Limb-kinetic apraxia affects activities of daily living in Parkinson's disease: a multi-center study.

BACKGROUND AND PURPOSE: Impaired dexterity (fine hand movements) is often present in Parkinson's disease (PD), even at early to moderate disease stages. It has a detrimental impact on activities of daily living (ADL) such as buttoning, contributing to reduced quality of life. Limb-kinetic apraxia, a loss of the ability to make precise, independent but coordinated finger and hand movements, may contribute to impaired dexterity even more than bradykinesia per se. However, the impact of limb-kinetic apraxia on ADL remains controversial. Our aim was to identify the strongest predictor of buttoning and unbuttoning in PD. It was hypothesized that coin rotation (a surrogate of limb-kinetic apraxia) represents the most important determinant. METHODS: Sixty-four right-handed, early to moderate PD patients were recruited from three movement disorder centers (Hoehn andYahr stages 1-3). Buttoning, unbuttoning and coin rotation (right and left hand) represented the target tasks. Motor impairment was assessed according to the Unified Parkinson's Disease Rating Scale. RESULTS: Multiple linear regression analysis showed that coin rotation with the right hand was the only significant predictor of buttoning (P < 0.001) and unbuttoning (P = 0.002). Notably, measures of bradykinesia or overall motor impairment did not represent significant predictors. CONCLUSIONS: Constituting the novel key finding, limb-kinetic apraxia seems to be particularly relevant for ADL requiring dexterity skills in PD, even at early to moderate disease stages. Our results prompt research into the pathophysiological background and therapeutic options to treat limb-kinetic apraxia. The simple coin rotation test provides valuable information about ADL-related dexterity skills.

Differential functional benefits of ultra highfield MR systems within the language network.

Several investigations have shown limitations of fMRI reliability with the current standard field strengths. Improvement is expected from ultra highfield systems but studies on possible benefits for cognitive networks are lacking. Here we provide an initial investigation on a prominent and clinically highly-relevant cognitive function: language processing in individual brains. 26 patients evaluated for presurgical language localization were investigated with a standardized overt language fMRI paradigm on both 3T and 7T MR scanners. During data acquisition and analysis we made particular efforts to minimize effects not related to static magnetic field strength differences. Six measures relevant for functional activation showed a large dissociation between essential language network nodes: although in Wernicke's area 5/6 measures indicated a benefit of ultra highfield, in Broca's area no comparison was significant. The most important reason for this discrepancy was identified as being an increase in susceptibility-related artifacts in inferior frontal brain areas at ultra high field. We conclude that functional UHF benefits are evident, however these depend crucially on the brain region investigated and the ability to control local artifacts.

Fractal image perception provides novel insights into hierarchical cognition.

Hierarchical structures play a central role in many aspects of human cognition, prominently including both language and music. In this study we addressed hierarchy in the visual domain, using a novel paradigm based on fractal images. Fractals are self-similar patterns generated by repeating the same simple rule at multiple hierarchical levels. Our hypothesis was that the brain uses different resources for processing hierarchies depending on whether it applies a "fractal" or a "non-fractal" cognitive strategy. We analyzed the neural circuits activated by these complex hierarchical patterns in an event-related fMRI study of 40 healthy subjects. Brain activation was compared across three different tasks: a similarity task, and two hierarchical tasks in which subjects were asked to recognize the repetition of a rule operating transformations either within an existing hierarchical level, or generating new hierarchical levels. Similar hierarchical images were generated by both rules and target images were identical. We found that when processing visual hierarchies, engagement in both hierarchical tasks activated the visual dorsal stream (occipito-parietal cortex, intraparietal sulcus and dorsolateral prefrontal cortex). In addition, the level-generating task specifically activated circuits related to the integration of spatial and categorical information, and with the integration of items in contexts (posterior cingulate cortex, retrosplenial cortex, and medial, ventral and anterior regions of temporal cortex). These findings provide interesting new clues about the cognitive mechanisms involved in the generation of new hierarchical levels as required for fractals.

The benefits of skull stripping in the normalization of clinical fMRI data.

Establishing a reliable correspondence between lesioned brains and a template is challenging using current normalization techniques. The optimum procedure has not been conclusively established, and a critical dichotomy is whether to use input data sets which contain skull signal, or whether skull signal should be removed. Here we provide a first investigation into whether clinical fMRI benefits from skull stripping, based on data from a presurgical language localization task. Brain activation changes related to deskulled/not-deskulled input data are determined in the context of very recently developed (New Segment, Unified Segmentation) and standard normalization approaches. Analysis of structural and functional data demonstrates that skull stripping improves language localization in MNI space - particularly when used in combination with the New Segment normalization technique.

Clinical fMRI: evidence for a 7T benefit over 3T.

Despite there being an increasing number of installations of ultra high field MR systems (>3T) in clinical environments, no functional patient investigations have yet examined possible benefits for functional diagnostics. Here we performed presurgical localization of the primary motor hand area on 3T and 7T Siemens scanners with identical investigational procedures and comparable system specific sequence optimizations. Results from 17 patients showed significantly higher functional sensitivity of the 7T system measured via percent signal change, mean t-values, number of suprathreshold voxels and contrast to noise ratio. On the other hand, 7T data suffered from a significant increase of artifacts (ghosting, head motion). We conclude that ultra high field systems provide a clinically relevant increase of functional sensitivity for patient investigations.

FMRI correlates of apraxia in Parkinson's disease patients OFF medication.

Impairment of hand dexterity in Parkinson's disease (PD) is usually attributed to bradykinesia. Recently, behavioral studies illustrated that decreased dexterity might also be due to limb-kinetic apraxia (LkA), as demonstrated by impaired performance in a coin rotation task. Here, we provide a first investigation on whether functional magnetic resonance imaging (fMRI) may reveal specific brain activation patterns for PD patients with impaired performance in a coin rotation task. We compared coin rotation as an apraxia task to simple finger tapping as a bradykinesia task in ten PD patients OFF medication and matched healthy controls. In addition to a tendency for general overactivation, PD patients showed a perirolandic dissociation with precentral overactivation and postcentral underactivation. This finding significantly separated PD patients from healthy controls.

[Methodological problems with clinical functional MRI investigations]. / Methodische Probleme klinischer funktioneller MRT-Untersuchungen.

During presurgical diagnostics clinical functional magnetic resonance imaging is increasingly being performed to improve the management of epilepsy and tumor patients. Rapid technical developments in fMRI technology continuously further new diagnostic applications. Safe clinical application requires a profound and critical handling of the various methodological problems inherent with this complex technique. This article reviews relevant problems and solutions for patient investigations up to the preparation of an individual clinical fMRI report.

Improvement of clinical language localization with an overt semantic and syntactic language functional MR imaging paradigm.

BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is a promising but, in some aspects, still debated noninvasive tool for functional language mapping. We developed a clinical fMRI overt language design at the sentential level to optimize sensitivity for language-related areas of the brain. To evaluate applicability and sensitivity, we investigated a consecutive series of presurgical patients with epilepsy with minimal morphologic brain abnormalities. MATERIALS AND METHODS: Thirty right-handed patients with temporal lobe epilepsy (TLE) and a control group of 23 right-handed healthy subjects participated in the study. The language design included semantic and syntactic error-detection tasks and was constructed to represent the most relevant aspects of everyday language demands. It was applied during block-designed fMRI runs. We performed image preprocessing and statistical analysis with SPM5 at a group level, applying widely used statistical criteria. The study was approved by the local ethics committee, and all participants gave written informed consent. RESULTS: Given the strict statistical criteria, the sensitivity for inferior frontal and posterior temporal activations (comprising Broca and Wernicke regions) was improved relative to previous findings in the literature. For both language areas, we found 100% sensitivity in healthy subjects (Brodmann areas, BA22 and BA44) and 97% sensitivity in patients (when including BA47). Lateralization results demonstrated the capability to detect atypical language lateralizations in patients, which were more frequent in than those in healthy subjects. CONCLUSIONS: We developed a clinical language fMRI design that integrates various relevant aspects of everyday language demands and provides robust localization of core language areas.

Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome.

OBJECTIVES: The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). METHODS: Twenty two patients (10 males, 12 females, mean age 39 years, range 10-65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. RESULTS: FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). CONCLUSIONS: The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

Dissociation of supplementary motor area and primary motor cortex in human subjects when comparing index and little finger movements with functional magnetic resonance imaging.

This study provides the first investigation of supplementary motor area (SMA) and primary motor cortex (MI) activation with similar movements differing only in subjective difficulty of motor control. Brain activation with simple tapping of the right index finger (well trained during daily life and easy to perform) was compared with tapping of the little finger (less trained and difficult to perform) using functional magnetic resonance imaging at 3 Tesla. Due to optimised movement standardisation, extrinsic influences on activation levels such as movement complexity, amplitude and frequency were minimised. Fifth finger tapping significantly increased the number of activated SMA voxels by 450% whereas MI activation showed no significant difference between fingers. We conclude that with similar movements the degree of subjective difficulty specifically modifies SMA but not MI activation.

Finger somatotopy in human motor cortex.

Although qualitative reports about somatotopic representation of fingers in the human motor cortex exist, up to now no study could provide clear statistical evidence. The goal of the present study was to reinvestigate finger motor somatotopy by means of a thorough investigation of standardized movements of the index and little finger of the right hand. Using high resolution fMRI at 3 Tesla, blood oxygenation level-dependent (BOLD) responses in a group of 26 subjects were repeatedly measured to achieve reliable statistical results. The center of mass of all activated voxels within the primary motor cortex was calculated for each finger and each run. Results of all runs were averaged to yield an individual index and little finger representation for each subject. The mean center of mass localizations for all subjects were then submitted to a paired t test. Results show a highly significant though small scale somatotopy of fingerspecific activation patterns in the order indicated by Penfields motor homunculus. In addition, considerable overlap of finger specific BOLD responses was found. Comparing various methods of analysis, the mean center of mass distance for the two fingers was 2--3 mm with overlapping voxels included and 4--5 mm with overlapping voxels excluded. Our data may be best understood in the context of the work of Schieber (1999) who recently described overlapping somatotopic gradients in lesion studies with humans.

Quantification of fMRI artifact reduction by a novel plaster cast head holder.

In light of artifact-induced high variability of activation in fMRI repeat studies, we developed and tested a clinically useful plaster cast head holder (PCH) with improved immobilization, repositioning, and comfort. With PCH, there were considerably lower levels of translational and rotational head motion components compared to head fixation with conventional restraining straps (CRS). Rotational components cannot be fully compensated by realignment and lead to "false activations." In addition, task-correlated head motion, which highly increases the risk of artifacts, was considerably reduced with PCH, especially in a motion prone subject. Compared with PCH, head motion was 133% larger with CRS in a highly cooperative subject. With a motion prone subject, head motion range was increased by 769% (PCH: 0.9 mm, CRS: 7.8 mm), which may indicate the usefulness of PCH for restless patients. In functional activation maps, PCH alone yielded fewer residual motion artifacts than CRS + image registration. Subject tolerance of the head holder during the long measurement times of up to 2.5 hr was good, and slice orientation on different days confirmed the quality of repositioning.

Electrophysiological, neuropsychological and clinical findings in multiple sclerosis patients receiving interferon beta-1b: a 1-year follow-up.

We assessed serial event-related potentials (ERPs) as well as neuropsychological and clinical test findings in a group of multiple sclerosis (MS) patients (n = 14) treated with interferon beta-1b (INF-beta-1b) compared to normal controls (n = 14). All investigations were done within 1 week before INF-beta-1b therapy was started and 12 months later. An auditory oddball paradigm was employed. No significant differences in the N100, P200, N200 or P300 latencies between patients and control group were found, but 3 out of 14 MS patients developed abnormal P300 latencies (more than 2 standard errors from the mean) after 1 year of INF-beta-1b therapy. This was not reflected by the respective neurological impairment as assessed by the Expanded Disability Status Scale score. ERPs might be a useful tool in clinical studies in order to evaluate drug effects on cognition, but for a final statement, the analysis of ERPs in a larger group of patients is required.

Improvement of presurgical patient evaluation by generation of functional magnetic resonance risk maps.

Recent functional magnetic resonance imaging (FMRI) replication studies show a high variability of active voxels within subjects and across runs - a potentially harmful situation for clinical applications. We tried to reduce these uncertainties inherent in current presurgical FMRI. For this, a new high quality head fixation device was used to detect reliably activated voxels over repeated measurements. In addition high correlation thresholds were applied to define the areas with highest probability of activation. The results show a focussing of such functional high risk areas to only a few voxels which localized close to intraoperative cortical stimulation. The generation of such FMRI risk maps may improve validity of clinical localization and facilitate the development of currently missing standards for maximized but still safe tumor resection.

Supplementary motor area activation preceding voluntary movement is detectable with a whole-scalp magnetoencephalography system.

Despite the fact that the knowledge about the structure and the function of the supplementary motor area (SMA) is steadily increasing, the role of the SMA in the human brain, e.g., the contribution of the SMA to the Bereitschaftspotential, still remains unclear and controversial. The goal of this study was to contribute further to this discussion by taking advantage of the increased spatial information of a whole-scalp magnetoencephalography (MEG) system enabling us to record the magnetic equivalent of the Bereitschaftspotential 1, the Bereitschaftsfeld 1 (BF 1) or readiness field 1. Five subjects performed a complex, and one subject a simple, finger-tapping task. It was possible to record the BF 1 for all subjects. The first appearance of the BF 1 was in the range of -1.9 to -1.7 s prior to movement onset, except for the subject performing the simple task (-1 s). Analysis of the development of the magnetic field distribution and the channel waveforms showed the beginning of the Bereitschaftsfeld 2 (BF 2) or readiness field 2 at about -0.5 s prior to movement onset. In the time range of BF 1, dipole source analysis localized the source in the SMA only, whereas dipole source analysis containing also the time range of BF 2 resulted in dipole models, including dipoles in the primary motor area. In summary, with a whole-head MEG system, it was possible for the first time to detect SMA activity in healthy subjects with MEG.

Mental representations of movements. Brain potentials associated with imagination of eye movements.

OBJECTIVE: Current research in motor imagery is focused on similarities between actual and imagined movements on a central and a peripheral level of the nervous system. The present study measured slow cortical potentials (DC-potentials) during execution and internal simulation of memorized saccadic eye movements. METHODS: In 19 healthy righthanded subjects DC-potentials were recorded from 28 electrodes during execution and during imagination of a sequence of memorized eye movements during a visual imagery condition. RESULTS: Both oculomotor conditions showed a similar global level and similar topography of performance related DC-potentials, both strongly differed from the visual imagery condition and were lateralized to the left hemisphere. CONCLUSION: This study therefore supports the hypothesis that cortical brain structures responsible for execution and imagination of memorized saccadic eye movements are similar. The observed left hemispheric lateralization is in contrast to a previous study using bimanual movements. This discrepancy is discussed in relation to recent observations in apractic patients with parietal lesions.