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Biomedical subjects

Stefan Knecht

Publications and source records attributed to Stefan Knecht.

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

Ionization spectra and electronic decay in small iodide clusters: fully relativistic results.

Singly ionized systems in high-lying energetic final states can stabilize themselves via various electronic decay mechanisms. With increasing system size interatomic and intermolecular processes dominate over intra-atomic (Auger) decay channels. For the small (HI)(2) and (LiI)(2) clusters fully relativistic ionization spectra are calculated and the subsequent electronic decay of the cations is investigated. Due to the presence of the iodine atom a fully relativistic description is mandatory and was performed by the algebraic diagrammatic construction technique in its four-component form. The lifetimes of the singly ionized final states are estimated by the application of Weisskopf-Wigner [Z. Phys. 63, 54 (1930)] theory.

Journal Article↗
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↗
PubMed2006

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.

Botulinum Toxins, Type A↗
PubMed2006

Cerebral small vessel diseases: manifestations in young women.

PURPOSE OF REVIEW: Cerebral small vessel diseases are responsible for 20-30% of ischemic strokes as well as for a considerable proportion of cerebral hemorrhages and encephalopathies. Less known than the manifestations in old age are those in young women comprising posterior encephalopathy and Susac's syndrome. RECENT FINDINGS: Magnetic resonance imaging has allowed us to identify posterior encephalopathy, characterized by headache, seizures, visual disturbances and hypertension, as a frequent complication of preeclampsia/eclampsia syndrome in the perinatal and postpartum period. Magnetic resonance findings are pathognomonic with bilateral cortical-subcortical lesions in the posterior hemispheres typically sparing the calcarine fissure. Conversely, white matter lesions on magnetic resonance imaging particularly involving the corpus callosum, and a (subclinical) sensorineural hearing loss are diagnostic of the retinocochleocerebral vasculopathy called Susac's syndrome. SUMMARY: Posterior encephalopathy can also follow from a broad spectrum of endotheliotoxic conditions like chemotherapy, immunosuppression and sepsis. Early recognition of the disorder is decisive for a benign outcome since therapy consists of removal of precipitating factors, lowering of blood pressure and treatment with magnesium sulfate. The retinocochleocerebral vasculopathy appears to be underdiagnosed. An autoimmune-mediated arteriolopathy is presumed and the disease is nearly always monophasic. A variety of therapeutic approaches have been recommended, none of which, however, is based on anything other than anecdotal evidence.

Adult↗
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

Abnormal brain activation during movement observation in patients with conversion paralysis.

Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis.

Adult↗
PubMed2005

Excellent cognitive performance despite massive cerebral white matter changes.

Marked cerebral white matter changes are a frequent finding in the daily routine of magnetic resonance imaging of elderly patients. These findings are often equated with a decrease of cognitive function. Here we present a case of massive white matter changes but excellent cognitive performance, to avoid the automatism of drawing conclusions on intellectual ability by just interpreting the imaging data of elderly patients.

Aged↗
PubMed2005

Dominance for language and spatial processing: limited capacity of a single hemisphere.

Using functional magnetic resonance imaging during word generation and spatial judgement (Landmark task), we investigated how hemispheric specializations for language and spatial processing interact in healthy individuals. We found individuals with atypical, right-hemispheric dominance for language to have more bilateral activation during spatial judgement than individuals with typical, disjunct hemispheric specialization, that is, left dominance for language and right dominance for spatial tasks. These findings suggest that hemispheric specializations for language and spatial functions interfere to some extent and favour additional recruitment of the opposite hemispheres for spatial functions.

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

Cortical processing of esophageal sensation is related to the representation of swallowing.

The esophagus plays a major role in the act of swallowing. The aim of the present investigation was to apply whole-head magnetoencephalography in order to study the cortical processing of esophageal sensation in healthy humans in whom the cortical representation of swallowing had been established previously. The proximal esophagus was stimulated in nine participants by intermittent 5 ml water infusion. Submental EMG recording was used to identify trials, which were contaminated by subsequent swallowing. Esophageal stimulation led to changes in rhythmic activity of the brain that were localized in the left lateral primary sensorimotor cortex. The pattern of cortical activation showed the same hemispheric lateralization as that of volitional swallowing, however, being localized more lateral. The close anatomical vicinity of these two functions points to an important physiological link between the cortical processing of esophageal sensation and the cortical control of swallowing.

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↗
PubMed2005

Crossed cerebro-cerebellar language dominance.

In addition to its traditional role in motor control, the cerebellum has been implicated in various cognitive and linguistic functions. Lesion, anatomic, and functional imaging studies indicate a link between left frontal language regions and the right cerebellum. To probe the specificity of this circuit, we examined the association between language-related lateralized activation of the frontal cortex with lateralized activation of the cerebellum. Functional magnetic resonance imaging (fMRI) was carried out during letter-cued word generation in 14 healthy subjects: 7 subjects displayed typical left-hemisphere and 7 subjects displayed atypical right-hemisphere language dominance. We found activation of the cerebellar hemisphere contralateral to the language-dominant cerebral hemisphere in each subject. The cerebellar activation was confined to the lateral posterior cerebellar hemisphere (lobule VI, VII B, Cr I, Cr II). This study demonstrates that crossed cerebral and cerebellar language dominance is a typical characteristic of brain organization. The functional significance of the reported activations can now be tested in patients with lesions of the lateral posterior cerebellum.

Adult↗
PubMed2005

Atypical hemispheric dominance for attention: functional MRI topography.

The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention.

Adult↗
PubMed2004

Shifting of cortical somatosensory areas in a man with amelia.

The human brain represents the body in a homuncular fashion. Although these cortical representations are to some degree plastic, it is unclear how extensive this plasticity can be. Examinations of amputated or amelic subjects can contribute to answering this question. We examined a man who lacked both arms since birth and was free of phantom pain. Magnetic source imaging revealed that not only had the somatotopically adjacent representation of the lip moved into the cortical space usually representing the hand; but the representation of the foot had similarly moved towards the cortical hand area. These data illustrate a case of extensive cortical reorganization and suggest that the potential overlap of different body parts is much greater than previously anticipated.

Adult↗
PubMed2004

Transcranial magnetic stimulation of the occipital pole interferes with verbal processing in blind subjects.

Recent neuroimaging studies in blind persons show that the occipital cortex, including the primary visual cortex (V1), is active during language-related and verbal-memory tasks. No studies, however, have identified a causal link between early visual cortex activity and successful performance on such tasks. We show here that repetitive transcranial magnetic stimulation (rTMS) of the occipital pole reduces accuracy on a verb-generation task in blind subjects, but not in sighted controls. An analysis of error types revealed that the most common error produced by rTMS was semantic; phonological errors and interference with motor execution or articulation were rare. Thus, in blind persons, a transient 'virtual lesion' of the left occipital cortex interferes with high-level verbal processing

Analysis of Variance↗