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Brain perfusion SPECT: age- and sex-related effects correlated with voxel-based morphometric findings in healthy adults.

PURPOSE: To investigate brain perfusion at single photon emission computed tomography (SPECT) as a function of age and sex in healthy adult volunteers and to correlate perfusion with gray matter concentration determined by using voxel-based morphometry (VBM). MATERIALS AND METHODS: Eighty-one healthy volunteers underwent both technetium 99m ethylene cysteine dimer SPECT and three-dimensional magnetization preparation rapid acquisition gradient-echo magnetic resonance (MR) imaging. Statistical parametric mapping was used to conduct VBM analysis of the morphologic data, which were compared voxel by voxel with the results of a similar analysis of the perfusion data and more specifically in brain areas showing significant perfusion changes. RESULTS: VBM data, as compared with perfusion changes, indicated a more symmetric age-related gray matter volume decrease along the Sylvian fissure and in subcortical regions (P < .001). The combination of functional and structural changes indicated a relatively lower functional decrease with aging, as compared with the structural atrophy in the visual, parietal, sensorimotor, and right prefrontal cortices. Significant relative morphologic sex-based differences were found in the cerebellar and temporal cortices, but the comparison did not reveal significant differences between the functional and morphometric data. CONCLUSION: Age-related perfusion changes are paralleled by similar more symmetric changes in gray matter concentration, which are more prominent than the perfusion changes in some regions. No sex-based differences between perfusion and gray matter concentration were found.

Adult↗

A disynaptic sensorimotor pathway in the lobster stomatogastric system.

1. In the lobster Homarus, muscle gm 1 that causes protraction of the medial tooth of the gastric mill system is innervated via a dorsal branch of the anterior gastric nerve by motoneurons (GM) arising in the stomatogastric ganglion (STG) (Fig. 1). 2. A ventral branch of the anterior gastric nerve (VAGN) contains a single unit that is mechanosensitive, responds to gentle pressure on the stomach wall in the vicinity of gm 1, and evokes reflex activation of GM motoneurons (Fig. 2). 3. This mechanoreceptor neuron (called anterior gastric receptor, AGR) has been identified morphologically (Fig. 3) and electrophysiologically (Figs. 4 and 5). The bipolar cell body is located in the dorsal ventricular nerve immediately posterior to the STG. It sends out long peripheral processes in the left and right VAGNs to ramify bilaterally in the epidermis of the stomach wall underlying muscle gm 1. The axon of the AGR runs anteriorly through the STG and projects to the left and right commissural ganglia (CoGs) via the stomatogastric (STN) and inferior esophageal nerves. 4. AGR activation of GM motoneurons disappears after cutting the STN, indicating that the reflex is mediated by an axonal pathway involving rostral ganglia (Fig. 6). 5. Electrophysiological (Fig. 7) and morphological (Fig. 8) methods were used to identify an interneuron (commissural gastric neuron, CG) located in each CoG and intercalated between AGR and GM. Axons of the two CGs project to the STG via the superior esophageal nerves and the STN. 6. Simultaneous intracellular recordings from the three cell types demonstrate that AGR excites CG, which in turn excites GM; in each case excitatory postsynaptic potentials follow presynaptic impulses one for one and at constant latency (Fig. 9). Raising the threshold for spiking with saline containing high divalent cation concentrations further indicates that both excitatory connections are monosynaptic and confirms that AGR does not directly excite GM motoneurons (Fig. 10). 7. The input/output properties of AGR in this disynaptic excitatory pathway (Fig. 11) are discussed as also are the functional implications of such a long-loop pathway for sensorimotor integration.

Afferent Pathways↗

Preserved ipsilateral-to-lesion motor map organization in the unilateral 6-OHDA-treated rat model of Parkinson's disease.

The classic view of dopamine (DA) loss in Parkinson's disease is that it produces a functional deafferentation in striatal-cortical circuitry that, in turn, contributes to sensorimotor deficits. The present study examines this view in the rat by assessing how DA-depletion affects the intracortical microstimulation (ICMS) topographic representation of movement in the rostral and caudal motor areas of the motor cortex. The ICMS map is used as an index of motor cortex function because it has been shown to reflect motor function and experience. Groups of rats received no training or skilled reach training and were then given unilateral 6-hydroxydopamine (6-OHDA) or sham lesions of the nigrostriatal bundle to deplete nigrostriatal DA. Lesion success was confirmed by abnormalities in skilled reaching, by apomorphine-induced rotation, and by loss of DA neurons in the substantia nigra. The size and threshold of the motor map in naive and skilled reach trained DA-depleted rats were preserved. In addition, there was an increase in distal limb representation in the caudal forelimb area (CFA) in the DA-depleted rats suggesting a possible plastic response to the behavioral effects of DA-depletion. The presence of preserved size and modified map organization in DA-depleted rats is discussed in relation to the hypothesis that preserved motor cortex functionality despite DA loss underlies the spared motor abilities of DA-depleted rats.

Analysis of Variance↗

Differential effect of spinal cord injury and functional impairment on human brain activation.

Reorganization of human brain function after spinal cord injury (SCI) has been shown in electrophysiological studies. However, it is less clear how far changes of brain activation in SCI patients are influenced by the extent of SCI (neuronal lesion) or the consequent functional impairment. Positron emission tomography ([15O]-H2O-PET) was performed during an unilateral hand movement in SCI patients and healthy subjects. SCI patients with paraplegia and normal hand function were compared to tetraplegic patients with impaired hand movements. Intergroup comparison between paraplegic patients and healthy subjects showed an increased activation of contralateral sensorimotor cortex (SMC), contralateral thalamus, ipsilateral superior parietal lobe, and bilateral cerebellum. In contrast to this, tetraplegic patients with impaired upper limb function revealed only a significant activation of supplementary motor area (SMA). Correlational analysis in the tetraplegic patients showed that the strength of hand movement was related to the activation of contralateral SMC. However, the severity of upper limb sensorimotor deficit was related to a reduced activation of contralateral SMA and ipsilateral cerebellum. The findings suggest that in paraplegic patients with normal hand function the spinal neuronal lesion itself induces a reorganization of brain activation unrelated to upper limb function. Compared to this, in tetraplegic patients changes of brain activation are related to the impaired upper limb function. Therefore, in patients with SCI a differential impact of spinal lesion and functional impairment on brain activation can be shown. The effect of impaired afferent feedback and/or increased compensatory use of non-impaired limbs in SCI patients needs further evaluation.

Adult↗

An associational model of birdsong sensorimotor learning II. Temporal hierarchies and the learning of song sequence.

Understanding the neural mechanisms underlying serially ordered behavior is a fundamental problem in motor learning. We present a computational model of sensorimotor learning in songbirds that is constrained by the known functional anatomy of the song circuit. The model subsumes our companion model for learning individual song "syllables" and relies on the same underlying assumptions. The extended model addresses the problem of learning to produce syllables in the correct sequence. Central to our approach is the hypothesis that the Anterior Forebrain Pathway (AFP) produces signals related to the comparison of the bird's own vocalizations and a previously memorized "template." This "AFP comparison hypothesis" is challenged by the lack of a direct projection from the AFP to the song nucleus HVc, a candidate site for the generator of song sequence. We propose that sequence generation in HVc results from an associative chain of motor and sensory representations (motor --> sensory --> next motor. ) encoded within the two known populations of HVc projection neurons. The sensory link in the chain is provided, not by auditory feedback, but by a centrally generated efference copy that serves as an internal prediction of this feedback. The use of efference copy as a substitute for the sensory signal explains the ability of adult birds to produce normal song immediately after deafening. We also predict that the AFP guides sequence learning by biasing motor activity in nucleus RA, the premotor nucleus downstream of HVc. Associative learning then remaps the output of the HVc sequence generator. By altering the motor pathway in RA, the AFP alters the correspondence between HVc motor commands and the resulting sensory feedback and triggers renewed efference copy learning in HVc. Thus, auditory feedback-mediated efference copy learning provides an indirect pathway by which the AFP can influence sequence generation in HVc. The model makes predictions concerning the role played by specific neural populations during the sensorimotor phase of song learning and demonstrates how simple rules of associational plasticity can contribute to the learning of a complex behavior on multiple time scales.

Animals↗

Effects of passive-active movement training on upper limb motor function and cortical activation in chronic patients with stroke: a pilot study.

OBJECTIVE: To explore how repetitive passive-active movement training effects upper limb motor function and cortical activation in patients with stroke. DESIGN: Single-group treatment trial with baseline comparisons. PATIENTS: Ten chronic patients with stroke with paresis of the upper limb. METHODS: Assessments were performed during a 4-week baseline period before and once after 4 weeks of training using the Motor Assessment Scale of the upper limb, Nine Hole Peg Test, goniometer for range of movement and the modified Ashworth scale for muscle tone. Two patients underwent functional magnetic resonance imaging pre- and post-training. The treatment consisted of daily sessions of repeated functional reaching and grasping movements guided passively and attempted actively during 4 weeks. RESULTS: The group improved in range of motion and Motor Assessment Scale scores. Subjects reported improvements in a variety of daily tasks requiring the use of the affected upper limb. Increases in cortical activation in prefrontal and sensorimotor areas were observed in parallel with improvements of upper limb motor function in the 2 patients scanned. CONCLUSION: The 4-week training programme improved hand motor function and ability. Cortical activation on functional magnetic resonance imaging changed in parallel suggesting reorganization of areas related to movements of the paretic limb.

Cerebral Cortex↗

Long-term effects of sequential cortical infarcts on scar size, brain volume and cognitive function.

Focal ischemia induces long-term pathophysiological consequences in widespread brain areas. Here we analyzed long-term effects of sequential cortical lesions on brain volume and cognitive function. Rats received either single photothrombotic lesions in the forelimb sensorimotor cortex (SL) or two lesions in sequence either immediately (DL0), 2 days (DL2), 7 days (DL7), or 10 days (DL10) after the first surgery in the homotopic contralateral area. Infarct and global brain volume were measured 7 days (SL and DL2 groups) and one month (all groups) after the last period of ischemia. In the weeks following a stroke, the single lesion shrank considerably. This shrinkage was accentuated by a further lesion received either earlier or later. Thirty-one days after obtaining the second lesion, the lesion scars on both sides had a mean volume of 5.8 +/- 2.3 mm3 in DL2 as compared to 8.5 +/- 3.5 mm3 in SL-animals. In addition, there was a super-additive loss of residual brain volume by 2.2-8.0% in each hemisphere in animals with sequential lesions. In the watermaze, this loss of brain volume corresponded to a slight but significant impairment in performance. The present study revealed a complex interaction of lesions in animals with sequential strokes associated with global reduction of brain volume and cognitive impairment indicating degenerative processes beyond the lesions itself.

Animals↗

Dopamine modulation of activity of cat sensorimotor cortex neurons during conditioned reflexes.

The effects of iontophoretic application of dopamine and selective D1 or D2 dopamine receptor agonists and antagonists on impulse activity of neurons of the deep layers of the sensorimotor cortex of cat were investigated during performance of a conditioned paw movement task. The application of dopamine, Quinpirole (selective D2 receptor agonist) or SKF 38393 (selective D1 receptor agonist) increased both background (P<0.001) and evoked impulse activity (P<0.05 for selective agonists). Selective D2 and D1 receptor antagonists (Sulpiride and SKF 83566, respectively) both increased the latency of neural responses and significantly increased the latency of the conditioned paw movements (P<0.01). These data suggest that during natural physiological functions subcortical dopamine neurons provide facilitation of activity pyramidal neurons of sensorimotor cortex.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Cortically driven immediate-early gene expression reflects modular influence of sensorimotor cortex on identified striatal neurons in the squirrel monkey.

Current understanding of basal ganglia function emphasizes their involvement in the focal, context-dependent release of motor and cognitive circuits in the brainstem and frontal lobes. How such selective action can arise despite the existence of massively convergent inputs from the cerebral cortex is unknown. However, anatomical work has suggested that specificity could be achieved in corticostriatal circuits by modular patterns of convergent and divergent cortical inputs to striatal projection neurons. To test for such modular activation of striatal neurons, we electrically microstimulated physiologically identified sites in the primary somatosensory (SI) and primary motor (MI) cortex of the squirrel monkey. We compared the efferent fiber distributions anterogradely traced from these sites to the distributions of striatal neurons activated by microstimulation to express Fos- and Jun B-like immediate-early gene proteins. We show that the microstimulation of sensorimotor cortex induces Fos and Jun B expression in localized cell clusters in the putamen and that these clusters match the anatomical input fiber clusters (matrisomes). The modular activation of striatal neurons by sensorimotor cortex seems likely. Unexpectedly, >75% of the Fos-positive nuclei in densely labeled cell clusters were in enkephalin-immunoreactive neurons. This expression pattern suggests that the primate sensorimotor cortex exerts a differential influence on the enkephalinergic (indirect pathway) as opposed to the substance P/dynorphin (direct pathway) projection neurons of the putamen. The densely labeled clusters of Fos-labeled enkephalinergic neurons occurred within larger zones containing sparsely distributed Fos-labeled parvalbumin neurons. Moreover, when the cortical stimulation induced expression of Fos-like protein only in sparsely distributed neurons, almost every putamenal neuron expressing Fos was a parvalbumin-containing (GABAergic) interneuron. These patterns suggest a model in which the primate sensorimotor cortex can target parvalbumin-containing inhibitory interneurons, which in turn depress the remaining neuronal activity within and around matrisomes in a feed-forward manner until sufficient coherent cortical input can overcome the inhibition to influence selectively enkephalinergic projection neurons in the activated matrisomes. Tuning of cortical input by striatal interneurons thus may be an important mechanism by which broader anatomical connections are dynamically adjusted to achieve selective flow of information through the basal ganglia.

Animals↗

Interactive use of cerebral angiography and magnetoencephalography in arteriovenous malformations: technical note.

OBJECTIVE: To minimize the risks associated with treating cortical cerebral arteriovenous malformations (AVMs), we developed a technique combining functional imaging and cerebral angiography. The functional loci obtained by performing magnetoencephalography (MEG) are projected onto stereoscopic pairs of a stereotactically derived digital subtraction angiogram. The result is a simultaneous three-dimensional perspective of the angioarchitecture of an AVM and its relationship to the sensorimotor cortex. METHODS: Eight patients underwent multimodality brain imaging, including magnetic resonance imaging, functional mapping via MEG, and stereotactic angiography using a modified Compass fiducial system (Compass International, Rochester, MN). The coordinates derived by performing MEG were superimposed onto stereotactic, stereoscopic, angiographic pairs using custom-made distortion correction and coordinate transfer software. RESULTS: The magnetoencephalographic angiogram allowed simultaneous viewing of the angioarchitecture of the AVM nidus, the feeding vessels, and the draining veins and their relationship to the normal cerebral vasculature and functional cortex. This imaging technique was particularly valuable in identifying en passant vessels that supplied functional cortex and was used during the treatment of these lesions. CONCLUSION: The techniques of MEG and cerebral angiography were combined to provide simultaneous viewing of both modalities in a three-dimensional perspective. This technique can aid in risk stratification in the management of patients with cerebral AVMs. In addition, this technique can facilitate the selective targeting of vessels, thus potentially reducing the risks associated with embolization of these formidable lesions.

Adolescent↗

[Modeling developmental aspects of sensorimotor control of speech production].

BACKGROUND: Detailed knowledge of the neurophysiology of speech acquisition is important for understanding the developmental aspects of speech perception and production and for understanding developmental disorders of speech perception and production. METHOD: A computer implemented neural model of sensorimotor control of speech production was developed. The model is capable of demonstrating the neural functions of different cortical areas during speech production in detail. RESULTS: (i) Two sensory and two motor maps or neural representations and the appertaining neural mappings or projections establish the sensorimotor feedback control system. These maps and mappings are already formed and trained during the prelinguistic phase of speech acquisition. (ii) The feedforward sensorimotor control system comprises the lexical map (representations of sounds, syllables, and words of the first language) and the mappings from lexical to sensory and to motor maps. The training of the appertaining mappings form the linguistic phase of speech acquisition. (iii) Three prelinguistic learning phases--i. e. silent mouthing, quasi stationary vocalic articulation, and realisation of articulatory protogestures--can be defined on the basis of our simulation studies using the computational neural model. These learning phases can be associated with temporal phases of prelinguistic speech acquisition obtained from natural data. CONCLUSIONS: The neural model illuminates the detailed function of specific cortical areas during speech production. In particular it can be shown that developmental disorders of speech production may result from a delayed or incorrect process within one of the prelinguistic learning phases defined by the neural model.

Brain Mapping↗

Preoperative functional magnetic resonance imaging (fMRI) of the motor system in patients with tumours in the parietal lobe.

Intracranial lesions may compromise structures critical for motor performance, and mapping of the cortex, especially of the motor hand area, is important to reduce postoperative morbidity. We investigated nine patients with parietal lobe tumours and used functional MRI sensitized to changes in blood oxygenation to define the different motor areas, especially the primary sensorimotor cortex, in relation to the localization of the tumour. Activation was determined by pixel-by-pixel correlation of the signal intensity time course with a reference waveform equivalent to the stimulus protocol. All subjects showed significant activation of the primary sensorimotor cortex while performing a finger opposition task with the affected and unaffected side. In five patients the finger opposition task additionally activated the ipsilateral sensorimotor cortex and the supplementary motor area (SMA). Extension and flexion of the foot, additionally performed in two patients, also activated the sensorimotor cortex, in one case within the perifocal oedema of the tumour. Tumour localization near the central sulcus induced displacement of the sensorimotor cortex as compared to the unaffected side in all patients with a relevant mass effect. The results of our study demonstrate that functional MRI at 1.5 T with a clinically used tomograph can reproducibly localize critical brain regions in patients with intracranial lesions.

Adult↗

A taxonomy of neurobehavioral functions applied to neuropsychological assessment after head injury.

Neuropsychological dysfunctions after traumatic brain injury are classified into a taxonomy to plan a comprehensive examination, and organize and report findings for diagnosis and treatment: consciousness, information processing, sensorimotor, neurophysiological, cerebral personality disorders, intelligence, memory, language, stress, psychodynamic, identity and weltanschauung, adaptation, complex adaptive functions, and development of children. Wide-range sampling enhances the detection of acute and late-developing dysfunctions, and diagnosis of complex syndromes. Historical, personality, and injury data are components of the assessment. Issues discussed include underestimation of brain injury, malingering, interaction of symptoms, symptom persistence, and noncerebral lesional contributors to impairment after mild head injury.

Brain Damage, Chronic↗

Maturation of escape circuit function during the early adulthood of cockroaches Periplaneta americana.

During postembryonic development of insects, sensorimotor pathways, which generate specific behaviors, undergo maturational changes. It is less clear whether such pathways are typically stable, or undergo further maturation, during the adult stage. In the present study, we have examined this issue by multilevel analysis of a simple model system, the escape behavior of the cockroach, from identified synapses to behavior. We show that the escape system is highly responsive immediately after the molt to adulthood, but that the latency of escape responses was not at its typical value immediately after the molt to adult. The latency of escape behavior increased over the first 30 days of adult life, perhaps indicating maturational adjustments of the escape sensorimotor pathway. The first station in the escape circuitry is the synaptic connections between the cercal wind receptors and the giant interneurons. We measured unitary excitatory synaptic potentials between single sensory neurons and an identified giant interneuron (GI(2)). We found a decrease in the synaptic strength between identified cercal hairs from a single column and GI(2) over the first month after the adult molt. Consequently, the latency and the number of action potentials of GI(2) in response to natural stimuli increased and decreased respectively during this time. Thus, we show that both behavioral performance and the wind sensitivity of GI(2) decreased over the first month after molt. We conclude that the cockroach escape system undergoes further sensorimotor maturation over a period of 1 month, and that cellular changes correlate with, or predict, some changes in behavioral performance.

Action Potentials↗

Cortical sensorimotor alterations in Unverricht-Lundborg disease patients without generalized seizures.

We investigated cortical functions of two Unverricht-Lundborg disease (ULD) patients suffering from myoclonic jerks, but no generalized tonic-clonic seizures. Somatosensory cortical responses were recorded to median nerve stimuli and coherence was calculated between cortical and muscle signals during isometric contraction of hand muscle. In contrast to ULD patients with generalized tonic-clonic seizures, responses of the primary somatosensory (SI) cortex were only slightly enhanced in the left and normal in the right hemisphere, and no early responses were observed in the ipsilateral SI. Cortex-muscle coherence was remarkably enhanced. We conclude that in ULD patients without generalized tonic-clonic seizures, both the excitability of the SI and transcallosal conduction are relatively normal, probably decreasing susceptibility to generalized seizures. Disturbed cortical control of muscle contraction indicates selective alteration of the motor cortex activation.

Adolescent↗

Differential magnetic resonance signal change in human sensorimotor cortex to finger movements of different rate of the dominant and subdominant hand.

Functional magnetic resonance tomography (fMRI) analysis of unimanual and bimanual sequential movements in righthanders showed the following effects. First, a rate-dependent activation of the somato-motor cortex was confirmed, with faster movement rates producing higher activation both in terms of signal intensity and number of activated voxels. Second, the right hemisphere showed more activation than the left hemisphere during unimanual tasks. Third, during bimanual movements, the left hemisphere showed greater activation than the right hemisphere. Finally, while the left hemisphere showed a marked change in activation patterns from unimanual to bimanual task, the right hemisphere activation patterns were not sensitive to task changes. The hemispheric asymmetries suggest substantial left hemisphere involvement in the coordination of bimanual tasks.

Adult↗

[Effects of a proprioceptive training program on sensorimotor capacities of the lower extremity in patients with anterior cruciate ligament instability].

Sensomotory function after ACL-reconstruction was tested prior and after a proprioceptive rehabilitation program with the Kinesthetic Ability Trainer (KAT 2000) which documented the static balance index (SBI). A control group consisting of healthy subjects was also tested two times with a time interval of six weeks. The results showed an adaptation effect to the testing device in the control group with an 17.12% increase of the SBI. There were no differences between the dominant and non dominant extremity. The active sensomotory function in the healthy knee of the operated patients showed no difference to the control group. Proprioceptive capabilities of the acl-reconstructed knee joints was significant reduced 6.42 weeks after surgery. A special proprioceptive rehabilitation program for six weeks significantly reduced this deficit. In the patient group sensomotory function of both knee joints could be increased to a level higher than in the control group. In the operated extremity the static balance index increased 27.75% and in the non injured extremity the SBI increased 16.88%.

Adult↗