Caterina Breitenstein

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.

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.

Degree of language lateralization determines susceptibility to unilateral brain lesions

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

Physical activity and memory functions: are neurotrophins and cerebral gray matter volume the missing link?

Epidemiological studies reveal better cognitive function in physically active individuals. Possible mediators for this effect are neurotrophins, which are up-regulated through physical exercise and induce neuronal growth and synaptogenesis in the animal model. Here we cross-sectionally assessed 75 healthy older individuals for levels of physical activity, aerobic fitness, and memory encoding, as well as neurotrophin levels and cerebral gray matter volume. We found that physical activity, but not cardiovascular fitness, was associated with better memory encoding after controlling for age, sex, education, depression, alcohol consumption, and smoking. Higher levels of physical activity were associated with higher levels of the neurotrophin granulocyte colony stimulating factor (G-CSF) and increased cerebral gray matter volume in prefrontal and cingulate cortex as assessed by magnetic resonance voxel-based morphometry. While mediating factors will need to be further elucidated, these findings indicate that even low-level physical activity exerts beneficial effects on memory functions in older individuals.

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. Ann Neurol 2005;58:121–130

Functional re-recruitment of dysfunctional brain areas predicts language recovery in chronic aphasia.

Functional recovery in response to a brain lesion, such as a stroke, can even occur years after the incident and may be accelerated by effective rehabilitation strategies. In eleven chronic aphasia patients, we administered a short-term intensive language training to improve language functions and to induce cortical reorganization under rigorously controlled conditions. Overt naming performance was assessed during functional magnetic resonance imaging (fMRI) prior to and immediately after the language training. Regions of interest (ROIs) for statistical analyses were constituted by areas with individually determined abnormally high densities of slow wave generators (identified by magnetoencephalography prior to the language intervention) that clustered mainly in left perilesional areas. Three additional individually defined regions served to control for the specificity of the results for the selected respective target region: the homologue area of the individual patients lesion, the mirror image of the delta ROI in the right hemisphere and left hemispheric regions that did not produce a significant amount of slow wave activity. Treatment-induced changes of fMRI brain activation were highly correlated with improved naming of the trained pictures, but selectively within the pre-training dysfunctional perilesional brain areas. Our results suggest that remodeling of cortical functions is possible even years after a stroke. The behavioral gain seems to be mediated by brain regions that had been partially deprived from input after the initial stroke. We therefore provide first time direct evidence for the importance of treatment-induced functional reintegration of perilesional areas in a heterogeneous sample of chronic aphasia patients.

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.

Short-Term Anomia Training and Electrical Brain Stimulation

Background and Purpose— Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy. Methods— In a randomized, double-blind, sham-controlled crossover trial, we assessed if anodal transcranial direct current stimulation compared to cathodal transcranial direct current stimulation and sham stimulation over the right temporo-parietal cortex would improve the success of short-term high-frequency anomia training. Twelve chronic poststroke aphasia patients were studied. Naming outcome was assessed after training and 2 weeks later. Results— All training conditions led to a significant increase in naming ability, which was retained for at least 2 weeks after the end of the training. Application of anodal transcranial direct current stimulation significantly enhanced the overall training effect compared to sham stimulation. Baseline naming ability significantly predicted anodal transcranial direct current stimulation effects. Conclusions— Anodal transcranial direct current stimulation applied over the nonlanguage dominant hemisphere can enhance language training outcome in chronic aphasia. Clinical Trial Registration— URL: www.clinicaltrials.gov/. Unique identifier: NCT00822068.

Dopaminergic effects on encoding of a motor memory in chronic stroke

The effects of a single oral dose of levodopa administered in a randomized, double-blind, placebo-controlled cross-over design on formation of a motor memory were studied by a training protocol in patients with chronic stroke. Levodopa enhanced the ability of motor training to encode an elementary motor memory relative to placebo. Up-regulation of dopaminergic function may enhance motor memory formation, crucial for successful rehabilitative treatments in patients with chronic stroke.

Non-invasive brain stimulation improves object-location learning in the elderly

Remembering the location of objects, an integral part of everyday life, is known to decline with advancing age and early in the course of neurodegenerative dementia. Here, we aimed to test if object-location learning and its retention could be modified by noninvasive brain stimulation. In a group of 20 elderly (mean age 62.1 years) right-handed individuals, we applied transcranial direct current stimulation (tDCS; 20 minutes, 1 mA) over the right temporoparietal cortex, while subjects acquired the correct position of buildings on a street map using an associative learning paradigm. Each subject participated in a randomized and balanced order in 1 session of anodal tDCS and 1 session of sham stimulation, in a double-blind design with 2 parallel versions of the task. Outcome measures were learning success at the end of each session, and immediate as well as delayed (1 week) free recall. We found that subjects performed comparably in the learning task in the 2 conditions, but showed improved recall 1 week after learning with anodal tDCS compared with learning with sham stimulation. In conclusion, retention of object-location learning in the elderly may be modulated by noninvasive brain stimulation, a finding of potential relevance not only for normal aging but also for memory deficits in pathological aging.