De grootsheid van de kleine hersenen

Rede, in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van de leerstoel Systeemfysiologie aan het Erasmus MC, faculteit van de Erasmus Universtiteit Rotterdam op 25 april 200

Single session imaging of cerebellum at 7 tesla: Obtaining structure and function of multiple motor subsystems in individual subjects

The recent increase in the use of high field MR systems is accompanied by a demand for acquisition techniques and coil systems that can take advantage of increased power and accuracy without being susceptible to increased noise. Physical location and anatomical complexity of targeted regions must be considered when attempting to image deeper structures with small nuclei and/or complex cytoarchitechtonics (i.e. small microvasculature and deep nuclei), such as the brainstem and the cerebellum (Cb). Once these obstacles are overcome, the concomitant increase in signal strength at higher field strength should allow for faster acquisition of MR images. Here we show that it is technically feasible to quickly and accurately detect blood oxygen level dependent (BOLD) signal changes and obtain anatomical images of Cb at high spatial resolutions in individual subjects at 7 Tesla in a single one-hour session. Images were obtained using two high-density multi-element surface coils (32 channels in total) placed beneath the head at the level of Cb, two channel transmission, and three-dimensional sensitivity encoded (3D, SENSE) acquisitions to investigate sensorimotor activations in Cb. Two classic sensorimotor tasks were used to detect Cb activations. BOLD signal changes during motor activity resulted in concentrated clusters of activity within the Cb lobules associated with each task, observed consistently and independently in each subject: Oculomotor vermis (VI/VII) and CrusI/II for pro- and anti-saccades; ipsilateral hemispheres IV-VI for finger tapping; and topographical separation of eye- and hand- activations in hemispheres VI and VIIb/VIII. Though fast temporal resolution was not attempted here, these functional patches of highly specific BOLD signal changes may reflect small-scale shunting of blood in the microvasculature of Cb. The observed improvements in acquisition time and signal detection are ideal for individualized investigations such as differentiation of functional zones prior to surgery. Copyright

Impact of transcranial direct current stimulation (tDCS) on neuronal functions

Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates neuronal excitability by the application of a small electrical current. The low cost and ease of the technique has driven interest in potential clinical applications. However, outcomes are highly sensitive to stimulation parameters, leading to difficulty maximizing the technique's effectiveness. Although reversing the polarity of stimulation often causes opposite effects, this is not always the case. Effective clinical application will require an understanding of how tDCS works; how it modulates a neuron; how it affects the local network; and how it alters inter-network signaling. We have summarized what is known regarding the mechanisms of tDCS from sub-cellular processing to circuit level communication with a particular focus on what can be learned from the polarity specificity of the effects

Superposition violations in the compensatory eye movement system

PURPOSE. Compensatory eye movements (CEM) maintain a stable image on the retina by minimizing retinal slip. The optokinetic reflex (OKR) and vestibulo-ocular reflex (VOR) compensate for low and high velocity stimuli, respectively. The OKR system is known to be highly nonlinear. The VOR is generally modeled as a linear system and assumed to satisfy the superposition and homogeneity principles. To probe CEM violation of the superposition principle, we recorded eye movement responses in C57BL/6 mice to sum of sine (SoS) stimulation, a combination of multiple nonharmonic inputs. METHODS. We tested the VOR, OKR, WOR (visually enhanced VOR), and SVOR (suppressed VOR). We used stimuli containing 0.6 Hz, 0.8 Hz, 1.0 Hz, and 1.9 Hz. Power spectra of SoS stimuli did not yield distortion products. Gains and delays of SoS and single sine (SS) responses were compared to yield relative gains and delays. RESULTS. We find the superposition principle is violated primarily in the OKR, VOR, and SVOR conditions. In OKR, we observed relative gain suppression of the lower SoS stimulus frequency component irrespective of the absolute frequency. Conversely, SVOR and VOR results showed gain enhancement of the lower frequency component and overall decrease in lead. Visually enhanced VOR results showed trends for overall gain suppression and delay decrease. CONCLUSIONS. Compensatory eye movements arguably depend on predictive signals. These results may reflect better prediction for SS stimuli. Natural CEM system stimulation generally involves complex frequency spectra. Use of SoS stimuli is a step toward unravelling the signals that really drive CEM and the predictive algorithms they depend on

Cerebellar tDCS does not enhance performance in an implicit categorization learning task

Background: Transcranial Direct Current Stimulation (tDCS) is a form of non-invasive electrical stimulation that changes neuronal excitability in a polarity and site-specific manner. In cognitive tasks related to prefrontal and cerebellar learning, cortical tDCS arguably facilitates learning, but the few studies investigating cerebellar tDCS, however, are inconsistent. Objective: We investigate the effect of cerebellar tDCS on performance of an implicit categorization learning task. Methods: Forty participants performed a computerized version of an implicit categorization learning task where squares had to be sorted into two categories, according to an unknown but fixed rule that integrated both the size and luminance of the square. Participants did one round of categorization to familiarize themselves with the task and to provide a baseline of performance. After that, 20 participants received anodal tDCS (20 min, 1.5 mA) over the right cerebellum, and 19 participants received sham stimulation and simultaneously started a second session of the categorization task using a new rule. Results: As expected, subjects performed better in the second session than in the first, baseline session, showing increased accuracy scores and reduced reaction times. Over trials, participants learned the categorization rule, improving their accuracy and reaction times. However, we observed no effect of anodal tDCS stimulation on overall performance or on learning, compared to sham stimulation. Conclusion: These results suggest that cerebellar tDCS does not modulate performance and learning on an implicit categorization task

Cerebellar tDCS does not affect performance in the N-back task

The N-back task is widely used in cognitive research. Furthermore, the cerebellums role in cognitive processes is becoming more widely recognized. Studies using transcranial direct current stimulation (tDCS) have demonstrated effects of cerebellar stimulation on several cognitive tasks. Therefore, the aim of this study was to investigate the effects of cerebellar tDCS on cognitive performance by using the N-back task. The cerebellum of 12 participants was stimulated during the task. Moreover, the cognitive load was manipulated in N = 2, N = 3, and N = 4. Every participant received three tDCS conditions (anodal, cathodal, and sham) divided over three separated days. It was expected that anodal stimulation would improve performance on the task. Each participant performed 6 repetitions of every load in which correct responses, false alarms, and reaction times were recorded. We found significant differences between the three levels of load in the rate of correct responses and false alarms, indicating that subjects followed the expected pattern of performance for the N-back task. However, no significant differences between the three tDCS conditions were found. Therefore, it was concluded that in this study cognitive performance on the N-back task was not readily influenced by cerebellar tDCS, and any true effects are likely to be small. We discuss several limitations in task design and suggest future experiments to address such issues

Cerebellar tDCS does not improve performance in probabilistic classification learning

In this study, the role of the cerebellum in a cognitive learning task using transcranial direct current stimulation (tDCS) was investigated. Using a weather prediction task, subjects had to learn the probabilistic associations between a stimulus (a combination of cards) and an outcome (sun or rain). This task is a variant of a probabilistic classification learning task, for which it has been reported that prefrontal tDCS enhances performance. Using a between-subject design, all 30 subjects learned to improve their performance with increasing accuracies and shortened response times over a series of 500 trials. Subjects also became more confident in their prediction during the experiment. However, no differences in performance and learning were observed between subjects receiving sham stimulation (n = 10) or anodal stimulation (2 mA for 20 min) over either the right cerebellum (n = 10) or the left prefrontal cortex (n = 10). This suggests that stimulating the brain with cerebellar tDCS does not readily influence probabilistic classification performances, probably due to the rather complex nature of this cognitive task

Visual search accelerates during adolescence

We studied changes in visual-search performance and behavior during adolescence. Search performance was analyzed in terms of reaction time and response accuracy. Search behavior was analyzed in terms of the objects fixated and the duration of these fixations. A large group of adolescents (N = 140; age: 12-19 years; 47% female, 53% male) participated in a visual-search experiment in which their eye movements were recorded with an eye tracker. The experiment consisted of 144 trials (50% with a target present), and participants had to decide whether a target was present. Each trial showed a search display with 36 Gabor patches placed on a hexagonal grid. The target was a vertically oriented element with a high spatial frequency. Nontargets differed from the target in spatial frequency, orientation, or both. Search performance and behavior changed during adolescence; with increasing age, fixation duration and reaction time decreased. Response accuracy, number of fixations, and selection of elements to fixate upon did not change with age. Thus, the speed of foveal discrimination increases with age, while the efficiency of peripheral selection does not change. We conclude that the way visual information is gathered does not change during adolescence, but the processing of visual information becomes faster

Cerebellar transcranial direct current stimulation effects on saccade adaptation

Saccade adaptation is a cerebellar-mediated type of motor learning in which the oculomotor system is exposed to repetitive errors. Different types of saccade adaptations are thought to involve distinct underlying cerebellar mechanisms. Transcranial direct current stimulation (tDCS) induces changes in neuronal excitability in a polarity-specific manner and offers a modulatory, noninvasive, functional insight into the learning aspects of different brain regions. We aimed to modulate the cerebellar influence on saccade gains during adaptation using tDCS. Subjects performed an inward (n = 10) or outward (n = 10) saccade adaptation experiment (25% intrasaccadic target step) while receiving 1.5 mA of anodal cerebellar tDCS delivered by a small contact electrode. Compared to sham stimulation, tDCS increased learning of saccadic inward adaptation but did not affect learning of outward adaptation. This may imply that plasticity mechanisms in the cerebellum are different between inward and outward adaptation. TDCS could have influenced specific cerebellar areas that contribute to inward but not outward adaptation. We conclude that tDCS can be used as a neuromodulatory technique to alter cerebellar oculomotor output, arguably by engaging wider cerebellar areas and increasing the available resources for learning

Performance on tasks of visuospatial memory and ability: A cross-sectional study in 330 adolescents aged 11 to 20

Cognitive functions mature at different points in time between birth and adulthood. Of these functions, visuospatial skills, such as spatial memory and part-to-whole organization, have often been tested in children and adults but have been less frequently evaluated during adolescence. We studied visuospatial memory and ability during this critical developmental period, as well as the correlation between these abilities, in a large group of 330 participants (aged 11 to 20 year