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Functional domains in dorsal striatum of the nonhuman primate are defined by the dynamic behavior of dopamine.

The dorsal striatum comprises a continuum of distinct functional domains, limbic, associative, and sensorimotor. In the primate it exclusively subdivides further into two nuclei, the putamen and caudate. Dopamine (DA) transmission is differentially affected between these nuclei in neurodegenerative diseases such as Parkinson's and by psychostimulants such as cocaine. Because rodent systems can offer only limited insight into DA systems of the human brain, a fuller appreciation of DA transmission and its role in dysfunction requires direct study in primates. DA behavior was explored in the major functional domains of the caudate nucleus and compared with the putamen, using fast-scan cyclic voltammetry in striatal sections from the marmoset (Callithrix jacchus). There was domain-specific variation in extracellular DA transients [i.e., concentration ([DA](o)) released by a single stimulus and the rate maximum of DA uptake, V(max)]. Across nuclei, functional rather than anatomical regions were differentiated by these dynamics. The largest, fastest DA transients were at motor-associated loci. Evoked [DA](o) at physiological frequencies was differently frequency-sensitive between functional domains but not between anatomical nuclei. In contrast, presynaptic depression was not an index of regional differentiation, recovering with similar kinetics at all loci. Within a given functional domain of dorsal striatum, the dynamics of DA release and uptake are similar for the putamen and the caudate nucleus. Conversely, distinct functional domains are defined by these DA dynamics, in a manner more marked in primates than in rodents. These data from the primate brain highlight differences in DA availability that may be central to DA function and dysfunction in the human.

Animals↗

Activation of cerebellum and basal ganglia on volitional swallowing detected by functional magnetic resonance imaging.

Although regions of the sensorimotor cortex, insula, and anterior cingulate gyrus are reported to be activated during swallowing, findings concerning contributions of the cerebellum and basal ganglia have been contradictory. We investigated cerebellar and basal ganglionic activation using functional magnetic resonance imaging (fMRI). In 11 subjects, single-shot gradient-echo echoplanar image volumes sensitive to BOLD contrast were acquired in block design fashion using an oblique orientation covering both cerebrum and cerebellum. Using statistical parametric mapping, regional activation upon swallowing was observed in the sensorimotor cortex, insula, cerebellum, putamen, globus pallidus, thalamus, anterior cingulate gyrus, supplementary motor area, superior temporal gyrus, and substancia nigra. The cerebellum was activated bilaterally, especially on the left; activation of the putamen and globus pallidus was also found bilaterally. Thus, volitional swallowing involves the cerebellum and basal ganglia as well as cortical structures. The method used was well tolerated by normal subjects and should also be applicable to patients with dysphagia.

Adult↗

A longitudinal fMRI study on motor activity in patients with multiple sclerosis.

Using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of motor activation than controls. Although functional changes are often interpreted as adaptive and as a contributing factor in limiting the clinical deficit, no longitudinal studies have yet been performed for multiple sclerosis. Sixteen patients with multiple sclerosis, two patients with possible multiple sclerosis and nine age-matched controls underwent two fMRI studies with a time interval of 15-26 months. The motor task consisted of a self-paced sequential finger opposition movement with the right hand. Patients with multiple sclerosis exhibited greater bilateral activation than controls in both fMRI studies. At follow-up, patients showed a reduction in functional activity in the ipsilateral sensorimotor cortex and in the contralateral cerebellum. No significant differences between the two fMRI studies were observed in controls. Activation changes in ipsilateral motor areas correlated inversely with age, extent and progression of T1 lesion load, and occurrence of a new relapse. This study may help the understanding of the evolution of brain plastic changes in multiple sclerosis indicating that, in younger patients with a less structural brain damage and benign clinical course, the brain reorganizes its functional activity towards a more lateralized pattern of brain activation. The tendency towards a normalization of brain functional activity is hampered in older patients and in those developing relapses or new irreversible brain damage.

Adult↗

Movement rate effect on activation and functional coupling of motor cortical areas.

We investigated changes in the activation and functional coupling of bilateral primary sensorimotor (SM1) and supplementary motor (SMA) areas with different movement rates in eight normal volunteers. An auditory-cued repetitive right-thumb movement was performed at rates of 0.5, 0.75, 1, 2, 3, and 4 Hz. As a control condition, subjects listened to pacing tones with no movements. Electroencephalogram (EEG) was recorded from 28 scalp electrodes and electromyogram was obtained from the hand muscles. The event-related changes in EEG band-power (ERpow: activation of each area) and correlation (ERcor: functional coupling between each pair of cortical areas) were computed every 32 ms. Modulations of ERpow and ERcor were inspected in alpha (8-12 Hz) and beta (16-20 Hz) bands. Motor cortical activation and coupling was greater for faster movements. With increasing movement rate, the timing relationship between movement and tone switched from synchronization (for 0.5-1 Hz) to syncopation (for 3-4 Hz). The results suggested that for slow repetitive movements (0.5-1 Hz), each individual movement is separately controlled, and EEG activation and coupling of the motor cortical areas were immediately followed by transient deactivation and decoupling, having clear temporal modulation locked to each movement. In contrast, for fast repetitive movements (3-4 Hz), it appears that the rhythm is controlled and the motor cortices showed sustained EEG activation and continuous coupling.

Adult↗

On the nature of the vestibular control of arm-reaching movements during whole-body rotations.

Recent studies report efficient vestibular control of goal-directed arm movements during body motion. This contribution tested whether this control relies (a) on an updating process in which vestibular signals are used to update the perceived egocentric position of surrounding objects when body orientation changes, or (b) on a sensorimotor process, i.e. a transfer function between vestibular input and the arm motor output that preserves hand trajectory in space despite body rotation. Both processes were separately and specifically adapted. We then compared the respective influences of the adapted processes on the vestibular control of arm-reaching movements. The rationale was that if a given process underlies a given behavior, any adaptive modification of this process should give rise to observable modification of the behavior. The updating adaptation adapted the matching between vestibular input and perceived body displacement in the surrounding world. The sensorimotor adaptation adapted the matching between vestibular input and the arm motor output necessary to keep the hand fixed in space during body rotation. Only the sensorimotor adaptation significantly altered the vestibular control of arm-reaching movements. Our results therefore suggest that during passive self-motion, the vestibular control of arm-reaching movements essentially derives from a sensorimotor process by which arm motor output is modified on-line to preserve hand trajectory in space despite body displacement. In contrast, the updating process maintaining up-to-date the egocentric representation of visual space seems to contribute little to generating the required arm compensation during body rotations.

Adaptation, Physiological↗

Intraoperative cortico-subcortical stimulations in surgery of low-grade gliomas.

In order to increase the impact of surgery on the natural history of low-grade glioma, resection should be of maximum importance. Nevertheless, since low-grade gliomas are frequently located in eloquent structures, function needs to be preserved. Therefore, studying the functional organization of the brain is mandatory for each patient due to the inter-individual anatomofunctional variability, increased in tumors due to cerebral plasticity. This strategy enables performance of a resection according to functional boundaries. However, preoperative neurofunctional imaging only allows the study of the gray matter. Consequently, since low-grade glioma invades cortical and subcortical structures and shows an infiltrative progression along the fibers, the goal of this review is to focus on the techniques able to map both cortical and subcortical regions. In addition to diffusion tensor imaging, which gives only anatomical information and still needs to be validated, intraoperative direct cortico-subcortical electrostimulation is the sole current method allowing a reliable study of the individual anatomofunctional connectivity, concerning sensorimotor, language and other cognitive functions. Its actual contribution is detailed, both in clinical issues, especially the improvement of the benefit/risk ratio of low-grade glioma resection, and in fundamental applications--namely, a new door to the connectionism and cerebral plasticity.

Brain Mapping↗

Atypically diffuse functional connectivity between caudate nuclei and cerebral cortex in autism.

BACKGROUND: Autism is a neurodevelopmental disorder affecting sociocommunicative behavior, but also sensorimotor skill learning, oculomotor control, and executive functioning. Some of these impairments may be related to abnormalities of the caudate nuclei, which have been reported for autism. METHODS: Our sample was comprised of 8 high-functioning males with autism and 8 handedness, sex, and age-matched controls. Subjects underwent functional MRI scanning during performance on simple visuomotor coordination tasks. Functional connectivity MRI (fcMRI) effects were identified as interregional blood oxygenation level dependent (BOLD) signal cross-correlation, using the caudate nuclei as seed volumes. RESULTS: In the control group, fcMRI effects were found in circuits with known participation of the caudate nuclei (associative, orbitofrontal, oculomotor, motor circuits). Although in the autism group fcMRI effects within these circuits were less pronounced or absent, autistic subjects showed diffusely increased connectivity mostly in pericentral regions, but also in brain areas outside expected anatomical circuits (such as visual cortex). CONCLUSION: These atypical connectivity patterns may be linked to developmental brain growth disturbances recently reported in autism and suggest inefficiently organized functional connectivity between caudate nuclei and cerebral cortex, potentially accounting for stereotypic behaviors and executive impairments.

Journal Article↗

Lighter or heavier than predicted: neural correlates of corrective mechanisms during erroneously programmed lifts.

A central concept in neuroscience is that the CNS signals the sensory discrepancy between the predicted and actual sensory consequences of action. It has been proposed that the cerebellum and parietal cortex are involved in this process. A discrepancy will trigger preprogrammed corrective responses and update the engaged sensorimotor memories. Here we use functional magnetic resonance imaging with an event-related design to investigate the neuronal correlates of such discrepancies. Healthy adults repeatedly lifted an object between their right index fingers and thumbs, and on some lifting trials, the weight of the object was unpredictably changed between light (230 g) and heavy (830 g). Regardless of whether the weight was heavier or lighter than predicted, activity was found in the right inferior parietal cortex (supramarginal gyrus). This suggests that this region is involved in the comparison of the predicted and actual sensory input and the updating of the sensorimotor memories. When the object was lighter or heavier than predicted, two different types of preprogrammed force corrections occurred. There was a slow force increase when the weight of the object was heavier than predicted. This corrective response was associated with activity in the left primary motor and somatosensory cortices. The fast termination of the excessive force when the object was lighter than predicted activated the right cerebellum. These findings show how the parietal cortex, cerebellum, and motor cortex are involved in the signaling of the discrepancy between predicated and actual sensory feedback and the associated corrective mechanisms.

Adult↗

Simultaneous recording of cerebral blood oxygenation changes during human brain activation by magnetic resonance imaging and near-infrared spectroscopy.

Changes in cerebral blood oxygenation due to functional activation of the primary sensorimotor cortex during a unilateral finger opposition task were simultaneously mapped by deoxyhemoglobin-sensitive magnetic resonance imaging (MRI) and monitored by near-infrared spectroscopy (NIRS). Activation foci along the contralateral central sulcus displayed task-associated increases in MRI signal intensity, indicating a concomitant decrease of the focal concentration of deoxyhemoglobin. This interpretation was confirmed by simultaneous reductions in deoxyhemoglobin measured optically. Since observation of the latter effect required exact spatial matching of the MRI-detected activation foci and position of the fiber optic bundles ("optodes") used for transmitting and receiving light, it may be concluded that optical recordings of changes in deoxyhemoglobin during functional challenge probe only a restricted brain tissue region. While deoxyhemoglobin responses seen by NIRS were smaller for ipsi- than for contralateral finger movements, task-related increases in oxyhemoglobin were rather similar between both conditions and, thus, seem to be less specific. Furthermore, no consistent changes were obtained for total hemoglobin during task performance, possibly due to the short timing of the repetitive protocol. In general, results underline, in humans, the hitherto assumed signal physiology for functional brain mapping by oxygenation-sensitive MRI and allow assessment of both constraints and practicability of functional studies by NIRS.

Adult↗

Functional neuronavigation with magnetoencephalography: outcome in 50 patients with lesions around the motor cortex.

The authors conducted a study to evaluate the clinical outcome in 50 patients with lesions around the motor cortex who underwent surgery in which functional neuronavigation was performed. The sensorimotor cortex was identified in all patients with the use of magnetoencephalography (MEG). The MEG-source localizations were superimposed onto a three-dimensional magnetic resonance image, and the image data set was then implemented into a neuronavigation system. Based on this setup, the surgeon chose the best surgical strategy. During surgery, the pre- and postcentral gyrus were identified by neuronavigation, and in addition, the central sulcus was localized using intraoperative recording of somatosensory evoked potentials. In all cases MEG localizations of the sensory or motor cortex were correct. In 30% of the patients preoperative paresis improved, in 66% no additional deficits occurred, and in only 4% (two patients) deterioration of neurological function occurred. In one of these patients the deterioration was not related to the method. The method of incorporating functional data into neuronavigation systems is a promising tool that can be used in more radical surgery to cause less morbidity around eloquent brain areas.

Journal Article↗

Event-related magnetic fields in the auditory cortex of man during unilateral movements: a discriminant function analysis.

It is often assumed that sensorimotor coordination is a feature of the sensorimotor areas of the neocortex only. The purpose of the present study was to examine how this phenomenon is reflected in the auditory cortex of man. Ten subjects were engaged in a stimulus-reaction paradigm, in which each of two acoustical tones was associated to either of two motor reactions. Magnetic fields recorded with a 122-channel magnetometer were modelled by current dipoles. The spatial coordinates as well as the amplitudes of the dipoles were analyzed from 90 to 110 ms after stimulus onset using discriminant analysis. The results suggest that the dipole trajectory in the auditory cortex of the right hemisphere and amplitudes of the dipoles in the auditory cortex of the left hemisphere already 90-110 ms after the beginning of the stimulus could be affected not only by physical features of the stimulus, but also by the motor task required as a reaction.

Acoustic Stimulation↗

Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors.

The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is deficient in schizophrenia patients and rodents treated with NMDA antagonists. Hence, PPI is widely used to study the neurobiology of schizophrenia. As the use of PPI as a model of gating deficits in schizophrenia has become more widespread, it has become increasingly important to assess such deficits accurately. Here we identify a possible role of mGluR5 in PPI by using wild type (WT) and mGluR5 knockout (KO) mice of two different background strains, 129SvPasIco and C57BL/6. In both strains, PPI was disrupted dramatically in the mGluR5 KO mice throughout a range of interstimulus intervals and sensory modalities. The present findings further support the glutamate hypothesis of schizophrenia and identify a functional role for mGluR5 in sensorimotor gating.

Animals↗

[The transmission of coded information over neuronal systems exemplified by the motor rhythmic dominant].

Functional organization of neurons in rabbit's sensorimotor cortex was studied before and within several days after formation of the rhythmical dominant focus. Functional reorganization of neurons in cortical microareas took place during actualization of the dominant. The number of functional interneuronal relations within neuronal pairs of a certain type could be increased in comparison with the control values and decreased within pairs of another type. As a result, the total percent of the interneuronal correlations in cortical microareas in the control animals and rabbits with the acting dominant was approximately equal. The total percent of correlations between neurons of the adjacent cortical areas during the actualization of the dominant was significantly higher than in the control due to increased number of correlations with participation of small and medium-sized neurons. A possibility of information circulation about the "stimulus image" in the closed chain of neurons was exemplified by the real micronetwork. The data suggest the reverberation of encoded information between adjacent microareas of the sensorimotor cortex within several days after application of the stimulus, which has formed the excitation focus.

Animals↗

[Analysis of grip force during object manipulation. Method for the objective measurement of physiological normal and impaired hand function].

The control of prehensile finger forces is an essential feature of all skilled manual performance. The basic aspects of healthy grip force control have been well documented within the past two decades. In healthy subjects, grip force is accurately adjusted to the mechanical object properties such as weight, surface friction, and shape: when we move a hand-held object, grip force is modulated in parallel with movement-induced load fluctuations without an apparent temporal delay. At all phases of the movement, grip force is always slightly higher than the minimum necessary to prevent the object from slipping. The absence of a temporal delay between grip and load force profiles implies that the central nervous system is able to predict load variations precisely before the intended manipulation, and consequently regulates grip force in anticipation. Feedback from the grasping fingertips is used to adjust the force level efficiently to the actual load requirements. Pathologic grip force control affects the efficiency of the forces produced and the predictive temporal coupling between grip and load force profiles. Here we demonstrate pathologic grip force control in various neurologic disorders. The analysis of grip force control is simple and highly sensitive for detecting healthy and pathologic motor behaviour. The examination of grip force control is well suited for an objective evaluation of therapy during sensorimotor rehabilitation of deficient hand function.

Diagnosis, Computer-Assisted↗

Commentary: eye movement research with clinical populations.

The preceding set of chapters span the disciplines of neurology and psychiatry, and provide a diverse introduction to clinical eye movement research. They illustrate how oculomotor paradigms can be used to learn about acute and chronic perturbations in brain function, disturbances in brain development, disturbances in sensorimotor as well as cognitive systems, and the effects of therapeutic and illicit drugs on brain function. This commentary discusses these contributions, provides an overview of broad methodological issues involved in applying eye movement studies to psychiatric populations using the antisaccade task as an exemplar, and considers the potential of collaborations between eye movement and brain imaging researchers to advance understanding of clinical eye movement abnormalities and of what they reveal about the organization of the oculomotor system.

Brain↗

Abnormal cerebral activation associated with a motor task in Tourette syndrome.

BACKGROUND AND PURPOSE: In Gilles de la Tourette syndrome, PET scanning and EEG suggest an abnormal organization of the sensorimotor cortex and basal ganglia. The purpose of this study was to use functional MR imaging to study activation in the sensorimotor cortex in patients with Tourette syndrome. METHODS: From echo-planar images acquired during intermittent performance of a finger-tapping task, the location of activated pixels was determined by means of conventional signal processing methods. In five patients with Tourette syndrome and five healthy volunteers, the number of activated pixels in the sensorimotor cortices and supplementary motor areas were counted. The area over which the activation was distributed was calculated. RESULTS: In the five patients, the average number of pixels activated during the finger-tapping task in the sensorimoter cortices and supplementary motor area (69.4 pixels) exceeded that in the volunteers (49.2 pixels). The difference was significant. The area over which the pixels was distributed was significantly larger (25.4 vs 13.8 cm2). CONCLUSION: Motor function is organized differently in patients with Tourette syndrome than in healthy subjects.

Adolescent↗

Functional relevance of abnormal fMRI activation pattern after unilateral schizencephaly.

Brain plasticity was investigated in a child with a hemiplegia due to unilateral schizencephaly involving the sensorimotor cortex. This focal lesion led to a dramatic functional reorganization of the undamaged hemisphere, as evidenced by the unusual pattern of fMRI activation during paretic finger movements. The functional relevance of the activation in the undamaged motor cortex was supported by the finding that TMS of this area yielded a response in the paretic hand, indicating that it controls both hands. However, this reorganization was not restricted to the primary motor cortex, but also concerned other structures involved in the control of movements, as shown by the activation of contralesional SMA and thalamus. In contrast, the fMRI activation in the damaged sensorimotor cortex during paretic hand movements appears functionally irrelevant.

Adaptation, Physiological↗

Cerebral and cerebellar motor activation abnormalities in a subject with Joubert syndrome: functional magnetic resonance imaging (MRI) study.

Joubert syndrome is an autosomal recessive disorder characterized by hypotonia, ataxia, developmental delay, and a distinctive hindbrain malformation involving the cerebellum and brain stem, visualized radiographically on magnetic resonance imaging (MRI) as the "molar tooth sign." In postmortem brains from subjects with Joubert syndrome, there is an apparent absence of decussation of both corticospinal and superior cerebellar tracts, although the functional significance has not been elucidated. We sought to explore the cerebral and cerebellar activation pattern elicited by finger tapping in an adolescent with Joubert syndrome and in a normal control subject using functional MRI. In contrast to the typical highly lateralized activation seen in our control subject, the subject with Joubert syndrome demonstrated striking bilateral activation of the sensorimotor and cerebellar cortex. Although our functional MRI data do not indicate a clear absence of decussation, the abnormal activation pattern observed suggests altered brain functional organization in relation to anatomic differences. Malformation of the hindbrain could result in recruitment of alternative pathways, similar to what has been observed following ischemic injury to the developing or mature central nervous system.

Adolescent↗