Papers by Anne-fleur Van Rootselaar
Brain, 2015
Although involvement of the cerebello-thalamo-cortical network has often been suggested in essent... more Although involvement of the cerebello-thalamo-cortical network has often been suggested in essential tremor, the source of oscillatory activity remains largely unknown. To elucidate mechanisms of tremor generation, it is of crucial importance to study the dynamics within the cerebello-thalamo-cortical network. Using a combination of electromyography and functional magnetic resonance imaging, it is possible to record the peripheral manifestation of tremor simultaneously with brain activity related to tremor generation. Our first aim was to study the intrinsic activity of regions within the cerebello-thalamo-cortical network using dynamic causal modelling to estimate effective connectivity driven by the concurrently recorded tremor signal. Our second aim was to objectify how the functional integrity of the cerebello-thalamo-cortical network is affected in essential tremor. We investigated the functional connectivity between cerebellar and cortical motor regions showing activations during a motor task. Twenty-two essential tremor patients and 22 healthy controls were analysed. For the effective connectivity analysis, a network of tremor-signal related regions was constructed, consisting of the left primary motor cortex, premotor cortex, supplementary motor area, left thalamus, and right cerebellar motor regions lobule V and lobule VIII. A measure of variation in tremor severity over time, derived from the electromyogram, was included as modulatory input on intrinsic connections and on the extrinsic cerebello-thalamic connections, giving a total of 128 models. Bayesian model selection and random effects Bayesian model averaging were used. Separate seed-based functional connectivity analyses for the left primary motor cortex, left supplementary motor area and right cerebellar lobules IV, V, VI and VIII were performed. We report two novel findings that support an important role for the cerebellar system in the pathophysiology of essential tremor. First, in the effective connectivity analysis, tremor variation during the motor task has an excitatory effect on both the extrinsic connection from cerebellar lobule V to the thalamus, and the intrinsic activity of cerebellar lobule V and thalamus. Second, the functional integrity of the motor network is affected in essential tremor, with a decrease in functional connectivity between cortical and cerebellar motor regions. This decrease in functional connectivity, related to the motor task, correlates with an increase in clinical tremor severity. Interestingly, increased functional connectivity between right cerebellar lobules I-IV and the left thalamus correlates with an increase in clinical tremor severity. In conclusion, our findings suggest that cerebello-dentato-thalamic activity and cerebello-cortical connectivity is disturbed in essential tremor, supporting previous evidence of functional cerebellar changes in essential tremor.
Nederlands tijdschrift voor geneeskunde
A 54-year-old man presented with headache and cognitive deterioration without other neurological ... more A 54-year-old man presented with headache and cognitive deterioration without other neurological signs, caused by intraventricular, thalamic, and caudate nucleus haemorrhage. He had longstanding hypertension, a known risk factor.
Parkinsonism & Related Disorders, 2015
Parkinsonism & related disorders, Jan 13, 2015
We investigated the relation between changes in clinician-based and patient-based measures of tre... more We investigated the relation between changes in clinician-based and patient-based measures of tremor severity, within the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) and Visual Analogue Scale (VAS) in essential tremor patients. Thirty-seven patients were assessed twice: on- and off-medication. Clinician-based, objective TRS assessments, consisting of part A (postures/movements) and part B (tremor-inducing tasks) were conducted by a blinded assessor using video-tapes. Patients completed TRS part C (limitations in activities of daily life) and indicated subjective tremor severity using VAS. Patients' total TRS and VAS scores improved on-medication (both p < 0.001). Mean improvement was 6.3 (sd 5.4) points on the total TRS and 2.3 (sd 2.3) points on the VAS score. Within the TRS, we found moderate correlations between changes in clinician-based TRS-B and patient-based TRS-C scores (ρ = 0.387, p = 0.011), but not between changes in clinician-based TRS-A and TRS-C scores (ρ = 0.12...
Trials, 2014
Electroencephalographic (EEG) status epilepticus is described in 10 to 35% of patients with posta... more Electroencephalographic (EEG) status epilepticus is described in 10 to 35% of patients with postanoxic encephalopathy after successful cardiopulmonary resuscitation and is associated with case fatality rates of 90 to 100%. It is unclear whether these EEG patterns represent a condition to be treated with anticonvulsants to improve outcome, or an expression of severe ischemic damage, in which treatment is futile. TELSTAR is a multicenter clinical trial with two parallel groups, randomized treatment allocation, open label treatment, and blinded endpoint evaluation (PROBE design). We aim to enroll 172 adult patients with postanoxic encephalopathy and electroencephalographic status epilepticus after successful cardiopulmonary resuscitation, admitted to the ICU, in whom continuous EEG monitoring is started within 24 hours after admission. Patients are randomly assigned to either medical treatment to suppress all electrographic seizure activity, or no treatment of electroencephalographic s...
Neurology, 2014
Objective: Propriospinal myoclonus (PSM) is a rare disorder with repetitive, usually flexor arrhy... more Objective: Propriospinal myoclonus (PSM) is a rare disorder with repetitive, usually flexor arrhythmic brief jerks of the trunk, hips, and knees in a fixed pattern. It has a presumed generation in the spinal cord and diagnosis depends on characteristic features at polymyography. Recently, a historical paradigm shift took place as PSM has been reported to be a functional (or psychogenic) movement disorder (FMD) in most patients. This review aims to characterize the clinical features, etiology, electrophysiologic features, and treatment outcomes of PSM.
Familial cortical myoclonic tremor with epilepsy (FCMTE) is characterized by a distal kinetic tre... more Familial cortical myoclonic tremor with epilepsy (FCMTE) is characterized by a distal kinetic tremor, infrequent epileptic attacks, and autosomal dominant inheritance. The tremor is thought to originate from the motor cortex. In our patient group, a premovement cortical spike could not be established on electroencephalogram (EEG) back-averaging. Corticomuscular and intermuscular coherence analysis can demonstrate a cortical common drive to muscles. We carried out coherence analysis of electromyography (EMG) of forearm muscles and EEG of contralateral motor cortex in 7 FCMTE patients, 8 essential tremor (ET) patients, and 7 healthy controls. Results showed strong cortico-and intermuscular coherence in the 8-to 30-Hz range in the FCMTE patients, with EEG preceding EMG. Healthy controls and ET patients showed normal weak coherence around 20 Hz. The ET patients showed some additional coherence at tremor frequency (6 Hz), probably the result of sensory information flowing back to the sensorimotor cortex. These findings point to a pathological cortical drive in FCMTE patients leading to tremulous movements. Coherence analysis is an easy and useful method to differentiate FCMTE from ET. Coherence analysis is helpful when investigating a cortical common drive in cortical tremor and other movement disorders.
Practical Neurology, 2009
NeuroImage: Clinical, 2014
Also, the use of multimodal neuroimaging techniques is a promising development in movement disord... more Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily clinical practice is limited.
Movement Disorders, 2005
Background: Over 60 Asian and European families with cortical myoclonic tremor and epilepsy have ... more Background: Over 60 Asian and European families with cortical myoclonic tremor and epilepsy have been reported under various names. Cerebellar changes may be part of the syndrome. In this study, we report the neuropathology findings in a new Dutch familial cortical myoclonic tremor with epilepsy case and review the literature on this syndrome.
Movement Disorders, 2007
Cortical hyperexcitability is a feature of “familial cortical myoclonic tremor with epilepsy” (FC... more Cortical hyperexcitability is a feature of “familial cortical myoclonic tremor with epilepsy” (FCMTE). However, neuropathological investigations in a single FCMTE patient showed isolated cerebellar pathology. Pathological investigations in a second FCMTE patient, reported here, confirmed cerebellar Purkinje cell degeneration and a normal sensorimotor cortex. Subsequently, we sought to explore the nature of cerebellar and motor system pathophysiology in FCMTE. Eye movement recordings and transcranial magnetic stimulation performed in six related FCMTE patients showed impaired saccades and smooth pursuit and downbeat nystagmus upon hyperventilation, as in patients with spinocerebellar ataxia type 6. In FCMTE patients short-interval intracortical inhibition (SICI) was significantly reduced. Resting motor threshold, recruitment curve, silent period, and intracortical facilitation were normal. The neuropathological and ocular motor abnormalities indicate cerebellar involvement in FCMTE patients. Decreased SICI is compatible with intracortical GABAA-ergic dysfunction. Cerebellar and intracortical functional changes could result from a common mechanism such as a channelopathy. Alternatively, decreased cortical inhibition may be caused by dysfunction of the cerebello-thalamo-cortical loop as a result of primary cerebellar pathology. © 2007 Movement Disorder Society
Movement Disorders, 2004
The clinical and neuropathological findings in a patient with familial cortical tremor with epile... more The clinical and neuropathological findings in a patient with familial cortical tremor with epilepsy (FCTE) are described. Clinically, the patient showed cortical myoclonus, tremor, and generalized seizures. Pathological investigation showed cerebellar degeneration and somal sprouting and loss of dendritic tree in Purkinje cells. Striking similarities were found in diseases caused by channelopathies such as spinocerebellar ataxia subtype 6.
Human Brain Mapping, 2012
The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating b... more The nucleus accumbens and medial frontal cortex (MFC) are part of a loop involved in modulating behavior according to anticipated rewards. However, the precise temporal landscape of their electrophysiological interactions in humans remains unknown because it is not possible to record neural activity from the nucleus accumbens using noninvasive techniques. We recorded electrophysiological activity simultaneously from the nucleus accumbens and cortex (via surface EEG) in humans who had electrodes implanted as part of deep-brain-stimulation treatment for obsessive-compulsive disorder. Patients performed a simple reward motivation task previously shown to activate the ventral striatum. Spectral Granger causality analyses were applied to dissociate ''top-down'' (cortex ! nucleus accumbens)-from ''bottom-up'' (nucleus accumbens ! cortex)-directed synchronization (functional connectivity). ''Topdown''-directed synchrony from cortex to nucleus accumbens was maximal over medial frontal sites and was significantly stronger when rewards were anticipated. These findings provide direct electrophysiological evidence for a role of the MFC in modulating nucleus accumbens reward-related processing and may be relevant to understanding the mechanisms of deep-brain stimulation and its beneficial effects on psychiatric conditions. Hum Brain Mapp 00:000-000,
Human Brain Mapping, 2008
Objective: To apply and validate the use of electromyogram (EMG) recorded during functional magne... more Objective: To apply and validate the use of electromyogram (EMG) recorded during functional magnetic resonance imaging (fMRI) in patients with movement disorders, to directly relate involuntary movements to brain activity. Methods: Eight ''familial cortical myoclonic tremor with epilepsy'' (FCMTE) patients, with tremor-like cortical myoclonus and cerebellar Purkinje cell degeneration, and nine healthy controls performed hand posture and movement in an on/off fashion (block design). Superfluous movements were quantified as deviations in EMG power, positive and negative, with respect to the average EMG per session. This measure, ''residual EMG'' (r-EMG), was derived by Gram-Schmidt orthogonalization. Activation maps resulting from conventional block regressors and novel r-EMG regressors were compared. Results: In healthy participants, the block posture regressor identified mainly cerebellar activity and some activity in other areas belonging to motor circuitry. In FCMTE patients, no cerebellar activity was seen with the block posture regressor, compatible with cerebellar Purkinje cell changes in FCMTE. EMG power showed little variation during posture in healthy controls. Therefore, the r-EMG regressor was almost constant and revealed no brain activity as expected. In contrast, in FCMTE patients the r-EMG posture regressor was highly variable due to continuous myoclonic jerks. It identified sensorimotor cortical areas, compatible with cortical hyperexcitability in FCMTE patients. Conclusion: Conventional block regressors can be used to identify neuronal circuitry associated with a specific motor task, whereas r-EMG regressors can help identify brain activation directly related to involuntary movements. Simultaneous EMG-fMRI is complementary to conventional fMRI and will facilitate studies of hyperkinetic movement disorders.
Human Brain Mapping, 2007
The goal of the present validation study is to show that continuous surface EMG recorded simultan... more The goal of the present validation study is to show that continuous surface EMG recorded simultaneously with 3T fMRI can be used to identify local brain activity related to (1) motor tasks, and to (2) muscle activity independently of a specific motor task, i.e. spontaneous (abnormal) movements. Five healthy participants performed a motor task, consisting of posture (low EMG power), and slow (medium EMG power) and fast (high EMG power) wrist flexion-extension movements. Brain activation maps derived from a conventional block design analysis (block-only design) were compared with brain activation maps derived using EMG-based regressors: (1) using the continuous EMG power as a single regressor of interest (EMG-only design) to relate motor performance and brain activity, and (2) using EMG power variability as an additional regressor in the fMRI block design analysis to relate movement variability and brain activity (mathematically) independent of the motor task. The agreement between the identified brain areas for the block-only design and the EMG-only design was excellent for all participants. Additionally, we showed that EMG power variability correlated well with activity in brain areas known to be involved in movement modulation. These innovative EMG-fMRI analysis techniques will allow the application of novel motor paradigms. This is an important step forward in the study of both the normally functioning motor system and the pathophysiological mechanisms in movement disorders. Hum Brain Mapp 28: [1117][1118][1119][1120][1121][1122][1123][1124][1125][1126][1127] 2007. V V C 2007 Wiley-Liss, Inc.
Experimental Neurology, 2013
Myoclonus-dystonia (MD) is a movement disorder characterized by myoclonic jerks, dystonic posture... more Myoclonus-dystonia (MD) is a movement disorder characterized by myoclonic jerks, dystonic postures and psychiatric co-morbidity. A mutation in the DYT11 gene underlies half of MD cases. We hypothesize that MD results from a dysfunctional basal ganglia network causing insufficient inhibitory motor control. To test this hypothesis functional MRI (fMRI) was performed using a validated &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Go/No go&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; task, in order to localize blood-oxygen-level dependence (BOLD) effects corresponding to Response Inhibition (RI). Twenty-four MD patients (fifteen DYT11 positive) and 24 matched controls responded with a button press to Go (Go-Response) or No go (referred to as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Stop&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;) cues, resulting in analyses of accurate response suppression to Stop cues (Stop-Inhibit), and incorrect responses to Go cues (Go-Inhibit), or to Stop cues (Stop-Response). Response accuracy in patients was impaired due to frequent Go-Inhibit errors. Image analysis of the Stop-Inhibit contrast demonstrated frontal, caudate and cingular activity in both groups. Compared to controls, MD patients showed increased primary motor cortex and insular activation. During Go-Inhibit trials, patients revealed increased activity in the contralateral thalamus (ventral lateral nucleus) and dorso-lateral-prefrontal cortex. In a post-hoc analysis comparing MD patients, DYT11 positive patients demonstrated anterior cerebellum hyperactivation on all contrasts and increased putaminal activation in the Stop-Response contrast. This study demonstrates a distinct association of motor symptoms in MD with the ventral lateral nucleus of the thalamus. Cerebellar dysfunction distinguishes DYT11 positive from negative patients. We suggest that MD might be best considered as a disorder of the cortico-ponto-cerebello-thalamo-cortical system.
Clinical Neurophysiology, 2006
mentalis or supraorbital nerves and intra-oral stimulation was delivered on the tongue. Analysis ... more mentalis or supraorbital nerves and intra-oral stimulation was delivered on the tongue. Analysis was performed using peristimulus time histograms and cumulative sum plots.
NeuroImage: Clinical, 2016
Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous researc... more Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies. We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations. Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V. Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.
Magnetic Resonance Imaging, 2016
Dedicated pairs of isometric wrist flexion tasks, with and without visual feedback of the exerted... more Dedicated pairs of isometric wrist flexion tasks, with and without visual feedback of the exerted torque, were designed to target activation of the CBL and BG in healthy subjects during functional magnetic resonance imaging (fMRI). Selective activation of the cerebellum (CBL) and basal ganglia (BG), often implicated in movement disorders such as tremor and dystonia, may help identify pathological changes and expedite diagnosis. A prototyped MR-compatible wrist torque measurement device, free of magnetic and conductive materials, allowed safe execution of tasks during fMRI without causing artifacts. A significant increase of activity in CBL and BG was found in healthy volunteers during a constant torque task with visual feedback compared to a constant torque task without visual feedback. This study shows that specific pairs of motor tasks using MR-compatible equipment at the wrist allow for targeted activation of CBL and BG, paving a new way for research into the pathophysiology of movement disorders.
Magnetic Resonance Imaging, 2016
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Papers by Anne-fleur Van Rootselaar