. At 12 months, brainstem norepinephrine markers were quantified with immunohistochemistry. Results demonstrated that vocal impairment and anxiety were increased in Pink1-/- rats, and increased anxiety was associated with greater vocal deficit in this model of PD. Further, brainstem noradrenergic markers including TH and α1 adrenoreceptor immunoreactivity in the locus coeruleus, and ß1 adrenoreceptor immunoreactivity in vagal nuclei differed by genotype, and were associated with vocalization and anxiety behavior. These findings demonstrate statistically significant relationships among vocal impairment, anxiety, and brainstem norepinephrine in the Pink1-/- rat model of PD.

Speech and swallowing deficits in X-Linked Dystonia-Parkinsonism.

INTRODUCTION: X-linked Dystonia-Parkinsonism (XDP) is a progressive, disabling disease characterized by the devastating impairment of bulbar function, including speech and swallowing. Despite these detrimental impacts, bulbar impairments in this population are not well characterized. OBJECTIVES: To identify impairments in the bulbar system measured by oromotor performance in individuals with XDP relative to healthy controls. Secondarily, to detect diagnostic bulbar markers that are sensitive and specific to the initial years of XDP. METHODS: This case-control study included 25 healthy controls and 30 participants with XDP, divided into two subgroups based on the median of their disease length. Multiple clinical and instrumental oromotor tasks and measures were used to evaluate bulbar motor function. RESULTS: Differences were found between both the subgroups with XDP and healthy controls on almost all measures, including maximum performance tasks such as tongue strength, alternating motion rate (AMR), and sequential motion rate (SMR) (p < 0.05). Differences were found between the XDP subgroups and the control group for the percentage of pause time during the speech, a rating of speech severity, and a swallowing task (ps < 0.05). Scores on self-reported questionnaires, tongue strength, the number of repetitions produced during an AMR, percent pause, and speech severity demonstrated good sensitivity and specificity to differentiate the initial years of XDP onset from healthy controls. CONCLUSIONS: Our findings revealed impairments across bulbar functions in participants within the first 7 years of the XDP onset. Highly sensitive and specific bulbar impairment measures were detected in instrumental and self-reported measures that are fundamental for monitoring disease.

Functional maps of direct electrical stimulation-induced speech arrest and anomia: a multicentre retrospective study.

Direct electrical stimulation, the transient 'lesional' method probing brain function, has been utilized in identifying the language cortex and preserving language function during epilepsy and neuro-oncological surgeries for about a century. However, comparison of functional maps of the language cortex across languages/continents based on cortical stimulation remains unclear. We conducted a retrospective multicentre study including four cohorts of direct electrical stimulation mapping from four centres across three continents, where three indigenous languages (English, French and Mandarin) are spoken. All subjects performed the two most common language tasks: number counting and picture naming during stimulation. All language sites were recorded and normalized to the same brain template. Next, Spearman's correlation analysis was performed to explore the consistency of the distributions of the language cortex across centres, a kernel density estimation to localize the peak coordinates, and a hierarchical cluster analysis was performed to detect the crucial epicenters. A total of 598 subjects with 917 speech arrest sites (complete interruption of ongoing counting) and 423 anomia sites (inability to name or misnaming) were included. Different centres presented highly consistent distribution patterns for speech arrest (Spearman's coefficient r ranged from 0.60 to 0.85, all pair-wise correlations P < 0.05), and similar patterns for anomia (Spearman's coefficient r ranged from 0.37 to 0.80). The combinational speech arrest map was divided into four clusters: cluster 1 mainly located in the ventral precentral gyrus and pars opercularis, which contained the peak of speech arrest in the ventral precentral gyrus; cluster 2 in the ventral and dorsal precentral gyrus; cluster 3 in the supplementary motor area; cluster 4 in the posterior superior temporal gyrus and supramarginal gyrus. The anomia map revealed two clusters: one was in the posterior part of the superior and middle temporal gyri, which peaked at the posterior superior temporal gyrus; and the other within the inferior frontal gyrus, peaked at the pars triangularis. This study constitutes the largest series to date of language maps generated from direct electrical stimulation mapping. The consistency of data provides evidence for common language networks across languages, in the context of both speech and naming circuit. Our results not only clinically offer an atlas for language mapping and protection, but also scientifically provide better insight into the functional organization of language networks.

Children Born Prematurely May Demonstrate Catch-Up Growth in Pre-Adolescence.

Introduction Children born prematurely often score lower on standardized tests of language in early childhood. Less is known about longer term outcomes. This investigation considered language outcomes in pre-adolescent children born very preterm/very low birthweight, as assessed by both standardized test scores and language sample measures, and explored attention abilities as a possible moderating factor. Method The present investigation provided a longitudinal follow-up to Mahurin Smith et al. (2014) by examining the language outcomes of 84 children at the 11-year time point (39 with a history of prematurity and 45 born at full term) and a total of 82 at the 12-year time point (37 with a history of prematurity, 45 born at full term). Assessments included subtests of the Clinical Evaluation of Language Fundamentals- Fourth Edition, productive language measures taken from narrative tasks, and parent and examiner ratings of attention. Results Gestational age significantly predicted standardized language scores at age 11 years, but this effect was no longer statistically significant at age 12 years. When parent ratings of attention were considered as additional variables, gestational age was no longer a significant predictor. Gestational age did not serve as a significant predictor for the productive language measures at either time point. Discussion Results indicate that catch-up growth in language may take place in pre-adolescence for many children born prematurely. Clinical implications focus on the need to utilize multiple forms of language assessment and to directly consider the potential role of attention on standard test results.

Robin Sequence: 5-Year Speech Outcomes-A Case-Control Study.

BACKGROUND: Pierre Robin sequence (Robin sequence) is defined as the triad of micrognathia, glossoptosis, and airway obstruction. It is frequently associated with palatal clefting. In recent years, increased interest in speech outcomes of cleft patients diagnosed with Robin sequence has been shown. METHODS: Speech outcomes of cleft patients with Robin sequence were assessed at age 5 in comparison with a cleft palate-only cohort. Speech parameters were evaluated according to the Cleft Audit Protocol for Speech-Augmented and analyzed using the National Audit Standards for Speech (United Kingdom). All patients were treated in the same institution during the same period (2005 to 2012). Subjects who needed nasopharyngeal airway support and those whose airway was managed by positioning only were eligible. RESULTS: Fifty-one cleft patients diagnosed with Robin sequence were included in this study. Outcomes were compared to those of 128 nonsyndromic cleft palate-only patients.Patients with Robin sequence were shown to present with a significantly higher rate of cleft speech characteristics in comparison to the reference cohort (p = 0.001). Furthermore, it was shown that Robin sequence is associated with a significantly higher rate of secondary speech surgery for velopharyngeal dysfunction before the age of 5 (p = 0.016). Robin sequence patients with a nasopharyngeal airway presented with a higher rate of cleft speech characteristics compared to Robin sequence patients managed with positioning only. CONCLUSION: Cleft patients with Robin sequence are more likely to need further surgery to correct velopharyngeal dysfunction before the age of 5 and are more prone to present with cleft speech characteristics at the age of 5. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Speech rate association with cerebellar white-matter diffusivity in adults with persistent developmental stuttering.

Speech rate is a basic characteristic of language production, which affects the speaker's intelligibility and communication efficiency. Various speech disorders, including persistent developmental stuttering, present altered speech rate. Specifically, adults who stutter (AWS) typically exhibit a slower speech rate compared to fluent speakers. Evidence from imaging studies suggests that the cerebellum contributes to the paced production of speech. People who stutter show structural and functional abnormalities in the cerebellum. However, the involvement of the cerebellar pathways in controlling speech rate remains unexplored. Here, we assess the association of the cerebellar peduncles with speech rate in AWS and control speakers. Diffusion MRI and speech-rate data were collected in 42 participants (23 AWS, 19 controls). We used deterministic tractography with Automatic Fiber segmentation and Quantification (AFQ) to identify the superior, middle, and inferior cerebellar peduncles (SCP, MCP, ICP) bilaterally, and quantified fractional anisotropy (FA) and mean diffusivity (MD) along each tract. No significant differences were observed between AWS and controls in the diffusivity values of the cerebellar peduncles. However, AWS demonstrated a significant negative association between speech rate and FA within the left ICP, a major cerebellar pathway that transmits sensory feedback signals from the olivary nucleus into the cerebellum. The involvement of the ICP in controlling speech production in AWS is compatible with the view that stuttering stems from hyperactive speech monitoring, where even minor deviations from the speech plan are considered as errors. In conclusion, our findings suggest a plausible neural mechanism for speech rate reduction observed in AWS.

Aberrant auditory system and its developmental implications for autism.

Most infants who are later diagnosed with autism show delayed speech and language and/or atypical language profile. There is a large body of research on abnormal speech and language in children with autism. However, auditory development has been relatively under-investigated in autism research, despite its inextricable relationship with language development and despite researchers' ability to detect abnormalities in brain development and behavior in early infancy. In this review, we synthesize research on auditory processing in the prenatal period through infancy and childhood in typically developing children, children at high risk for autism, and children diagnosed with autism. We conclude that there are clear neurobiological and behavioral links between abnormal auditory development and the deficits in social communication seen in autism. We then offer perspectives on the need for a systematic characterization of early auditory development in autism, and identified questions to be addressed in future research on the development of autism.

Examining speech motor planning difficulties in apraxia of speech and aphasia via the sequential production of phonetically similar words.

This study investigated the underlying nature of apraxia of speech (AOS) by testing two competing hypotheses. The Reduced Buffer Capacity Hypothesis argues that people with AOS can plan speech only one syllable at a time Rogers and Storkel [1999. Planning speech one syllable at a time: The reduced buffer capacity hypothesis in apraxia of speech. Aphasiology, 13(9-11), 793-805. https://doi.org/10.1080/026870399401885]. The Program Retrieval Deficit Hypothesis states that selecting a motor programme is difficult in face of competition from other simultaneously activated programmes Mailend and Maas [2013. Speech motor programming in apraxia of speech: Evidence from a delayed picture-word interference task. American Journal of Speech-Language Pathology, 22(2), S380-S396. https://doi.org/10.1044/1058-0360(2013/12-0101)]. Speakers with AOS and aphasia, aphasia without AOS, and unimpaired controls were asked to prepare and hold a two-word utterance until a go-signal prompted a spoken response. Phonetic similarity between target words was manipulated. Speakers with AOS had longer reaction times in conditions with two similar words compared to two identical words. The Control and the Aphasia group did not show this effect. These results suggest that speakers with AOS need additional processing time to retrieve target words when multiple motor programmes are simultaneously activated.

Rapid computations of spectrotemporal prediction error support perception of degraded speech.

Human speech perception can be described as Bayesian perceptual inference but how are these Bayesian computations instantiated neurally? We used magnetoencephalographic recordings of brain responses to degraded spoken words and experimentally manipulated signal quality and prior knowledge. We first demonstrate that spectrotemporal modulations in speech are more strongly represented in neural responses than alternative speech representations (e.g. spectrogram or articulatory features). Critically, we found an interaction between speech signal quality and expectations from prior written text on the quality of neural representations; increased signal quality enhanced neural representations of speech that mismatched with prior expectations, but led to greater suppression of speech that matched prior expectations. This interaction is a unique neural signature of prediction error computations and is apparent in neural responses within 100 ms of speech input. Our findings contribute to the detailed specification of a computational model of speech perception based on predictive coding frameworks.

Auditory processing in children: Role of working memory and lexical ability in auditory closure.

We examined the relationship between cognitive-linguistic mechanisms and auditory closure ability in children. Sixty-seven school-age children recognized isolated words and keywords in sentences that were interrupted at a rate of 2.5 Hz and 5 Hz. In essence, children were given only 50% of speech information and asked to repeat the complete word or sentence. Children's working memory capacity (WMC), attention, lexical knowledge, and retrieval from long-term memory (LTM) abilities were also measured to model their role in auditory closure ability. Overall, recognition of monosyllabic words and lexically easy multisyllabic words was significantly better at 2.5 Hz interruption rate than 5 Hz. Recognition of lexically hard multisyllabic words and keywords in sentences was better at 5 Hz relative to 2.5 Hz. Based on the best fit generalized "logistic" linear mixed effects models, there was a significant interaction between WMC and lexical difficulty of words. WMC was positively related only to recognition of lexically easy words. Lexical knowledge was found to be crucial for recognition of words and sentences, regardless of interruption rate. In addition, LTM retrieval ability was significantly associated with sentence recognition. These results suggest that lexical knowledge and the ability to retrieve information from LTM is crucial for children's speech recognition in adverse listening situations. Study findings make a compelling case for the assessment and intervention of lexical knowledge and retrieval abilities in children with listening difficulties.

Disfluencias típicas del habla en niños fluentes de Santiago de Chile / Typical speech dysfluencies in fluent children from Santiago de Chile

El estudio de la fluidez del habla, en distintas etapas del ciclo vital, es relevante porque contribuye tanto a la comprensión del desarrollo típico del habla como a la comprensión del habla patológica, lo que aporta al diagnóstico y al tratamiento. Los objetivos del trabajo son: a) determinar la presencia y distribución de las disfluencias en distintos grupos etarios y b) determinar si existe variación en la distribución de las disfluencias en relación con el género de los informantes. La muestra estuvo compuesta por 60 niños y adolescentes entre los 4.01 años y 15.0 años distribuidos en tres grupos. Los resultados indican que la prolongación de vocal fue la disfluencia más frecuente, mientras que la repetición de sílaba fue la menos presente en los grupos analizados. En el grupo de mujeres de menor edad hubo una cantidad significativamente alta de repetición de palabras. No se encontraron otras diferencias en relación con el género de los informantes. Finalmente, se discuten los resultados y algunas consideraciones relacionadas con la metodología en este tipo de investigaciones.

The study of fluency of speech, at different stages of the life cycle, is relevant in that it contributes both to the understanding of typical speech development and to the understanding of pathological speech, which is useful for diagnosis and treatment. The objectives of this work are a) to determine the presence and distribution of the disfluencies present in different age groups and b) to determine if there is variation in the distribution of disfluencies in relation to the gender of the informants. Thesample consisted of 60 children and adolescents between 4.01 years old and 15.0 years old distributed in three groups. The results indicate that vowel prolongation was the most frequent disfluency, while syllable repetition was the least present inthe groups analyzed. In the group of younger women, there was a significantly high amount of word repetition when comparing the presence of this disfluency in the other two groups. There were no more differences reported in relation to the gender ofthe informants. Finally, the results and some considerations related to the methodology in this type of research are discussed

Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes.

The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.

The evolution of parkinsonism in primary progressive apraxia of speech: A 6-year longitudinal study.

INTRODUCTION: Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome in which patients present with an isolated motor speech disorder. Some PPAOS patients develop parkinsonism and other features of progressive supranuclear palsy (PSP) and/or corticobasal syndrome (CBS) over time. We aimed to assess the evolution of parkinsonian characteristics in PPAOS patients who had been followed yearly for at least six years. METHODS: From a large cohort of 46 PPAOS patients, eight were followed yearly for > 6-years in multiple NIH-funded grants. Parkinsonian and other features, including bradykinesia, tremor, rigidity, postural instability, apraxia, ocular motor function and cognition were assessed at each visit, and research criteria applied for PSP and CBS diagnosis. Neurological, speech-language test scores, and [18F]fluorodeoxyglucose PET (FDG-PET) and MRI midbrain volumes were assessed. RESULTS: A Parkinson's plus syndrome developed in all eight patients (100%). Bradykinesia was the earliest feature, followed by rigidity and postural instability. Tremor was not a significant feature. Parkinsonism, limb apraxia and ocular motor impairment tended to develop four-to-five years after onset with some patients having slight asymmetric parkinsonism. Six patients (75%) met research criteria for probable PSP, although only one for PSP-Richardson's syndrome; three patients met criteria for possible CBS. Slightly asymmetric, left-sided, hypometabolism was observed on FDG-PET, not matching asymmetry of Parkinsonism. Midbrain hypometabolism was absent-minimal. Three patients had progressive midbrain volumes in the PSP-Richardson's syndrome range. CONCLUSIONS: A Parkinson's plus syndrome may inevitably develop in PPAOS supporting PPAOS as an early presentation of a Parkinson's plus disorder.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Similar activation patterns in the prefrontal cortex for Chinese and Japanese verbal fluency tests with syllable cues as revealed by near-infrared spectroscopy.

The verbal fluency test (VFT) is utilized in neuropsychology to evaluate the cognitive function of the prefrontal cortex (PFC) in the human brain. We present a novel Chinese VFT similar to the established Japanese VFT; both tests prompt a syllable to the subject. However, it was uncertain whether the Chinese VFT can activate the PFC and whether PFC activation patterns are similar between the two tests. Here we administered the Chinese VFT to 30 native Chinese speakers and the Japanese VFT to 30 native Japanese speakers. We used near-infrared spectroscopy (NIRS) to observe PFC activation. Then we compared the similarities between the Chinese VFT and the Japanese VFT. The subjects generated an average of 12.8 ± 4.7 words during the Chinese VFT. NIRS indicates that the concentration of oxygenated hemoglobin during the test was significantly higher than those before and after the test. It exhibited similar PFC activation patterns with the Japanese VFT. The novel Chinese VFT can activate the PFC in the human brain effectively in Chinese speakers. Our work thus provides the first validated phonetically cued Chinese VFT, unique from other not strictly phonemic Chinese VFTs, and facilitates the diagnosis of various PFC-related cognitive impairments.

A Methodology to Differentiate Parkinson's Disease and Aging Speech Based on Glottal Flow Acoustic Analysis.

Speech is controlled by axial neuromotor systems, therefore, it is highly sensitive to the effects of neurodegenerative illnesses such as Parkinson's Disease (PD). Patients suffering from PD present important alterations in speech, which are manifested in phonation, articulation, prosody, and fluency. These alterations may be evaluated using statistical methods on features obtained from glottal, spectral, cepstral, or fractal descriptions of speech. This work introduces an evaluation paradigm based on Information Theory (IT) to differentiate the effects of PD and aging on glottal amplitude distributions. The study is conducted on a database including 48 PD patients (24 males, 24 females), 48 age-matched healthy controls (HC, 24 males, 24 females), and 48 mid-age normative subjects (NS, 24 males, 24 females). It may be concluded from the study that Hierarchical Clustering (HiCl) methods produce a clear separation between the phonation of PD patients from NS subjects (accuracy of 89.6% for both male and female subsets), but the separation between PD patients and HC subjects is less efficient (accuracy of 75.0% for the male subset and 70.8% for the female subset). Conversely, using feature selection and Support Vector Machine (SVM) classification, the differentiation between PD and HC is substantially improved (accuracy of 94.8% for the male subset and 92.8% for the female subset). This improvement was mainly boosted by feature selection, at a cost of information and generalization losses. The results point to the possibility that speech deterioration may affect HC phonation with aging, reducing its difference to PD phonation.

Semantic Similarity Analysis Reveals Robust Gene-Disease Relationships in Developmental and Epileptic Encephalopathies.

More than 100 genetic etiologies have been identified in developmental and epileptic encephalopathies (DEEs), but correlating genetic findings with clinical features at scale has remained a hurdle because of a lack of frameworks for analyzing heterogenous clinical data. Here, we analyzed 31,742 Human Phenotype Ontology (HPO) terms in 846 individuals with existing whole-exome trio data and assessed associated clinical features and phenotypic relatedness by using HPO-based semantic similarity analysis for individuals with de novo variants in the same gene. Gene-specific phenotypic signatures included associations of SCN1A with "complex febrile seizures" (HP: 0011172; p = 2.1 × 10-5) and "focal clonic seizures" (HP: 0002266; p = 8.9 × 10-6), STXBP1 with "absent speech" (HP: 0001344; p = 1.3 × 10-11), and SLC6A1 with "EEG with generalized slow activity" (HP: 0010845; p = 0.018). Of 41 genes with de novo variants in two or more individuals, 11 genes showed significant phenotypic similarity, including SCN1A (n = 16, p < 0.0001), STXBP1 (n = 14, p = 0.0021), and KCNB1 (n = 6, p = 0.011). Including genetic and phenotypic data of control subjects increased phenotypic similarity for all genetic etiologies, whereas the probability of observing de novo variants decreased, emphasizing the conceptual differences between semantic similarity analysis and approaches based on the expected number of de novo events. We demonstrate that HPO-based phenotype analysis captures unique profiles for distinct genetic etiologies, reflecting the breadth of the phenotypic spectrum in genetic epilepsies. Semantic similarity can be used to generate statistical evidence for disease causation analogous to the traditional approach of primarily defining disease entities through similar clinical features.