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ABSTRACT: Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1(HAND)) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression (LTD)-like or long-term potentiation (LTP)-like plasticity in left M1(HAND) through different afferents. We hypothesized that the left M1(HAND) would integrate LTP- and LTD-like plasticity in a homeostatic fashion. In ten healthy volunteers, low-intensity repetitive transcranial magnetic stimulation (rTMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1(HAND) via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve and left M1(HAND) to induce spike-time-dependent plasticity in sensory-to-motor inputs to left M1(HAND). We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PAS(N20+2ms)) or an LTD-like decrease (PAS(N20-5ms)) in corticospinal excitability. The amplitude of motor-evoked potentials was recorded from intrinsic hand muscles to assess stimulation-induced changes in corticospinal excitability. Premotor-to-motor preconditioning triggered a homeostatic response to subsequent sensory-to-motor PAS. After facilitatory 5 Hz rTMS, "facilitatory" PAS(N20+2ms) suppressed corticospinal excitability. Likewise, "inhibitory" PAS(N20-5ms) facilitated corticospinal excitability after "inhibitory" 1 Hz rTMS. There was a negative linear relationship between the excitability changes induced by PMD rTMS and those elicited by subsequent PAS. Excitability changes were not paralleled by changes in performance during a finger-tapping task. These results provide evidence for a homeostatic response pattern in the human M1(HAND) that integrates acute plastic changes evoked through different "input channels."
Journal of Neurophysiology 10/2009; 102(6):3180-90. · 3.32 Impact Factor
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ABSTRACT: We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same (n = 30) or neighboring microelectrodes (n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1-100 Hz. The distribution of significant oscillations across the theta (1-8 Hz), alpha (8-12 Hz), beta (12-35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test (P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease.
Journal of Neurophysiology 09/2008; 100(5):2515-24. · 3.32 Impact Factor
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ABSTRACT: The separation between physiologic tremor (PT) in normal subjects and the pathological tremors of essential tremor (ET) or Parkinson's disease (PD) was investigated on the basis of monoaxial accelerometric recordings of 35 s hand tremor epochs. Frequency and amplitude were insufficient to separate between these conditions, except for the trivial distinction between normal and pathologic tremors that is already defined on the basis of amplitude. We found that waveform analysis revealed highly significant differences between normal and pathologic tremors, and, more importantly, among different forms of pathologic tremors. We found in our group of 25 patients with PT and 15 with ET a reasonable distinction with the third momentum and the time reversal invariance. A nearly complete distinction between these two conditions on the basis of the asymmetric decay of the autocorrelation function. We conclude that time series analysis can probably be developed into a powerful tool for the objective analysis of tremors. (c) 1995 American Institute of Physics.
Chaos (Woodbury, N.Y.) 04/1995; 5(1):48-51. · 1.80 Impact Factor
