Patrick Santens

Objective: We aim to provide clinical evidence for the occurrence of disease anticipation in families with FTD and/or ALS caused by a C9orf72 repeat expansion. Background: We have recently provided evidence for an association of the G4C2 repeat expansion size with onset age and methylation state of the 59 flanking CpG island. We also identified in several informative C9orf72 parent-child transmissions earlier onset ages, increasing expansion sizes and/or increasing methylation states of the 59 CpG island in accordance with anticipation. (Gijselinck I. et al., Mol Psychiatry 2015) Methods: We investigated differences in onset age and disease duration between successive generations of 29 C9orf72 families and within 30 individual parent-offspring pairs, and investigated differences in phenotype between successive generations of 43 families and within 86 parent-child pairs. Results: Patients from the youngest generation had a significantly younger onset age than patients from the second generation. We also observed a significantly younger onset age in the offspring of parent-offspring pairs with a mean difference of 7.2 +/- 7.8 years. Disease duration was not significantly different between generations or between parents and their offspring, but (FTD-)ALS patients had a significantly shorter disease duration than patients with pure dementia. A significantly higher proportion of patients from the second generation was diagnosed with ALS in comparison with patients from the third generation. Furthermore, we observed a significant association between the phenotype in a parent and the phenotype in the child. No clear differences were observed between maternal and paternal transmission. Conclusions: We provided clinical arguments for disease anticipation in C9orf72 families with an earlier onset age, but no shorter disease duration, in younger generations. The gender of the transmitting parent apparently had no effect. The clinical phenotype of the parent however, was significantly associated with the phenotype of the affected child. Disclosure: Dr. Van Mossevelde has nothing to disclose. Dr. Van Der Zee has nothing to disclose. Dr. Gijselinck has nothing to disclose. Dr. Sleegers has nothing to disclose. Dr. Van Langenhove has nothing to disclose. Dr. Sieben has nothing to disclose. Dr. De Bleecker has nothing to disclose. Dr. Ivanoiu has received research support from GEHC as an investigator. Dr. Deryck has nothing to disclose. Dr. Santens has nothing to disclose. Dr. Baumer has nothing to disclose. Dr. Van Den Broeck has nothing to disclose. Dr. Mattheijssens has nothing to disclose. Dr. Peeters has nothing to disclose. Dr. De Jonghe has nothing to disclose. Dr. De Deyn has nothing to disclose. Dr. Cras has nothing to disclose. Dr. Vandenberghe has received research support from GE Healthcare, Wyeth, Eli Lilly & Company, Medivation, and Pfizer, Inc. Dr. Martin has nothing to disclose. Dr. Cruts has nothing to disclose. Dr. Engelborghs has nothing to disclose. Dr. Van Broeckhoven has nothing to disclose.

Progressive supranuclear palsy is a progressive neurodegenerative disorder for which no specific treatment is known at present. In this report we treated a small group of clinically diagnosed patients with rapid-rate repetitive transcranial magnetic stimulation of the motor cortex for five days. This resulted in modest and transient improvements, especially of the axial symptomatology. Side-effects were not reported.

Neurodegeneratieve aandoeningen worden gekenmerkt door een prodromale fase waarin het pathologische proces reeds is ingezet, maar de dominante klinische symptomen zich nog niet hebben gemanifesteerd. Het identificeren van diagnostische biomerkers voor de vroegdetectie van deze aandoeningen biedt de mogelijkheid tot het plannen van vroegtijdige interventies en het afremmen van het pathologisch proces en geassocieerde klinische symptomen. Een biomerker is idealiter objectief, non-invasief en voldoende beschikbaar. Elektro-encefalografie (EEG) is een techniek die voldoet aan deze criteria en is mogelijk in staat subtiele veranderingen in de prodromale fase te detecteren. Ook de ziekte van Parkinson (PD) en Primair Progressieve Afasie (PPA) worden doorgaans pas laattijdig gediagnosticeerd op basis van de dominante motorische en talige symptomen, respectievelijk. In wat volgt geven wij een systematisch overzicht van potentiele elektrofysiologische biomerkers in het logopedische en audiologische onderzoeksdomein. Talige en auditieve elektrofysiologische biomerkers lijken veelbelovend voor de vroegdetectie van respectievelijk PPA en PD.

... Please use this identifier to cite or link to this item: Record Details. Record ID, 252139. Record Type, journalArticle. Author, P SANTENS; Jacques De Reuck [801000166674] - Ghent University; D DECOO; Luc Crevits [801000331675] - Ghent University Luc.Crevits@UGent.be; ...

Background - Hypokinetic dysarthria in patients with idiopathic Parkinson’s disease (PD) has been traditionally attributed to classic signs of the disease, namely muscle rigidity and bradykinesia. To date, research recognizes a broader alternative view in which hypokinetic dysarthria is considered to be more than a pure production deficit. This study aimed to examine a possible relationship between hypokinetic speech production and speech intensity perception in PD. Methods - Subjects included 14 patients with idiopathic PD and 14 one-to-one matched healthy control speakers (HC) with normal hearing and cognition. First, speech production was objectified through a standardized and norm-referenced speech intelligibility assessment at sentence level (DIA-S) and through acoustic analysis (F0 variability, amplitude variability, F2 transition, VSA, spectral centroid, speech diadochokinetic rate, jitter, shimmer, and MPT). Correlations between acoustic analysis and speech intelligibility were computed. Speech intensity was examined based on different tasks (spontaneous speech, reading and sustained phonation). Second, overall speech perception was determined by an overall estimation task, performed in two different conditions (immediate versus playback perception) based on two different tasks (spontaneous speech and reading). An intensity estimation task was addressed to evaluate speech intensity perception. Finally, the interaction between speech production and speech intensity perception was investigated by an intensity imitation task. Results - Concerning speech production, F0 variability and MPT were significantly decreased in patients with PD. Significant positive correlations were found between F0 variability, F2 transition, spectral centroid, and speech intelligibility. Speech intensity seemed to be task dependent. Concerning speech perception, significant differences between the different conditions and tasks in the overall estimation task were only found in the PD group. These results emphasize the discrepancy between spontaneous speech and cued regulation (e.g. non-propositional speech, auditory feedback) in patients with PD and point at the role of attention and feedback processes in the auditory perception of speech in PD. Despite the low cognitive load of the intensity estimation and imitation task, a different pattern in the auditory perception of speech intensity could be demonstrated in the PD group. Conclusions - Auditory perceptual deficits may influence speech production in patients with PD. The present results suggest a disturbed auditory perception related to an automatic monitoring deficit in PD.

Phoneme perception/discrimination and word recognition is subserved by dorsal and ventral language circuitries, in a widespread fronto-temporo-parietal cortical network (Binder et al., 1997; Friederici, 2012; Hickok and Poeppel, 2004, 2007). Demographic factors, such as age and gender, and attention-related effects seem to influence (electrophysiological) activation of cortical language areas (Shaywitz et al., 1995; Shtyrov et al., 2009; Tremblay et al., 2013). The present study aimed to explore the specific interaction between auditory and motor dorsal and ventral language areas on a millisecond time basis, with respect to (1) auditory phoneme discrimination (APD) and (2) auditory word recognition (AWR). Additionally, potential effects of age and/or gender were examined. For this, 47 subjects were included with an equal distribution of men (n=23) and women (n=24) and younger (≤50 years; n=23) and older (>50 years; n=24) subjects. APD was investigated using six oddball paradigms with a differentiation between three phonemic contrasts (voicing, place and manner of articulation) and an automatic, pre-attentive and controlled, attentive condition. AWR was investigated by contrasting real words with pseudowords in an oddball paradigm as well, though only in an automatic setting. An electroencephalogram (EEG) was recorded through 24 Ag/AgCl-electrodes placed on the scalp according to the international 10-20 system. Data was analyzed using BrainVision Analyzer (Brain Products, Munich, Germany) to elicit the cognitive ERPs of interest (Mismatch Negativity, P300 during APD; N100, P200 and N400 during AWR). Source imaging was performed using the “multiple sparse priors” algorithm (SPM8) (Friston et al., 2008). A sensor space analysis was first performed to determine time frames of interest during which statistical comparisons were made between different conditions (phonemic contrasts and attention; wordness; gender and age) in a subsequent analysis at source level. During APD several time windows demonstrated significant differences in activation of auditory and motor dorsal regions, influenced by the phonemic contrasts. The automatic and controlled condition showed differences in an early time window (50-110 msec) whereas only the controlled condition revealed other, later time windows (130-175 msec; 200-225 msec) holding distinct neuroanatomical activation patterns determined by the phonemic contrasts. Furthermore, controlled APD showed attention-related influences in frontal regions, early in time (50-110 msec) for MoA and voicing, but later in time (130-175 msec) for PoA. Moreover, automatic attention-allocation during APD based on MoA and voicing required more auditory processing, PoA mainly required more motor processing. AWR revealed early (150-300 msec) higher sensorimotor activation for real words followed by a switch to higher inferior frontal and parietal activation for pseudowords (300-550 msec). Remarkably, right hemisphere was involved during both language tasks and, unexpectedly, no differences between men and women or younger and older subjects were found for either language process. In sum, the present study evidenced significant interactions between auditory and motor language areas in distinct millisecond time frames with a differentiation in phonemic contrasts and attention during APD and wordness during AWR, though without a differentiation in age or gender. In future research, the above-mentioned methodological procedure can be “field-tested” in the clinical evaluation of aphasia patients.

Background In order to facilitate the diagnostic process for adult patients suffering from a rare disease, the Undiagnosed Disease Program (UD-PrOZA) was founded in 2015 at the Ghent University Hospital in Belgium. In this study we report the five-year results of our multidisciplinary approach in rare disease diagnostics. Methods Patients referred by a healthcare provider, in which an underlying rare disease is likely, qualify for a UD-PrOZA evaluation. UD-PrOZA uses a multidisciplinary clinical approach combined with state-of-the-art genomic technologies in close collaboration with research facilities to diagnose patients. Results Between 2015 and 2020, 692 patients (94% adults) were referred of which 329 (48%) were accepted for evaluation. In 18% (60 of 329) of the cases a definite diagnosis was made. 88% (53 of 60) of the established diagnoses had a genetic origin. 65% (39 of 60) of the genetic diagnoses were made through whole exome sequencing (WES). The mean time interval betwe...

Behavioral studies on auditory deviance detection in patients with Parkinson’s disease (PD) have reported contradictory results. The primary aim of this study was to investigate auditory deviance detection of multiple auditory features in patients with PD by means of objective and reliable electroencephalographic (EEG) measurements. Twelve patients with early-stage PD and twelve age- and gender-matched healthy controls (HCs) were included in this study. Patients with PD participated without their regular dopaminergic medication. All subjects underwent an audiometric screening and performed a passive multi-feature mismatch negativity (MMN) paradigm. Repeated-measures analysis of variance (ANOVA) demonstrated no significant differences between patients with PD and HCs regarding MMN mean amplitude and latency for frequency, duration and gap deviants. Nevertheless, a trend towards increased MMN mean amplitude and latency was found in response to intensity deviants in patients with PD compared to HCs. Increased intensity MMN amplitude may indicate that more neural resources are allocated to the processing of intensity deviances in patients with PD compared to HCs. The interpretation of this intensity-specific MMN alteration is further discussed in the context of a compensatory mechanism for auditory intensity processing and involuntary attention switching in PD.

Purpose Several studies have demonstrated increased auditory thresholds in patients with Parkinson's disease (PD) based on subjective tonal audiometry. However, the pathophysiological mechanisms underlying auditory dysfunction in PD remain elusive. The primary aim of this study was to investigate cochlear and olivocochlear function in PD using objective measurements and to assess the effect of dopaminergic medication on auditory function. Method Eighteen patients with PD and 18 gender- and age-matched healthy controls (HCs) were included. Patients with PD participated in medication on and off conditions. Linear mixed models were used to determine the effect of PD on tonal audiometry, transient evoked and distortion product otoacoustic emissions (OAEs), and efferent suppression (ES). Results Tonal audiometry revealed normal auditory thresholds in patients with PD for their age across all frequencies. OAE signal amplitudes demonstrated a significant interaction effect between grou...

... Record Details. Record ID, 289562. Record Type, journalArticle. Author, Luc Crevits [801000331675] - Ghent University Luc.Crevits@UGent.be; Patrick Santens [801001011887] - Ghent University Patrick.Santens@UGent.be; Jacques De Reuck [801000166674] - Ghent ...

ABSTRACT Background: Syntactic priming is the phenomenon by which the production or processing of a sentence is facilitated when that sentence is preceded by a sentence with a simi- lar syntactic structure. Previous research has shown that this phenomenon also occurs across languages, i.e., hearing a sentence in one language can facilitate the production of a sentence with the same structure in another language. This suggests that syntactic representations are shared across languages. Aims: The aim of the current study is to investigate this cross-lingual syntactic priming in patients with bilingual aphasia. To address this aim, we asked the following three research questions: (1) do patients with bilingual aphasia show priming effects within and across languages? (2) do these priming effects differ from the priming effects observed in control participants? and (3) does the pattern of priming effects interact with the type of aphasia? Methods & Procedures: We tested two groups of patients: one group had similar impair- ments in both languages (parallel aphasia); in the other group, the impairments were larger in one of the languages (differential aphasia). We investigated syntactic priming within and across languages by means of a dialogue experiment. Outcomes & results: We found significant cross-lingual priming effects in both patient groups as well as in a control group. In addition, the effect size of both patient groups was similar to that of the control group. Conclusions: These findings support models that incorporate shared syntactic representa- tions across languages, and are in favour of a non-localised account of differential aphasia in bilingual aphasia.

ABSTRACT Categorical and associative relationships among words are two key forms of semantic knowledge. In this study, we examined ageing and gender effects on the processing of both types of semantic relationships by using the event-related potential technique. Moreover, we aimed to develop normative electrophysiological data for clinical purposes. One hundred and ten healthy subjects were divided among three age groups and subjected to two auditory word priming paradigms. Early auditory processing was influenced by increasing age as shown by larger P1 amplitudes and by delayed onsets of the N1 and P2. Conversely, ageing effects on the main N400 effect were limited to an increased right hemispheric lateralisation pattern for associative relationships. Gender effects could be demonstrated, with women showing larger P2 amplitudes and larger semantic priming effects in comparison to men. The interpretation of these findings is discussed and the practical utility of the obtained normative data is emphasised.

The present study aimed to evaluate whether increased activity related to speech motor preparation preceding fluently produced words reflects a successful compensation strategy in stuttering. For this purpose, a contingent negative variation (CNV) was evoked during a picture naming task and measured by use of electro-encephalography. A CNV is a slow, negative event-related potential known to reflect motor preparation generated by the basal ganglia-thalamo-cortical (BGTC) - loop. In a previous analysis, the CNV of 25 adults with developmental stuttering (AWS) was significantly increased, especially over the right hemisphere, compared to the CNV of 35 fluent speakers (FS) when both groups were speaking fluently (Vanhoutte et al., (2015) doi: 10.1016/j.neuropsychologia.2015.05.013). To elucidate whether this increase is a compensation strategy enabling fluent speech in AWS, the present analysis evaluated the CNV of 7 AWS who stuttered during this picture naming task. The CNV preceding AWS stuttered words was statistically compared to the CNV preceding AWS fluent words and FS fluent words. Though no difference emerged between the CNV of the AWS stuttered words and the FS fluent words, a significant reduction was observed when comparing the CNV preceding AWS stuttered words to the CNV preceding AWS fluent words. The latter seems to confirm the compensation hypothesis: the increased CNV prior to AWS fluent words is a successful compensation strategy, especially when it occurs over the right hemisphere. The words are produced fluently because of an enlarged activity during speech motor preparation. The left CNV preceding AWS stuttered words correlated negatively with stuttering frequency and severity suggestive for a link between the left BGTC - network and the stuttering pathology. Overall, speech motor preparatory activity generated by the BGTC - loop seems to have a determining role in stuttering. An important divergence between left and right hemisphere is hypothesized.

Purpose: The clinical use of event-related potentials in patients with language disorders is increasingly acknowledged. For this purpose, normative data should be available. Within this context, healthy aging and gender effects on the electrophysiological correlates of semantic sentence comprehension were investigated. Method: One hundred and ten healthy subjects (55 men and 55 women), divided among three age groups (young, middle aged, and elderly), performed a semantic sentence congruity task in the visual modality during electroencephalographic recording. Results: The early visual complex was affected by increasing age as shown by smaller P2 amplitudes in the elderly compared to the young. Moreover, the N400 effect in the elderly was smaller than in the young and was delayed compared to latency measures in both middle-aged and young subjects. The topography of age-related amplitude changes of the N400 effect appeared to be gender specific. The late positive complex effect was inc...

Language evaluation: • Speech samples: screened for semantic and phonological paraphasias by 2 SLP’s independently • Token Test of Aachen Aphasia Test • Auditory phoneme discrimination and word recognition • PALPA 1, 2, 5 • Neurophysiological evaluation Neurophysiological evaluation of motor preparation in adults who stutter Sarah Vanhoutte , John Van Borsel , Marjan Cosyns , Katja Batens , Pieter van Mierlo , Dimitri Hemelsoet , Dirk Van Roost , Paul Corthals , Miet De Letter , Patrick Santens a,d

De ziekte van Parkinson (PD) is een neurodegeneratieve aandoening die zowel de spraakproductie als de spraakperceptie kan aantasten. Op dit moment is de gedragsmatige en neurofysiologische achtergrond van de gestoorde auditieve perceptie niet gekend en is het onduidelijk welke onderdelen van de auditieve spraakperceptie al dan niet betrokken zijn bij PD. In dit onderzoek wordt de auditieve perceptie van spraak en intensiteit gedragsmatig onderzocht bij 14 personen met PD en 14 gematchte controlepersonen. De resultaten van deze studie tonen aan dat bij personen met PD de auditieve spraakperceptie verschillend beinvloed wordt door de activatie van expliciete versus impliciete monitoring processen. Bovendien kan er ook een verschillend patroon in de perceptie van spreekintensiteit tussen beide groepen worden weerhouden. Naar de klinische praktijk toe adviseren we dat de logopedist tijdens zowel diagnostiek als behandeling van PD rekening houdt met de mogelijke aanwezigheid van een audi...

Arnout.Bruggeman@UGent.be The involvement of subcortical nuclei in auditory phonological input processing has only been studied by measuring neuromodulation effects on different aspects of auditory comprehension. Although these phonological effects of subcortical modulation have been well described, it is unclear if phonologically related local field potentials can be elicited in the main subcortical nuclei. The current study applied direct electrophysiological registration in thalamus, subthalamic nucleus (STN) and pedunculopontine nucleus (PPN) to determine if they are involved in phoneme discrimination and word recognition. Introduction