Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Na&#239;ve Adolescents at High Risk for Psychosis

Growing evidence suggests that movement abnormalities are a core feature of psychosis. One marker of movement abnormality, dyskinesia, is a result of ...

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Parkinson's disease (PD) patients, matched elderly controls, and normal young subjects were tested using a visuo-motor adaptation paradigm in which the gain of the vertical component of the visual feedback of handwriting was manipulated in real-time. Handwriting was performed on a digitizer tablet and displayed in real-time on a computer screen in front of the participant. Vision of the hand and pen was occluded. Feedback could be normal (pre- and post-exposure conditions), smaller, or larger than the actual handwriting (exposure conditions). All groups showed a gradual adaptation that compensated for the distorted visual feedback during the exposure conditions. Moreover, all the groups showed significant after-effects during the post-exposure conditions suggesting that all the participants learned to compensate for the novel display gains. Taken together, these data suggest that the mechanisms for visuo-motor adaptation to changes in vertical display gain during handwriting are robust to aging and early stage of PD. These results may have implications for the treatment of micrographia in Parkinsonism.

Adaptation to changes in vertical display gain during handwriting in Parkinson's disease patients, elderly and young controls.

Patients de la maladie de Parkinson (MP), t&eacute;moins appari&eacute;s de personnes &acirc;g&eacute;es et les jeunes sujets normaux ont &eacute;t&eacute; test&eacute;s &agrave; l&#39;aide d&#39;un paradigme d&#39;adaptation visuo-motrice o&ugrave; le gain de la composante verticale de la r&eacute;troaction visuelle de l&#39;&eacute;criture manuscrite a &eacute;t&eacute; manipul&eacute; en temps r&eacute;el. &Eacute;criture manuscrite a &eacute;t&eacute; effectu&eacute; sur une tablette du num&eacute;riseur et affiche en temps r&eacute;el sur un &eacute;cran d&#39;ordinateur devant le participant. Vision de la main et le stylo &eacute;tait occluse. R&eacute;troaction pourrait &ecirc;tre normal (conditions pre- et post-exposition), plus petit ou plus grand que l&#39;&eacute;criture r&eacute;elle (conditions d&#39;exposition). Tous les groupes ont montr&eacute; une adaptation progressive qui compense la r&eacute;troaction visuelle d&eacute;form&eacute;e durant les conditions d&#39;exposition. En outre, tous les groupes ont montr&eacute; des s&eacute;quelles importantes pendant les conditions post-exposition sugg&eacute;rant que tous les participants ont appris &agrave; compenser le roman affichent des gains. Ensemble, ces r&eacute;sultats sugg&egrave;rent que les m&eacute;canismes d&#39;adaptation visuo-motrice aux changements dans l&#39;affichage vertical gain au cours de l&#39;&eacute;criture manuscrite sont robustes pour l&#39;&eacute;tape de vieillissement et au d&eacute;but du PD. Ces r&eacute;sultats peuvent avoir des implications pour le traitement de la micrographie dans la maladie de Parkinson.

Adaptation aux changements dans l&#39;affichage vertical gain au cours de l&#39;&eacute;criture manuscrite dans les contr&ocirc;les de patients, les personnes &acirc;g&eacute;es et les jeunes de la maladie de Parkinson.

Pazienti con malattia di Parkinson (PD), controlli abbinati anziani e soggetti giovani normali sono stati testati utilizzando un paradigma di adattamento visuo-motor in cui il guadagno della componente verticale del feedback visivo della scrittura a mano &egrave; stato manipolato in tempo reale. Grafia &egrave; stata eseguita su una tavoletta di digitalizzatore e visualizzata tempo reale sullo schermo del computer di fronte al partecipante. Visione della mano e penna era occluso. Feedback potrebbe essere normale (condizioni pre e post-esposizione), pi&ugrave; piccoli, o pi&ugrave; grande della scrittura effettiva (condizioni di esposizione). Tutti i gruppi hanno mostrato un adattamento graduale che compensate per il feedback visivo distorto durante le condizioni di esposizione. Inoltre, tutti i gruppi hanno mostrato significativi postumi durante le condizioni post-esposizione che suggerisce che tutti i partecipanti hanno imparati a compensare il romanzo visualizzano guadagni. Presi insieme, questi dati suggeriscono che i meccanismi per visuo-motor adattamento ai cambiamenti nel display verticale guadagno durante la grafia sono resistenti alla fase di invecchiamento e l&#39;inizio del PD. Questi risultati possono avere implicazioni per il trattamento di micrographia nel parkinsonismo.

Adattamento ai cambiamenti nel display verticale guadagno durante della grafia nei controlli di pazienti, anziani e giovani di morbo di Parkinson.

Monitoring drug-induced side effects is especially important for patients who undergo treatment with antipsychotic medications, as these drugs often produce extrapyramidal side effects (EPS) resulting in movement abnormalities similar to parkinsonism. Scientists have developed several objective laboratory tests to measure and research drug-induced movement disorders, but equipment and tests are complex and costly and have not become accepted in large-scale, multi-site clinical trials. The goals of this study were to test whether a simple handwriting measure can discriminate between individuals with psychotropic-induced parkinsonism, Parkinson's disease, and healthy individuals, and to examine some of the psychometric properties of the measure. We examined pen movement kinematics during cursive writing of a standard word in 13 patients with idiopathic Parkinson's disease (PD), 10 schizophrenia patients with drug-induced parkinsonism (SZ), and 12 normal healthy control participants (NC). Participants were instructed to write the word "hello" in cursive twice, at three vertical height scales. Software was used for data acquisition and analysis of vertical stroke velocities, velocity scaling, and smoothness. There were four important results from this study: (1) both SZ patients with drug-induced EPS and PD participants exhibited impaired movement velocities and velocity scaling; (2) performance on the velocity scaling measure distinguished drug-induced EPS from normal with 90% accuracy; (3) SZ, but not PD participants displayed abnormalities in movement smoothness; and (4) there was a positive correlation between age and magnitude of the velocity scaling deficit in PD participants. This study demonstrates that kinematic analyses of pen movements during handwriting may be useful in detecting and monitoring subtle changes in motor control related to the adverse effects of psychotropic medications.

Quantitative measurement of handwriting in the assessment of drug-induced parkinsonism.

During the past 20 years graphonomic research has become a major contributor to the understanding of human movement science. Graphonomic research investigates the relationship between the planning and generation of fine motor tasks, in particular, handwriting and drawing. Scientists in this field are at the forefront of using new paradigms to investigate human movement. The 16 articles in this special issue of Human Movement Science show that the field of graphonomics makes an important contribution to the understanding of fine motor control, motor development, and movement disorders. Topics discussed include writer's cramp, multiple sclerosis, Parkinson's disease, schizophrenia, drug-induced parkinsonism, dopamine depletion, dysgraphia, motor development, developmental coordination disorder, caffeine, alertness, arousal, sleep deprivation, visual feedback transformation and suppression, eye-hand coordination, pen grip, pen pressure, movement fluency, bimanual interference, dominant versus non-dominant hand, tracing, freehand drawing, spiral drawing, reading, typewriting, and automatic segmentation.

Advances in graphonomics: studies on fine motor control, its development and disorders.

We examined the disruptive effects of stuttering on manual performance during simultaneous speaking and drawing tasks. Fifteen stuttering and fifteen non-stuttering participants drew continuous circles with a pen on a digitizer tablet under three conditions: silent (i.e., neither reading nor speaking), reading aloud, and choral reading (i.e., reading aloud in unison with another reader). We counted the frequency of stuttering events in the speaking tasks and measured pen stroke duration and pen stroke dysfluency (normalized jerk) in all three tasks. The control group was stutter-free and did not increase manual dysfluency in any condition. In the silent condition, the stuttering group performed pen movements without evidence of dysfluency, similar to the control group. However, in the reading aloud condition, the stuttering group stuttered on 12% of the syllables and showed increased manual dysfluency. In the choral reading condition stuttering was virtually eliminated (reduced by 97%), but manual dysfluency was reduced by only 47% relative to the reading aloud condition. Trials where more stuttered events were generally positively correlated with higher manual dysfluency. The results are consistent with a model in which episodes of stuttering and motor dysfluency are related to neural interconnectivity between manual and speech processes.

Differential levels of speech and manual dysfluency in adults who stutter during simultaneous drawing and speaking tasks.

Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization. A quantitative analysis of handwriting kinematics was used to evaluate effects of antipsychotic medication type and dose in schizophrenia patients. Twenty-seven schizophrenia patients treated with risperidone, six schizophrenia patients who received no antipsychotic medication and 47 healthy comparison participants were enrolled. Participants performed a 20-min handwriting task consisting of loops of various sizes and a sentence. Data were captured and analyzed using MovAlyzeR software. Results indicated that risperidone-treated participants exhibited significantly more dysfluent handwriting movements than either healthy or untreated SZ participants. Risperidone-treated participants exhibited lower movement velocities during production of simple loops compared to unmedicated patients. Handwriting dysfluency during sentence writing increased with dose. A 3-factor model consisting of kinematic variables derived from sentence writing accounted for 83% (r=.91) of the variability in medication dose. In contrast, we found no association between observer-based EPS severity ratings and medication dose. These findings support the importance of handwriting-based measures to monitor EPS in medicated schizophrenia patients.

Handwriting movement analyses for monitoring drug-induced motor side effects in schizophrenia patients treated with risperidone.

Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as Parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system.

Handwriting movement kinematics for quantifying extrapyramidal side effects in patients treated with atypical antipsychotics.

This study investigated the extent to which manual fluency was associated with speech fluency in fluent speakers engaged in dual motor tasks. Thirteen right-handed adult females repeatedly drew circles with a pen on a digitizer tablet under five conditions: (1) a baseline (without reading or listening to speech), (2) reading fluently, (3) reading disfluently, (4) listening to fluent speech, and (5) listening to disfluent speech. The primary measure of disfluency was normalized mean squared jerk (NJ) in the pen strokes. Pen stroke time (ST) and pressure (PP) were also measured. NJ of the circle movements was significantly increased in both the disfluent reading and the disfluent listening conditions (p<0.05), compared to the baseline condition. In the fluent listening and reading conditions, NJ in circle drawing was unaltered compared to the baseline condition. Relative to baseline, ST increased significantly (p<0.05), but to a similar extent in all experimental conditions. Significantly (p<.05) greater pen pressure were also found in the disfluent versus fluent conditions. Positive correlations (r=0.33-0.63) were found between NJ and ST across conditions. These findings demonstrate that in dual-tasks, speech fluency can influence manual fluency. This is consistent with the corpus of data showing neural connectivity between manual and speech tasks, as well between perception and production. The mirror neuron system is implicated as a mechanism involved in forging these links.

Hans-Leo Teulings

NeuroScript LLC

Handwriting Analysis Indicates Spontaneous Dyskinesias in Neuroleptic Naïve Adolescents at High Risk for Psychosis