Faculty Bibliography

[This corrects the article DOI: 10.1016/j.mex.2023.102230.].

A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson's disease [1,2] was performed on participants with Parkinson's disease and multiple system atrophy as well as age- and sex-matched healthy participants with typical development. Participants underwent twelve videotaped procedures rated by a trained examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items (3.4 Finger tapping, 3.5 Hand movements, 3.6 Pronation-supination movements of hands, 3.7 Toe tapping, and 3.8 Leg agility) [1] underwent processing to fast Fourier [5] and amor and bump continuous wavelet transforms [6], [7], [8], [9], [10], [11], [12], [13]. Images of the signals and their transforms [4], [5], [6] of the five repetitive tasks of each participant were randomly expressed as panels on an electronic framework for rating by 35 trained examiners who did not know the source of the original output [14]. The team of international raters completed ratings of the signals and their transforms independently using criteria like the scoring systems for live assessments of movements in human participants [1,2]. The raters scored signals and transforms for deficits in the sustained performance of rhythmic movements (interruptions, slowing, and amplitude decrements) often observed in people with Parkinson's disease [15], [16], [17], [18], [19], [20]. Raters were first presented the images of the signals and transforms of a man with multiple system atrophy as a test and a retest in a different random order. After the raters completed the assessments of the man with multiple system atrophy, they were presented random test and retest panels of the images of signals and transforms of ten participants with Parkinson's disease who completed a single rating session. After the raters completed the assessments of the participants with Parkinson's disease who completed one set of ratings, they were presented random test and retest panels of the images of signals and transforms of (A) ten participants with Parkinson's disease and (B) eight age- and sex-match healthy participants with typical development who completed two rating session separated by a month or more [15], [16], [17], [18], [19], [20]. The data provide a framework for further analysis of the acquired information. Additionally, the data provide a template for the construction of electronic frameworks for the remote analysis by trained raters of signals and transforms of rhythmic processes to verify that the systems are operating smoothly without interruptions or changes in frequency and amplitude. Thus, the data provide the foundations to construct electronic frameworks for the virtual quality assurance of a vast spectrum of rhythmic processes. The dataset is a suitable template for solving unsupervised and supervised machine learning algorithms. Readers may utilize this procedure to assure the quality of rhythmic processes by confirming the absence of deviations in rate and rhythm. Thus, this procedure provides the means to confirm the quality of the vast spectrum of rhythmic processes.

Objective and quantitative monitoring of movement impairments is crucial for detecting progression in neurological conditions such as Parkinson's disease (PD). This study examined the ability of deep learning approaches to grade motor impairment severity in a modified version of the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) using low-cost wearable sensors. A convolutional neural network architecture, XceptionTime, was used to classify lower and higher levels of motor impairment in persons with PD, across five distinct rhythmic tasks: finger tapping, hand movements, pronation-supination movements of the hands, toe tapping, and leg agility. In addition, an aggregate model was trained on data from all tasks together for evaluating bradykinesia symptom severity in PD. The model performance was highest in the hand movement tasks with an accuracy of 82.6% in the hold-out test dataset; the accuracy for the aggregate model was 79.7%, however, it demonstrated the lowest variability. Overall, these findings suggest the feasibility of integrating low-cost wearable technology and deep learning approaches to automatically and objectively quantify motor impairment in persons with PD. This approach may provide a viable solution for a widely deployable telemedicine solution.

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR₅) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR₅ expression provide conflicting findings about the nature of dysregulation of cerebral mGluR₅ pathways in subtypes of ASD. The demonstration of reduced mGluR₅ expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR₅ expression in ASD. We aimed to (A) compare and contrast mGluR₅ expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[¹⁸F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([¹⁸F]FPEB), a novel, specific mGluR₅ PET ligand to quantitatively measure the density and the distribution of mGluR₅s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR₅ expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR₅ expression in clinical trials of individuals with IASD and FXS and related conditions.

Glutamatergic receptor expression is mostly unknown in adults with fragile X syndrome (FXS). Favorable behavioral effects of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR₅) in fmr1 knockout (KO) mouse models have not been confirmed in humans with FXS. Measurement of cerebral mGluR₅ expression in humans with FXS exposed to NAMs might help in that effort. We used positron emission tomography (PET) to measure the mGluR₅ density as a proxy of mGluR₅ expression in cortical and subcortical brain regions to confirm target engagement of NAMs for mGluR₅s. The density and the distribution of mGluR₅ were measured in two independent samples of men with FXS (N = 9) and typical development (TD) (N = 8). We showed the feasibility of this complex study including MRI and PET, meaning that this challenging protocol can be accomplished in men with FXS with an adequate preparation. Analysis of variance of estimated mGluR₅ expression showed that mGluR₅ expression was significantly reduced in cortical and subcortical regions of men with FXS in contrast to age-matched men with TD.

A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson's disease [1,2] was performed on people with Parkinson's disease, multiple system atrophy, and age-matched healthy volunteers. Participants underwent twelve videotaped procedures rated by a trained examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items [1,2] underwent processing to fast Fourier [5] and continuous wavelet transforms [6]. The dataset [7] includes the coding form with scores of the live ratings [1,2], the raw files [3], the converted spreadsheets [4], and the fast Fourier [5] and continuous wavelet transforms [6]. All files are unfiltered. The data also provide findings suitable to compare and contrast with data obtained by investigators applying the same procedure to other populations. Since this is an inexpensive procedure to quantitatively measure motions in Parkinson's disease and other movement disorders, this will be a valuable resource to colleagues, particularly in underdeveloped regions with limited budgets. The dataset will serve as a template for other investigations to develop novel techniques to facilitate the diagnosis, monitoring, and treatment of Parkinson's disease, other movement disorders, and other nervous and mental conditions. The procedure will provide the basis to obtain objective quantitative measurements of participants in clinical trials of new agents.

Introduction: Schizophrenia, a devastating disorder with onset in adolescence or young adulthood, afflicts 1% of the population leading to severe social, educational, and occupational impairments. Lumateperone is a first-in-class investigational drug under development for the treatment of multiple neuropsychiatric and neurodegenerative disorders including schizophrenia. Its unique receptor affinity profile together with synergistic modulation of serotonergic, glutamatergic, and dopaminergic pathways imparts efficacy over a broad-spectrum of symptoms associated with schizophrenia.Areas covered: This narrative drug evaluation includes a review of lumateperone tosylate (lumateperone, ITI-007, ITI-722, Intra-Cellular Therapies, Inc.) for patients with schizophrenia. This review describes the receptor affinity profile, pharmacodynamics, pharmacokinetics, distribution, metabolism, and clinical trials that address how lumateperone could potentially emerge as an important therapeutic option for schizophrenia patients.Expert opinion: The unique pharmacological properties of lumateperone may provide the key to dramatically ameliorate the symptoms of schizophrenia as indicated by some clinical trials. Future clinical trials may be enhanced by the administration of more comprehensive long-term behavioral measures and utilization of molecular imaging to confirm the target engagement of the many possible sites of action. The results of ongoing and future studies will provide the evidence to determine if lumateperone will revolutionize the therapy of schizophrenia.

AIMS/OBJECTIVE:RPR 102681, a cholecystokinin-B antagonist, increased dopamine (DA) release and reduced cocaine self-administration in animals. This pilot study sought to assess the safety and pharmacokinetics (PK) of co-administration of RPR 102681 and cocaine, and to confirm the DA release mechanism of RPR 102681. METHODS:C]raclopride positron emission tomography scans were conducted at baseline and at each RPR102681 dose. RESULTS:C]raclopride in the ventral striatum (t test, P < .001) and caudate nucleus (t test, P < .0001) in a small subset of patients, suggesting that it may reduce intrasynaptic striatal DA. CONCLUSION/CONCLUSIONS:Overall, this pilot study suggests that RPR 102681 would be unlikely candidate, as an agonist medication for the treatment for cocaine addiction but worth investigating further for possible role in reducing craving.

The assessment of Parkinson's disease currently relies on the history of the present illness, the clinical interview, the physical examination, and structured instruments. Drawbacks to the use of clinical ratings include the reliance on real-time human vision to quantify small differences in motion and significant inter-rater variability due to inherent subjectivity in scoring the procedures. Rating tools are semi-quantitative by design, however, in addition to significant inter-rater variability, there is inherent subjectivity in administering these tools, which are not blinded in clinical settings. Sophisticated systems to quantify movements are too costly to be used by some providers with limited resources. A simple procedure is described to obtain continuous quantitative measurements of movements of people with Parkinson's disease for objective analysis and correlation with visual observation of the movements. •Inexpensive accelerometers are attached to the upper and lower extremities of patients with Parkinson's disease and related conditions to generate a continuous, three-dimensional recorded representation of movements occurring while performing tasks to characterize the deficits of Parkinson's disease.•Movements of the procedure are rated by trained examiners live in real-time and later by videotapes.•The output of the instrumentation can be conveyed to experts for interpretation for diagnostic and therapeutic purposes.