Temporal dynamics of the sensorimotor convergence underlying voluntary limb movement.

Descending motor drive and somatosensory feedback play important roles in modulating muscle activity. Numerous studies have characterized the organization of neuronal connectivity in which descending motor pathways and somatosensory afferents converge on spinal motor neurons as a final common pathway. However, how inputs from these two pathways are integrated into spinal motor neurons to generate muscle activity during actual motor behavior is unknown. Here, we simultaneously recorded activity in the motor cortices (MCx), somatosensory afferent neurons, and forelimb muscles in monkeys performing reaching and grasping movements. We constructed a linear model to explain the instantaneous muscle activity using the activity of MCx (descending input) and peripheral afferents (afferent input). Decomposition of the reconstructed muscle activity into each subcomponent indicated that muscle activity before movement onset could first be explained by descending input from mainly the primary motor cortex and muscle activity after movement onset by both descending and afferent inputs. Descending input had a facilitative effect on all muscles, whereas afferent input had a facilitative or suppressive effect on each muscle. Such antagonistic effects of afferent input can be explained by reciprocal effects of the spinal reflex. These results suggest that descending input contributes to the initiation of limb movement, and this initial movement subsequently affects muscle activity via the spinal reflex in conjunction with the continuous descending input. Thus, spinal motor neurons are subjected to temporally organized modulation by direct activation through the descending pathway and the lagged action of the spinal reflex during voluntary limb movement.

Optogenetic recruitment of spinal reflex pathways from large-diameter primary afferents in non-transgenic rats transduced with AAV9/Channelrhodopsin 2.

KEY POINTS: We demonstrated optical activation of primary somatosensory afferents with high selectivity to fast-conducting fibres by means of adeno-associated virus 9 (AAV9)-mediated gene transduction in dorsal root ganglion (DRG) neurons. AVV9 expressing green fluorescent protein showed high selectivity and transduction efficiency for fast-conducting, large-sized DRG neurons. Compared with conventional electrical stimulation, optically elicited volleys in primary afferents had higher sensitivity with stimulus amplitude, but lower sensitivity with stimulus frequency. Optically elicited dorsal root volleys activated postsynaptic neurons in the segmental spinal pathway. This proposed technique will help establish the causal relationships between somatosensory afferent inputs and neural responses in the CNS as well as behavioural outcomes in higher mammals where transgenic animals are not available. ABSTRACT: Previously, fundamental structures and their mode of action in the spinal reflex circuit were determined by confirming their input-output relationship using electrophysiological techniques. In those experiments, the electrical stimulation of afferent fibres was used as a core element to identify different types of reflex pathways; however, a major disadvantage of this technique is its non-selectivity. In this study, we investigated the selective activation of large-diameter afferents by optogenetics combined with a virus vector transduction technique (injection via the sciatic nerve) in non-transgenic male Jcl:Wistar rats. We found that green fluorescent protein gene transduction of rat dorsal root ganglion (DRG) neurons with a preference for medium-to-large-sized cells was achieved using the adeno-associated virus 9 (AAV9) vector compared with the AAV6 vector (P = 0.021). Furthermore, the optical stimulation of Channelrhodopsin 2 (ChR2)-expressing DRG neurons (transduced by AAV9) produced compound action potentials in afferent nerves originating from fast-conducting nerve fibres. We also confirmed that physiological responses to different stimulus amplitudes were comparable between optogenetic and electrophysiological activation. However, compared with electrically elicited responses, the optically elicited responses had lower sensitivity with stimulus frequency. Finally, we showed that afferent volleys evoked by optical stimulation were sufficient to activate postsynaptic neurons in the spinal reflex arc. These results provide new ways for understanding the role of sensory afferent input to the central nervous system regarding behavioural control, especially when genetically manipulated animals are not available, such as higher mammals including non-human primates.

Decoding of muscle activity from the sensorimotor cortex in freely behaving monkeys.

Remarkable advances have recently been made in the development of Brain-Machine Interface (BMI) technologies for restoring or enhancing motor function. However, the application of these technologies may be limited to patients in static conditions, as these developments have been largely based on studies of animals (e.g., non-human primates) in constrained movement conditions. The ultimate goal of BMI technology is to enable individuals to move their bodies naturally or control external devices without physical constraints. Here, we demonstrate accurate decoding of muscle activity from electrocorticogram (ECoG) signals in unrestrained, freely behaving monkeys. We recorded ECoG signals from the sensorimotor cortex as well as electromyogram signals from multiple muscles in the upper arm while monkeys performed two types of movements with no physical restraints, as follows: forced forelimb movement (lever-pull task) and natural whole-body movement (free movement within the cage). As in previous reports using restrained monkeys, we confirmed that muscle activity during forced forelimb movement was accurately predicted from simultaneously recorded ECoG data. More importantly, we demonstrated that accurate prediction of muscle activity from ECoG data was possible in monkeys performing natural whole-body movement. We found that high-gamma activity in the primary motor cortex primarily contributed to the prediction of muscle activity during natural whole-body movement as well as forced forelimb movement. In contrast, the contribution of high-gamma activity in the premotor and primary somatosensory cortices was significantly larger during natural whole-body movement. Thus, activity in a larger area of the sensorimotor cortex was needed to predict muscle activity during natural whole-body movement. Furthermore, decoding models obtained from forced forelimb movement could not be generalized to natural whole-body movement, which suggests that decoders should be built individually and according to different behavior types. These results contribute to the future application of BMI systems in unrestrained individuals.

Medication Adherence/Persistence and Demographics of Japanese Dyslipidemia Patients on Statin-Ezetimibe as a Separate Pill Combination Lipid-Lowering Therapy　- An Observational Pharmacy Claims Database Study.

BACKGROUND: This study aimed to identify potential predictors of medication adherence and persistence with statin-ezetimibe combinational lipid-lowering therapy (LLT) as a separate pill combination in a real-world setting in Japan.Methods and Results:Patients newly switched to statin-ezetimibe combinational LLT from statin monotherapy were identified within a Japanese national pharmacy claims database during January 2015 to April 2018. Adherence and persistence were measured by the proportion of days covered (PDC), time to treatment discontinuation and persistence rate at 1 year. A stepwise multivariate logistic regression model and Cox proportional hazards regression model were used to explore potential predictors associated with adherence and persistence, respectively. Among 6,921 patients, 71.9% were adherent (PDC ≥80%), and 83.6% were persistent at 1 year after initiation. Patients aged ≤54 years and ≥75 years were prone to be more non-adherent. Secondary prevention was associated with better adherence and longer persistence. Concomitant use of medications for depression/anxiety was associated with shorter persistence, whereas use of antihypertensive drugs was associated with better adherence and persistence. CONCLUSIONS: Age, concomitant use of certain classes of medications (or the existence of these diseases) and secondary prevention were associated with adherence and persistence of statin-ezetimibe combinational LLT. Given that dyslipidemia is a chronic disease requiring life-long control, active interventions are required for patients with poor adherence and persistence.

Low-Density Lipoprotein Cholesterol Goal Attainment Rates by Initial Statin Monotherapy Among Patients With Dyslipidemia and High Cardiovascular Risk in Japan　- A Retrospective Database Analysis.

BACKGROUND: To understand the recent management status in Japan, we determined the low-density lipoprotein cholesterol (LDL-C) goal attainment (GA) rate of patients initiating statin monotherapy for dyslipidemia.Methods and Results:Dyslipidemic patients undergoing either primary prevention with high cardiovascular risk or secondary prevention (defined by 2012 Japan Atherosclerosis Society Guidelines) were retrospectively analyzed from a hospital-based claims database. In both groups, the LDL-C levels and GA rates of patients treated with intensive or standard statin monotherapy for ≥4 weeks (January 2012-August 2016) were evaluated. Among 1,501,013 dyslipidemic patients, 11,695 and 9,642 were included in the primary and secondary prevention groups, respectively. A total of 94% of patients underwent statin monotherapy as the initial lipid-lowering therapy, of which most (≥80%) took intensive statins. The proportions of patients in the primary prevention group who achieved an LDL-C goal <120 mg/dL by intensive and standard statins were 81.1% and 61.2%, respectively, and the proportions of those who achieved a goal <100 mg/dL in the secondary prevention group were 73.3% and 48.1%, respectively. The GA rates were similar regardless of disease complications. CONCLUSIONS: Most patients (>70%) in both groups achieved LDL-C management goals using intensive statin monotherapy. Further treatment approaches are required for high-risk patients not achieving LDL-C goals by initial statin monotherapy. Continuous efforts are crucial for adherence and persistence of lipid-lowering therapies.

Causal Link between the Cortico-Rubral Pathway and Functional Recovery through Forced Impaired Limb Use in Rats with Stroke.

Intensive rehabilitation is believed to induce use-dependent plasticity in the injured nervous system; however, its causal relationship to functional recovery is unclear. Here, we performed systematic analysis of the effects of forced use of an impaired forelimb on the recovery of rats after lesioning the internal capsule with intracerebral hemorrhage (ICH). Forced limb use (FLU) group rats exhibited better recovery of skilled forelimb functions and their cortical motor area with forelimb representation was restored and enlarged on the ipsilesional side. In addition, abundant axonal sprouting from the reemerged forelimb area was found in the ipsilateral red nucleus after FLU. To test the causal relationship between the plasticity in the cortico-rubral pathway and recovery, loss-of-function experiments were conducted using a double-viral vector technique, which induces selective blockade of the target pathway. Blockade of the cortico-rubral tract resulted in deficits of the recovered forelimb function in FLU group rats. These findings suggest that the cortico-rubral pathway is a substrate for recovery induced by intensive rehabilitation after ICH. SIGNIFICANCE STATEMENT: The research aimed at determining the causal linkage between reorganization of the motor pathway induced by intensive rehabilitative training and recovery after stroke. We clarified the expansion of the forelimb representation area of the ipsilesional motor cortex by forced impaired forelimb use (FLU) after lesioning the internal capsule with intracerebral hemorrhaging (ICH) in rats. Anterograde tracing showed robust axonal sprouting from the forelimb area to the red nucleus in response to FLU. Selective blockade of the cortico-rubral pathway by the novel double-viral vector technique clearly revealed that the increased cortico-rubral axonal projections had causal linkage to the recovery of reaching movements induced by FLU. Our data demonstrate that the cortico-rubral pathway is responsible for the effect of intensive limb use.

Time course of recovery of different motor functions following a reproducible cortical infarction in non-human primates.

A major challenge in human stroke research is interpatient variability in the extent of sensorimotor deficits and determining the time course of recovery following stroke. Although the relationship between the extent of the lesion and the degree of sensorimotor deficits is well established, the factors determining the speed of recovery remain uncertain. To test these experimentally, we created a cortical lesion over the motor cortex using a reproducible approach in four common marmosets, and characterized the time course of recovery by systematically applying several behavioral tests before and up to 8 weeks after creation of the lesion. Evaluation of in-cage behavior and reach-to-grasp movement revealed consistent motor impairments across the animals. In particular, performance in reaching and grasping movements continued to deteriorate until 4 weeks after creation of the lesion. We also found consistent time courses of recovery across animals for in-cage and grasping movements. For example, in all animals, the score for in-cage behaviors showed full recovery at 3 weeks after creation of the lesion, and the performance of grasping movement partially recovered from 4 to 8 weeks. In addition, we observed longer time courses of recovery for reaching movement, which may rely more on cortically initiated control in this species. These results suggest that different recovery speeds for each movement could be influenced by what extent the cortical control is required to properly execute each movement.

Differential contributions of rostral and caudal frontal forelimb areas to compensatory process after neonatal hemidecortication in rats.

Following brain damage, especially in juvenile animals, large-scale reorganization is known to occur in the remaining brain structures to compensate for functional deficits. In rats with neonatal hemidecortication, corticospinal fibers originating from the undamaged side of the sensorimotor cortex issue collateral sprouts to the ipsilateral spinal gray matter that mediate cortical excitation to ipsilateral forelimb motoneurons and compensate for the deficit in forelimb movements. The present study was designed to investigate the origins of the ipsilateral corticospinal projection in neonatally hemidecorticated rats. Corticospinal neurons (CSNs) were labeled in adults by injecting retrograde neural tracers, cholera toxin subunit B with different fluorescent probes, into either side of the cervical spinal gray matter. In the undamaged cortex, double-labeled neurons were rarely found. CSNs with contralateral projections (contra-CSNs) and those with ipsilateral projections (ipsi-CSNs) were distributed both in the rostral forelimb motor area (RFA) and the caudal forelimb motor area (CFA). However, there was a difference in the distributions of the ipsi-CSNs between the two forelimb areas. Whereas the distribution of the ipsi-CSNs largely overlapped with that of the contra-CSNs in the RFA, the ipsi-CSNs tended to be segregated from the contra-CSNs in the CFA. The results suggested that the RFA and the CFA contribute to the compensatory process in different ways.

A display of combined left ventricular function and dyssynchrony using Doppler tissue imaging: its application in acute response to cardiac resynchronization therapy.

BACKGROUND: We have recently proposed a novel method for displaying left ventricular (LV) function and mechanical dyssynchrony, which is based on the "vector analysis" using Doppler tissue imaging (DTI). The aim of this study was to examine acute-phase impact of cardiac resynchronization therapy (CRT) on the parameters assessed by this method. METHODS: We studied a total of 25 patients with systolic heart failure, 14 undergoing simultaneous acute pacing-hemodynamic study and DTI; and 11 patients DTI within a few days before and one week after CRT. Parameters derived from the displaying method were followings: (1) percentage area of the hexagon, the area divided by the overall graph area, reflecting global LV systolic function; (2) net-delay magnitude, the length of the composite vector for the six vectors, a dyssynchrony index; and (3) delayed contraction site, graphical position of the composite vector. RESULTS: CRT significantly increased cardiac output (3.1 ± 1.0 to 3.4 ± 0.7 L/min, P = 0.02) and +dp/dt (782 ± 149 to 1,089 ± 270 mm Hg/s, P < 0.01), and decreased mitral regurgitaion jet area (7.9 ± 3.0 to 4.8 ± 2.4 cm(2) , P < 0.01). As with the new method, there were significant decreases in the percentage area of the hexagon (20.7 ± 6.6 to 18.6 ± 6.5%, P < 0.01) and the net-delay magnitude (122 ± 59 to 72 ± 48 ms, P < 0.01). The reduction of net-delay magnitude accompanied alteration of delayed contraction site; 16 patients had the most delayed site between the lateral and inferior segments before CRT, and seven patients after CRT (P = 0.02). CONCLUSIONS: The new method would be a useful tool to assess efficacy of CRT in patients with systolic heart failure.

Kinase-dead knock-in mouse reveals an essential role of kinase activity of Ca2+/calmodulin-dependent protein kinase IIalpha in dendritic spine enlargement, long-term potentiation, and learning.

Ca2+/calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) is an essential mediator of activity-dependent synaptic plasticity that possesses multiple protein functions. So far, the autophosphorylation site-mutant mice targeted at T286 and at T305/306 have demonstrated the importance of the autonomous activity and Ca2+/calmodulin-binding capacity of CaMKIIalpha, respectively, in the induction of long-term potentiation (LTP) and hippocampus-dependent learning. However, kinase activity of CaMKIIalpha, the most essential enzymatic function, has not been genetically dissected yet. Here, we generated a novel CaMKIIalpha knock-in mouse that completely lacks its kinase activity by introducing K42R mutation and examined the effects on hippocampal synaptic plasticity and behavioral learning. In homozygous CaMKIIalpha (K42R) mice, kinase activity was reduced to the same level as in CaMKIIalpha-null mice, whereas CaMKII protein expression was well preserved. Tetanic stimulation failed to induce not only LTP but also sustained dendritic spine enlargement, a structural basis for LTP, at the Schaffer collateral-CA1 synapse, whereas activity-dependent postsynaptic translocation of CaMKIIalpha was preserved. In addition, CaMKIIalpha (K42R) mice showed a severe impairment in inhibitory avoidance learning, a form of memory that is dependent on the hippocampus. These results demonstrate that kinase activity of CaMKIIalpha is a common critical gate controlling structural, functional, and behavioral expression of synaptic memory.

Formation of descending pathways mediating cortical command to forelimb motoneurons in neonatally hemidecorticated rats.

Neonatally hemidecorticated rats show fairly normal reaching and grasping behaviors of the forelimb contralateral to the lesion at the adult stage. Previous experiments using an anterograde tracer showed that the corticospinal fibers originating from the sensorimotor cortex of the intact side projected aberrant collaterals to the spinal gray matter on the ipsilateral side. The present study used electrophysiological methods to investigate whether the aberrant projections of the corticospinal tract mediated the pyramidal excitation to the ipsilateral forelimb motoneurons and, if so, which pathways mediate the effect in the hemidecorticated rats. Electrical stimulation to the intact medullary pyramid elicited bilateral negative field potentials in the dorsal horn of the spinal cord. In intracellular recordings of forelimb motoneurons, oligosynaptic pyramidal excitation was detected on both sides of the spinal cord in the hemidecorticated rats, whereas pyramidal excitation of motoneurons on the side ipsilateral to the stimulation was much smaller in normal rats. By lesioning the dorsal funiculus at the upper cervical level, we clarified that the excitation was transmitted to the ipsilateral motoneurons by at least two pathways: one via the corticospinal tract and spinal interneurons and the other via the cortico-reticulo-spinal pathways. These results suggested that in the neonatally hemidecorticated rats, the forelimb movements on the side contralateral to the lesion were modulated by motor commands through the indirect ipsilateral descending pathways from the sensorimotor cortex of the intact side either via the spinal interneurons or reticulospinal neurons.

Large-scale reorganization of corticofugal fibers after neonatal hemidecortication for functional restoration of forelimb movements.

As an experimental model to study the mechanism of large-scale network plasticity of the juvenile brain, functional compensation after neonatal brain damage was studied in rats that received unilateral decortication at postnatal day 5. These animals exhibited a marked ability in reaching and grasping movements in the contralesional side of the forelimb when tested at 10-14 weeks of age. Additional lesion of the sensorimotor cortex in the remaining contralesional hemisphere at this stage resulted in severe impairment of both forelimbs. It was suggested that the sensorimotor cortex on the contralesional side was controlling the movements of both forelimbs. Following the injection of an anterograde tracer into the remaining sensorimotor cortex, the corticofugal axons from the remaining sensorimotor cortex were found to issue aberrant projections to the contralateral red nucleus, contralateral superior colliculus, contralateral pontine nuclei, ipsilateral dorsal column nucleus and ipsilateral gray matter of the cervical spinal cord, all of which appeared to be necessary for the control of contralesional forelimb movements. These results suggest that the forelimb movements on the contralesional side were compensated by large-scale reorganization of the corticofugal axons from the remaining sensorimotor cortex.

The somatosensory cortex receives information about motor output.

During voluntary movement, the somatosensory system not only passively receives signals from the external world but also actively processes them via interactions with the motor system. However, it is still unclear how and what information the somatosensory system receives during movement. Using simultaneous recordings of activities of the primary somatosensory cortex (S1), the motor cortex (MCx), and an ensemble of afferent neurons in behaving monkeys combined with a decoding algorithm, we reveal the temporal profiles of signal integration in S1. While S1 activity before movement initiation is accounted for by MCx activity alone, activity during movement is accounted for by both MCx and afferent activities. Furthermore, premovement S1 activity encodes information about imminent activity of forelimb muscles slightly after MCx does. Thus, S1 receives information about motor output before the arrival of sensory feedback signals, suggesting that S1 executes online processing of somatosensory signals via interactions with the anticipatory information.

RFamide peptide QRFP43 causes obesity with hyperphagia and reduced thermogenesis in mice.

QRFP, an RFamide peptide, was recently identified as an endogenous ligand of an orphan G protein-coupled receptor, GPR103. Recent investigation revealed that acute intracerebroventricular (ICV) administration of QRFP26/P518/26RFa, a constitutive part of QRFP43 (43-amino acid-residue form of QRFP), increases appetite in mice, but its role in long-term energy homeostasis remains unknown. In the present study, we examined the effects of chronic administration of QRFP43 on feeding behavior, body weight regulation, and energy expenditure in mice. Intracerebroventricular infusion of QRFP43 for 13 d resulted in a significant increase in body weight and fat mass with hyperphagia. Weight gain and hyperphagia were more evident when mice were fed a moderately high-fat diet. Pair feeding of QRFP43-infused mice did not increase body weight but significantly increased fat mass and plasma concentrations of insulin, leptin, and cholesterol when compared with controls. Moreover, significant decreases in rectal temperature and expression of brown adipose tissue uncoupling protein-1 mRNA were observed in QRFP43-infused ad libitum- and pair-fed mice. The present results suggest that QRFP plays an important role in energy homeostasis by regulating appetite and energy expenditure.

Postsynaptic expression of a new calcium pathway in hippocampal CA3 neurons and its influence on mossy fiber long-term potentiation.

Long-term potentiation (LTP) in the CA1 region of the hippocampus is induced by postsynaptic Ca(2+) influx via NMDA receptors (NMDARs). However, this synaptic plasticity occurs independently of NMDARs when Ca(2+)-permeable AMPA receptors (AMPARs) are expressed at postsynaptic sites using various genetic techniques, indicating that an increase in Ca(2+) level at critical postsynaptic sites, regardless of its entry pathway, triggers the induction of LTP at CA1 synapses. In contrast, NMDARs are sparsely distributed on mossy fiber (MF) synapses in CA3 hippocampal neurons, and most evidence favors the presynaptic mechanism for LTP induction, although some reports suggested a postsynaptic mechanism. In this study, we examined whether Ca(2+) influx through the newly produced postsynaptic receptors during high-frequency stimulation affects the induction of MF LTP. For this purpose, we expressed Ca(2+)-permeable AMPARs in CA3 pyramidal neurons by Sindbis viral-mediated gene transfer of the unedited form of the glutamate receptor 2 (GluR2Q) subunit, as a new pathway for postsynaptic Ca(2+) entry, in rat hippocampal organotypic cultures. Virally expressed myc-tagged GluR2Q was detected at the complex spines known as the thorny excrescences, which serve as postsynaptic targets for MF synaptic input, on the proximal apical dendrites of CA3 pyramidal cells. Furthermore, endogenous Ca(2+)-impermeable AMPARs at MF synapses were converted into Ca(2+)-permeable receptors by GluR2Q expression. However, the postsynaptic expression of Ca(2+)-permeable AMPARs had no significant influence on the two types of MF LTP induced by different stimulus protocols. These results supported the notion that MF LTP is independent of postsynaptic Ca(2+).

Comparison of frequency of thromboembolic events and echocardiographic findings in patients with chronic nonvalvular atrial fibrillation and coarse versus fine electrocardiographic fibrillatory waves.

In patients with nonvalvular atrial fibrillation, the electrocardiographic fibrillatory wave reflects the structural and electrical remodeling of the atria. This study examined whether the fibrillatory wave amplitude could predict the risk of thromboembolism and demonstrated that this amplitude was related to the duration of atrial fibrillation. We also showed that the presence of fine fibrillatory waves (<1 mm in amplitude) could predict the thromboembolic potential in patients with chronic nonvalvular atrial fibrillation.

Electroporation-mediated gene transfer system applied to cultured CNS neurons.

Electroporation is effective in transferring foreign genes into immature neurons in intact brain tissue. We utilized this approach to transfect genes into developing rodent hippocampi. Transfected hippocampi were subsequently dissociated and allowed to differentiate in culture. By optimizing developmental stage of the hippocampus, promoters to drive the marker cDNA, and culture conditions, neurons kept strong expression of multiple marker genes for more than two weeks after electroporation. We could also induce transient expression in mature neurons by combining electroporation of plasmids containing loxP-flanked stopper sequences and infection of Cre-producing recombinant adenoviruses. The system described here is useful in analyzing biological roles of multiple genes in specific stages of neuronal development.

Gated blood pool SPECT improves reproducibility of right and left ventricular Fourier phase analysis in radionuclide angiography.

OBJECTIVES: The ventricular phase angle, a parametric method applied to Fourier phase analysis (FPA) in radionuclide ventriculography, allows the quantitative analysis of ventricular contractile synchrony. However, FPA reproducibility using gated blood pool SPECT (GBPS) has not been fully evaluated. The present study evaluates whether by using GBPS, the reproducibility of FPA could be improved over that in planar radionuclide angiography (PRNA). METHODS: Forty-three subjects underwent both GBPS and PRNA, of which 10 subjects were normal controls, 25 had dilated cardiomyopathy, and 8 had various heart diseases. Interventricular contractile synchrony was measured as the absolute difference in RV and LV mean ventricular phase angle as delta(phi) (RV - LV). Intraventricular contractile synchrony was measured as the standard deviation of the mean phase angle for the RV and LV blood pools (RVSD(phi), LVSD(phi)). Two nuclear physicians processed the same phase images of GBPS to evaluate the interobserver reproducibility of the phase angles using data from the 43 study participants. Phase images acquired from PRNA were processed in the same manner. RESULTS: Excellent reproducibility of delta(phi) (RV - LV) was obtained with both GBPS (Y = -3.10 + 0.89 x X; r = 0.901) and PRNA (Y = -4.51 + 0.81 x X; r = 0.834). In regard to RVSD(phi) reproducibility was not adequate with PRNA (Y = 18.56 + 0.35 x X; r = 0.424), while it was acceptable with GBPS (Y = 5.22 + 0.85 x X; r = 0.864). LVSD(phi) reproducibility was superior using both GBPS (Y = 4.15 + 0.97 x X; r = 0.965) and PRNA (Y = -0.55 + 0.98 x X; r = 0.910). CONCLUSION: Our results demonstrate FPA obtained using GBPS to be highly reproducible for evaluating delta(phi) (RV - LV), RVSD(phi) and LVSD(phi), in comparison with the PRNA method. We thus consider GBPS appropriate for evaluating ventricular contractile synchrony.

Reorganization of motor circuits after neonatal hemidecortication.

It is well recognized that a juvenile brain is more plastic than an adult brain and often undergoes better functional recovery following cortical injury. Infants treated with hemispherectomy to cure intractable epilepsy often exhibit restored normal motor function in the extremities contralateral to the lesion. Neuronal mechanisms of functional recovery after such a large cortical damage at a young age have been studied using animals with a similar lesion, hemidecortication. In such animals, descending pathways from the undamaged sensorimotor cortex to the ipsilateral forelimb motoneurons are reorganized as restoring normal motor function of the forelimb contralateral to the injury. Similar aberrant pathways from the motor cortex to the ipsilateral motoneurons are also generated following suppression of cortical activity in the other hemisphere, suggesting the development of contralateral connections in an activity-dependent manner in normal animals. Thus, formation of ipsilateral descending pathways following neonatal hemidecortication might be due to a loss of balance in cortical activity between the two hemispheres. Studies using animal models of neonatal cortical injury can reveal mechanisms of neural development and may help to establish therapeutic strategies to facilitate recovery from human juvenile cortical injury.

Reorganization of sensory pathways after neonatal hemidecortication in rats.

We investigated ascending somatosensory pathways in neonatally hemidecorticated rats. Injection of an anterograde tracer, biotinylated dextran amine (BDA), into the contralesional dorsal root ganglions revealed ipsilateral projections to the dorsal column nuclei (DCN) in hemidecorticated rats as well as in normal rats. Injection of BDA into the DCN on the same side revealed that while most axons projected to the contralateral thalamus, some axons were detected in the ipsilateral thalamus in hemidecorticated rats while such projections were rarely detected in normal rats. The results suggest that aberrant ipsilateral projections of DCN neurons contralateral to the lesion developed after the hemidecortication.