Biomedical subjects

Matthias Mölle

Publications and source records attributed to Matthias Mölle.

11 recordsLinked to original sources

PubMed2006

Elevated sleep spindle density after learning or after retrieval in rats.

Non-rapid eye movement sleep has been strongly implicated in consolidation of both declarative and procedural memory in humans. Elevated sleep-spindle density in slow-wave sleep after learning has been shown recently in humans. It has been proposed that sleep spindles, 12-15 Hz oscillations superimposed on slow waves (<1 Hz), in concert with high-frequency hippocampal sharp waves/ripples, promote neural plasticity underlying remote memory formation. The present study reports the first indication of learning-associated increase in spindle density in the rat, providing an animal model to study the role of brain oscillations in memory consolidation during sleep. An odor-reward association task, analogous in many respects to human paired-associate learning, is rapidly learned and leads to robust memory in rats. Rats learned the task over 10 massed trials within a single session, and EEG was monitored for 3 h after learning. Learning-induced increase in spindle density is reliably reproduced in rats in two different learning situations, differing primarily in the behavioral component of the task. This increase in spindle density is also present after reactivation of remote memory and in situations when memory update is required; it is not observed after noncontingent exposure to reward and training context. The latter results substantially extend findings in humans. The magnitude of increase (approximately 25%) and the time window of maximal effect (approximately 1 h after sleep onset) were remarkably similar to human data, making this a valid rodent model to study network interactions through the use of simultaneous unit recordings and local field potentials during postlearning sleep.

Action Potentials↗

PubMed2006

Boosting slow oscillations during sleep potentiates memory.

There is compelling evidence that sleep contributes to the long-term consolidation of new memories. This function of sleep has been linked to slow (<1 Hz) potential oscillations, which predominantly arise from the prefrontal neocortex and characterize slow wave sleep. However, oscillations in brain potentials are commonly considered to be mere epiphenomena that reflect synchronized activity arising from neuronal networks, which links the membrane and synaptic processes of these neurons in time. Whether brain potentials and their extracellular equivalent have any physiological meaning per se is unclear, but can easily be investigated by inducing the extracellular oscillating potential fields of interest. Here we show that inducing slow oscillation-like potential fields by transcranial application of oscillating potentials (0.75 Hz) during early nocturnal non-rapid-eye-movement sleep, that is, a period of emerging slow wave sleep, enhances the retention of hippocampus-dependent declarative memories in healthy humans. The slowly oscillating potential stimulation induced an immediate increase in slow wave sleep, endogenous cortical slow oscillations and slow spindle activity in the frontal cortex. Brain stimulation with oscillations at 5 Hz--another frequency band that normally predominates during rapid-eye-movement sleep--decreased slow oscillations and left declarative memory unchanged. Our findings indicate that endogenous slow potential oscillations have a causal role in the sleep-associated consolidation of memory, and that this role is enhanced by field effects in cortical extracellular space.

Adult↗

PubMed2006

Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave sleep.

Slow oscillations originating in the prefrontal neocortex during slow-wave sleep (SWS) group neuronal network activity and thereby presumably support the consolidation of memories. Here, we investigated whether the grouping influence of slow oscillations extends to hippocampal sharp wave-ripple (SPW) activity thought to underlie memory replay processes during SWS. The prefrontal surface EEG and multiunit activity (MUA), along with hippocampal local field potentials (LFP) from CA1, were recorded in rats during sleep. Average spindle and ripple activity and event correlation histograms of SPWs were calculated, time-locked to half-waves of slow oscillations. Results confirm decreased prefrontal MUA and spindle activity during EEG slow oscillation negativity and increases in this activity during subsequent positivity. A remarkably close temporal link was revealed between slow oscillations and hippocampal activity, with ripple activity and SPWs being also distinctly decreased during negative half-waves and increased during slow oscillation positivity. Fine-grained analyses of temporal dynamics revealed for the slow oscillation a phase delay of approximately 90 ms with reference to up and down states of prefrontal MUA, and of only approximately 60 ms with reference to changes in SPWs, indicating that up and down states in prefrontal MUA precede corresponding changes in hippocampal SPWs by approximately 30 ms. Results support the notion that the depolarizing surface-positive phase of the slow oscillation and the associated up state of prefrontal excitation promotes hippocampal SPWs via efferent pathways. The preceding disfacilitation of hippocampal events temporally coupled to the negative slow oscillation half-wave appears to serve a synchronizing role in this neocorticohippocampal interplay.

Action Potentials↗

PubMed2005

Bifrontal transcranial direct current stimulation slows reaction time in a working memory task.

BACKGROUND: Weak transcortical direct current stimulation (tDCS) applied to the cortex can shift the membrane potential of superficial neurons thereby modulating cortical excitability and activity. Here we test the possibility of modifying ongoing activity associated with working memory by tDCS. The concept of working memory applies to a system that is capable of transiently storing and manipulating information, as an integral part of the human memory system. We applied anodal and cathodal transcranial direct current (tDCS) stimulation (260 microA) bilaterally at fronto-cortical electrode sites on the scalp over 15 min repeatedly (15 sec-on/15 sec-off) as well as sham-tDCS while subjects performed a modified Sternberg task. RESULTS: Reaction time linearly increased with increasing set size. The slope of this increase was closely comparable for real and sham stimulation indicating that our real stimulation did not effect time required for memory scanning. However, reaction time was slowed during both anodal and cathodal stimulation as compared to placebo (p < 0.05) indicating that real stimulation hampered neuronal processing related to response selection and preparation. CONCLUSION: Intermittent tDCS over lateral prefrontal cortex during a working memory task impairs central nervous processing related to response selection and preparation. We conclude that this decrease in performance by our protocol of intermittent stimulation results from an interference mainly with the temporal dynamics of cortical processing as indexed by event-related sustained and oscillatory EEG activity such as theta.

Adult↗

PubMed2004

Transcranial direct current stimulation during sleep improves declarative memory.

In humans, weak transcranial direct current stimulation (tDCS) modulates excitability in the motor, visual, and prefrontal cortex. Periods rich in slow-wave sleep (SWS) not only facilitate the consolidation of declarative memories, but in humans, SWS is also accompanied by a pronounced endogenous transcortical DC potential shift of negative polarity over frontocortical areas. To experimentally induce widespread extracellular negative DC potentials, we applied anodal tDCS (0.26 mA) [correction] repeatedly (over 30 min) bilaterally at frontocortical electrode sites during a retention period rich in SWS. Retention of declarative memories (word pairs) and also nondeclarative memories (mirror tracing skills) learned previously was tested after this period and compared with retention performance after placebo stimulation as well as after retention intervals of wakefulness. Compared with placebo stimulation, anodal tDCS during SWS-rich sleep distinctly increased the retention of word pairs (p < 0.005). When applied during the wake retention interval, tDCS did not affect declarative memory. Procedural memory was also not affected by tDCS. Mood was improved both after tDCS during sleep and during wake intervals. tDCS increased sleep depth toward the end of the stimulation period, whereas the average power in the faster frequency bands (,alpha, and beta) was reduced. Acutely, anodal tDCS increased slow oscillatory activity <3 Hz. We conclude that effects of tDCS involve enhanced generation of slow oscillatory EEG activity considered to facilitate processes of neuronal plasticity. Shifts in extracellular ionic concentration in frontocortical tissue (expressed as negative DC potentials during SWS) may facilitate sleep-dependent consolidation of declarative memories.

Adult↗

PubMed2004

Learning increases human electroencephalographic coherence during subsequent slow sleep oscillations.

Learning is assumed to induce specific changes in neuronal activity during sleep that serve the consolidation of newly acquired memories. To specify such changes, we measured electroencephalographic (EEG) coherence during performance on a declarative learning task (word pair associations) and subsequent sleep. Compared with a nonlearning control condition, learning performance was accompanied with a strong increase in coherence in several EEG frequency bands. During subsequent non-rapid eye movement sleep, coherence only marginally increased in a global analysis of EEG recordings. However, a striking and robust increase in learning-dependent coherence was found when analyses were performed time-locked to the occurrence of slow oscillations (<1 Hz). Specifically, the surface-positive half-waves of the slow oscillation resulting from widespread cortical depolarization were associated with distinctly enhanced coherence after learning in the slow-oscillatory, delta, slow-spindle, and gamma bands. The findings identify the depolarizing phase of the slow oscillations in humans as a time period particularly relevant for a reprocessing of memories in sleep.

Adult↗

PubMed2004

Transcortical direct current potential shift reflects immediate signaling of systemic insulin to the human brain.

Circulating insulin is thought to provide a major feedback signal for the hypothalamic regulation of energy homeostasis and food intake, although this signaling appears to be slowed by a time-consuming blood-to-brain transport. Here we show, by recording direct current potentials, a rapid onset of the effects of circulating insulin on human brain activity. Recordings were obtained from 27 men who were intravenously injected with insulin (0.1 mU/kg body wt as bolus) and placebo. In a euglycemic condition, hypoglycemia was prevented, while in the hypoglycemic condition, plasma glucose reached a postinjection nadir of 43 mg/dl. Insulin injection induced a marked negative direct current (DC) potential shift starting within 7 min in all subjects. With euglycemic conditions, the DC potential at 10-60 min postinsulin injection averaged -621.3 microV (compared with preinjection baseline). Hypoglycemia reduced this potential to an average of -331.2 microV. While insulin per se did not affect oscillatory electroencephalographic activity, hypoglycemia peaking 25 min after insulin injection was accompanied by an immediate increase in theta activity. The rapid emergence of the DC potential shift, reflecting gross ionic changes in brain tissues, indicates that systemic insulin can serve as an immediate feedback signal in the control of hypothalamic and higher brain functions.

Adult↗

PubMed2003

Acute influences of estrogen and testosterone on divergent and convergent thinking in postmenopausal women.

Previous studies indicated an enhanced capability of divergent creative thinking in young women during the ovulatory phase, which expressed itself also by an increased dimensional complexity of ongoing electroencephalographic (EEG) activity. Considering the enhanced plasma levels of estrogen and testosterone characterizing the ovulatory phase, we tested whether short-term administration of estrogen or testosterone in postmenopausal women with constantly low levels of gonadal steroids induces similar changes in divergent thinking. In two placebo-controlled cross-over studies, healthy postmenopausal women (n=12, in each study, mean age 58 years, range 47-65 years) were treated transdermally over 3 days with estrogen and testosterone, respectively, at doses inducing plasma hormone concentrations comparable with those observed in young women around ovulation. Capabilities of divergent thought and convergent analytical thought, performance on motor perseveration, and verbal memory were examined. EEG activity was recorded while subjects performed on tasks of thinking and during mental relaxation. Estrogen impaired divergent thinking (p <0.01) and enhanced convergent thinking, motor perseveration, and memory for the initial word list (p <0.05 for all tests). In parallel, EEG dimensional complexity was reduced (p <0.05). Overall, these changes indicate an estrogen-induced shift from a "divergent" towards a more "convergent" mode of processing. However, overall less consistent, effects of testosterone were opposite to those of estrogen. It increased performance on some of the divergent thinking tasks (p <0.05), and tended to increase EEG dimensional complexity during divergent thinking. Data indicate a differential sensitivity of modes of thinking to short-term treatment with estrogen and testosterone in postmenopausal women.

Aged↗

PubMed2002

Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep.

Based on findings primarily in cats, the grouping of spindle activity and fast brain oscillations by slow oscillations during slow-wave sleep (SWS) has been proposed to represent an essential feature in the processing of memories during sleep. We examined whether a comparable grouping of spindle and fast activity coinciding with slow oscillations can be found in human SWS. For negative and positive half-waves of slow oscillations (dominant frequency, 0.7-0.8 Hz) identified during SWS in humans (n = 13), wave-triggered averages of root mean square (rms) activity in the theta (4-8 Hz), alpha (8-12 Hz), spindle (12-15 Hz), and beta (15-25 Hz) range were formed. Slow positive half-waves were linked to a pronounced and microV (23.4%; p < 0.001, with reference to baseline) at the midline central electrode (Cz). In contrast, spindle activity was suppressed during slow negative half-waves, on average by -0.65 +/- 0.06 microV at Cz (-22%; p < 0.001). An increase in spindle activity 400-500 msec after negative half-waves was more than twofold the increase during slow positive half-waves (p < 0.001). A similar although less pronounced dynamic was observed for beta activity, but not for alpha and theta frequencies. Discrete spindles identified during stages 2 and 3 of non-rapid eye movement (REM) sleep coincided with a discrete slow positive half-wave-like potential preceded by a pronounced negative half-wave (p < 0.01). These results provide the first evidence in humans of grouping of spindle and beta activity during slow oscillations. They support the concept that phases of cortical depolarization during slow oscillations, reflected by surface-positive (depth-negative) field potentials, drive the thalamocortical spindle activity. The drive is particularly strong during cortical depolarization, expressed as surface-positive field potentials.

Adolescent↗

PubMed2002

Learning-dependent increases in sleep spindle density.

Declarative memory consolidation is enhanced by sleep. In the investigation of underlying mechanisms, mainly rapid eye movement (REM) sleep and slow-wave sleep have been considered. More recently, sleep stage 2 with sleep spindles as a most prominent feature has received increasing attention. Specifically, in rats hippocampal ripples were found to occur in temporal proximity to cortical sleep spindles, indicating an information transfer between the hippocampus and neocortex, which is supposed to underlie the consolidation of declarative memories during sleep. This study in humans looks at the changes in EEG activity during nocturnal sleep after extensive training on a declarative learning task, as compared with a nonlearning control task of equal visual stimulation and subjectively rated cognitive strain. Time spent in each sleep stage, spindle density, and EEG power spectra for 28 electrode locations were determined. During sleep after training, the density of sleep spindles was significantly higher after the learning task as compared with the nonlearning control task. This effect was largest during the first 90 min of sleep (p < 0.01). Additionally, spindle density was correlated to recall performance both before and after sleep (r = 0.56; p < 0.05). Power spectra and time spent in sleep stages did not differ between learning and nonlearning conditions. Results indicate that spindle activity during non-REM sleep is sensitive to previous learning experience.

Adolescent↗

PubMed2002

EEG theta synchronization conjoined with alpha desynchronization indicate intentional encoding.

The involvement of different oscillating neuronal systems activated during intentional learning was investigated by measuring ongoing EEG activity. In 17 subjects, the EEG was recorded while learning pairs of words and faces. Subjective task difficulty was rated and a control condition of mental relaxation was also run. Spontaneous EEG activity during epochs which subsequently resulted in efficient encoding was associated with upper alpha desynchronization (10-12 Hz) and theta synchronization (4-8 Hz) when compared with spontaneous EEG activity during epochs of poor recall performance. The combined measure of theta synchronization plus upper alpha desynchronization was enhanced selectively over left frontotemporal cortical regions during efficient learning of words and over right parietal cortical regions during efficient learning of faces (P < 0.001). This striking topographical dissociation between learning materials for the combined measure of theta and upper alpha EEG activity suggests that the mode of intentional learning relies essentially on an interdependent regulation of two neuronal circuits: the thalamo-cortical circuit and the hippocampo-cortical circuit.

Action Potentials↗