Speech Disorder

The goal of this interventional study is to learn about the clinical outcomes of acute ischemic stroke treated with mechanical thrombectomy resulting in a selective ischemia of the basal ganglia. The main question it aims to answer is: • defining the prevalence and clinical features of possible cognitive, motor and sleep disfuncions occuring after acute ischemic stroke treated with thrombectomy Participants will be tested for cognitive, movement and sleep disorders in the acute phase and successively in the long term follow-up.

The aim of the present study is to assess the changes of palatal morphology among growing patients with different vertical facial growth patterns treated with rapid palatal expander. Thirty-six patients referred to "Policlinico Agostino Gemelli" university hospital will be selected. The eligible criteria are posterior cross-bite, mixed dentition, skeletal Class I relationship and prepubertal stage of cervical vertebral maturation. The patients will be split into three groups according to facial divergency (hyper-, hypo-, normodivergent subjects). For each subject, digital dental casts will be recorded before and after treatment using an intraoral scanner. To evaluate two-dimensional maxillary arch changes, linear measurements will be done. To study comprehensively the palatal shape, a set of 240 landmark and semi-landmarks will be digitized on the palatal vault. Then, Geometric Morphometric Analysis (GMA) will be performed to compare morphological variations of the palate among different vertical facial growth pattern groups.

Cochlear implant patients exhibit improved speech perception in quiet environments after surgery, but their music perception and speech perception under noise are still unsatisfactory. Gene therapy is a novel and promising treatment for congenital hearing loss to recover natural hearing sensations. To date, for patients with congenital deafness, there has been no study on their ability to perceive and understand sounds, such as speech perception in noise, music and directional perception, after hearing recovery owing to gene therapy. In addition, the difference between the two treatments in those perceptual levels postoperatively remains unknown. Therefore, the investigators designed a single-center cohort study. Based on the intervention method, congenital deafness patients are divided into two groups: the cochlear implant group and the gene therapy group. In the present study, a full-scale evaluation of the two groups will be conducted. The battery encompasses auditory speech perception, cognition, psychological status, and auditory cortex development. A comparative analysis will be conducted to examine multidimensional differences between the two groups, shedding light on the divergent outcomes of gene therapy and cochlear implants for patients with congenital deafness.

The developmental approach taken here combines what is already known about morpho-syntactic deficits in DLD with recent developments in the fields of linguistics and language acquisition. First, it is possible to divide phonological and morphological patterns into three pattern types (Single Feature, OR/Disjunction, Family Resemblance/Prototype), with these types having a long history of study in visual pattern learning. Importantly, children with DLD appear to have maximum difficulty with morpho-syntactic patterns of the OR type (e.g., regular past tense; add a "t" if the final consonant is voiceless OR a "d" if the final consonant is voiced). In contrast, studies using artificial grammars show that infants who are typically developing are highly adept at learning Single Feature and OR pattern types; Family Resemblance patterns may be weaker. Family resemblance patterns relate to similarity, and may be more closely tied to the lexicon than to grammar (e.g., beagles and terriers are similar and they are both dogs; the words "goat" and "boat" are similar). Typical adults are adept at Single Feature and Family Resemblance patterns, but appear to be, at least superficially, more like children with DLD in their performance on the OR pattern. With these developmental findings as a starting point, the proposed research links phonological and morphological sequence learning in children with developmental language disorder (DLD). In the studies focused on children, the investigators ask if 4- to 6-year-olds who are typically developing as well as those with DLD (both with and without co-occurring speech sound deficits) and speech sound disorder (SSD; without co-occurring morpho-syntactic deficits) are sensitive to input examples that fit one of these three patterns. The hypothesis is that, consistent with their long-documented morpho-syntactic deficit, children with DLD will have particular difficulty with the OR pattern. Consistent with their intact morpho-syntactic skills, children with SSD should show no deficits in the OR pattern, revealing a link between OR pattern learning, phonology, and morpho-syntax. The endpoint measure is that children with DLD (both with and without an accompanying SSD) do not show sensitivity to the OR pattern, as measured by sound pattern (e.g., phonetic accuracy, syllable sequence stability) and motor learning (e.g., articulatory and acoustic variability) measures. This hypothesis is assessed by indexing the learning trajectory across the training period and during generalization to new nonwords that are consistent or inconsistent with the training pattern. In the generalization phase, children are asked to name new novel words that are either consistent (i.e., that fit the training rule) or inconsistent (i.e., that do not fit the training rule) nonwords. It is predicted that children with TD and SSD, who are still in a period of language learning plasticity (they can still learn the sound patterns and grammar of a second language) will be sensitive to all three patterns. However, children with DLD (both with and without accompanying SSD) are predicted to show sensitivity to the family resemblance and single feature patterns, but not to the critical OR pattern-the one associated with sound pattern and grammatical learning, This would reveal an important connection between sound pattern and grammatical learning, which could lead to earlier diagnosis (phonological patterns emerge earlier than grammar) and to more general intervention practices that focus on sequential pattern learning rather than specific language goals may be efficacious. A second aim explores whether the inclusion of a semantic subcategory cue facilitates learning the OR pattern. The hypothesis is that children with DLD (as well as typical adults) who initially are predicted to have the most difficulty with the OR pattern, will show increases in sensitivity following the addition of a semantic category cue (e.g., animals for the voiced consonant rule OR tools for the voiceless consonant rule). This result would be especially important for learners with DLD, as it may provide a pathway for intervention of a core learning deficit. Critically, these studies are developmental in nature. In the adult component of this research (conducted under a separate clinical trial, Gerken, University of Arizona), the investigators ask if adults are sensitive to input examples that fit one of these three patterns. The hypothesis, based on previous findings from the Gerken lab, is that adults, like children with DLD, do not show sensitivity to the OR pattern. However, adults are sensitive to single feature and Family Resemblance patterns. Adults still learn words readily and are sensitive to family resemblance prototype relationships. For adults, perceptual measures index sensitivity. Similar to the children with typical development, DLD and SSD, the investigators explore whether the inclusion of a semantic subcategory cue facilitates learning the OR pattern in adults. The hypothesis is that all learners, including adults, will show increases in sensitivity following the addition of a semantic category cue (e.g., animals for voiced rule OR tools for voiceless rule). The findings from adults contribute to a dynamic developmental framework. Because of the dramatic developmental changes in sensitivity to phonological sound patterns and the presumed linkage of such patterns to morpho-syntax, the data from adults are essential in identifying the underlying mechanism(s) of DLD and to suggesting possible intervention strategies, such as employing semantic cues to the OR pattern and strengthening lexical organization. From previous work, it is known that infants are sensitive to the OR rule. In the studies focused on toddlers (also in a separate clinical trial conducted by Gerken at the University of Arizona), the investigators ask if dependence on the associatively organized lexicon can account for the infant-to-adult developmental changes observed for the OR pattern (which is not associatively organized) and thereby explores the possibility that children with DLD rely on their lexicons to compensate for their sequential pattern learning deficit. The hypothesis is that 20-month-old children, who are just entering a period of rapid vocabulary learning, will show increased sensitivity (based on looking time to words that are consistent vs. inconsistent within the training set) in the family resemblance condition when a visual referent (i.e., semantic cue) is added, but decreased sensitivity in the OR condition when a visual referent is added. These results will also be related to vocabulary size as reported on the MacArthur-Bates Communicative Development Inventory, with the prediction that robust patterns are smaller for children who received referents or who have smaller vocabularies for the OR pattern and greater for children who received referents or who have larger vocabularies for the family resemblance pattern. The results from toddlers, who are just entering a period of rapid vocabulary learning, provide an essential framework for understanding how different types of phonological patterns apply to lexical and morpho-syntactic learning. The results of the proposed studies provide a critical developmental framework for identifying the underlying mechanism(s) of DLD. These findings will also lead to the development of intervention strategies, such as strengthening lexical organization, to support problematic aspects of sequential pattern learning.

60 patients with PPA will be recruited from IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia; IRCCS Fondazione Istituto Neurologico Nazionale C. Mondino, Pavia; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan and Fondazione Don Carlo Gnocchi - ONLUS, Milan. The diagnostic evaluation will include cognitive and language testing, neurologic examination and neuroimaging (Magnetic Resonance Imaging (MRI) or Positron Emission Tomography PET)). All the patients will undergo five consecutive days a week for two weeks of treatment sessions of 25 minutes: * 30 patients will receive Active tDCS over dorsolateral prefrontal cortex-DLPFC (anode over the left DLPFC with the cathode over the right supraorbital region) while performing an individualized language training; * 30 patients will receive Placebo tDCS during an individualized language training. The two groups will be matched for sex, age, education, language severity (as defined in the Frontotemporal Dementia Clinical Dementia Rating subscale), and overall severity according to the FTD Clinical Dementia Rating. Two trained neuropsychologists will administer the neuropsychological testing at baseline (T0), post-treatment (T1) and 3-months (T2) follow-up. All of assessments will be conducted by the same assessor. To elucidate the mechanisms underlying tDCS effects, Magnetic Resonance Imaging (MRI) and bimolecular data will be collected at T0 and T1 (after the treatment).

Seventy-two children with CAS, between the ages of 2.5 and 7.11 years of age will be treated with DTTC. This work will employ a delayed treatment control group design across multiple behaviors. Participants will be seen in two groups: an Immediate Treatment group and a Delayed Treatment group. Probe data will be collected during the Pre-Treatment (5 data points), Treatment (12 data points) and Maintenance (minimum 5 data points) phases. The study duration is 28 weeks in total duration for all participants. The study will address the following specific aims: Aim 1: Quantify the effects of DTTC on improved speech production (perceptual ratings) in treated words that are maintained post-treatment and generalized to untreated words in children with CAS. The working hypothesis is that DTTC will increase accuracy of treated words (primary outcome measure) and this effect will be maintained post-treatment and generalized to untreated words. We also predict that DTTC will increase speech intelligibility pre to post-treatment (secondary outcome measure). Aim 2: Quantify the effects of DTTC on refined speech motor control (kinematic/acoustic measures) in treated words that are maintained post-treatment and generalized to untreated words in children with CAS. The working hypothesis is that DTTC will be associated with decreases in speech motor variability and duration of treated words (secondary outcome measures) that are maintained pre- to post-treatment and generalized to untreated words. Aim 3: Characterize the effects of speech motor variability (within-subject) at baseline as a predictor of DTTC efficacy in children with CAS. The working hypothesis is that children with CAS who demonstrate higher levels of speech motor variability at baseline will display greater improvements in speech production accuracy following DTTC than children with lower levels of variability at baseline. Treatment will be provided four times/week for 45-minute sessions. Principles of motor learning will be incorporated into sessions by controlling the type of practice (blocked vs. randomized), type of feedback (knowledge of results vs. knowledge of performance) and amount of feedback provided.

The goal of this clinical trial is to determine the efficacy of Clemastine Fumarate in the presence of engineered sound to treat age-related central auditory processing disorder (CAPD). This disorder impacts 800M patients worldwide, including \~1/3 people over 40 years of age and \~1/2 people over 65, resulting in an inability to hear in noisy environments. The primary hypothesis this study aims to test is: engineered sound, driving localized neural circuit activity, will enable Clemastine Fumarate to mature Oligodendrocyte cells and thus remyelinate these activated neural circuits. This Localized Oligodendrocyte Optimization Therapy (LOOT) was highly effective in preclinical animal studies so this clinical trial aims to answer if this therapy will translate to humans. The study is an adaptive design intended to compare the efficacy of the drug in the presence or absence of the engineered sound for improving hearing in noise ability. Trial participants will be tested for hearing thresholds and ability to isolate a sound signal from background noise. If they meet the inclusion criteria, they will be enrolled into one of the four arms of the study and undergo the proposed one-month treatment (drug and sound or respective placebos). After the treatment period, trial participants will be tested again for hearing thresholds and their ability to isolate s sound source of interest from background noise. The hypothesis to be tested in this clinical trial is that the one-month treatment will significantly improve the participant's ability to isolate a sound source of interest from background noise. The design has four arms, drug+sound, placebo+sound, drug+white noise, and placebo+white noise. Based on our preclinical data, control arms are all expected to show identical results, thus our adaptive design includes interim analyses to allow for dropping of two of the three placebo arms should the preclinical results be replicated as anticipated. We will also monitor each participant's general health during the duration of the clinical trial, which will be done by performing a number of blood tests, an EKG and a general physical before and after the one-month treatment period. We expect no significant changes since participants will take the drug for the one-month period at dosages already demonstrated safe in several Phase II studies of multiple sclerosis. Similarly, the engineered sound will be listened to for one hour per day during this month at sound intensities well below threshold that might cause noise-induced hearing damage.

This cross-sectional observational study aims to characterise acoustic, respiratory, and clinical speech parameters in adults with acquired brain injury (ABI) and to examine their associations with the presence and severity of dysarthria. The study is limited to baseline assessment and does not include therapeutic intervention or longitudinal follow-up. Participants complete a standardised evaluation protocol conducted in a controlled clinical setting. All assessments are performed within a short and predefined evaluation period to minimise fatigue and contextual variability. The protocol comprises three assessment sessions: (1) acoustic and aerodynamic speech evaluation based on sustained phonation vowels /a/, /i/, /u/, /o/ and connected speech tasks; (2) objective assessment of respiratory function using spirometry; and (3) clinical assessment of dysarthria using the Frenchay Dysarthria Assessment-2 (FDA-2). Speech recordings are obtained under standardised conditions to ensure consistency across participants and reliable extraction of acoustic measures. Respiratory assessments are performed according to established international guidelines to ensure validity and reproducibility. Data from acoustic, respiratory, and clinical assessments are analysed jointly to explore associations between phonorespiratory function and dysarthria severity in adults with ABI.

The investigators propose an AAC device comprising a versatile access method that automatically learns and customizes a keyboard interface to the residual motor function of the individual. The team comprising scientists, speech researchers and clinicians is developing a prototype AAC system comprising versatile access method and personalized, comprehensive communication software. This will be achieved by developing hardware to support streamlined access across multiple points on the body, designing automated algorithms to rapidly create an expanded AAC interface, inclusive of letters, numbers, symbols, emojis, and word completion options, that is personalized based on the residual motor function of user-specific access points, creating software for point-of-care use of the access technology and interface, and evaluating the resulting AAC system for communication efficacy in individuals with severe motor impairments. The milestone will be to demonstrate that our AAC system improves Information Transfer Rate (ITR) and user experience over conventional AAC devices. The final AAC deliverable will be easily integrated with existing AAC tablets and mobile devices to provide those in need of alternative communication methods with an automatically customized, efficient, and intuitive solution to restore communication access in their daily lives. The project's involvement of human subjects for the purpose of research is primarily focused on testing our AAC system for usability, improved performance, acceptance, and perceived benefit among individuals with severe motor impairments.

Study 2: Evaluate the benefits of adaptive trial scheduling. Study design: Investigators will enroll 32 people with aphasia in a randomized within-subjects crossover design comparing an adaptive scheduling condition to two non-adaptive conditions. For each condition, all treatment procedures will be matched except for the number of treated words and the trial spacing manipulation. Participants will receive 10 weeks of computer-based training per condition, with probes administered at baseline and at 1 week, 3 months, and 6 months post-treatment. Condition order will be randomly assigned and counter-balanced across participants. In total, Study 2 will include typically 3-4 (but up to 6) assessment sessions, 120 one-on-one treatment sessions, and 24 baseline and follow-up probe sessions per participant over an \~1-year period, or up to 18 months. All assessment, treatment, and probe sessions will take place via telehealth. Treatment description: For each condition, all treatment procedures will be matched except for the number of treated words and the trial spacing manipulation. The treatment phase for each of the three conditions will consist of ten weeks of one-on-one treatment four times per week in which the treating clinician will work alongside participants to complete flashcard practice four days a week. The treatment sessions will each last 30 minutes to approximate realistic treatment dosage in outpatient or home health practice settings. Treatment will consist of effortful retrieval practice: on each trial, participants will see a picture of the target and attempt to name it, then rate their naming accuracy by button press. The experimenter will code their response time and perceived accuracy. Finally, the experimenter will code their accuracy which will reveal the target in verbal and written form. If they are unable to name the word correctly, they will be able to replay the answer and repeat it three times prior to moving on to the next trial, per Conroy et al.