Two different reorganization patterns after rehabilitative therapy: an exploratory study with fMRI and TMS

We used two complementary methods to investigate cortical reorganization in chronic stroke patients during treatment with a defined motor rehabilitation program. BOLD ("blood oxygenation level dependent") sensitive functional magnetic resonance imaging (fMRI) and intracortical inhibition (ICI) and facilitation (ICF) measured with transcranial magnetic stimulation (TMS) via paired pulse stimulation were used to investigate cortical reorganization before and after "constraint-induced movement therapy" (CI). The motor hand function improved in all subjects after CI. BOLD signal intensity changes within affected primary sensorimotor cortex (SMC) before and after CI showed a close correlation with ICI (r = 0.93) and ICF (r = 0.76) difference before and after therapy. Difference in number of voxels and ICI difference before and after CI also showed a close correlation (r = 0.92) in the affected SMC over the time period of training. A single subject analysis revealed that patients with intact hand area of M1 ("the hand knob") and its descending motor fibers (these patients revealed normal motor evoked potentials [MEP] from the affected hand) showed decreasing ipsilesional SMC activation which was paralleled by an increase in intracortical excitability. This pattern putatively reflects increasing synaptic efficiency. When M1 or its descending pyramidal tract was lesioned (MEP from the affected hand was pathologic) ipsilesional SMC activation increased, accompanied by decreased intracortical excitability. We suggest that an increase in synaptic efficiency is not possible here, which leads to reorganization with extension, shift and recruitment of additional cortical areas of the sensorimotor network. The inverse dynamic process between both complementary methods (activation in fMRI and intracortical excitability determined by TMS) over the time period of CI illustrates the value of combining methods for understanding brain reorganization.     

Modulation of behavior and cortical motor activity in healthy subjects by a chronic administration of a serotonin enhancer

SSRIs are postulated to modulate motor behavior. A single dose of selective serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or fluvoxamine, has been shown to improve motor performance and efficiency of information processing for simple sensorimotor tasks in healthy subjects. At a cortical level, a single dose of SSRI was shown to induce a hyperactivation of the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, I., Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow Metab. 19 1365--1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C., Manelfe, C., Rascol, O., Celsis, P., and Chollet, F., 2002. A Single Dose of Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double-blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26--36). Since SSRIs are usually given for several weeks, we assessed the behavioral and cerebral effects of a one-month chronic administration of paroxetine on a larger group. In a double-blind, placebo controlled and crossover study, 19 subjects received daily 20 mg paroxetine or placebo, respectively, over a period of 30 days separated by a wash-out period of 3 months. After each period, the subjects underwent an fMRI (active or passive movement, dexterity task, sensory discrimination task) and a behavioral evaluation. Concurrently, a TMS (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A., Loubinoux, I., Tombari, D., Rascol, O., Chollet, F., Simonetta-Moreau, M., 2005. Chronic administration of selective serotonin re-uptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects. NeuroImage 27,314--322). RESULTS: On the one hand, paroxetine improved motor performances at the finger tapping test (P=0.02) without affecting choice reaction time, strength and dexterity significantly. Subjects were also faster in processing the spatial incongruency between a stimulus and the motor response (P=0.04). In order to differentiate behavioral components, a principal component analysis was performed on all motor tests, and several characteristics were differentiated: strength, speed, skill, attention, and motor response coding. Paroxetine would improve the efficiency of motor response coding (MANOVA on the factors; factor 3, P=0.01). On the other hand, the chronic administration induced a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple or complex (random effect analysis, P<0.05). The hypoactivation correlated with the improvement of performances at the finger tapping test (P<0.05) suggesting more efficiency in cerebral motor processing. CONCLUSIONS: Our results showed a clear modulation of sensory and motor cerebral activation after a chronic paroxetine administration. An improvement in both behavior and cerebral efficiency was suggested. It could be hypothesized that monoamines, by an unspecific effect, may tune the response of pyramidal neurons to optimize performances.     

Enduring representational plasticity after somatosensory stimulation

Somatosensory stimulation (SS), leading to increases in motor cortical excitability, influences motor performance in patients with brain lesions like stroke. The mechanisms by which SS modulates motor function are incompletely understood. Here, we used functional magnetic resonance imaging (fMRI, blood-oxygenation-level-dependent (BOLD), and perfusion imagings simultaneously acquired in a 3 T magnet) to assess the effects of SS on thumb-movement-related activation in three regions of interest (ROI) in the motor network: primary motor cortex (M1), primary somatosensory cortex (S1), and dorsal premotor cortex (PMd) in healthy volunteers. Scans were obtained in different sessions before and after 2-h electrical stimulation applied to the median nerve at the wrist (MNS), to the skin overlying the shoulder deltoid muscle (DMS), and in the absence of stimulation (NOSTIM) in a counterbalanced design. We found that baseline perfusion intensity was comparable within and across sessions. MNS but not DMS nor NOSTIM led to an increase in signal intensity and number of voxels activated by performance of median nerve-innervated thumb movements in M1, S1, and PMd for up to 60 min. Task-related fMRI activation changes were most prominent in M1 followed by S1 and to a lesser extent in PMd. MNS elicited a displacement of the center of gravity for the thumb movement representation towards the other finger representations within S1. These results indicate that MNS leads to an expansion of the thumb representation towards other finger representations within S1, a form of plasticity that may underlie the influence of SS on motor cortical function, possibly supporting beneficial effects on motor control.     

Transcranial direct current stimulation over the primary motor cortex during fMRI

Measurements of motor evoked potentials (MEPs) have shown that anodal and cathodal transcranial direct current stimulations (tDCS) have facilitatory or inhibitory effects on corticospinal excitability in the stimulated area of the primary motor cortex (M1). Here, we investigated the online effects of short periods of anodal and cathodal tDCS on human brain activity of healthy subjects and associated hemodynamics by concurrent blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) at 3T. Using a block design, 20s periods of tDCS at 1 mA intensity over the left M1 altered with 20s periods without tDCS. In different fMRI runs, the effect of anodal or cathodal tDCS was assessed at rest or during finger tapping. A control experiment was also performed, in which the electrodes were placed over the left and right occipito-temporo-parietal junction. Neither anodal nor cathodal tDCS over the M1 for 20s stimulation duration induced a detectable BOLD signal change. However, in comparison to a voluntary finger tapping task without stimulation, anodal tDCS during finger tapping resulted in a decrease in the BOLD response in the supplementary motor area (SMA). Cathodal stimulation did not result in significant change in BOLD response in the SMA, however, a tendency toward decreased activity could be seen. In the control experiment neither cathodal nor anodal stimulation resulted in a significant change of BOLD signal during finger tapping in any brain area including SMA, PM, and M1. These findings demonstrate that the well-known polarity-dependent shifts in corticospinal excitability that have previously been demonstrated using measurements of MEPs after M1 stimulation are not paralleled by analogous changes in regional BOLD signal. This difference implies that the BOLD signal and measurements of MEPs probe diverse physiological mechanisms. The MEP amplitude reflects changes in transsynaptic excitability of large pyramidal neurons while the BOLD signal is a measure of net synaptic activity of all cortical neurons.     

The relationship between motor deficit and hemisphere activation balance after stroke: A 3T fMRI study

Functional imaging during movement of the hand affected by a stroke has shown excess activation of the contralesional motor network, implying less physiological hemisphere activation balance. Although this may be adaptive, the relationship between the severity of motor deficit and the hemisphere activation balance for the four major cortical motor areas has not been systematically studied. We prospectively studied 19 right-handed patients with first-ever stroke (age range 61+/-10 years) in the stable phase of recovery (>3 months after onset), using auditory-paced index-thumb (IT) tapping of the affected hand at 1.25 Hz as the fMRI paradigm. The hemisphere activation balance for the primary motor (M1), primary somatosensory (S1), supplementary motor (SMA) and dorsal premotor (PMd) areas was measured by a modified weighted laterality index (wLI), and correlations with motor performance (assessed by the affected/unaffected ratio of maximum IT taps in 15 s, termed IT-R) were computed. There were statistically significant negative correlations between IT-R and the wLI for M1 and S1, such that the more the hemispheric balance shifted contralesionally, the worse the performance. Furthermore, worse performance was related to a greater amount of contralesional, but not ipsilesional, activation. No significant correlation between IT-R and the wLI was obtained for the SMA and PMd, which functionally have stronger bilateral organization. These findings suggest that the degree of recovery of fine finger motion after stroke is determined by the extent to which activation balance in the primary sensory motor areas--where most corticospinal fibers originate--departs from normality. This observation may have implications for therapy.     

Changes of cerebral blood flow, oxygenation, and oxidative metabolism during graded motor activation.

In the present studies fMRI and a hypercapnic calibration procedure were used to monitor simultaneous changes in cerebral blood flow (CBF), cerebral blood oxygenation, and cerebral metabolic rate of oxygen (CMRO(2)) during activation in the sensorimotor cortex. In the first set of experiments seven volunteers performed bilateral, self-paced finger tapping and in the second set of experiments six volunteers performed bilateral finger tapping with six different frequencies (0.5-3 Hz). During the latter task relative CBF and BOLD signal intensity changes varied linearly as a function of stimulus frequency. In good agreement with recent PET and fMRI data increases in CMRO(2) were smaller than the corresponding changes in CBF during self-paced finger tapping and at all levels of graded motor activation. At a single level of activation and during graded activation there was a positive linear relationship between CBF and CMRO(2) with ratios of approximately 3:1. Comparable proportionality constants have been found in the visual cortex and primary sensory cortex, indicating similarities between the relationship of CBF and CMRO(2) in various cortical regions.     

Self-modulation of primary motor cortex activity with motor and motor imagery tasks using real-time fMRI-based neurofeedback

Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROI_m) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROI_m fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROI_m during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROI_m during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system.     

Modulation of cortical oscillatory activities induced by varying single-pulse transcranial magnetic stimulation intensity over the left primary motor area: a combined EEG and TMS study

Combined transcranial magnetic stimulation/electroencephalography (TMS/EEG) was used to study the activation and interaction of cortical regions to a variety of focused sub- and suprathreshold magnetic pulses over the left primary motor cortex (M1) in ten healthy subjects. Five single-pulse TMS conditions were performed based on the individual resting motor threshold (RMT): (1) 80%; (2) 100%; (3) 120%; (4) 130%; and (5) sham. Simple self-paced movements of the right first finger were also executed. We evaluated the reactions to magnetic stimulation and movement conditions using event-related power and event-related coherence transformations of alpha and beta rhythms. Event-related power reflected regional oscillatory activity of neural assemblies, while event-related coherence reflected the inter-regional functional coupling of oscillatory neural activity. The event-related power transformation revealed that the magnetic pulse modulated cortical oscillations within the first half second for both frequency ranges. For the alpha rhythm, threshold TMS induced a small decrease in the amplitude of EEG oscillations over the stimulation site, while for both rhythms, a progressive synchronization was observed as the intensity of TMS was increased in both hemispheres. Movement onset produced a greater bilateral decrease of power compared with the effects of a magnetic pulse. The event-related coherence revealed that TMS enhanced the electrode connectivity of both hemispheres. Additionally, it was more enhanced within the first 500 ms following stimulation and was seen only for the alpha frequency rhythm. The increase of functional connectivity between cortical areas was minor for magnetic stimulation conditions compared with that for finger movements. The single-pulse TMS over M1 partially modulated the motor cortex generators of oscillatory activity, while a simple active self-paced movement of the right first finger induced greater cortex activation and coupling between cortical regions. We propose that finger movements impose higher functional demands on the motor system compared to artificial magnetic stimulation. These findings are consistent with the possibility that the human motor system may be based on network-like oscillatory cortical activity and might be modulated by brief electromagnetic sub- and suprathreshold pulses applied to M1, suggesting a phenomenon of resetting.     

Reduction of excitability ("inhibition") in the ipsilateral primary motor cortex is mirrored by fMRI signal decreases

Functional magnetic resonance imaging (fMRI) was used to investigate how focal cortical inhibition affects the blood oxygen level-dependent (BOLD) signal. Phasic low force pinch grip reduces excitability of the ipsilateral primary motor cortex. This task was used to study BOLD signal changes during inhibition. Six right-handed normal volunteers participated in the study. They were asked to perform a right-handed pinch grip repetitively at 1 Hz and 5% of their individual maximal voluntary contraction (MVC). Data were acquired with a 1.5 Tesla Magnetom and continuous multislice T2*-weighted images. The contralateral primary motor cortex (M1) revealed an activation in the knob-shaped hand representation of the central sulcus area. More importantly, a decreased (often referred to as "negative") BOLD signal in the ipsilateral M1 was observed. We suggest phasic low force pinch grip as a reproducible, easy model of focal inhibition. Decreased cortical excitability presents as decreased BOLD signal using fMRI.     

Cross-modal plasticity for sensory and motor activation patterns in blind subjects

Experimental data on cortical reorganization in blind subjects using H(2)(15)O positron emission tomography and functional magnetic resonance imaging (fMRI) showed activation of the visual cortex related to Braille reading and tactile discrimination tasks in congenitally and early blind subjects. The purpose of our study was to differentiate whether occipital activation of blind subjects during Braille reading is task specific or only triggered by sensory or motor area activation. Twelve congenitally and early-onset blind subjects were studied with fMRI during Braille reading, discriminating nonsense dots, sensory stimulation with electromagnetic pulses, and finger tapping. All experiments were performed utilizing a block design with 6 active epochs alternating with 6 rest conditions lasting 34 s each. Echo-planar imaging sequences with 34 transversal slices were performed on a 1.5-T MR scanner. All blind individuals reading Braille and discriminating nonsense dots showed robust activation of the primary, secondary, and higher visual cortex. Application of peripheral electrical stimuli to the reading hand revealed expected sensory activation of the primary somatosensory cortex, but no activation in the visual cortex. Pure motor activation during finger tapping with the reading hand showed expected precentral activation and no activation of visual cortex. In conclusion, occipital activation during Braille reading and discrimination tasks is not due to plasticity of sensory or motor function; pure motor or sensory tasks do not lead to an activation of striate cortex. The brain learns to differentiate between "finger touching" and "finger reading." Our results suggest that activation of the visual cortex in blind subjects is related to higher and more complex brain functions.     

针刺穴位联合康复训练治疗急性脑梗死 上肢运动功能障碍并功能磁共振研究

目的:观察针刺穴位联合康复训练治疗急性脑梗死上肢运动功能障碍的疗效,并借助功能磁共振探讨对神经功能重塑的影响。方法:选取急性脑梗死上肢运动功能障碍患者60例,随机分为对照组及治疗组,各30例。对照组行常规药物治疗和运动康复训练,治疗组在对照组的基础上给予针刺穴位治疗;均治疗3个月。于治疗前、后,对2组患者行美国国立卫生院脑卒中量表(NIHSS)评分、Fugl-Meyer上肢运动量表(FMA-UE)评分、患肢的食指轻叩试验检查、握力测量及运动任务态的功能磁共振扫描。结果:治疗后,2组的NIHSS评分、FMA-UE评分、患肢食指轻叩试验及握力测量均较治疗前改善(均P<0.01),且治疗组改善程度较对照组明显(均P<0.01)。治疗前,2组患者左手握拳运动可稳定激活对侧初级运动区(M1)及辅助运动区(SMA);治疗后,2组患者左手握拳运动时,对侧M1区及双侧SAM区较治疗前激活增强(P<0.01),且治疗组较对照组激活增强明显(P<0.01)。结论:针刺穴位联合康复训练治疗急性脑梗死上肢运动功能障碍疗效肯定,促进对侧M1及双侧SAM脑区的激活、调节神经功能重塑可能是其机制之一。     

Modulation of language areas with functional MR image-guided magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) can interfere with linguistic performance when delivered over language areas. At low frequency (1 Hz), rTMS is assumed to decrease cortical excitability; however, the degree of TMS effect on cortical language areas may depend on the localization of the stimulation coil with respect to the inter-individual anatomo-functional variations. Hence, we aimed at investigating individual brain areas involved in semantic and phonological auditory processes. We hypothesized that active rTMS targeted over Wernicke's area might modify the performance during a language-fragment-detection task. Sentences in native or foreign languages were presented to 12 right-handed male healthy volunteers during functional magnetic resonance imaging (fMRI). 3D-functional maps localized the posterior temporal activation (Wernicke) in each subject and MRI anatomical cortical landmarks were used to define Broca's pars opercularis (F3Op). A frameless stereotaxy system was used to guide the TMS coil position over Wernicke's and F3Op areas in each subject. Active and placebo randomized rTMS sessions were applied at 1 Hz, 110% of motor threshold, during the same language-fragment-detection task. Accuracy and response time (RT) were recorded. RT was significantly decreased by active rTMS compared to placebo over Wernicke's area, and was more decreased for native than for foreign languages. No significant RT change was observed for F3Op area. rTMS conditions did not impair participants' accuracy. Thus, low-frequency rTMS over Wernicke's area can speed-up the response to a task tapping on native language perception in healthy volunteers. This individually-guided stimulation study confirms that facilitatory effects are not confined to high-frequency rTMS.     

Differences in short-term primary motor cortex synaptic potentiation as assessed by repetitive transcranial magnetic stimulation in migraine patients with and without aura

To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5 Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5 Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5 Hz-rTMS in the three groups tested. The 5 Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5 Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.     

The cortical motor threshold reflects microstructural properties of cerebral white matter

Transcranial magnetic stimulation (TMS) can be used to probe distinct aspects of excitability of the primary motor hand area (M1(Hand)). The motor threshold (MT) reflects the trans-synaptic excitability of corticospinal output neurons. The MT corresponds to the minimal intensity at which TMS evokes a contralateral motor response. Here, we employed diffusion-weighted imaging (DWI) to examine whether inter-individual differences in MT of the left and right M1(Hand), an index of cortical excitability, are associated with variations in fractional anisotropy (FA), an index of white matter microstructure. Resting and active MT showed an inverse linear relationship with regional FA values in large bihemispheric clusters, including the white matter underlying primary motor, premotor and posterior prefrontal cortices, as well as the genu of the internal capsule, cerebral peduncles and corpus callosum. The linear increase in FA with cortical excitability as indexed by the MT remained significant after controlling for differences in handedness or coil-cortex distance. The posterior limb of the internal capsule, where fast-conducting corticospinal fibres from M1(Hand) pass through, showed only a weak linear relationship between FA and MT. The FA measurements show that a high level of corticospinal excitability is associated with a higher fibre coherence in large parts of cerebral white matter. The higher FA values in the white matter beneath premotor and motor cortices may reflect a structural property of cortico-cortical connections that renders M1(Hand) more susceptible to TMS-induced trans-synaptic excitation of the corticospinal fibres and may account for the inverse linear relationship between MT and FA.     

Age-related changes in causal interactions between cortical motor regions during hand grip

Brain activity during motor performance becomes more widespread and less lateralized with advancing age in response to ongoing degenerative processes. In this study, we were interested in the mechanism by which this change in the pattern of activity supports motor performance with advancing age. We used both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to assess age related changes in motor system connectivity during isometric hand grip. Paired pulse TMS was used to measure the change in interhemispheric inhibition (IHI) from contralateral M1 (cM1) to ipsilateral M1 (iM1) during right hand grip. Dynamic Causal Modelling (DCM) of fMRI data was used to investigate the effect of age on causal interactions throughout the cortical motor network during right hand grip. Bayesian model selection was used to identify the causal model that best explained the data for all subjects. Firstly, we confirmed that the TMS and DCM measures both demonstrated a less inhibitory/more facilitatory influence of cM1 on iM1 during hand grip with advancing age. These values correlated with one another providing face validity for our DCM measures of connectivity. We found increasing reciprocal facilitatory influences with advancing age (i) between all ipsilateral cortical motor areas and (ii) between cortical motor areas of both hemispheres and iM1. There were no differences in the performance of our task with ageing suggesting that the ipsilateral cortical motor areas, in particular iM1, play a central role in maintaining performance levels with ageing through increasingly facilitatory cortico-cortical influences.     

Effects of oxygen saturation on BOLD and arterial spin labelling perfusion fMRI signals studied in a motor activation task

Effects of oxygen availability on blood oxygenation level dependent (BOLD) and arterial spin labelling (ASL) perfusion functional magnetic resonance imaging (fMRI) signal changes upon motor activation were studied. Mild hypoxic hypoxia was induced by reducing the inspired oxygen content (FIO(2)) to 12%, decreasing blood oxygen saturation (Y) from 0.99 +/- 0.01 to 0.85 +/- 0.03. The fMRI signal characteristics were determined during finger tapping. BOLD activation volume decreased as a function of declining Y in the brain structures involved in execution of the motor task, however, the BOLD signal increase in activated parenchyma was not influenced by Y. ASL fMRI showed that the baseline CBF of 61.8 +/- 3.6 ml/100 g/min was not affected by hypoxic hypoxia. Similar to the BOLD fMRI, the volume of motor cortex areas displaying increase in perfusion by ASL fMRI decreased, but the signal change due to perfusion increase was not influenced in hypoxia. The present fMRI results show distinct patterns of haemodynamic and metabolic responses in the brain to motor task between normoxia and hypoxia. On one hand, neither BOLD nor ASL fMRI signal changes are influenced by hypoxia during motor activation. On the other hand, hypoxia attenuates increase in both BOLD and perfusion fMRI signals upon finger tapping from the levels determined in normoxia. These observations indicate that haemodynamic and metabolic responses may be heterogeneous in brain during execution of motor functions in mild hypoxia.     

fMRI Evaluation of Somatotopic Representation in Human Primary Motor Cortex

We used fMRI to map foot, elbow, fist, thumb, index finger, and lip movements in 30 healthy subjects. For each movement type confidence intervals of representational sites in the primary motor cortex (M1) were evaluated. In order to improve the precision of their anatomical localization and to optimize the mapping of cortical activation sites, we used both the assessment of locations in the conventional 3D system and a 2D projection method. In addition to the computation of activation maxima of activation clusters within the precentral gyrus, centers of gravity were determined. Both methods showed a high overlap of their representational confidence intervals. The 2D-projection method revealed statistically significant distinct intralimb locations, e.g., elbow versus index finger movements and index finger versus thumb movements. Increased degree of complexity of finger movements resulted in a spread of the somatotopic location toward the arm representation. The 2D-projection method-based fMRI evaluation of limb movements showed high precision and was able to reveal differences in intralimb movement comparisons. fMRI activation revealed a clear somatotopic order of movement representation in M1 and also reflected different degrees of complexity of movement.     

Hand movement distribution in the motor cortex: the influence of a concurrent task and motor imagery

The aim of this work was to study the relevance of the primary motor cortex (M1) for motor functions different to the simple execution of motor orders. The M1 activity during the performance with individual fingers of a simple motor task (tonic flexion), a motor task that includes a complex motor computation but not motor execution (motor imagery), and a motor task that involves both the computation and execution of movements (phasic movement) was evaluated by functional magnetic resonance imaging (fMRI). The possible influence of other cortical tasks on the M1 activation induced by finger movements was assessed by evaluating the effect of a distracting concurrent task (numeric calculation). Data show that both the dimension of the area activated and the intensity of response were higher during motor planning than during motor execution. There is a mosaic-like distribution for motor-planning M1 functions, with the movement of individual fingers being controlled from several M1 loci. The concurrent mental-task induces a rapid functional reconfiguration of M1, adding M1 subsets to motor programming but excluding others. Present data support the involvement of the M1 in more than just simple motor execution, showing broader and more intense modifications during motor tasks not accompanied by movements (motor imagery) than during the execution of simple motor acts (tonic flexion).     

Cortical activity in multiple motor areas during sequential finger movements: an application of independent component analysis

Multiple cortical regions such as the supplementary motor area (SMA), premotor cortex (PM), and primary motor cortex (M1) are involved in the sequential execution of hand movements, but it is unclear how these areas collaborate in the preparation and execution of ipsilateral and contralateral hand movements. In this study, we used right-handed subjects to examine the spatial distribution and temporal profiles of motor-related activity during visually cued sequential finger movements by applying independent component analysis (ICA) to event-related functional magnetic resonance imaging (fMRI) signals. The particular merit of the ICA method is that it allows brain activity in individual subjects to be elucidated without making a priori assumptions about the anatomical areas that are activated or the temporal profile of activity. By applying ICA, we found that (1) the SMA contributed to both the preparation and execution of movements of the right and left hand; (2) the left M1 and dorsal premotor cortex (PMd) contributed to both the preparation and execution of movements of the right and left hand, whereas the right M1 and PMd contributed mainly to the execution of movements of the left hand; (3) pre-SMA areas were activated in some subjects in concert with the posterior parietal and prefrontal cortex; and (4) fMRI signals over superficial cortical draining veins could be distinguished from cortical activation. We suggest that ICA is useful for categorizing distributed task-related activities in individual subjects into several spatially independent activities that represent functional units in motor control.     

High frequency rTMS modulation of the sensorimotor networks: behavioral changes and fMRI correlates

Repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex (M1) may induce functional modulation of motor performance and sensory perception. To address the underlying neurophysiological modulation following 10 Hz rTMS applied over M1, we examined cortical activation using 3T functional magnetic resonance imaging (fMRI), as well as the associated motor and sensory behavioral changes. The motor performance measure involved a sequential finger motor task that was also used as an activation task during fMRI. For sensory assessment, current perception threshold was measured before and after rTMS outside the MR scanner, and noxious mechanical stimulation was used as an activation task during fMRI. We found that significant activation in the bilateral basal ganglia, left superior frontal gyrus, bilateral pre-SMA, right medial temporal lobe, right inferior parietal lobe, and right cerebellar hemisphere correlated with enhanced motor performance in subjects that received real rTMS compared with sham-stimulated controls. Conversely, significant deactivation in the right superior and middle frontal gyri, bilateral postcentral and bilateral cingulate gyri, left SMA, right insula, right basal ganglia, and right cerebellar hemisphere were associated with an increase in the sensory threshold. Our findings reveal that rTMS induced rapid changes in the sensorimotor networks associated with sensory perception and motor performance and demonstrate the complexity of such intervention.