Valentina Cettolo

Primary Motor and Sensory Cortex Activation during Motor Performance and Motor Imagery: A Functional Magnetic Resonance Imaging Study

The intensity and spatial distribution of functional activation in the left precentral and postcentral gyri during actual motor performance (MP) and mental representation [motor imagery (MI)] of self-paced finger-to-thumb opposition movements of the dominant hand were investigated in fourteen right-handed volunteers by functional magnetic resonance imaging (fMRI) techniques. Significant increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) tasks were found in a region including the anterior bank and crown of the central sulcus, the presumed site of the primary motor cortex, during both MP (mean percentage increase, 2.1%) and MI (0.8%). In the anterior portion of the precentral gyrus and the postcentral gyrus, mean functional activity levels were also increased during both conditions (MP, 1.7 and 1.2%; MI, 0.6 and 0.4%, respectively). To locate activated foci during MI, MP, or both conditions, the time course of the signal intensities of pixels lying in the precentral or postcentral gyrus was plotted against single-step or double-step waveforms, where the steps of the waveform corresponded to different tasks. Pixels significantly (r > 0.7) activated during both MP and MI were identified in each region in the majority of subjects; percentage increases in signal intensity during MI were on average 30% as great as increases during MP. The pixels activated during both MP and MI appear to represent a large fraction of the whole population activated during MP. These results support the hypothesis that MI and MP involve overlapping neural networks in perirolandic cortical areas.

Functional activity mapping of the mesial hemispheric wall during anticipation of pain.

The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system.

Ipsilateral involvement of primary motor cortex during motor imagery

To investigate whether motor imagery involves ipsilateral cortical regions, we studied haemodynamic changes in portions of the motor cortex of 14 right‐handed volunteers during actual motor performance (MP) and kinesthetic motor imagery (MI) of simple sequences of unilateral left or right finger movements, using functional magnetic resonance imaging (fMRI). Increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) task were found during both MP and MI in the posterior part of the precentral gyrus and supplementary motor area, both on the contralateral and ipsilateral hemispheres. In the left lateral premotor cortex, fMRI signals were increased during imagery of either left or right finger movements. Ipsilateral cortical clusters displaying fMRI signal changes during both MP and MI were identified by correlation analyses in 10 out of 14 subjects; their extent was larger in the left hemisphere. A larger cortical population involved during both contralateral MP and MI was found in all subjects. The overall spatial extent of both the contralateral and the ipsilateral MP + MI clusters was ∼ 90% of the whole cortical volume activated during MP. These results suggest that overlapping neural networks in motor and premotor cortex of the contralateral and ipsilateral hemispheres are involved during imagery and execution of simple motor tasks.

Influence of phosphagen concentration on phosphocreatine breakdown kinetics. Data from human gastrocnemius muscle.

At the onset of a square-wave exercise of moderate intensity, in the absence of any detectable lactate production, the hydrolysis of phosphocreatine (PCr) fills the gap between energy requirement and energy yield by oxidative pathways, thus representing a readily available source of energy for the muscle. We verified experimentally the relationships between high-energy phosphates and/or their changes and the time constant of PCr concentration ([PCr]) kinetics in humans (tau(PCr)). High-energy phosphate concentration (by (31)P-NMR spectroscopy) in the calf muscles were measured during three repetitions of the rest-to-work transition of moderate aerobic square-wave exercise on nine healthy volunteers, while resting [PCr] was estimated from the appropriate spectroscopy data. PCr concentration decreased significantly (22 +/- 6%) from rest to steady-state exercise, without differences among the three repetitions. Absolute resting [PCr] and tau(PCr) were consistent with literature values, amounting to 27.5 +/- 2.2 mM and 23.9 +/- 2.9 s, respectively. No significant relationships were detected between individual tau(PCr) and mechanical power, fraction or absolute amount of PCr hydrolyzed, or change in ADP concentration. On the contrary, individual tau(PCr) (s) was linearly related to absolute resting [PCr] (mM), the relationship being described by: tau(PCr) = 0.656 + 0.841.[PCr] (n = 9, R = 0.708, P < 0.05). These data support the view that in humans PCr concentration sets the time course of the oxidative metabolism in skeletal muscle at the start of exercise, being one of the main controllers of oxidative phosphorylation.

Two-pedal ergometer for in vivo MRS studies of human calf muscles

This article describes an ergometer that enables human subjects to exercise one or both limbs while 31P NMR spectra are obtained. Two independent pedals, equipped with position and force transducers, were mounted on the ergometer in order to calculate mechanical work performance. First, the effect of the magnetic field upon the signal coming from the transducers was investigated. Then the ergometer was tested by performing a series of steady‐state exercises of increasing intensity. Experimental data showed that actual mechanical power ranged from 1.5 ± 0.2 W to 11.0 ± 1.6 W, while the corresponding oxygen consumption increased from 0.28 ± 0.04 l/min at rest to 0.48 ± 0.10 l/min at the highest load, and the PCr/(PCr+Pi) ratio, as calculated from the 31P spectra, decreased from 0.94 ± 0.01 at rest to 0.73 ± 0.04. These results are consistent with the values reported in the literature and show that this ergometer, which is easy to use, is suitable for in vivo spectroscopy research when metabolic steady‐state conditions are required. Magn Reson Med 46:1000–1005, 2001.

T1 measurement of 31P metabolites at rest and during steady-state dynamic exercise using a clinical nuclear magnetic resonance scanner

This article illustrates some problems and possible solutions to determine the apparent spin–lattice relaxation time (T1) of the muscular 31P metabolites at rest and during dynamic steady‐state exercise using a clinical 1.5 T NMR scanner and a surface coil. T1 was first estimated on a phosphates solution (phantom) using four different acquisition protocols, all based on the multiple‐point “progressive saturation” method, and by fitting each data set with two different mathematical models. Subsequently, two of the four protocols and both models were used to estimate T1 both at rest and during exercise on the calf muscles of 10 healthy volunteers. Experimental results obtained on the phantom showed that T1 is greatly affected by the longest nominal explored repetition time (P < 0.001) and by the mathematical model (P < 0.001), ranging from 0.65 ± 0.10 to 8.4 ± 0.8 s. The two acquisition protocols applied on volunteers yielded significantly different T1 (P < 0.001), which were also rather different from the literature values for the same metabolites. Nevertheless, independently of the acquisition protocol and/or the fitting procedure, T1 of all muscular phosphagens did not change statistically from rest to steady‐state aerobic exercise. Magn Reson Med, 2006.

Confidence intervals for the parameters estimated from simulated O2 uptake kinetics: effects of different data treatments

•  What is the central question of this study? Is the accuracy and/or precision of the O2 uptake kinetics parameters, estimated by non‐linear regression, affected by different data treatments applied to reduce the noise of breath fluctuations? •  What is the main finding and its importance? Simulations showed that, even after the averaging of more repetitions, the width of the asymptotic confidence intervals was narrower than the real ones, in particular when the O2 uptake responses were resampled at time intervals shorter than the average breath duration (e.g. 1 s). The reasons for this discrepancy were investigated, allowing us to identify simple methods to obtain the correct confidence interval of the O2 uptake kinetics parameters.

Oxygen uptake kinetics at work onset: role of cardiac output and of phosphocreatine breakdown.

The hypothesis that variability in individuals cardiac output response affects the kinetics of pulmonary O₂ uptake (VO₂) was tested by investigating the time constants of cardiac output (Q) adjustment (τ(Q)), of PCr splitting (τ(PCr)), and of phase II pulmonary O₂ uptake (τ(VO₂)) in eight volunteers. VO₂, Q, and gastrocnemius [PCr] (by (31)P-MRS) were measured at rest and during low intensity two-legged exercise. Steady state VO₂ and Q increased (ΔVO₂(s) = 182 ± 58 mL min⁻¹; ΔQ = 1.3 ± 0.4 L min⁻¹), whereas [PCr] decreased significantly (21 ± 8%). τ(VO₂), τ(PCr) and τ(Q) were significantly different from each other (38.3 ± 4.0, 23.9 ± 2.5, 11.6 ± 4.6 s, respectively; p<0.001). τ(PCr) assumed to be equal to the time constant of VO₂ at the muscle level (τ(mVO₂)), was not related to τ(Q), whereas τ(VO₂) and τ(Q) were significantly related (p<0.05) as were τ(VO₂) and τ(PCr) (p<0.05). Venous blood O₂ stores changes, as determined from arterio-to-mixed-venous O₂ content, were essentially equal to those estimated as (τ(VO₂)-τ(PCr))·ΔVO₂(s). This suggests that cardiac output responses affect O₂ stores utilization and hence τ(VO₂) : thus τ(VO₂) is not necessarily a good estimate of τ(mVO₂).

Functional Activity Mapping of the Perirolandic Cortex During Motor Performance and Motor Imagery

The development of noninvasive magnetic resonance imaging (MRI) techniques sensitive to the local changes of blood flow, volume, and oxygenation which accompany neuronal activation has provided the scientific community with a new and powerful tool for investigating the spatio-temporal dynamics of human brain function [1,2]. One of the most exciting application of brain mapping techniques, such as single photon emission tomography (SPET), positron emission tomography (PET), and functional MRI (fMRI) is the study of neural correlates of mental activity, such as the internal representation of sensory events or motor acts. It is still debated to what extent brain networks activated during mental rehearsal of, for instance, a visual scene or a motor sequence (visual or motor imagery) overlap those involved in the perception of visual stimuli or the preparation and execution of motor acts, respectively [3]. With regard to the motor system, the results of previous SPET and PET studies have demonstrated the activation of higher-order motor areas (such as the supplementary motor cortex) during motor imagery, whereas no change was found in the primary sensory-motor cortex [4]. However, the relatively poor spatial resolution of the employed techniques may have prevented the detection of areas characterized by less intense activation. The present study was therefore undertaken to evaluate by high-resolution fMRI the activity pattern of the perirolandic region (including pre- and postcentral gyri) during execution and imagery of a sequential motor task.

Interpreting the confidence intervals of model parameters of breath‐by‐breath pulmonary O2 uptake

Keir et al. (2014) have recently compared different techniques used to assemble breath-by-breath pulmonary O2 uptake data from repeated step transitions in the moderate-intensity exercise domain. In particular, the authors evaluated the quality of the assembling methods by comparing what they called the ‘model confidence CI95’, where ‘CI95 is equal to the SE (derived from the sum of squared residuals from the model parameter estimates) multiplied by the t-distribution value for the 2.5% two-tailed dimensions’. The authors conclude that the data-processing technique had no effect on parameter estimates. However, ‘the narrowest interval for CI95 occurred when individual trials were linearly interpolated on a second-by-second basis and ensemble averaged’ before running the non-linear regression procedure. It can be easily demonstrated, and Keir et al. (2014) can do it using their experimental data, that a linear interpolation on a 0.5 s-by-0.5 s basis or 0.1 s-by-0.1 s basis results in a decrease of the SE, better called asymptotic standard error or ASE, which is calculated from the variance–covariance matrix of parameter estimates on the basis of the number of data points used by the linear regression procedure. As a consequence, the corresponding CI95 will also be narrower, in comparison to the values obtained by the linear interpolation on a second-by-second basis, roughly by the factor √ 1 s 0.5 s = √2 or √ 1s 0.1s = √10 , respectively (Francescato et al. 2014b). Following this reasoning, the narrowest CI95 would be obtained by linearly interpolating the data on an infinitesimal-by-infinitesimal basis. As discussed in detail by Francescato et al. (2014b), this phenomenon is due to the fact that the linear interpolation increases the number of data points used by the non-linear regression procedure without adding new information (‘cloning’ effect). Indeed, it can easily be shown that the same phenomenon takes place even for the average (and corresponding standard error) of a simple series of data, analysed as raw data or taking them twice. In the above conditions, the CI95 no longer meets the definition of confidence interval, i.e. the range of values that, over a set of notional repeated samples, would contain the true parameter of interest with a prespecified probability, usually set at 95%. The simulation performed by Francescato et al. (2014a) highlighted that when the individual trials were processed to obtain regular 1 s bins and then ensemble averaged before running the non-linear regression procedure, the ‘true’ (known) phase II time constant was included within the estimated CI95 in only 70% of cases. This means that, for this data-processing technique, the estimated CI95 does not satisfy the statistical definition of confidence interval at 95% level. The same simulation showed that when the individual trials are simply combined into a single data set, the ‘true’ (known) phase II time constant was included within the estimated CI95 in more than 94% of cases, thus being very close to the definition of the confidence interval at 95% level. In conclusion, the non-linear regression procedure applied following interpolation of individual trials on a second-by-second basis and ensemble averaging results in misleading CI95. As a consequence, in contrast to Keir et al. (2014), we believe that the CI95 estimated in this manner cannot be used as figure of merit to evaluate the quality of different data-processing techniques. Narrower confidence intervals should be obtained by increasing the information used (e.g. increasing the number of repeats).