Magnetic field strength and reproducibility of neodymium magnets useful for transcranial static magnetic field stimulation of the human cortex

[Abstract] Objective. The application of transcranial static magnetic field stimulation (tSMS) in humans reduces the excitability of the motor cortex for a few minutes after the end of stimulation. However, when tSMS is applied in humans, the cortex is at least 2 cm away, so most of the strength of the magnetic field will not reach the target. The main objective of the study was to measure the strength and reproducibility of static magnetic fields produced by commercial neodymium magnets. Methods. We measured the strength and reproducibility of static magnetic fields produced by four different types of neodymium cylindrical magnets using a magnetic field-to-voltage transducer. Results. Magnetic field strength depended on magnet size. At distances 1.5 cm, the measurements made on the cylinder axis and 1.5 cm off the axis were comparable. The reproducibility of the results (i.e., the consistency of the field strength across magnets of the same size) was very high. Conclusions. These measurements offer a quantitative empirical reference for developing devices useful for tSMS protocols in both humans and animals.Ministerio de Educacion y Ciencia; BFU2009-0816

Passive exercise of the hind limbs after complete thoracic transection of the spinal cord promotes cortical reorganization.

Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain

Amplitude and frequency modulation of subthalamic beta oscillations jointly encode the dopaminergic state in Parkinson's disease.

Brain states in health and disease are classically defined by the power or the spontaneous amplitude modulation (AM) of neuronal oscillations in specific frequency bands. Conversely, the possible role of the spontaneous frequency modulation (FM) in defining pathophysiological brain states remains unclear. As a paradigmatic example of pathophysiological resting states, here we assessed the spontaneous AM and FM dynamics of subthalamic beta oscillations recorded in patients with Parkinson's disease before and after levodopa administration. Even though AM and FM are mathematically independent, they displayed negatively correlated dynamics. First, AM decreased while FM increased with levodopa. Second, instantaneous amplitude and instantaneous frequency were negatively cross-correlated within dopaminergic states, with FM following AM by approximately one beta cycle. Third, AM and FM changes were also negatively correlated between dopaminergic states. Both the slow component of the FM and the fast component (i.e. the phase slips) increased after levodopa, but they differently contributed to the AM-FM correlations within and between states. Finally, AM and FM provided information about whether the patients were OFF vs. ON levodopa, with partial redundancy and with FM being more informative than AM. AM and FM of spontaneous beta oscillations can thus both separately and jointly encode the dopaminergic state in patients with Parkinson's disease. These results suggest that resting brain states are defined not only by AM dynamics but also, and possibly more prominently, by FM dynamics of neuronal oscillations

Transcranial static magnetic field stimulation of the human motor cortex

[Abstract] The aim of the present study was to investigate in healthy humans the possibility of a non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp. Static magnetic fields were obtained by using cylindrical NdFeB magnets. We performed four sets of experiments. In Experiment 1, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex before and after 10min of transcranial static magnetic field stimulation (tSMS) in conscious subjects. We observed an average reduction of motor cortex excitability of up to 25%, as revealed by TMS, which lasted for severalminutes after the end of tSMS, andwas dose dependent (intensity of the magnetic field) but not polarity dependent. In Experiment 2, we confirmed the reduction of motor cortex excitability induced by tSMS using a double-blind sham-controlled design. In Experiment 3, we investigated the duration of tSMS that was necessary to modulate motor cortex excitability. We found that 10 min of tSMS (compared to 1min and 5 min) were necessary to induce significant effects. In Experiment 4, we used transcranial electric stimulation (TES) to establish that the tSMS-induced reduction ofmotor cortex excitability was not due to corticospinal axon and/or spinal excitability, but specifically involved intracortical networks. These results suggest that tSMS using small static magnets may be a promising tool to modulate cerebral excitability in a non-invasive, painless, and reversible way

Emergent dynamics of fast ripples in the epileptic hippocampus

Fast ripples are a type of transient high-frequency oscillations recorded from the epileptogenic regions of the hippocampus and the temporal cortex of epileptic humans and rodents. These events presumably reflect hypersynchronous bursting of pyramidal cells. However, the oscillatory spectral content of fast ripples varies from 250 to 800 Hz, well above the maximal firing frequency of most hippocampal pyramidal neurons. How such high-frequency oscillations are generated is therefore unclear. Here, we combine computational simulations of fast ripples with multisite and juxtacellular recordings in vivo to examine the underlying mechanisms in the hippocampus of epileptic rats. We show that populations of bursting cells firing individually at 100-400 Hz can create fast ripples according to two main firing regimes: (1) in-phase synchronous firing resulting in >pure> fast ripples characterized by single spectral peaks that reflect single-cell behavior and (2) out-of-phase firing that results in >emergent> fast ripples. Using simulations, we found that fast ripples generated under these two different regimes can be quantitatively separated by their spectral characteristics, and we took advantage of this separability to examine their dynamics in vivo.We found that in-phase firing can reach frequencies up to 300 Hz in the CA1and up to 400Hzin the dentate gyrus. The organization of out-of-phase firing is determined by firing delays between cells discharging at low frequencies. The two firing regimes compete dynamically, alternating randomly from one fast ripple event to the next, and they reflect the functional dynamic organization of the different regions of the hippocampus. Copyright © 2010 the authors.Peer Reviewe

A framework to assess the impact of number of trials on the amplitude of motor evoked potentials

The amplitude of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) is a common yet highly variable measure of corticospinal excitability. The tradeoff between maximizing the number of trials and minimizing experimental time remains a hurdle. It is therefore important to establish how many trials should be used. The aim of this study is not to provide rule-of-thumb answers that may be valid only in specific experimental conditions, but to offer a more general framework to inform the decision about how many trials to use under different experimental conditions. Specifically, we present a set of equations that show how the number of trials affects single-subject MEP amplitude, population MEP amplitude, hypothesis testing and test–retest reliability, depending on the variability within and between subjects. The equations are derived analytically, validated with Monte Carlo simulations, and representatively applied to experimental data. Our findings show that the minimum number of trials for estimating single-subject MEP amplitude largely depends on the experimental conditions and on the error considered acceptable by the experimenter. Conversely, estimating population MEP amplitude and hypothesis testing are markedly more dependent on the number of subjects than on the number of trials. These tools and results help to clarify the impact of the number of trials in the design and reproducibility of past and future experiments

Interaction between rhythms in the human basal ganglia: application of bispectral analysis to local field potentials

IEEE Transactions on Neural Systems and Rehabilitation Engineering, 15(4): pp. 483-492.The application of deep brain stimulation (DBS) for the treatment of Parkinson’s disease offered a direct “insight” into the human electrical activity in subcortical structures. The analysis of the oscillatory activity [local field potentials (LFPs)] disclosed the importance of rhythms and of interactions between rhythms in the human basal ganglia information processing. The aim of this study wasto investigate the existence of possible nonlinear interactions between LFP rhythms characterizing the output structure of the basal ganglia, the globus pallidus internus, by means of bispectral analysis. The results of this study disclosed that the rhythms expressed in the globus pallidus internus of the untreated parkinsonian patient are not independent and, in particular, the low-beta (13–20Hz)band generates harmonics that are included in the high-beta (20–35 Hz) band. Conversely, in the dystonic globus pallidus, as well as in the parkinsonian globus pallidus afterdopaminergic medication (i.e., in the more “normal” condition), the rhythms are substantially independent and characterized by a strong activity in the low-frequency band that generates a second harmonic (4–14 Hz), mostly included in the same band. The interactions between rhythms in the human globus pallidus are therefore different in different pathologies and in different patient’s states. The interpretation of these interactions is likely critical for fully understanding the role of LFP rhythms in the pathophysiology of human basal ganglia

Eight-hours adaptive deep brain stimulation in patients with Parkinson disease

To assess the feasibility and clinical efficacy of local field potentials (LFPs)-based adaptive deep brain stimulation (aDBS) in patients with advanced Parkinson disease (PD) during daily activities in an open-label, nonblinded study. METHODS: We monitored neurophysiologic and clinical fluctuations during 2 perioperative experimental sessions lasting for up to 8 hours. On the first day, the patient took his/her daily medication, while on the second, he/she additionally underwent subthalamic nucleus aDBS driven by LFPs beta band power. RESULTS: The beta band power correlated in both experimental sessions with the patient's clinical state (Pearson correlation coefficient r = 0.506, p < 0.001, and r = 0.477, p < 0.001). aDBS after LFP changes was effective (30% improvement without medication [3-way analysis of variance, interaction day 7 medication p = 0.036; 30.5 \ub1 3.4 vs 22.2 \ub1 3.3, p = 0.003]), safe, and well tolerated in patients performing regular daily activities and taking additional dopaminergic medication. aDBS was able to decrease DBS amplitude during motor "on" states compared to "off" states (paired t test p = 0.046), and this automatic adjustment of STN-DBS prevented dyskinesias. CONCLUSIONS: The main findings of our study are that aDBS is technically feasible in everyday life and provides a safe, well-tolerated, and effective treatment method for the management of clinical fluctuations. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with advanced PD, aDBS is safe, well tolerated, and effective in controlling PD motor symptoms

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