Plasticity Resembling Spike-Timing Dependent Synaptic Plasticity: The Evidence in Human Cortex

Spike-timing dependent plasticity (STDP) has been studied extensively in a variety of animal models during the past decade but whether it can be studied at the systems level of the human cortex has been a matter of debate. Only recently newly developed non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) have made it possible to induce and assess timing dependent plasticity in conscious human subjects. This review will present a critical synopsis of these experiments, which suggest that several of the principal characteristics and molecular mechanisms of TMS-induced plasticity correspond to those of STDP as studied at a cellular level. TMS combined with a second phasic stimulation modality can induce bidirectional long-lasting changes in the excitability of the stimulated cortex, whose polarity depends on the order of the associated stimulus-evoked events within a critical time window of tens of milliseconds. Pharmacological evidence suggests an NMDA receptor mediated form of synaptic plasticity. Studies in human motor cortex demonstrated that motor learning significantly modulates TMS-induced timing dependent plasticity, and, conversely, may be modulated bidirectionally by prior TMS-induced plasticity, providing circumstantial evidence that long-term potentiation-like mechanisms may be involved in motor learning. In summary, convergent evidence is being accumulated for the contention that it is now possible to induce STDP-like changes in the intact human central nervous system by means of TMS to study and interfere with synaptic plasticity in neural circuits in the context of behavior such as learning and memory

The effects of NMDA receptor blockade on TMS-evoked EEG potentials from prefrontal and parietal cortex

Measuring the brain's response to transcranial magnetic stimulation (TMS) with electroencephalography (EEG) offers unique insights into the cortical circuits activated following stimulation, particularly in non-motor regions where less is known about TMS physiology. However, the mechanisms underlying TMS-evoked EEG potentials (TEPs) remain largely unknown. We assessed TEP sensitivity to changes in excitatory neurotransmission mediated by n-methyl-d-aspartate (NMDA) receptors following stimulation of non-motor regions. In fourteen male volunteers, resting EEG and TEPs from prefrontal (PFC) and parietal (PAR) cortex were measured before and after administration of either dextromethorphan (NMDA receptor antagonist) or placebo across two sessions in a double-blinded pseudo-randomised crossover design. At baseline, there were amplitude differences between PFC and PAR TEPs across a wide time range (15-250 ms), however the signals were correlated after ~80 ms, suggesting early peaks reflect site-specific activity, whereas late peaks reflect activity patterns less dependent on the stimulated sites. Early TEP peaks were not reliably altered following dextromethorphan compared to placebo, although findings were less clear for later peaks, and low frequency resting oscillations were reduced in power. Our findings suggest that early TEP peaks (<80 ms) from PFC and PAR reflect stimulation site specific activity that is largely insensitive to changes in NMDA receptor-mediated neurotransmission.Nigel C. Rogasch, Carl Zipser, Ghazaleh Darmani, Tuomas P. Mutanen, Mana Biabani, Christoph Zrenner, Debora Desideri, Paolo Belardinelli, Florian Müller-Dahlhaus, Ulf Zieman

Bayesian Wavelet Shrinkage of the Haar-Fisz Transformed Wavelet Periodogram.

It is increasingly being realised that many real world time series are not stationary and exhibit evolving second-order autocovariance or spectral structure. This article introduces a Bayesian approach for modelling the evolving wavelet spectrum of a locally stationary wavelet time series. Our new method works by combining the advantages of a Haar-Fisz transformed spectrum with a simple, but powerful, Bayesian wavelet shrinkage method. Our new method produces excellent and stable spectral estimates and this is demonstrated via simulated data and on differenced infant electrocardiogram data. A major additional benefit of the Bayesian paradigm is that we obtain rigorous and useful credible intervals of the evolving spectral structure. We show how the Bayesian credible intervals provide extra insight into the infant electrocardiogram data

Characterization of GABAB-receptor mediated neurotransmission in the human cortex by paired-pulse TMS–EEG

GABAB-receptor (GABABR) mediated inhibition is important in regulating neuronal excitability. The paired-pulse transcranial magnetic stimulation (TMS) protocol of long-interval intracortical inhibition (LICI) likely reflects this GABABergic inhibition. However, this view is based on indirect evidence from electromyographic (EMG) studies. Here we combined paired-pulse TMS with simultaneous electroencephalography (paired-pulse TMS–EEG) and pharmacology to directly investigate mechanisms of LICI at the cortical level. We tested the effects of a conditioning stimulus (CS100) applied 100 ms prior to a test stimulus (TS) over primary motor cortex on TS-evoked EEG-potentials (TEPs). Healthy subjects were given a single oral dose of baclofen, a GABABR agonist, or diazepam, a positive modulator at GABAARs, in a placebo-controlled, pseudo-randomized double-blinded crossover study. LICI was quantified as the difference between paired-pulse TEPs (corrected for long-lasting EEG responses by the conditioning pulse) minus single-pulse TEPs. LICI at baseline (i.e. pre-drug intake) was characterized by decreased P25, N45, N100 and P180 and increased P70 TEP components. Baclofen resulted in a trend towards the enhancement of LICI of the N45 and N100, and significantly enhanced LICI of the P180. In contrast, diazepam consistently suppressed LICI of late potentials (i.e. N100, P180), without having an effect on LICI of earlier (i.e. P25, N45 and P70) potentials. These findings demonstrate for the first time directly at the system level of the human cortex that GABABR-mediated cortical inhibition contributes to LICI, while GABAAR-mediated inhibition occludes LICI. Paired-pulse TMS–EEG allows investigating cortical GABABR-mediated inhibition more directly and specifically than hitherto possible, and may thus inform on network abnormalities caused by disordered inhibition, e.g. in patients with schizophrenia or epilepsy

Perception of Leitmotives in Richard Wagner's Der Ring des Nibelungen

The music of Richard Wagner tends to generate very diverse judgments indicative of the complex relationship between listeners and the sophisticated musical structures in Wagner’s music. This paper presents findings from two listening experiments using the music from Wagner’s Der Ring des Nibelungen that explores musical as well as individual listener parameters to better understand how listeners are able to hear leitmotives, a compositional device closely associated with Wagner’s music. Results confirm findings from a previous experiment showing that specific expertise with Wagner’s music can account for a greater portion of the variance in an individual’s ability to recognize and remember musical material compared to measures of generic musical training. Results also explore how acoustical distance of the leitmotives affects memory recognition using a chroma similarity measure. In addition, we show how characteristics of the compositional structure of the leitmotives contributes to their salience and memorability. A final model is then presented that accounts for the aforementioned individual differences factors, as well as parameters of musical surface and structure. Our results suggest that that future work in music perception may consider both individual differences variables beyond musical training, as well as symbolic features and audio commonly used in music information retrieval in order to build robust models of musical perception and cognition

Unsound Seeds

With this image of a curtain hiding and at the same time heightening some terrible secret, Max Kalbeck began his review of the first Viennese performance of Richard Strauss’s Salome. Theodor W. Adorno picked up the image of the curtain in the context of Strauss’s fabled skill at composing non-musical events, when he identified the opening flourish of Strauss’s Salome as the swooshing sound of the rising curtain. If this is so, the succès de scandale of the opera was achieved, in more than one sense, as soon as the curtain rose at Dresden’s Semperoper on 10 December 1905. Critics of the premiere noted that the opera set ‘boundless wildness and degeneration to music’; it brought ‘high decadence’ onto the operatic stage; a ‘composition of hysteria’, reflecting the ‘disease of our time’, Salome is ‘hardly music any more’.The outrage did not end there