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Modeling sensorimotor learning with linear dynamical systems.

Recent studies have employed simple linear dynamical systems to model trial-by-trial dynamics in various sensorimotor learning tasks. Here we explore the theoretical and practical considerations that arise when employing the general class of linear dynamical systems (LDS) as a model for sensorimotor learning. In this framework, the state of the system is a set of parameters that define the current sensorimotor transformation-the function that maps sensory inputs to motor outputs. The class of LDS models provides a first-order approximation for any Markovian (state-dependent) learning rule that specifies the changes in the sensorimotor transformation that result from sensory feedback on each movement. We show that modeling the trial-by-trial dynamics of learning provides a substantially enhanced picture of the process of adaptation compared to measurements of the steady state of adaptation derived from more traditional blocked-exposure experiments. Specifically, these models can be used to quantify sensory and performance biases, the extent to which learned changes in the sensorimotor transformation decay over time, and the portion of motor variability due to either learning or performance variability. We show that previous attempts to fit such models with linear regression have not generally yielded consistent parameter estimates. Instead, we present an expectation-maximization algorithm for fitting LDS models to experimental data and describe the difficulties inherent in estimating the parameters associated with feedback-driven learning. Finally, we demonstrate the application of these methods in a simple sensorimotor learning experiment: adaptation to shifted visual feedback during reaching.

Algorithms↗

Cortical microstimulation thresholds adjacent to sensorimotor cortex injury.

The initial severe contralateral impairment of motor function after unilateral damage to a portion of sensorimotor (SM) cortex lessens within a few weeks after injury. In this study, two hypotheses proposed to explain recovery of behavioral function after cortical injury were tested: (1) Intact cortex adjacent to the injury reorganizes to take over the function of the destroyed area. (2) Intact SM cortex adjacent or connected to the injured area undergoes a transient shock (diaschisis), and as this dissipates, some behavioral recovery occurs. Using microstimulation of the cortex of the adult rat, movements evoked from areas near cortical injuries were studied at various times after undercut laceration, contusion, or suction ablation of an area of SM cortex. Stimulation areas were compared to those obtained from uninjured control animals and to the contralateral uninjured hemisphere. No evidence was obtained for any reorganization of stimulated motor responses in the injured hemisphere even in animals followed for as long as 475 days postinjury, suggesting other mechanisms underlying functional recovery. In intact cortex at some distance from contusion and laceration injuries, there was a marked elevation of thresholds to evoke movements that returned to normal by 9-15 days postinjury. Some intact hindlimb responses were observed after contusion injury that were absent in animals after 15 days postinjury, indicating a slow-growing lesion after this type of trauma. Surprisingly, no elevation in thresholds was noted for ablation injuries up to the edge of the cavity at any time postinjury, indicating that threshold changes near the boundary may be uncorrelated with functional recovery.

Animals↗

Transient versus persistent functional and structural changes associated with facilitation of Aplysia sensorimotor synapses are second messenger dependent.

Increases in activity of both protein kinase A (PKA) and protein kinase C (PKC) contribute to short-term facilitation of Aplysia sensorimotor synapses evoked by serotonin (5-HT). We report here that increasing levels of cAMP in sensory neurons evokes increases in both synaptic efficacy and in the number of sensory neuron varicosities contacting the major axons of motor cell L7 at intermediate times (3 hr) that persist for 24 hr. Treatment with phorbol esters results in a large transient increase in synaptic efficacy that is accompanied by a large transient increase in the number of sensory neuron varicosities with the newest varicosities most susceptible to elimination. The reversal of the synaptic facilitation and the structural changes does not appear to be the result of long-term inhibitory actions of persistent PKC activation by phorbol esters, since changes in synaptic efficacy can be evoked by additional applications of either phorbol esters or 5-HT. The short-lived changes in structure evoked by phorbol esters occur in preexisting sensory neurites and not by new growth, since increases in PKC activity with phorbol esters lead to reductions in neurite extension and to retractions by sensory neuron growth cones. The action of phorbol esters on growth cone extension is reversible with washout. The results suggest that increases in PKA and PKC activities by 5-HT contribute to short (minutes) and intermediate (hours) forms of facilitation of sensorimotor synapses while increases in PKA activity also mediate long-term (days) maintenance of synaptic facilitation.

Animals↗

Sensorimotor cortex and supplementary motor area changes in schizophrenia. A study with functional magnetic resonance imaging.

BACKGROUND: Neurological soft signs (NSS) such as a disturbed finger-to-thumb opposition are frequently found in schizophrenia. To identify the underlying cerebral changes we investigated sensorimotor cortex and supplementary motor area (SMA) activation during finger-to-thumb opposition using functional magnetic resonance imaging (fMRI). METHOD: Ten DSM-III-R schizophrenics and seven healthy controls were included. All subjects were right-handed. fMRI was carried out in a resting condition followed by an activation state (finger-to-thumb opposition) and the activities in the sensorimotor cortices and SMA recorded. RESULTS: All subjects showed a significant activation of the SMA and both ipsilateral and contralateral sensorimotor cortices. In the controls, ipsilateral finger-to-thumb opposition was associated with a greater left than right hemispheric sensorimotor cortex coactivation. When compared with the healthy controls, the schizophrenic patients showed a decreased activation of both sensorimotor cortices and SMA, as well as a reversed lateralisation effect. CONCLUSION: Sensorimotor cortex and SMA dysfunction are associated with motor disturbances in schizophrenia.

Adult↗

Rectal sensorimotor dysfunction in patients with urge faecal incontinence: evidence from prolonged manometric studies.

BACKGROUND AND AIMS: Although external anal sphincter dysfunction is the major cause of urge faecal incontinence, approximately 50% of such patients have evidence of rectal hypersensitivity and report exaggerated stool frequency and urgency. The contribution of rectosigmoid contractile activity to the pathophysiology of this condition is unclear, and thus the relations between symptoms, rectal sensation, and rectosigmoid motor function were investigated. METHODS: Fifty two consecutive patients with urge faecal incontinence, referred to a tertiary surgical centre, and 24 volunteers, underwent comprehensive anorectal physiological investigation, including prolonged rectosigmoid manometry. Patients were classified on the basis of balloon distension thresholds into those with rectal hypersensitivity (n = 27) and those with normal rectal sensation (n = 25). Automated quantitative analysis of overall rectosigmoid contractile activities and, specifically, high amplitude contractions and rectal motor complex activity was performed. RESULTS: External anal sphincter dysfunction was similar in both patient groups. Overall, phasic activity and high amplitude contraction frequency were greater, and rectal motor complex variables significantly altered, in those with rectal hypersensitivity. Symptoms, more prevalent in the rectal hypersensitivity group, were also more often associated with rectosigmoid contractile events. For individuals, reduced compliance and increased rectal motor complex frequency were only observed in patients with rectal hypersensitivity. CONCLUSIONS: We have identified a subset of patients with urge faecal incontinence-namely, those with rectal hypersensitivity-who demonstrated increased symptoms, enhanced perception, reduced compliance, and exaggerated rectosigmoid motor activity. Comprehensive assessment of rectosigmoid sensorimotor function, in addition to evaluation of anal function, should be considered in the investigation of patients with urge faecal incontinence.

Adolescent↗

Modulation of the BOLD-response in early recovery from sensorimotor stroke.

BACKGROUND: The BOLD signal in functional MRI (fMRI) is closely related to neural activity. OBJECTIVE: To investigate if this relationship is disrupted after ischemic stroke. METHODS: BOLD activity during tactile exploration of objects was measured with fMRI at 1 week (subacute), 2 to 4 weeks (early chronic), and after 1 month (chronic) after the first completed brain infarction affecting the sensorimotor cortex in eight patients. Functional integrity of the motor cortical output system was assessed with transcranial magnetic stimulation (TMS). RESULTS: Early after infarction the BOLD-response occurred in the adjacent cortical vicinity related to finger movements of the affected hand. However, during the early chronic stage there was a transient lack of this activation despite clinical improvement of hand function and preserved motor evoked potentials. The BOLD activity reappeared after further improvement in the chronic stage. CONCLUSIONS: Our findings suggest a transient hemodynamic-electrical decoupling in the post-ischemic cerebral cortex during the early phase of spontaneous clinical recovery.

Aged↗

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia↗

T1-selective diffusion weighted fMRI at 1.5T.

Apparent diffusion coefficients (ADC) of protons contributing to the functional signal can be determined from diffusion weighted functional magnetic resonance imaging (MRI) studies. An earlier study indicated that ADCs calculated from the functional signal of an activated primary sensorimotor cortex are large, and consistent with a CSF or intravascular contribution to the functional signal. We have added inversion recovery pulses to isotropic diffusion weighted imaging to null CSF protons selectively within the imaging slice, or to null the outer volume blood flowing into the imaging slice. With the use of gradient recalled diffusion weighted echo-planar imaging at low gradient b factors, and without the use of inversion pulses, the ADCs x 10(3) in mm2/s (+/- SD) from the functional signal were 6.81 +/- 1.19. These ADCs were significantly higher than resting primary sensorimotor cortex ADCs of 2.26 +/- 1.49, measured at the same b factors. When CSF nulling was applied, the functional signal ADCs remained high. Application of inflow nulling decreased the functional signal to such a small value, that ADCs estimated from these functional signals were not assessed. The results are consistent with an intravascular contribution to the functional signal and to its large ADC.

Adult↗

The relationship among handedness, sighting dominance, and acuity dominance in elementary school children.

The present study was an attempt to clarify the relationship between handedness, sighting dominance, and eye-acuity in children. Ninety-four males and ninety-seven females between the ages of five and eleven were assessed on standardized measures of handedness, sighting dominance, and visual acuity. Right-handers were more likely to show right-sighting dominance, whereas left-handers had an equal chance of being right-sighted or left-sighted. Acuity dominance was not consistently associated with handedness or sighting dominance. No effects for sex or age were found. It is suggested that further clarification of the function of various lateralized sensorimotor measures is needed before an understanding of how these measures may be related to cortical dominance is possible.

Child↗

Integrated technology for evaluation of brain function and neural plasticity.

The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mirror movements, but it more likely reflects activity redistribution within preexisting bilateral, large-scale motor networks. Finally, activation of areas not normally engaged in the dysfunctional tasks, such as the dorsolateral prefrontal cortex or the superior parietal cortex in motor paralysis, might reflect the implication of compensatory cognitive strategies. An integrated approach with technologies able to investigate functional brain imaging is of considerable value in providing information on the excitability, extension, localization, and functional hierarchy of cortical brain areas. Deepening knowledge of the mechanisms regulating the long-term recovery (even if partial), observed for most neurologic sequelae after neural damage, might prompt newer and more efficacious therapeutic and rehabilitative strategies for neurologic diseases.

Animals↗

Resection of a dominant-hemisphere intraventricular meningioma facilitated by functional magnetic resonance imaging. Case report.

Intraventricular meningiomas of the lateral ventricle occur relatively rarely, but they are often large at the time of detection and present more commonly on the left side. Although the ability to resect these tumors safely has greatly improved over time, standard surgical approaches often traverse cortex close to areas of specific cortical function. Precise cortical mapping of language and sensorimotor cortices can be accomplished noninvasively by using functional magnetic resonance (fMR) imaging. The authors used fMR imaging in planning the cortical incision for resection of a large intraventricular trigone meningioma in the dominant hemisphere of a patient who, postoperatively, suffered no aphasia or hemiparesis. The authors discuss the advantages of mapping cortical function preoperatively with fMR imaging when approaching intraventricular lesions.

Adult↗

Relations between aging sensory/sensorimotor and cognitive functions.

Recent evidence is reviewed to examine relations among sensory, sensorimotor, and cognitive aging. Age-heterogeneous cross-sectional data sets show substantial covariation among sensory, sensorimotor and intellectual abilities, and an increase in covariation from adulthood to old and very old age. Recent longitudinal analyses suggest that changes in sensory and intellectual functioning are interrelated. Experimental studies investigate the interdependence between cognitive and sensory/sensorimotor aging by examining the effects of simulated sensory loss on cognitive performance, or the effects of cognitive load manipulations on sensory or motor performance. Generally, both types of manipulations hinder older adults' performance more than that of younger adults. Theoretically, the age-associated intensification of the links among sensory, sensorimotor and cognitive functions observed both correlationally and experimentally may point to (a). common causes influencing all three functions; (b). an increase in resource overlap, cross-domain resource competition, and compensatory tradeoffs; and (c). a combination of the two. Future research aiming at discerning the relative import of these possibilities would profit from an integration of experimental and correlational research strategies.

Aging↗

Roles and functions of occupational therapy in early childhood intervention (position paper). American Occupational Therapy Association.

Occupational therapy is based on the belief that purposeful activity, or occupation, may be used to generate adaptive skills of children with developmental dysfunction. Developmental activities such as feeding, movement, play, and interaction with others are the primary occupation of infants and young children. By using intrinsic motivation and purposeful activities, occupational therapy personnel encourage the child to acquire an increasing repertoire of developmental skills and coping behavior patterns. Intervention promotes sensorimotor, psychosocial, and cognitive functions and may prevent disability or decrease dysfunction in order for the child to meet personal needs and adapt to the demands of the environment. Occupational therapy facilitates the occupational performance of parents in coping effectively with the challenges of care giving and family life.

Certification↗

The influence of postural control on motility and hand function in a group of 'high risk' preterm infants at 1 year of age.

The functional outcome of a group of 75 'high-risk' preterm infants was studied at the corrected age of 12 months. Only infants with high-risk for developmental deviance with gestational ages below 32 weeks and/or birthweights less than 1500 g were included in the study. Additionally the infants were categorised according to their medical history conforming with the 'Neonatal Medical Index' (NMI I to V), with category I describing infants with few medical problems and V characterizing those with the most serious complications. In this study we included only infants with 'high-risk' as categorised in NMI III to V, since infants with 'low-risk' have been described earlier. Infants with cerebral ultrasonographic abnormalities were incorporated into the NMI categories, but also analysed separately to compare outcomes. At 12 months (corrected age) apart from pediatric follow-up, a full neurological assessment was done with emphasis on postural control, spontaneous motility and hand function. Special attention was given to symmetrical development. The infants were then categorised as having optimal, non-optimal or asymmetrical outcomes. An overall optimal outcome on postural control was found in 64% of all infants (67% in NMI III, 60% in NMI IV and 62.5% in NMI V). Too much extension interfering with postural control was found significantly more often in infants in NMI V (15%), compared to infants in NMI IV (8%) and NMI III (4.5%). Poor postural control had a significant influence on other domains of development such as motility (P=0.00), asymmetry (P=0.00) and hand function (P=0.00). Cerebral ultrasonographic abnormalities seemed to have an influence on motility (P=0.03), while no direct relationship was found with postural control, hand function or asymmetry. It is unclear whether this poor coordination of gross motor function will have consequences for appropriate visual-motor and sensorimotor integration therewith hampering later cognitive function, as often described in preterm infants. It is suggested that the poor postural control found in many infants is the result of both myogenic and/or neurogenic deviations and associated with cerebral pathology, but is also caused by the preterm birth and its nursing consequences.

Echoencephalography↗

Enhancement of sensorimotor behavioral recovery in hemiparkinsonian rats with intrastriatal, intranigral, and intrasubthalamic nucleus dopaminergic transplants.

One of the critical variables that influences the efficacy of clinical neural transplantation for Parkinson's disease (PD) is optimal graft placement. The current transplantation paradigm that focuses on ectopic placement of fetal grafts in the striatum (ST) fails to reconstruct the basal ganglia circuitry or normalize neuronal activity in important basal ganglia structures, such as the substantia nigra (SN) and the subthalamic nucleus (STN). The aim of this study was to investigate a multitarget neural transplantation strategy for PD by assessing whether simultaneous dopaminergic transplants in the ST, SN, and STN induce functional recovery in hemiparkinsonian rats. Forty-six female Wistar rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway were randomly divided into eight groups and received lesions only or injections of 900,000 embryonic rat ventral mesencephalic cells in the (1) ST, (2) SN, (3) STN, (4) ST and SN, (5) ST, SN, and STN, (6) ST and STN, or (7) SN and STN. The number of cells transplanted was equally divided among grafting sites. Animals with two grafts received 450,000 cells in each structure, and animals with three grafts received 300,000 cells per structure. Recovery was assessed by amphetamine-induced rotations and the stepping tests. Graft survival was assessed using tyrosine hydroxylase immunohistochemistry. At 8 weeks after transplantation, simultaneous dopaminergic transplants in the ST, SN, and STN induced significant improvement in rotational behavior and stepping test scores. Intrastriatal transplants were associated with significant recovery of rotational asymmetry, whereas SN and STN transplants were associated with improved forelimb function scores. These results suggest that restoration of dopaminergic activity to multiple basal ganglia targets, such as the ST and SN, or the ST and STN, promotes a more complete functional recovery of complex sensorimotor behaviors. A multitarget transplant strategy aimed at optimizing dopaminergic reinnervation of the basal ganglia may be crucial in improving clinical outcomes in PD patients.

Animals↗

Interruption of functional recovery by the NMDA glutamate antagonist MK801 after compression of the sensorimotor cortex: implications for treatment of tumors or other mass-related brain injuries.

Glutamate antagonists have recently been shown to limit tumor growth, providing potential new therapeutic targets and strategies against brain tumors. Here, we demonstrate that the glutamate NMDA receptor antagonist MK801, after a delay, adversely reverses functional recovery in rats with compressive mass lesions of the sensorimotor cortex. Our data suggest that the controlled focal cortical compression model may be a valuable pre-clinical tool to screen compounds for the treatment of brain tumors. It may be possible to use this model to develop interventions that maintain anti-cancer effects but with diminished harm to bystander tissue and brain plasticity.

Animals↗

The sensorimotor transformation of cross-modal spatial information in the anterior intraparietal sulcus as revealed by functional MRI.

The parietal cortex in monkeys and humans has been shown to play an important role in the transformation of sensory information to motor commands. However, it is still unclear whether in humans, these areas are divided functionally into subregions based on different combinations of sensory and motor modalities. To identify subregions in the parietal cortex involved in the sensorimotor information transformation between different modalities, functional MRI was used to examine brain areas activated during tasks requiring different sensorimotor transformations--i.e., various combinations of eye (saccade) or finger movements triggered by visual or somatosensory cues. We then compared the activations between cross-modal conditions (eye movements triggered by somatosensory cues and finger movements triggered by visual cues) and intramodal (eye movements triggered by visual cues and finger movements triggered by somatosensory cues) conditions. Although the parietal cortex was involved in all tasks regardless of sensorimotor combinations, the only region activated to a greater degree in the cross-modal conditions compared to the intramodal conditions was the anterior portion of the intraparietal sulcus (a-IPS). The results suggest that the a-IPS plays an important role in the sensorimotor transformation of cross-modal spatial information.

Adult↗