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Biomedical subjects

Caterina Breitenstein

Publications and source records attributed to Caterina Breitenstein.

At least 19 recordsLinked to original sources
PubMed2006

High impact running improves learning.

Regular physical exercise improves cognitive functions and lowers the risk for age-related cognitive decline. Since little is known about the nature and the timing of the underlying mechanisms, we probed whether exercise also has immediate beneficial effects on cognition. Learning performance was assessed directly after high impact anaerobic sprints, low impact aerobic running, or a period of rest in 27 healthy subjects in a randomized cross-over design. Dependent variables comprised learning speed as well as immediate (1 week) and long-term (>8 months) overall success in acquiring a novel vocabulary. Peripheral levels of brain-derived neurotrophic factor (BDNF) and catecholamines (dopamine, epinephrine, norepinephrine) were assessed prior to and after the interventions as well as after learning. We found that vocabulary learning was 20 percent faster after intense physical exercise as compared to the other two conditions. This condition also elicited the strongest increases in BDNF and catecholamine levels. More sustained BDNF levels during learning after intense exercise were related to better short-term learning success, whereas absolute dopamine and epinephrine levels were related to better intermediate (dopamine) and long-term (epinephrine) retentions of the novel vocabulary. Thus, BDNF and two of the catecholamines seem to be mediators by which physical exercise improves learning.

Adult↗
PubMed2006

Tonic dopaminergic stimulation impairs associative learning in healthy subjects.

Endogenous dopamine plays a central role in salience coding during associative learning. Administration of the dopamine precursor levodopa enhances learning in healthy subjects and stroke patients. Because levodopa increases both phasic and tonic dopaminergic neurotransmission, the critical mechanism mediating the enhancement of learning is unresolved. We here probed how selective tonic dopaminergic stimulation affects associative learning. Forty healthy subjects were trained in a novel vocabulary of 45 concrete nouns over the course of 5 consecutive training days in a prospective, randomized, double-blind, placebo-controlled design. Subjects received the tonically stimulating dopamine-receptor agonist pergolide (0.1 mg) vs placebo 120 min before training on each training day. The dopamine agonist significantly impaired novel word learning compared to placebo. This learning decrement persisted up to the last follow-up 4 weeks post-training. Subjects treated with pergolide also showed restricted emotional responses compared to the PLACEBO group. The extent of 'flattened' affect with pergolide was related to the degree of learning inhibition. These findings suggest that tonic occupation of dopamine receptors impairs learning by competition with phasic dopamine signals. Thus, phasic signaling seems to be the critical mechanism by which dopamine enhances associative learning in healthy subjects and stroke patients.

Adult↗
PubMed2006

A shift of paradigm: from noradrenergic to dopaminergic modulation of learning?

d-Amphetamine coupled with behavioral training has been effective for improving functional recovery after stroke. d-amphetamine acts on multiple brain transmitter systems, but the recovery enhancing effect has been attributed to its noradrenergic actions. Another potent modulator of learning is dopamine, which may also enhance stroke recovery in humans. Based on data from previous studies of our group, we compared the learning enhancing effects of d-amphetamine with a more selective dopaminergic substance (levodopa) in identical protocols. Using a prospective, randomized, double-blind, placebo-controlled design, we had taught 60 male healthy subjects a miniature lexicon of 50 concrete nouns over the course of five consecutive training days using an associative learning principle. Subjects had received either d-amphetamine (0.25 mg/kg), levodopa/carbidopa (fixed dose of 100/25 mg), or placebo 90 min prior to training on each of the 5 days. Novel word learning was significantly enhanced in both the d-amphetamine and levodopa groups as compared to the placebo group. The learning superiority was maintained at the two re-assessments (1 week and 1 month post training). Both d-amphetamine and levodopa are thus potent drugs in enhancing learning in humans. We here discuss why the efficiency of both d-amphetamine and levodopa may be related to dopaminergic rather than noradrenergic actions.

Adrenergic Agents↗
PubMed2005

Transcranial magnetic stimulation--a sandwich coil design for a better sham.

OBJECTIVE: To improve the quality of TMS studies by developing a new sham condition. METHODS: We describe a novel and easily arranged TMS set-up of two standard TMS coils and a magnetic shield, stacked like a sandwich. In a first step we compare the magnetic field in the sham and verum conditions. In a second step we ask six subjects to rate the stimulation intensity. RESULTS: The magnetic field in the sham mode is reduced to about one eighth of that during verum stimulation. The attenuation of the magnetic field is not limited to the actual stimulation site but also effective at neighbouring brain areas, avoiding direct and indirect stimulation via connected neural pathways. This also minimizes stimulation of the skin, but as a consequence allows subjects to distinguish between verum and sham conditions when these are contrasted directly. The position of the coil system and the acoustic sensations are indistinguishable between sham and verum condition. Subjects are not able to discriminate TMS position and condition by external cues. CONCLUSIONS: The proposed TMS setup is simple and allows verum and sham TMS without interaction of the researcher. If used with the magnetic shield, the magnetic field in the brain is attenuated most. SIGNIFICANCE: With the sandwich TMS coil system it is possible to improve the quality of TMS studies.

Adult↗
PubMed2005

Hippocampus activity differentiates good from poor learners of a novel lexicon.

Language proficiency is a key to academic and workplace success for native and non-native speakers. It is largely unknown, however, why some people pick up languages more easily than others. We used event-related functional magnetic resonance imaging (e-fMRI) to elucidate which brain regions are modulated during the acquisition of a novel lexicon and which of these learning-related activity changes correlated with general semantic language knowledge. Fourteen healthy young subjects learned a novel vocabulary of 45 concrete nouns via an associative learning principle over the course of five blocks during e-fMRI. As a control condition, subjects took part in a structurally identical "No-Learning" condition lacking any learning principle. Overall, increasing vocabulary proficiency was associated with (intercorrelated) modulations of activity within the left hippocampus and the left fusiform gyrus, regions involved in the binding and integration of multimodal stimuli, and with an increasing activation of the left inferior parietal cortex, the presumed neural store of phonological associations. None of these activity changes were observed during the control condition. Furthermore, subjects who showed less suppression of hippocampal activity over learning blocks scored higher on semantic knowledge in their native language and learned the novel vocabulary more efficiently. Our findings indicate that (a) the successful acquisition of a new lexicon depends on correlated amplitude changes between the left hippocampus and neocortical regions and (b) learning-related hippocampus activity is a stable marker of individual differences in the ability to acquire and master vocabularies.

Adult↗
PubMed2005

Dopaminergic influences on formation of a motor memory.

The ability of the central nervous system to form motor memories, a process contributing to motor learning and skill acquisition, decreases with age. Dopaminergic activity, one of the mechanisms implicated in memory formation, experiences a similar decline with aging. It is possible that restoring dopaminergic function in elderly adults could lead to improved formation of motor memories with training. We studied the influence of a single oral dose of levodopa (100mg) administered preceding training on the ability to encode an elementary motor memory in the primary motor cortex of elderly and young healthy volunteers in a randomized, double-blind, placebo-controlled design. Attention to the task and motor training kinematics were comparable across age groups and sessions. In young subjects, encoding a motor memory under placebo was more prominent than in older subjects, and the encoding process was accelerated by intake of levodopa. In the elderly group, diminished motor memory encoding under placebo was enhanced by intake of levodopa to levels present in younger subjects. Therefore, upregulation of dopaminergic activity accelerated memory formation in young subjects and restored the ability to form a motor memory in elderly subjects; possible mechanisms underlying the beneficial effects of dopaminergic agents on motor learning in neurorehabilitation.

Adult↗
PubMed2004

Levodopa: faster and better word learning in normal humans.

Dopamine is a potent modulator of learning and has been implicated in the encoding of stimulus salience. Repetition, however, as required for the acquisition and reacquisition of sensorimotor or cognitive skills (e.g., in aphasia therapy), decreases salience. We here tested whether increasing brain levels of dopamine during repetitive training improves learning success. Forty healthy humans took 100mg of the dopamine precursor levodopa or placebo daily for 5 days in a randomized double-blind and parallel-group design. Ninety minutes later on each day, subjects were trained on an artificial vocabulary using a high-frequency repetitive approach. Levodopa significantly enhanced the speed, overall success, and long-term retention of novel word learning in a dose-dependent manner. These findings indicate new ways to potentiate learning in a variety of domains if conventional training alone fails.

Adult↗
PubMed2004

D-amphetamine boosts language learning independent of its cardiovascular and motor arousing effects.

D-Amphetamine (AMPH) was effective in a number of studies on motor and language recovery after stroke, but given safety concerns, its general use after stroke is still debated. Most stroke patients are excluded from treatment because of a significant risk of cardiovascular dysregulation. AMPH acts on multiple transmitter systems, and mainly the noradrenergic actions are related to the cardiovascular effects. If AMPH's cardiovascular and arousal effects were correlated with its plasticity-enhancing effects in humans, this would imply that desired and undesired effects are inevitably tied. If not, improved cerebral reorganization may not be mediated by AMPH's arousing effects and could be achieved with substances lacking the undesired cardiovascular effects. As a model for language recovery after stroke, we used a prospective, randomized, double-blind, placebo-controlled design and taught 40 healthy male subjects an artificial vocabulary of 50 concrete nouns over the course of five consecutive training days (high-frequency training). The associative learning principle involved higher co-occurrences of 'correct' picture-pseudoword pairings as compared to 'incorrect' pairings. Subjects received either AMPH (0.25 mg/kg) or placebo 90 min prior to training on each day. Novel word learning was significantly faster and better in the AMPH as compared to the placebo group. Increased learning success was maintained 1 month post-training. No correlation was found between training success and drug-induced increases in blood pressure, heart rate, or a facilitation of simple motor reaction time. Our data show that AMPH's plasticity-enhancing effect in humans is not related to its cardiovascular arousal. This suggests that the beneficial effects in stroke patients could also be obtained by less cardiovascular active drugs.

Adult↗
PubMed2004

Transcranial direct current stimulation disrupts tactile perception.

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.

Adult↗
PubMed2004

Specific and nonspecific effects of transcranial magnetic stimulation on picture-word verification.

Repetitive transcranial magnetic stimulation (rTMS) can temporarily impair or improve performance, including language processing. It remains unclear, however, (i) which scalp sites are most appropriate to achieve the desired effects and (ii) which experimental setups produce facilitation or inhibition of language functions. We assessed the effects of TMS at different stimulation sites on picture-word verification in healthy volunteers. Twenty healthy volunteers with left language lateralization, as determined by functional transcranial Dopplersonography, performed picture-word verification prior to and after rTMS (1 Hz for 600 s at 110% of subjects' resting motor thresholds). Stimulation sites were the classical language areas (Broca's and Wernicke's), their homolog brain regions of the right hemisphere, and the occipital cortex. Additionally, sham stimulation over Broca's area was applied in a subsample of 11 subjects. As a control task, 10 volunteers performed a colour-tone matching task under the same experimental conditions. There was a general nonspecific arousal effect for both verum and sham TMS for both the picture-word verification and for the control task. However, superimposed there were opposite effects on picture-word verification for stimulation of Wernicke's area and Broca's area, namely a relative inhibition in the case of Wernicke's area and a relative facilitation in the case of Broca's area. These results demonstrate that low frequency rTMS has both general arousing effects and domain-specific effects.

Adult↗
PubMed2004

Word learning can be achieved without feedback: implications for aphasia therapy.

PURPOSE: Children acquire new words through exposure, without the necessity for explicit feedback by caregivers. In aphasia therapy, feedback to the patient is considered an important asset even though the empirical base demonstrating superior learning with online feedback is lacking. The present study examined if healthy adults and patients with chronic aphasia can acquire a new lexicon by intense frequency of exposure alone. METHODS: We compared learning rates with "frequency of exposure alone" (no-feedback condition: n=19 healthy adults; two patients with chronic Broca's and Wernicke's aphasia, respectively) with a condition where subjects additionally received online feedback (feedback condition; n=19). The learning principle was higher statistical co-occurrences of "correct" picture-pseudoword pairings as compared to "incorrect" pairings. In the feedback condition, immediate online feedback on the correctness of respective choices was additionally provided. RESULTS: Both healthy groups successfully acquired the vocabulary. Feedback led to a slight initial acceleration of learning but did not improve latency to peak performance or long-term retention of lexical knowledge. These findings show that high frequency interactive exposure is a potent word learning mechanism in adults and that feedback is not crucial. This is further corroborated by our successful training of two patients with chronic aphasia without online feedback. CONCLUSIONS: Our findings demonstrate that word re-learning in aphasia could benefit from maximizing on the frequency of exposure and exploiting the therapeutic principle of "massed practice", which has been successful in physical rehabilitation after stroke. Additionally, economizing on feedback may prevent patients becoming discouraged by continuous confrontation with their deficits.

Adult↗
PubMed2003

Changing cortical excitability with low-frequency transcranial magnetic stimulation can induce sustained disruption of tactile perception.

Transcranial magnetic stimulation (TMS) is promising as a therapeutic tool, and TMS of the motor system has served as a model for regionally specific modulations of cortical excitability. It is unclear, however, to what extent response characteristics of the motor cortex are representative of other brain systems. We wanted to determine whether TMS could induce a sustained disruption of somatosensory processing beyond the stimulation duration, similar to observations in the motor system. We applied 1-Hz TMS at 110% of subjects' motor thresholds for a variable duration over the right and left somatosensory cortex before subjects performed a tactile frequency discrimination task with the left hand. Tactile discrimination was impaired only after TMS over the right somatosensory cortex (analysis of variance: p <.01). The duration of this impairment correlated with the duration of the preceding TMS; the effect lasted approximately 2 min after 5 min of TMS, 4 min after 10 min of TMS, and 8 min after 20 min of TMS. Two conclusions arise: 1) low-frequency TMS can interfere with tactile perception in a robust and sustained way, and 2) TMS dosing parameters effective in the motor system are also effective in the somatosensory system and may reflect a modality-independent response characteristic of the cerebral cortex.

Adult↗
PubMed2003

Learning of tactile frequency discrimination in humans.

Learning is based on the remodeling of neural connections in the brain. The purpose of the present study was to examine the extent to which training-induced improvements in tactile frequency discrimination in humans are correlated with an increase of cortical representations in the primary somatosensory cortex. Healthy male subjects (n = 16) were trained in a tactile frequency discrimination task of the left ring finger. During the first 15 days of training, there was a steep improvement in frequency discrimination, which generalized from the trained finger to its homologue on the opposite hand, and to a lesser extent, to the other fingers on both hands. During the following 15 days of training, there was only a minor improvement in tactile frequency discrimination. Retention of improved performance in frequency discrimination 30 days after training was demonstrated for all digits. Cortical finger representation in the primary somatosensory cortex, as measured by magnetic source imaging, did not change during training. Because of the generalized training effect and the lack of detectable increase in the cortical field evoked from the trained finger, we assume that skill improvement was mediated predominantly by regions outside the primary somatosensory cortex.

Adult↗
PubMed2003

Language perception activates the hand motor cortex: implications for motor theories of speech perception.

The precise mechanisms of how speech may have developed are still unknown to a large extent. Gestures have proven a powerful concept for explaining how planning and analysing of motor acts could have evolved into verbal communication. According to this concept, development of an action-perception network allowed for coding and decoding of communicative gestures. These were manual or manual/articulatory in the beginning and then became increasingly elaborate in the articulatory mode. The theory predicts that listening to the 'gestures' that compose spoken language should activate an extended articulatory and manual action-perception network. To examine this hypothesis, we assessed the effects of language on cortical excitability of the hand muscle representation by transcranial magnetic stimulation. We found the hand motor system to be activated by linguistic tasks, most notably pure linguistic perception, but not by auditory or visuospatial processing. The amount of motor system activation was comparable in both hemispheres. Our data support the theory that language may have evolved within a general and bilateral action-perception network.

Adult↗
PubMed2002

Development and validation of a language learning model for behavioral and functional-imaging studies.

To obtain a more precise understanding of the mechanisms involved in language acquisition in healthy subjects and the re-acquisition of language following brain damage, we developed a word learning model which can be used in behavioral and functional-imaging studies. We generated a set of spoken pseudowords, which were normalized with respect to duration and loudness, and (based on a rating study with 40 students) selected 50 pseudowords, which yielded few associations with existing words and were of neutral emotional valence. The selected pseudowords were paired with object drawings in a pseudo-randomized manner and each subject received a different combination of pairings. These auditory-visual pairs were used to train ten subjects solely on the basis of different frequencies of 'correct' and 'incorrect' pairings. This procedure resembles the acquisition of the first words during childhood. During a five-session training protocol, with one session per day, there was a linear increase of the learning curves, which then reached a plateau. Learning remained stable at 1 and 4 weeks retest intervals. Furthermore, subjects correctly translated the pseudowords into their native language, demonstrating the acquisition of word meanings. These findings indicate that the described associative learning program meets the requirements for a robust and ecologically meaningful model to study the neural mechanisms of language learning and plasticity.

Adult↗
PubMed2002

Reproducibility of hemispheric blood flow increases during line bisectioning.

OBJECTIVES: To determine if attention-related changes of hemispheric perfusion increases, as assessed by blood-flow sensitive techniques, are as reliable as language-related hemispheric perfusion increases. METHODS: The reproducibility of hemispheric blood flow velocity increases during a line bisection task was assessed with functional transcranial Doppler sonography. RESULTS: Over repeated examinations, the index of lateralization of 20 healthy subjects showed a high test-retest reproducibility (r=0.9, P<0.01). No practice effects were detected over the course of 10 re-assessments of one subject. CONCLUSIONS: Hemispheric lateralization of visuospatial attention is a robust phenomenon and can be reliably determined using perfusion sensitive measurements. Future studies should focus on investigating lesion-related reorganization of attentional processing with blood-flow sensitive techniques.

Adult↗
PubMed1998

Emotional processing following cortical and subcortical brain damage: contribution of the fronto-striatal circuitry.

The present study examined the differential contribution of cortical and subcortical brain structures in emotional processing by comparing patients with focal cortical lesions (n = 32) to those with primarily subcortical dysregulation of the basal ganglia (Parkinson's disease n = 14). A standardized measure of emotional perception (Tübingen Affect Battery) was used. Only patients in the more advanced stages of Parkinson's disease and patients with focal damage to the (right) frontal lobe differed significantly from controls in both facial expression and affective prosody recognition. The findings imply involvement of the fronto-striatal circuitry in emotional processing.

Journal Article↗