Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

<p>Abstract</p> <p>Objective</p> <p>To study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinson's disease (PD) with deficient haptic perception.</p> <p>Methods</p> <p>Twelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices.</p> <p>Results</p> <p>We found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearman's ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients.</p> <p>Conclusion</p> <p>PD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.</p

Combining Repetitive Transcranial Magnetic Stimulation and Video Game-Based Training to Improve Dexterity in Parkinson's Disease: Study Protocol of a Randomized Controlled Trial

Introduction: Patients with Parkinson’s disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL) due to dysfunctional supplementary motor area (SMA). The aim of this clinical trial protocol work is to describe how the effectiveness of a combined repetitive transcranial magnetic stimulation (rTMS) over SMA and video-game-based skill training (VBT) in PD will be evaluated. The short and long-term benefits are assessed. Methods and analysis: A single-blind (patients) stratified (based on Hoehn & Yahr) parallel randomized sham-controlled rTMS-VBT study with a baseline and two follow-up measurements (3 and 12 weeks) is being conducted. These measurements include the dexterity questionnaire 24 (DextQ-24) as a primary outcome, and nine hole peg test and coin rotation task as main secondary dexterity outcomes. Further secondary outcomes will be the subscale II of the movement disorders society unified PD rating scale (MDS-UPDRS) to assess improvements on overall ADL and the Parkinson’s Disease Questionnaire-39 to assess quality of life. Thirty-six outpatients (from one neurorehabilitation center) with PD (diagnosis based on brain bank criteria) will be recruited who report difficulties with dexterity in performing ADL. All PD patients will receive a 45-min VBT three times a week for 3 weeks. The PD patients randomized in the experimental group will receive VBT preceded by real rTMS, being intermittent theta burst (iTBS) stimulation sessions. The PD patients randomized to the control group receive a VBT with sham rTMS. Discussion: The study will provide evidence to determine whether a combined iTBS and VBT skill intervention is more effective than a VBT intervention alone to improve dexterity in PD. Ethics and dissemination: The study was approved by the Ethics Committee for Northwest and Central Switzerland (EKNZ), Switzerland 2019–00433. The study will be conducted in accordance with the Helsinki Declaration and the Guidelines of Good Clinical Practice. Informed consent will be signed prior to subject enrolment. Dissemination will include submission to international peer-reviewed professional journals and presentation at international congresses. The study protocol has been registered in the clinicaltrials.gov registry with the identification code: NCT04699149

Patient-tailored multimodal neurorehabilitation: The Lucerne model

Neurorehabilitation is a rapidly developing subspecialty of neurology due to medical advances and growing knowledge on functional recovery from brain injury such as plasticity and regeneration in the nervous system. Furthermore, progress in modern technologies facilitate new therapeutic concepts. Patient-tailored, flexible multimodal neurorehabilitation is essential in neurological diseases due to the diversity of symptoms. In addition, rehabilitative treatment should be realized from disease onset. To fulfill these goals, the neurocenter of the Cantonal Hospital Lucerne established an uninterrupted treatment chain from the emergency stage to the social and occupational reintegration, which is described in this article with a focus on stroke, Parkinson’s disease, and multiple sclerosis patients

Validation of the Apraxia Screen TULIA (AST) in Schizophrenia.

INTRODUCTION Deficits in social interaction and community functioning, including impaired use, performance, and perception of hand gestures, are key features in schizophrenia. A well-established tool to assess gesture deficits is the test of upper limb apraxia (TULIA). However, given its time-consuming application based on video analyses, research has proposed the bedside apraxia screen of TULIA (AST). This study aims to test the validity and reliability of the AST to detect gesture abnormalities at bedside in a sample of 27 patients diagnosed with schizophrenia, schizotypal disorder, acute and transient psychotic disorders, or schizoaffective disorder. METHODS Patients completed the 48-item TULIA and the 12-item AST. Two different raters assessed the AST: one at bedside (online) and the other based on the video recordings. RESULTS The total AST scores demonstrated a high parallel reliability, moderate inter-rater reliability on a single-item level, and good construct validities. CONCLUSIONS The psychometric properties of the AST suggest it can well be used for the clinical assessment of gesture deficits in schizophrenia. However, when detailed information is required, the AST rated from video or conducting the full TULIA is recommended. The findings call for refining the selection of the TULIA items for a psychosis-AST bedside test to increase specificity

Nonverbal Social Communication and Gesture Control in Schizophrenia

Schizophrenia patients are severely impaired in nonverbal communication, including social perception and gesture production. However, the impact of nonverbal social perception on gestural behavior remains unknown, as is the contribution of negative symptoms, working memory, and abnormal motor behavior. Thus, the study tested whether poor nonverbal social perception was related to impaired gesture performance, gestural knowledge, or motor abnormalities. Forty-six patients with schizophrenia (80%), schizophreniform (15%), or schizoaffective disorder (5%) and 44 healthy controls matched for age, gender, and education were included. Participants completed 4 tasks on nonverbal communication including nonverbal social perception, gesture performance, gesture recognition, and tool use. In addition, they underwent comprehensive clinical and motor assessments. Patients presented impaired nonverbal communication in all tasks compared with controls. Furthermore, in contrast to controls, performance in patients was highly correlated between tasks, not explained by supramodal cognitive deficits such as working memory. Schizophrenia patients with impaired gesture performance also demonstrated poor nonverbal social perception, gestural knowledge, and tool use. Importantly, motor/frontal abnormalities negatively mediated the strong association between nonverbal social perception and gesture performance. The factors negative symptoms and antipsychotic dosage were unrelated to the nonverbal tasks. The study confirmed a generalized nonverbal communication deficit in schizophrenia. Specifically, the findings suggested that nonverbal social perception in schizophrenia has a relevant impact on gestural impairment beyond the negative influence of motor/frontal abnormalitie

Altered activation and connectivity of the supplementary motor cortex at motor initiation in Parkinson's disease patients with freezing

OBJECTIVE Motor initiation failure is a key feature of freezing of gait (FOG) due to Parkinson's disease (PD). The supplementary motor cortex (SMC) plays a central role in its pathophysiology. We aimed at investigating SMC activation, connectivity and plasticity with regard to motor initiation in FOG. METHODS Twelve patients with FOG and eleven without FOG underwent a multimodal electrophysiological evaluation of SMC functioning including the Bereitschaftspotential and movement-related desynchronisation of cortical beta oscillations. SMC plasticity was modulated by intermittent theta burst stimulation (iTBS) and its impact on gait initiation was assessed by a three-dimensional gait analysis. RESULTS Prior to volitional movements the Bereitschaftspotential was smaller and beta power was less strongly attenuated over the SMC in patients with FOG compared to those without. Pre-motor coherence between the SMC and the primary motor cortex in the beta frequency range was also stronger in patients with FOG. iTBS resulted in a relative deterioration of gait initiation. CONCLUSIONS Reduced activation of the SMC along with increased SMC connectivity in the beta frequency range hinder a flexible shift of the motor set as it is required for gait initiation. SIGNIFICANCE Altered SMC functioning plays an important role for motor initiation failure in PD-related FOG

The right anterior temporal lobe critically contributes to magnitude knowledge

Cognitive estimation is a mental ability applied to solve numerical problems when precise facts are unknown, unavailable or impractical to calculate. It has been associated with several underlying cognitive components, most often with executive functions and semantic memory. Little is known about the neural correlates of cognitive estimation. To address this issue, the present cross-sectional study applied lesion-symptom mapping in a group of 55 patients with left hemineglect due to right-hemisphere stroke. Previous evidence suggests a high prevalence of cognitive estimation impairment in these patients, as they might show a general bias towards large magnitudes. Compared to 55 age- and gender-matched healthy controls, the patient group demonstrated impaired cognitive estimation. However, the expected large magnitude bias was not found. Lesion-symptom mapping related their general estimation impairment predominantly to brain damage in the right anterior temporal lobe. Also critically involved were the right uncinate fasciculus, the anterior commissure and the right inferior frontal gyrus. The main findings of this study emphasize the role of semantic memory in cognitive estimation, with reference to a growing body of neuroscientific literature postulating a transmodal hub for semantic cognition situated in the bilateral anterior temporal lobe. That such semantic hub function may also apply to numerical knowledge is not undisputed. We here propose a critical contribution of the right anterior temporal lobe to at least one aspect of number processing, i.e. the knowledge about real-world numerical magnitudes

Screening for language disorders in stroke: german validation of the language screening test (last)

Background: Screening of aphasia in acute stroke is crucial for directing patients to early language therapy. The Language Screening Test (LAST), originally developed in French, is a validated language screening test that allows detection of a language deficit within a few minutes. The aim of the present study was to develop and validate two parallel German versions of the LAST. Methods: The LAST includes subtests for naming, repetition, automatic speech, and comprehension. For the translation into German, task constructs and psycholinguistic criteria for item selection were identical to the French LAST. A cohort of 101 stroke patients were tested, all of whom were native German speakers. Validation of the LAST was based on (1) analysis of equivalence of the German versions, which was established by administering both versions successively in a subset of patients, (2) internal validity by means of internal consistency analysis, and (3) external validity by comparison with the short version of the Token Test in another subset of patients. Results: The two German versions were equivalent as demonstrated by a high intraclass correlation coefficient of 0.91. Furthermore, an acceptable internal structure of the LAST was found (Cronbach's α = 0.74). A highly significant correlation (r = 0.74, p < 0.0001) between the LAST and the short version of the Token Test indicated good external validity of the scale. Conclusion: The German version of the LAST, available in two parallel versions, is a new and valid language screening test in stroke

Improved gesturing in left-hemispheric stroke by right inferior parietal theta burst stimulation

ObjectivesApraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation.Materials and methodsNineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model.ResultsPairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 – 18.13, p &lt; 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI –0.20 – 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI –0.49 – 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R.ConclusionOne single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia

Improved gesturing in left-hemispheric stroke by right inferior parietal theta burst stimulation.

OBJECTIVES Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation. MATERIALS AND METHODS Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model. RESULTS Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R. CONCLUSION One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia