Real-world smartphone data can trace the behavioural impact of epilepsy: A case study.

BACKGROUND: Neurobehavioural comorbidities have a detrimental effect on the quality of life of people with epilepsy, yet tracking their impact is challenging as behaviour may vary with seizures and anti-seizure medication (ASM) side effects. Smartphones have the potential to monitor day-to-day neurobehavioural patterns objectively. We present the case of a man in his late twenties with drug-resistant focal epilepsy in whom we ascertained the effects of ASM withdrawal and a convulsive seizure on his touchscreen interactions. METHODS: Using a dedicated app, we recorded over 185 days the timestamps of 718,357 interactions. We divided the various smartphone behaviours according to the next-interval dynamics of the interactions by using a joint interval distribution (JID). During two ASM load transitions, namely before versus during tapering and tapering versus restarting medication, we used cluster-based permutation tests to compare the JIDs. We also compared the JID of the seizure day to the average of the previous 3 days. RESULTS: The cluster-based permutation tests revealed significant differences, with accelerated next-interval dynamics during tapering and a reversal upon medication restart. The day of the convulsion exhibited a marked slowing of next-interval dynamics compared to the preceding 3 days. CONCLUSION: Our findings suggest that the temporal dynamics of smartphone touchscreen interactions may help monitor neurobehavioural comorbidities in neurological care.

QUality of life and Economic evaluation after neuroSTimulation for Epilepsy (QUESTE) in adolescents and adults with drug-resistant epilepsy: protocol for a multicentre, prospective observational cohort study in The Netherlands.

INTRODUCTION: Epilepsy is one of the most common chronic neurological disorders. Antiseizure medication (ASM) is the first choice of treatment, however, 30% of epilepsy patients are drug-resistant. For these patients, neuromodulation can be an option, especially when epilepsy surgery is not possible or did not lead to seizure freedom. Epilepsy is associated with reduced quality of life (QoL), which heavily depends on seizure control.The most recent Cochrane reviews have shown that vagus nerve stimulation and deep brain stimulation of the anterior nucleus of the thalamus, lead to a responder rate OR of, respectively, 1.93 and 1.20. The question arises if neuromodulation for drug-resistant epilepsy (DRE) will be more cost-effective than sole treatment with ASM. The current study aims to determine the change in QoL after neuromodulation. Secondarily, we will aim to study the cost-effectiveness of these treatments. METHODS AND ANALYSIS: This prospective cohort study aims at including 100 patients aged 16 or above who will be referred for neuromodulation, from January 2021 to January 2026. After informed consent, QoL and other relevant parameters will be assessed at baseline, 6 months, 1, 2 and 5 years after surgery. Data on seizure frequency will be derived from patient charts. We expect that DRE patients will report better QoL after neuromodulation. Even if they would still report seizures, the treatment can be seen as useful. This is especially true when patients can participate in society again to a greater extent than before treatment. ETHICS AND DISSEMINATION: The board of directors of participating centres all gave permission for this study to commence. The medical ethics committees decided that this study does not fall under the Medical Research Involving Human Subjects Act (WMO). The findings of this study will be presented at (inter)national conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NL9033.

Reduced drift rate: a biomarker of impaired information processing in functional movement disorders.

Functional neurological disorder is a common and phenomenologically diverse condition. Resultant disability is caused by both the dominant clinical presentation, e.g. paralysis or tremor and additional symptomatology such as cognitive symptoms. Recently the similarity of neuropsychiatric profiles across a range of functional syndromes has been highlighted. This is suggestive of a common underlying mechanism with a theoretical deficit of information processing proposed. Identification of an experimental biomarker for such deficits could offer novel assessment and therapeutic strategies. In this study, we took the temporal discrimination threshold as a paradigm that can be used to model sensory processing in functional movement disorders. Our hypothesis was that we would be able to delineate markers of slowed information processing in this paradigm removed from the phenomenological presentation with a movement disorder. We recorded both response accuracy and reaction time in a two-choice temporal resolution/discrimination task in 36 patients with functional movement disorders and 36 control subjects. A psychometric function was fitted to accuracy data for each individual revealing both abnormally high threshold values (P = 0.0053) and shallow psychometric slopes in patients (P = 0.0015). Patients with functional movement disorders also had significantly slower response times (P = 0.0065). We then used a well-established model for decision-making (the drift diffusion model) that uses both response accuracy and reaction time data to estimate mechanistic physiological dimensions of decision-making and sensory processing. This revealed pathologically reduced drift rate in the patient group, a parameter that quantifies the quality and rate of information accumulation within this sensory task (P = 0.002). We discuss how the deficits we observed in patients with functional movement disorders are likely to stem from abnormal allocation of attention that impairs the quality of sensory information available. Within a predictive coding framework sensory information could be down-weighted in favour of predictions encoded by the prior. Our results therefore offer a parsimonious account for a range of experimental and clinical findings. Reduced drift rate is a potential experimental marker for a generalized deficit in information processing across functional disorders that allows diverse symptomatology to be quantified under a common disease framework.

Abnormal beta power is a hallmark of explicit movement control in functional movement disorders.

OBJECTIVE: To determine whether sensorimotor beta-frequency oscillatory power is raised during motor preparation in patients with functional movement disorders (FMD) and could therefore be a marker of abnormal "body-focused" attention. METHODS: We analyzed motor performance and beta-frequency cortical oscillations during a precued choice reaction time (RT) task with varying cue validity (50% or 95% congruence between preparation and go cues). We compared 21 patients with FMD with 13 healthy controls (HCs). RESULTS: In HCs, highly predictive cues were associated with faster RT and beta desynchronization in the contralateral hemisphere (contralateral slope -0.045 [95% confidence interval (CI) -0.057 to -0.033] vs ipsilateral -0.033 [95% CI -0.046 to -0.021], p < 0.001) and with a tendency for reaching lower contralateral end-of-preparation beta power (contralateral -0.482 [95% CI -0.827 to -0.137] vs ipsilateral -0.328 [95% CI -0.673 to 0.016], p = 0.069). In contrast, patients with FMD had no improvement in RTs with highly predictive cues and showed an impairment of beta desynchronization and lateralization before movement. CONCLUSIONS: Persistent beta synchronization during motor preparation could reflect abnormal explicit control of movement in FMD. Excessive attention to movement itself rather than the goal might maintain beta synchronization and impair performance.

A Simplified Version of the Psychogenic Movement Disorders Rating Scale: The Simplified Functional Movement Disorders Rating Scale (S-FMDRS).

BACKGROUND: The Psychogenic Movement Disorders Rating Scale (PMDRS) has potential as a useful objective assessment in clinical research, but the current scale has limitations. We developed a simplified version (S-FMDRS) and assessed inter-rater reliability, concurrent validity, and sensitivity. METHODS: Fifty-two videos of subjects with functional (psychogenic) movement disorders (FMD) were rated according to the PMDRS and S-FMDRS by three neurologists. Inter-rater reliability was assessed using intraclass correlation coefficient (ICC). Agreement of symptomatic body regions and movement disorder classification was assessed using Light's kappa. Spearman's correlation coefficient was used to assess concurrent validity. A physiotherapist also rated videos on the S-FMDRS. The simplified scale was piloted in a feasibility study of physiotherapy for FMD to assess sensitivity. RESULTS: ICC of total scores was 0.84 for the original scale and 0.85 for the simplified scale. Light's kappa for agreement of symptomatic body regions and movement disorder classification was moderate to low. Concurrent validity was demonstrated by Spearman's correlation between the two scales ranging from 0.84 to 0.95. The simplified scale was sensitive to change, with an effect size in the feasibility study of 0.79. Inter-rater reliability between physiotherapist and neurologist was high (ICC 0.85). DISCUSSION: Both versions of the scale had good inter-rater reliability for the total score. Low agreement on movement disorder classification and identification of symptomatic body regions support our argument for a simplified scale. CONCLUSIONS: The S-FMDRS has high inter-rater reliability and good sensitivity to change. Further psychometric evaluation is warranted.

Task-specific dystonia: pathophysiology and management.

Task-specific dystonia is a form of isolated focal dystonia with the peculiarity of being displayed only during performance of a specific skilled motor task. This distinctive feature makes task-specific dystonia a particularly mysterious and fascinating neurological condition. In this review, we cover phenomenology and its increasingly broad-spectrum risk factors for the disease, critically review pathophysiological theories and evaluate current therapeutic options. We conclude by highlighting the unique features of task-specific dystonia within the wider concept of dystonia. We emphasise the central contribution of environmental risk factors, and propose a model by which these triggers may impact on the motor control of skilled movement. By viewing task-specific dystonia through this new lens which considers the disorder a modifiable disorder of motor control, we are optimistic that research will yield novel therapeutic avenues for this highly motivated group of patients.

Lateral and Medial Ventral Occipitotemporal Regions Interact During the Recognition of Images Revealed from Noise.

Several studies suggest different functional roles for the medial and the lateral sections of the ventral visual cortex in object recognition. Texture and surface information is processed in medial sections, while shape information is processed in lateral sections. This begs the question whether and how these functionally specialized sections interact with each other and with early visual cortex to facilitate object recognition. In the current research, we set out to answer this question. In an fMRI study, 13 subjects viewed and recognized images of objects and animals that were gradually revealed from noise while their brains were being scanned. We applied dynamic causal modeling (DCM)-a method to characterize network interactions-to determine the modulatory effect of object recognition on a network comprising the primary visual cortex (V1), the lingual gyrus (LG) in medial ventral cortex and the lateral occipital cortex (LO). We found that object recognition modulated the bilateral connectivity between LG and LO. Moreover, the feed-forward connectivity from V1 to LG and LO was modulated, while there was no evidence for feedback from these regions to V1 during object recognition. In particular, the interaction between medial and lateral areas supports a framework in which visual recognition of objects is achieved by networked regions that integrate information on image statistics, scene content and shape-rather than by a single categorically specialized region-within the ventral visual cortex.

Anterior temporal atrophy and posterior progression in patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is characterized by specific motor and nonmotor impairments. This suggests that PD is characterized by disease-specific regional cortical atrophy. Given the change of symptoms over time, a concurrent increase in regional atrophy may further be assumed to reflect the dynamic process of disease progression. METHODS: In this study we retrospectively collected T1-weighted MRI scans from previous studies performed in our center, enabling the comparison of gray matter atrophy in 77 PD patients with 87 controls using voxel-based morphometry (VBM). This large VBM analysis provided the opportunity to investigate cortical atrophy in relation with disease progression. RESULTS: We found significant PD-related reductions of gray matter density bilaterally in the anterior temporal cortex, the left inferior frontal and left extrastriate visual cortex, independent from normal aging. The anterior temporal cortex did not show major progression, whereas particularly the posterior parts of the lateral temporal cortex and adjacent extrastriate visual cortex occurred at a later stage of disease. CONCLUSIONS: Temporal pole atrophy as an early sign of PD is consistent with the PD pathology classification of Braak. The initial anterior temporal atrophy with spread to occipitotemporal and posterior parietal regions may subserve 'emotion-based' sensorimotor transformations and deficits in the visual domain, respectively, which may be regarded as premotor symptoms.

Regional cortical grey matter loss in Parkinson's disease without dementia is independent from visual hallucinations.

In our previous functional magnetic resonance imaging study, Parkinson's disease (PD) patients with visual hallucinations (VH) showed reduced activations in ventral/lateral visual association cortices preceding image recognition, compared with both PD patients without VH and healthy controls. The primary aim of the current study was to investigate whether functional deficits are associated with grey matter volume changes. In addition, possible grey matter differences between all PD patients and healthy controls were assessed. By using 3-Tesla magnetic resonance imaging (MRI) and voxel-based morphometry (VBM), we found no differences between PD patients with (n = 11) and without VH (n = 13). However, grey matter decreases of the bilateral prefrontal and parietal cortex, left anterior superior temporal, and left middle occipital gyrus were found in the total group of PD patients, compared with controls (n = 14). This indicates that previously demonstrated functional deficits in PD patients with VH are not associated with grey matter loss. The strong left parietal reduction in both nondemented patient groups was hemisphere specific and independent of the side of PD symptoms.

Transcutaneous port for continuous duodenal levodopa/carbidopa administration in Parkinson's disease.

Motor fluctuations in Parkinson's disease (PD) can be reduced by intraduodenal infusion of levodopa-carbidopa (Duodopa®) via percutaneous endoscopic gastrojejunostomy (PEG). We applied the transcutaneous soft-tissue anchored titanium port (T-port) in 15 PD patients with motor fluctuations; 7 Duodopa-naive (non-PEG), and 8 previously receiving Duodopa (former-PEG). Motor scores (UPDRS-III) and quality of life (QOL, PDQ-8) were assessed at baseline and 6 month follow-up. Six patients had local irritation shortly after implantation, persisting in one patient at 6 month follow-up, which led to explantation. After having finished the protocol, four T-ports were explanted in total. UPDRS-III and PDQ-8 scores improved moderately in the non-PEG patients, but remained similar in the former-PEG users. Two former-PEG users developed polyneuropathy. No obstructions, retractions, or leakages occurred. Technical and hygienic properties of the T-port were preferred by most patients. The T-port seems to be suitable for most PD patients qualifying for Duodopa therapy, although local infection may lead to explantation during longer-term follow-up.

Attentional and perceptual impairments in Parkinson's disease with visual hallucinations.

Visual hallucinations (VH) are common in Parkinson's Disease (PD). Both deficits of perception and attention seem to play a role in the pathogenesis of VH in PD. However, the possible coexistence of impairments in attention and visual perception in PD with VH is not known. This study investigated both attention and visual perception in non-demented PD patients with VH, compared to PD patients without VH and healthy controls. Fourteen participants were included in each group. All patients were assessed with sustained visual attention and object and space perception tests. Only PD patients with VH showed impairments on object and space perception. In addition, PD patients with and without VH showed impairments on sustained visual attention, being more severely affected in PD patients with VH. Only in PD patients with VH sustained visual attention was associated with a decreased object and space perception. The results of our study thus suggest that in PD patients with VH an impairment of object and space perception, possibly in association with a decreased sustained visual attention, might play a role in the pathogenesis of VH.

Impaired visual processing preceding image recognition in Parkinson's disease patients with visual hallucinations.

Impaired visual processing may play a role in the pathophysiology of visual hallucinations in Parkinson's disease. In order to study involved neuronal circuitry, we assessed cerebral activation patterns both before and during recognition of gradually revealed images in Parkinson's disease patients with visual hallucinations (PDwithVHs), Parkinson's disease patients without visual hallucinations (PDnonVHs) and healthy controls. We hypothesized that, before image recognition, PDwithVHs would show reduced bottom-up visual activation in occipital-temporal areas and increased (pre)frontal activation, reflecting increased top-down demand. Overshoot of the latter has been proposed to play a role in generating visual hallucinations. Nine non-demented PDwithVHs, 14 PDnonVHs and 13 healthy controls were scanned on a 3 Tesla magnetic resonance imaging scanner. Static images of animals and objects gradually appearing out of random visual noise were used in an event-related design paradigm. Analyses were time-locked on the moment of image recognition, indicated by the subjects' button-press. Subjects were asked to press an additional button on a colour-changing fixation dot, to keep attention and motor action constant and to assess reaction times. Data pre-processing and statistical analysis were performed with statistical parametric mapping-5 software. Bilateral activation of the fusiform and lingual gyri was seen during image recognition in all groups (P < 0.001). Several seconds before image recognition, PDwithVHs showed reduced activation of the lateral occipital cortex, compared with both PDnonVHs and healthy controls. In addition, reduced activation of extrastriate temporal visual cortices was seen just before image recognition in PDwithVHs. The association between increased vulnerability for visual hallucinations in Parkinson's disease and impaired visual object processing in occipital and temporal extrastriate visual cortices supported the hypothesis of impaired bottom-up visual processing in PDwithVHs. Support for the hypothesized increased top-down frontal activation was not obtained. The finding of activation reductions in ventral/lateral visual association cortices in PDwithVHs before image recognition further helps to explain functional mechanisms underlying visual hallucinations in Parkinson's disease.

The effects of apomorphine on visual perception in patients with Parkinson disease and visual hallucinations: a pilot study.

Visual hallucinations (VHs) often occur in patients with advanced Parkinson disease (PD). Overstimulation of dopamine receptors has been considered as one of the causes for VHs in PD. However, several clinical studies suggested that apomorphine infusion did not worsen existing VHs in PD, but could even improve VHs in some PD patients. This pilot study included 4 PD patients with VHs, who were examined before, during, and after an intravenous infusion with apomorphine. The examinations included tests for lower- and higher-order visual functions, attention, and motor functions. Apomorphine had a significantly positive effect on contrast sensitivity and showed a significantly negative effect on attention. These results may explain why apomorphine is able to improve VHs in PD in some patients with mainly visual perceptive problems, but may also worsen VHs in other patients because of impaired attention.

Visual object recognition and attention in Parkinson's disease patients with visual hallucinations.

Visual hallucinations (VH) are common in Parkinson's disease (PD) and are hypothesized to be due to impaired visual perception and attention deficits. We investigated whether PD patients with VH showed attention deficits, a more specific impairment of higher order visual perception, or both. Forty-two volunteers participated in this study, including 14 PD patients with VH, 14 PD patients without VH and 14 healthy controls (HC), matched for age, gender, education level and for level of executive function. We created movies with images of animals, people, and objects dynamically appearing out of random noise. Time until recognition of the image was recorded. Sustained attention was tested using the Test of Attentional Performance. PD patients with VH recognized all images but were significantly slower in image recognition than both PD patients without VH and HC. PD patients with VH showed decreased sustained attention compared to PD patients without VH who again performed worse than HC. In conclusion, the recognition of objects is intact in PD patients with VH; however, these patients where significantly slower in image recognition than patients without VH and HC, which was not explained by executive dysfunction. Both image recognition speed and sustained attention decline in PD, in a more progressive way if VH start to occur.