Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

A fresh look at an old nano-technology: catalysis.

The development of model catalyst systems for heterogeneous catalysis going beyond the metal single crystal approach, including phenomena involving the limited size of metal nanoparticles supported on oxide surfaces, as well as the electronic interaction through the oxide-metal interface, is exemplified on the basis of two case studies from the laboratory of the authors. In the first case study the reactivity of supported Pd nanoparticles is studied in comparison with Pd single crystals. The influence of carbon contaminants on the hydrogenation reaction of unsaturated hydrocarbons is discussed. Carbon contaminants are identified as a key parameter in those reactions as they control the surface and sub-surface concentration of hydrogen on and in the particles. In the second case study, scanning probe techniques are used to determine electronic and structural properties of supported Au particles as a function of the number of Au atoms in the particle. It is demonstrated how charge transfer between the support and the particle determines the shape of nanoparticles and a concept is developed that uses charge transfer control through dopants in the support to understand and design catalytically active materials.

Morphological and chemical influences on alumina-supported palladium catalysts active for the gas phase hydrogenation of crotonaldehyde.

A series of five alumina-supported palladium catalysts have previously been prepared and characterised by a combination of CO chemisorption and infrared spectroscopy. The reactive attributes of these catalysts are examined using the hydrogenation of crotonaldehyde as a test reaction, using a modified infrared gas cell as a batch reactor. Periodic scanning of the infrared spectrum of the gaseous phase present over the Pd/Al(2)O(3) catalysts was used to construct reaction profiles. Four of the catalysts were able to facilitate a 2-stage hydrogenation process (crotonaldehyde → butanal → butanol), whilst one catalyst was totally selective for the first stage hydrogenation process (crotonaldehyde → butanal). Rate coefficients for the first and second stage hydrogenation processes are normalised to the number of surface palladium atoms for the particular catalyst. Correlation of these kinetic parameters as a function of mean particle size indicates the first stage process to be structure insensitive, whilst the second stage hydrogenation is structure sensitive. Chlorine residues associated with the preparative process of one of the catalysts is seen to selectively poison the second stage hydrogenation process for that catalyst. Structure/activity relationships are considered to explain the observed trends.

Real-time 3T fMRI data of brain tumour patients for intra-operative localization of primary motor areas.

INTRODUCTION: In patients with tumours in or near the motor cortex reliable intra-operative identification of the precentral gyrus can be difficult due to anatomical dislocation. Maps of functional magnetic resonance imaging (fMRI) based on the blood oxygen level dependent (BOLD) effect are used to localize eloquent functional areas of the brain but require postprocessing for reduction of false positive activations. We set the focus of this study on the evaluation of feasibility and clinical usefulness of using real-time fMRI t-maps without postprocessing for pre-operative planning and intra-operative localization of functional motor areas. METHODS: Real-time fMRI t-maps from a 3-T MRI scanner were co-registered with MRI data. Ten patients were operated under general anaesthesia using 3D neuronavigation with integrated real-time fMRI t-maps. Surgical and functional outcome was compared to results of 12 patients who previously underwent wake surgeries. RESULTS: Good neurological outcome was achieved in all treated patients. Main activation clusters on fMRI real-time maps were easily identified. Co-registered real-time fMRI data without additional postprocessing were useful in planning the surgical approach. However, due to brain shift and large voxel size of BOLD contrast signals on t-maps exact localization of borders between tumours and functional areas was not possible intra-operatively. CONCLUSION: Our method is very simple to use and effective in guiding the neurosurgeon safely through minimally invasive craniotomies to tumours in eloquent areas without setting lesions to functional areas. Furthermore, the neurosurgeon is more independent when tumour location requires acquisition of fMRI data for pre-operative planning and intra-operative navigation.

Oxygen-deficient line defects in an ultrathin aluminum oxide film.

A model for the straight antiphase domain boundary of the ultrathin aluminum oxide film on the NiAl(110) substrate is derived from scanning tunneling microscopy measurements and density-functional theory calculations. Although the local bonding environment of the perfect film is maintained, the structure is oxygen deficient and possesses a favorable adsorption site. The domain boundary exhibits a downwards band bending and three characteristic unoccupied electronic states, in excellent agreement with scanning tunneling spectroscopy measurements.

Representational cortical plasticity associated with brain tumours: evidence from laser-induced interstitial thermotherapy.

OBJECTIVES: To test the hypothesis that cortical plasticity related to destructive tumour growth is functionally relevant. This hypothesis predicts that function is dependent on the intactness of tissue surrounding the tumour. MATERIAL AND METHODS: Eight patients underwent laser-induced interstitial thermotherapy (LITT) for minimally invasive palliative treatment of brain tumours located in eloquent frontal motor regions including the primary motor cortex. A multimodal approach was used to assess the functional outcome of patients after LITT in detail. RESULTS: Following LITT, motor function deteriorated in four patients. In three of these four patients the LITT-induced lesion involved minimal parts of adjacent non-tumorous tissue. By contrast, the other four patients whose LITT-induced signal changes were confined to the tumour, showed no functional deficits. CONCLUSION: These findings support the idea that peri-tumorous neuronal circuitry in motor competent areas may permanently take over those functions that were formerly represented in the neuronal tissue destroyed by the tumour.

Evaluation of healthcare utilization and health status of patients with Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: To assess the effects on motor functioning, health status and direct medical costs of high-frequency stimulation of the subthalamic nucleus (DBS-STN) in patients with idiopathic Parkinson's disease (PD). In addition, the cost-effectiveness of DBS-STN vs. drug treatment was investigated. METHODS: 16 consecutive patients with PD from two centers (Düsseldorf/Cologne; Kiel) treated by DBS-STN were prospectively evaluated. Clinical evaluations were done at baseline and 1, 3, 6, 12 months following surgery by means of the Unified Parkinson's disease Rating Scale (UPDRS). Health status of PD patients was assessed using the Sickness Impact Profile (SIP) at baseline and 6 months following surgery. Relevant economic data were taken from the medical records and costs (1999) were derived from different German medical economic resources. Costs were determined from the perspective of the health care provider. RESULTS: Following DBS-STN UPDRS scores (subscores and sum score) as well as health status improved considerably in PD patients. The overall SIP score and the physical dimension score (p < 0.009) were significantly different (p < 0.01) six month after surgery compared with baseline values. Mean costs of DM 40,020 (US dollars 20,810, EURO 20,410, GB pounds 12,810) per patient were spent during the 12 month observation period for in-patient and out-patient care. These expenses included already the costs for the electronic device for bilateral stimulation. Following DBS-STN medication was considerably reduced. Mean daily drug costs at baseline were DM 46.7+/-21.8 (US dollars 24, EURO 24, GB pounds 15) and DM 18.3+/-17.7 (US dollars 10, EURO 9, GB pounds 6) at 12 months following DBS-STN. Accounting for the decreased drug consumption, total annual costs amounted to DM 31,400 (US dollars 16,330, EURO 16,010, GB pounds 10,050). Further, we estimated the incremental cost effectiveness as DBS-STN had higher costs but was more effective than baseline treatment. The incremental total cost-effectiveness ratio for DBS-STN was DM 1.800 (US dollars 940, EURO 920, GB pounds 580) for one point decrease of the UPDRS. CONCLUSION: DBS-STN is an effective treatment that considerably alleviates the severity of signs and symptoms and improves the health status of patients with PD. Compared with drug treatment, however, the expenditures associated with DBS-STN are increased when only direct medical costs are considered in a one year horizon. However, on a long-term basis costs will decrease considerably because of the reduction of the drug expenditure and improved functioning in all activities of daily living. To adequately evaluate the cost-effectiveness of DBS-STN compared with standard drug regimen for PD it is necessary to include direct, indirect and intangible costs on a long-term basis and under standardized circumstances.

Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson's disease.

Bilateral high-frequency stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) both alleviate akinesia, rigidity, and tremor in idiopathic Parkinson's disease. To test the specific effect of these procedures on gait, we used quantitative gait analysis in addition to relevant subscores of the Unified Parkinson's Disease Rating Scale in a group of 10 patients with advanced Parkinson's disease treated by GPi stimulation and eight patients treated by STN stimulation. Patients were assessed before and 3 months after surgery. Thirty age-matched healthy subjects served as controls. The non-random selection allowed a descriptive but no direct statistical comparison of the respective procedure. Gait analysis showed significant stimulation-induced improvements of spatiotemporal gait and step parameters in both patient groups. Moreover, the effects on step length and cadence suggested a differential effect of both basal ganglia targets. Hence, the increase in gait velocity in the STN group was almost exclusively due to a significant increase in step length, while in the GPi group statistically non-significant increases in both step length and cadence contributed.

Deep brain stimulation of the internal pallidum did not improve chorea in a patient with neuro-acanthocytosis.

We report the failure of bilateral globus pallidus internus deep brain stimulation to improve chorea in a patient with chorea-acanthocytosis. Prior to this surgery the patient had experienced a striking but short lived amelioration of symptoms with clozapine therapy.

Neuromagnetic correlates of sensorimotor synchronization.

Sensorimotor synchronization tasks, in which subjects have to tap their finger in synchrony with an isochronous auditory click, typically reveal a synchronization error with the tap preceding the click by about 20 to 50 msec. Although extensive behavioral studies and a number of different explanatory accounts have located the cause of this so-called "negative asynchrony" on different levels of processing, the underlying mechanisms are still not completely understood. Almost nothing is known about the central processes, in particular, which sensory or motor events are synchronized by subjects. The present study examined central-level processing in synchronization tasks with magnetoencephalography (MEG). Eight subjects synchronized taps with their right index finger to an isochronous binaural pacing signal presented at an interstimulus interval of 800 msec. To gain information on central temporal coupling between "tap" and "click," evoked responses were averaged time-locked to the auditory signal and the tap onset. Tap-related responses could be explained with a three dipole model: One source, peaking at approximately 77 msec before tap onset, was localized in contralateral primary motor cortex (MI); the two other sources, peaking approximately at tap onset and 75 msec after tap onset, in contralateral primary somatosensory cortex (SI). Temporal coupling of these sources was compared in relation to different trigger points. The second SI source was equally well time-locked to the tap and to the auditory click. Furthermore, analysis of the time locking of this source activity as a function of the temporal order of tap and click showed that the second event - irrespective whether tap or click - was decisive in triggering the second SI source. This suggests that subjects use mainly sensory feedback in judging and evaluating whether they are "keeping time."

Cortical activation during oesophageal stimulation: a neuromagnetic study.

We investigated the neuromagnetic responses to mechanical stimulation of the oesophagus. In six healthy right-handed volunteers (mean age 31.6 years) the proximal and distal oesophagus were stimulated by electronically controlled pump-inflation of a silicone balloon once every 4.5-5.5 sec (dwell time 145 msec). The balloon volume was adjusted to induce different sensation levels (i) just above threshold of perception, (ii) strong sensation and (iii) painful sensation. Evoked magnetic brain responses were recorded time-locked to stimulus onset with a Neuromag-122TM whole-head neuromagnetometer and modelled as equivalent current diploe (ECD) sources. ECDs were superimposed on individual magnetic resonance imaging (MRI) scans. Magnetic brain responses following distal oesophageal stimulation were adequately explained by a time-varying 2-4 dipole model with unilateral or bilateral sources in second somatosensory cortex and later sources in the frontal cortex. With increasing stimulus intensities, latencies of the sources decreased and amplitudes increased. Proximal oesophageal stimulation led to activation of source areas spatially similar to those of distal oesophageal stimulation but with shorter response latencies. Both painful and nonpainful mechanical stimulation of the oesophagus activate the second somatosensory cortex (SII). Evidence for topographic organization of oesophageal afferents in SII is poor.

The role of ventral medial wall motor areas in bimanual co-ordination. A combined lesion and activation study.

Two patients with midline tumours and disturbances of bimanual co-ordination as the presenting symptoms were examined. Both reported difficulties whenever the two hands had to act together simultaneously, whereas they had no problems with unimanual dexterity or the use of both hands sequentially. In the first patient the lesion was confined to the cingulate gyrus; in the second it also invaded the corpus callosum and the supplementary motor area. Kinematic analysis of bimanual in-phase and anti-phase movements revealed an impairment of both the temporal adjustment between the hands and the independence of movements between the two hands. A functional imaging study in six volunteers, who performed the same bimanual in-phase and anti-phase tasks, showed strong activations of midline areas including the cingulate and ventral supplementary motor area. The prominent activation of the ventral medial wall motor areas in the volunteers in conjunction with the bimanual co-ordination disorder in the two patients with lesions compromising their function is evidence for their pivotal role in bimanual co-ordination.

Force regulation is deficient in patients with parietal lesions: a system-analytic approach.

By means of a quantitative system-analytic investigation strategy, the postural motor control of the fingers was evaluated, to characterise the possible deficit of force regulation in patients with parietal lesions. In spite of a normal response to short torque pulses, the parietal-lesion patients had difficulties in returning to the preload level after the application of an additional step torque load to fingers II-IV of their left or right hands. The control offset (measured 500 ms after step torque application) was significantly larger in the patient group. This deficit in the investigated patients with parietal lesions to compensate for step torque loads was not due to a paresis, but rather resulted from a disturbance in the generation of a sufficient counterforce against the applied step torque within an adequate time window and motor pattern. This distinct force-regulation deficit was found in patients with left- and right-sided parietal lesions.

Functional organization of the auditory cortex is different in stutterers and fluent speakers.

Impaired auditory feedback has been suggested to cause stuttering, and subtle irregularities of audition have been reported in behavioural studies. To characterize processing at the auditory cortical level, we recorded neuromagnetic responses to monaural tones in nine stutterers and 10 fluent speakers while the subjects were reading silently, with mouth movements only, aloud, and in chorus with another person. The basic functional organization of the auditory cortices was found to be different in stutterers and controls. The altered interhemispheric balance in stutterers was affected by speech production, due to changes in the left auditory cortical representation, and more severely by self-paced than accompanied speech. This may lead to transient non-optimal interpretation of the auditory input and affect speech fluency.

Interaction of finger representation in the human first somatosensory cortex: a neuromagnetic study.

Neuromagnetic responses to separate tactile stimulation of digits I, II and V and simultaneous stimulation of digit pairs II and I, and II and V, were recorded in six healthy adult subjects using a 122-channel whole-head neuromagnetometer in order to investigate functional overlap of finger representations in primary somatosensory cortex (SI). Evoked responses to single digit stimulation were explained by time-varying equivalent current dipoles (ECDs) located in SI. These ECDs were then used to explain responses to stimulation of digit pairs. A cortical interaction ratio (IR) was defined as the vector sum of peak source amplitudes to separate stimulations of two fingers divided by the vector sum of source amplitudes to simultaneous stimulation of the two digits. Mean IR was significantly higher (P<0.05; Wilcoxon test) for digit pair II + I (1.69+/- 0.15) compared to digit pair II + V (1.14+/- 0.12). These results indicate that there is an overlap of finger representations in human SI which differs between anatomically adjacent and non-adjacent digit pairs.

Precentral glioma location determines the displacement of cortical hand representation.

OBJECTIVE: Low-grade brain tumors may remain asymptomatic in contrast to malignant gliomas. The mechanisms underlying the preservation of cerebral function in such gliomas are not well understood. METHODS: We used positron emission tomography and transcranial magnetic stimulation for presurgical monitoring of motor hand function in six patients with gliomas of the precentral gyrus. All patients were able to perform finger movements of the contralesional hand. RESULTS: Movement-related increases of the regional cerebral blood flow occurred only outside the tumor in surrounding brain tissue. Compared with the contralateral side, these activations were shifted by 20 +/- 13 mm (standard deviation) within the dorsoventral dimension of the precentral gyrus. This shift of cortical hand representation could not be explained by the deformation of the central sulcus as determined from the spatially aligned magnetic resonance images but was closely related to the location of the maximal tumor growth. Dorsal tumor growth resulted in ventral displacement of motor hand representation, leaving the motor cortical output system unaffected, whereas ventral tumor growth leading to dorsal displacement of motor hand representation compromised the motor cortical output, as evident from transcranial magnetic stimulation. In two patients, additional activation of the supplementary motor area was present. CONCLUSION: Our data provide evidence for the reorganization of the human motor cortex to allow for preserved hand function in Grade II astrocytomas.

Late diagnosis of Wilson's disease in a case without onset of symptoms.

Wilson's disease (WD) was diagnosed on the basis of a liver biopsy, blood investigations and a radio copper test in a 60-year-old, neurologically normal female with uncharacteristic gastrointestinal complaints. Since this patient never developed symptoms indicative for WD this case suggests the possibility of a subclinical course of untreated WD.

Large-scale plasticity of the human motor cortex.

The adult primate brain is capable of modifying rapidly the size of cortical receptive fields or motor output modules in response to altered synaptic input. We used positron emission tomography (PET) to map the regional cerebral blood flow changes related to voluntary finger movements in patients with tumours occupying the hand area of motor cortex. All patients showed activations solely outside the tumour. Compared with the unaffected side, the activations were shifted by 9-43 mm either along the mediolateral body representation of motor cortex or into premotor or parietal somatosensory cortex. These results provide evidence that slowly developing lesions can induce large-scale reorganization that is not confined to changes within the somatotopic body representation in motor cortex.