Brain functional connectivity in individuals with psychogenic nonepileptic seizures (PNES): An application of graph theory.

OBJECTIVE: To determine brain functional connectivity (FC), based on the graph theory, in individuals with psychogenic nonepileptic seizures (PNES), in order to better understand the mechanisms underlying this disease. METHODS: Twenty-three patients with PNES and twenty-five healthy control subjects were examined. Alterations in FC within the whole brain were examined using resting-state functional magnetic resonance imaging (MRI). We calculated measures of the nodal degree, a major feature of the graph theory, for all the cortical and subcortical regions in the brain. Pearson correlation was performed to determine the relationship between nodal degree in abnormal brain regions and patient characteristics. RESULTS: The nodal degrees in the right caudate (CAU), left orbital part of the left inferior frontal gyrus (ORBinf), and right paracentral lobule (PCL) were significantly greater (i.e. hyper-connectivity) in individuals with PNES than in healthy control subjects. On the other hand, a lesser nodal degree (i.e. hypo-connectivity) was detected in several other brain regions including the left and right insula (INS), as well as the right putamen (PUT), and right middle occipital gyrus (MOG). CONCLUSION: Our findings suggest that the FC of several major brain regions can be altered in individuals with PNES. Areas with hypo-connectivity may be involved in emotion processing (e.g., INS) and movement regulation (e.g., PUT), whereas areas with hyper-connectivity may play a role in the inhibition of unwanted movements and cognitive processes (e.g., CAU).

Effective connectivity between emotional and motor brain regions in people with psychogenic nonepileptic seizures (PNES).

OBJECTIVE: To characterize the effective connectivity (EC) between the emotion and motor brain regions in patients with psychogenic nonepileptic seizures (PNES), based on resting-state spectral dynamic causal modeling (spDCM). METHODS: Twenty-three patients with PNES and twenty-five healthy control (HC) subjects underwent resting-state fMRI scanning. The coupling parameters indicating the causal interactions between eight brain regions associated with emotion, executive control, and motion were estimated for both groups, using resting-state fMRI spDCM. RESULTS: Compared to the HC subjects, in patients with PNES: (i) the left insula (INS) and left and right inferior frontal gyri (IFG) are more inhibited by the amygdala (AMYG), anterior cingulate cortex (ACC), and precentral gyrus (PCG); (ii) the left AMYG has greater inhibitory effects on the INS, IFG, dorsolateral prefrontal cortex (DLPFC), PCG, and supplementary motor area (SMA); (iii) the left ACC has more inhibitory effects on the INS and IFG; (iv) the right ACC is more inhibited by the INS and IFG, and has a less inhibitory effect on the SMA and PCG; and (v) the left caudate (CAU) had increased inhibitory effects on the AMYG and IFG and a more excitatory effect on the SMA. CONCLUSION: Our results suggest that in patients with PNES, the emotion-processing regions have inhibitory effects on the executive control areas and motor regions. Our findings may provide further insight into the influence of emotional arousal on functional movements and the underlying mechanisms of involuntary movements during functional seizures. Furthermore, they may suggest that emotion regulation through cognitive behavioral psychotherapies can be a potentially effective treatment modality.

Facilitatory effects of anti-spastic medication on robotic locomotor training in people with chronic incomplete spinal cord injury.

BACKGROUND: The objective of this study was to investigate whether an anti-spasticity medication can facilitate the effects of robotic locomotor treadmill training (LTT) to improve gait function in people with incomplete spinal cord injury (SCI). METHODS: Individuals with chronic incomplete SCI were recruited and carried out a 4 week intervention of either locomotor treadmill training (LTT) alone (n = 26) or LTT combined with Tizanidine (TizLTT), an anti-spasticity medication (n = 22). Gait function was evaluated using clinical outcome measures of gait, speed and endurance. To better understand the underlying mechanisms of the therapeutic effects, maximal strength, active range of motion (AROM) and peak velocity (Vp) of ankle dorsi- and planter-flexor muscles were also measured. Differences were assessed using two-way mixed design analysis of variance. The number of subjects that achieved the minimal important difference (MID) for clinical scores was also measured for each group, and the results of those that did attain the MID were compared with those that did not. RESULTS: Both LTT and TizLTT resulted in significant improvements in walking speed and dorsiflexion maximum strength, with no significant differences between them, using group-averaging analysis. However, using the MID analysis, a higher proportion of subjects in the TizLTT group achieved the MID for walking speed (40%) compared with LTT alone (13%). Those that achieved the MID for walking speed were significantly higher functioning at baseline than those that did not in the TizLTT group, and the change in walking speed was associated with the change in dorsiflexion peak velocity (R(2) = 0.40; P < 0.05). CONCLUSION: Tizanidine appears to facilitate the effects of LTT on gait function in individuals with chronic SCI that are higher functioning at baseline. We speculate that this may be due to restoration of inhibitory mechanisms by Tizanidine, resulting in greater stretch in the planterflexor muscles during the LTT.

Ankle voluntary movement enhancement following robotic-assisted locomotor training in spinal cord injury.

BACKGROUND: In incomplete spinal cord injury (iSCI), sensorimotor impairments result in severe limitations to ambulation. To improve walking capacity, physical therapies using robotic-assisted locomotor devices, such as the Lokomat, have been developed. Following locomotor training, an improvement in gait capabilities-characterized by increases in the over-ground walking speed and endurance-is generally observed in patients. To better understand the mechanisms underlying these improvements, we studied the effects of Lokomat training on impaired ankle voluntary movement, known to be an important limiting factor in gait for iSCI patients. METHODS: Fifteen chronic iSCI subjects performed twelve 1-hour sessions of Lokomat training over the course of a month. The voluntary movement was qualified by measuring active range of motion, maximal velocity peak and trajectory smoothness for the spastic ankle during a movement from full plantar-flexion (PF) to full dorsi-flexion (DF) at the patient's maximum speed. Dorsi- and plantar-flexor muscle strength was quantified by isometric maximal voluntary contraction (MVC). Clinical assessments were also performed using the Timed Up and Go (TUG), the 10-meter walk (10MWT) and the 6-minute walk (6MWT) tests. All evaluations were performed both before and after the training and were compared to a control group of fifteen iSCI patients. RESULTS: After the Lokomat training, the active range of motion, the maximal velocity, and the movement smoothness were significantly improved in the voluntary movement. Patients also exhibited an improvement in the MVC for their ankle dorsi- and plantar-flexor muscles. In terms of functional activity, we observed an enhancement in the mobility (TUG) and the over-ground gait velocity (10MWT) with training. Correlation tests indicated a significant relationship between ankle voluntary movement performance and the walking clinical assessments. CONCLUSIONS: The improvements of the kinematic and kinetic parameters of the ankle voluntary movement, and their correlation with the functional assessments, support the therapeutic effect of robotic-assisted locomotor training on motor impairment in chronic iSCI.

Prediction of gait recovery in spinal cord injured individuals trained with robotic gait orthosis.

BACKGROUND: Motor impairment is a major consequence of spinal cord injury (SCI). Earlier studies have shown that robotic gait orthosis (e.g., Lokomat) can improve an SCI individual's walking capacity. However, little is known about the differential responses among different individuals with SCI. The present longitudinal study sought to characterize the distinct recovery patterns of gait impairment for SCI subjects receiving Lokomat training, and to identify significant predictors for these patterns. METHODS: Forty SCI subjects with spastic hypertonia at their ankles were randomly allocated to either control or intervention groups. Subjects in the intervention group participated in twelve 1-hour Lokomat trainings over one month, while control subjects received no interventions. Walking capacity was evaluated in terms of walking speed, functional mobility, and endurance four times, i.e. baseline, 1, 2, and 4 weeks after training, using the 10-Meter-Walking, Timed-Up-and-Go, and 6-Minute-Walking tests. Growth Mixture Modeling, an analytical framework for stratifying subjects based on longitudinal changes, was used to classify subjects, based on their gait impairment recovery patterns, and to identify the effects of Lokomat training on these improvements. RESULTS: Two recovery classes (low and high walking capacity) were identified for each clinical evaluation from both the control and intervention groups. Subjects with initial high walking capacity (i.e. shorter Timed-Up-and-Go time, higher 10-Meter-Walking speed and longer 6-Minute-Walking distance) displayed significant improvements in speed and functional mobility (0.033 m/s/week and-0.41 s/week respectively); however no significant change in endurance was observed. Subjects with low walking capacity exhibited no significant improvement. The membership in these two classes-and thus prediction of the subject's gait improvement trajectory over time-could be determined by the subject's maximum voluntary torque at the ankle under both plantar-and dorsi-flexion contractions determined prior to any training. CONCLUSION: Our findings demonstrate that subjects responded to Lokomat training non-uniformly, and should potentially be grouped based on their likely recovery patterns using objective criteria. Further, we found that the subject's ankle torque can predict whether he/she would benefit most from Lokomat training prior to the therapy. These findings are clinically significant as they can help individualize therapeutic programs that maximize patient recovery while minimizing unnecessary efforts and costs.

Effective connectivity between deep brain stimulation targets in individuals with treatment-resistant depression.

The therapeutic effect of deep brain stimulation on patients with treatment-resistant depression is strongly dependent on the connectivity of the stimulation region with other regions associated with depression. The aims of this study are to characterize the effective connectivity between the brain regions playing important roles in depression and further investigate the underlying pathophysiological mechanisms of treatment-resistant depression and the mechanisms involving deep brain stimulation. Thirty-three individuals with treatment-resistant depression and 29 healthy control subjects were examined. All subjects underwent resting-state functional MRI scanning. The coupling parameters reflecting the causal interactions among deep brain stimulation targets and medial prefrontal cortex were estimated using spectral dynamic causal modelling. Our results showed that compared to the healthy control subjects, in the left hemisphere of treatment-resistant depression patients, the nucleus accumbens was inhibited by the inferior thalamic peduncle and excited the ventral caudate and the subcallosal cingulate gyrus, which in turn excited the lateral habenula. In the right hemisphere, the lateral habenula inhibited the ventral caudate and the nucleus accumbens, both of which inhibited the inferior thalamic peduncle, which in turn inhibited the cingulate gyrus. The ventral caudate excited the lateral habenula and the cingulate gyrus, which excited the medial prefrontal cortex. Furthermore, these effective connectivity links varied between males and females, and the left and right hemispheres. Our findings suggest that intrinsic excitatory/inhibitory connections between deep brain stimulation targets are impaired in treatment-resistant depression patients, and that these connections are sex dependent and hemispherically lateralized. This knowledge can help to better understand the underlying mechanisms of treatment-resistant depression, and along with tractography, structural imaging, and other relevant clinical information, may assist to determine the appropriate region for deep brain stimulation therapy in each treatment-resistant depression patient.

Contribution of altered corticospinal microstructure to gait impairment in children with cerebral palsy.

OBJECTIVE: Corticospinal tract (CST) injury may lead to motor disorders in children with Cerebral Palsy (CP). However, the precise underlying mechanisms are still ambiguous. We aimed to characterize the CST structure and function in children with CP and determine their contributions to balance and gait impairments. METHOD: Twenty-six children with spastic CP participated. Transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) were utilized to characterize CST structure and function. Common clinical measures were used to assess gait speed, endurance and balance, and mobility. RESULTS: CST structure and function were significantly altered in children with CP. Different abnormal patterns of CST structure were identified as either abnormal appearance of brain hemispheres (Group-1) or semi-normal CST appearance (Group-2). We found significant correlations between the DTI parameters of the more affected CST and gait features only in Group-1. CONCLUSION: CST structure and function are abnormal in children with CP and these abnormalities may contribute to balance and gait impairment in some children with CP. SIGNIFICANCE: Our findings may lead to the development of further investigations on the mechanisms underlying gait impairment in children with CP and on decision-making for more effective rehabilitation.

Characterization of brain functional connectivity in treatment-resistant depression.

OBJECTIVE: To characterize the functional connectivity (FC) of target brain regions for deep brain stimulation (DBS) in patients with treatment-resistant depression (TRD), and to evaluate its gender and brain lateralization dependence. METHODS: Thirty-one TRD patients and twenty-nine healthy control (HC) subjects participated. FC of subcallosal cingulate gyrus (SCG), ventral caudate (VCa), nucleus accumbens (NAc), lateral habenula (LHb), and inferior thalamic peduncle (ITP) were evaluated using resting-state fMRI. FC was characterized by calculating the nodal 'degree', a major feature of the graph theory. RESULTS: The degree measures of the left and right VCa, the left LHb, and the left ITP were significantly greater in the TRD than in the HC group. The degree was greater in females with TRD in all these regions except the right LHb. Finally, the left hemisphere was generally more affected by depression and presented significant degrees in LHb and ITP regions of the patients. CONCLUSION: Our findings demonstrate the ability of degree to characterize brain FC and identify the regions with abnormal activities in TRD patients. This implies that the degree may have the potential to be used as an important graph-theoretical feature to further investigate the mechanisms underlying TRD, and consequently along with other diagnostic markers, to assist in the determination of the appropriate target region for DBS treatment in TRD patients.

Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique.

BACKGROUND: Despite numerous investigations, the impact of tizanidine, an anti-spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components. METHODS: A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed. RESULTS: Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine. CONCLUSIONS: Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects.

Therapeutic effects of robotic rehabilitation on Neural and Muscular Abnormalities associated with the Spastic Ankle in Stroke Survivors.

Spasticity is a common ailment following stroke, which can cause pain, contracture, abnormal limb posture and functional limitation. Early management of post-stroke spasticity is vital to reduce these complications, and improve function and help patients become independent. We propose a therapeutic program based on applying a series of vibrations to the ankle joints at specific ankle position as well as over the range of motion using a rehabilitation robotic system to reduce the neural and muscular abnormalities associated with spasticity. We provided a 30-minute perturbation training, 3 times a week for 10 sessions for 8 stroke survivor subjects. Ankle stiffness was calculated using the hysteresis curves. Other kinematic and kinetic parameters were also used to evaluate the mechanical abnormalities. We evaluated participants before starting the therapeutic program, immediately after first session of training and after 10 sessions of training.Our results showed that all subjects had substantial improvements in stiffness, max voluntary contraction, energy loss, passive range of motion, and voluntary movement after both short- and long-term therapeutic program. Surprisingly, for most of these measures the maximum improvement obtained at short-term training. Interestingly, these improvements became persistent over the long-term training. These findings suggest that vibration therapy can be considered as an effective rehabilitation intervention to reduce neuromuscular abnormalities associated with the spasticity in stroke.

Graph theory application with functional connectivity to distinguish left from right temporal lobe epilepsy.

OBJECTIVE: To investigate the application of graph theory with functional connectivity to distinguish left from right temporal lobe epilepsy (TLE). METHODS: Alterations in functional connectivity within several brain networks - default mode (DMN), attention (AN), limbic (LN), sensorimotor (SMN) and visual (VN) - were examined using resting-state functional MRI (rs-fMRI). The study accrued 21 left and 14 right TLE as well as 17 nonepileptic control subjects. The local nodal degree, a feature of graph theory, was calculated foreach of the brain networks. Multivariate logistic regression analysis was performed to determine the accuracy of identifying seizure laterality based on significant differences in local nodal degree in the selected networks. RESULTS: Left and right TLE patients showed dissimilar patterns of alteration in functional connectivity when compared to control subjects. Compared with right TLE, patients with left TLE exhibited greater nodal degree' (i.e. hyperconnectivity) with right superomedial frontal gyrus (in DMN), inferior frontal gyrus pars triangularis (in AN), right caudate and left superior temporal gyrus (in LN) and left paracentral lobule (in SMN), while showing lesser nodal degree (i.e. hypoconnectivity) with left temporal pole (in DMN), right insula (in LN), left supplementary motor area (in SMN), and left fusiform gyrus (in VN). The LN showed the highest accuracy of 82.9% among all considered networks in determining laterality of the TLE. By combinations of local degree attributes in the DMN, AN, LN, and VN, logistic regression analysis demonstrated an accuracy of 94.3% by comparison. CONCLUSION: Our study demonstrates the utility of graph theory application to brain network analysis as a potential biomarker to assist in the determination of TLE laterality and improve the confidence in presurgical decision-making in cases of TLE.

Time-course of changes in arm impairment after stroke: variables predicting motor recovery over 12 months.

OBJECTIVES: To characterize the time-course of changes in motor recovery in the upper extremity of hemiparetic stroke survivors over a 1-year interval after stroke, and to use kinematic and kinetic recordings of elbow voluntary movement at 1 month to predict recovery over this 1-year period. DESIGN: Motor impairment was assessed using the Fugl-Meyer Assessment (FMA) of the upper extremity. The angular elbow movement trajectory and its derivatives were recorded. Limb kinetics were quantified using maximum voluntary contractions. Subjects were examined at 1, 2, 3, 6, and 12 months after stroke. The growth mixture model was used to characterize the recovery patterns of the FMA over 1 year, and a logistic regression analysis was used to predict these patterns with the kinematic and kinetic measures recorded at 1 month. SETTING: A hospital-based laboratory with a movement testing system including position and torque sensors. PARTICIPANTS: Hemiparetic stroke survivors (N=20) with upper-extremity impairment recruited within 4 weeks poststroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Kinematic parameters, including active range of motion, peak velocity, peak acceleration, movement smoothness, and movement speed; kinetic parameters, including isometric voluntary contraction of elbow extensors and flexors; and clinical measurement of motor impairment (FMA). RESULTS: We found 2 classes of recovery patterns. Class 1 subjects started with a low-level FMA score and then increased quickly before tapering off gradually. Conversely, class 2 subjects started with a high-level FMA score that remained constant or increased slightly. Using logistic regression, the impact of each kinematic and kinetic measure on class membership was characterized. The class assignment helped predict the recovery pattern of motor impairment for each subject. CONCLUSIONS: Using elbow kinematic and kinetic measures 1 month after stroke, we were able to predict accurately the recovery of arm impairment in subjects with hemiparetic stroke at different time points in the first year. This information is of potential value for planning targeted therapeutic interventions.

The relation between Ashworth scores and neuromechanical measurements of spasticity following stroke.

BACKGROUND: Spasticity is a common impairment that follows stroke, and it results typically in functional loss. For this reason, accurate quantification of spasticity has both diagnostic and therapeutic significance. The most widely used clinical assessment of spasticity is the modified Ashworth scale (MAS), an ordinal scale, but its validity, reliability and sensitivity have often been challenged. The present study addresses this deficit by examining whether quantitative measures of neural and muscular components of spasticity are valid, and whether they are strongly correlated with the MAS. METHODS: We applied abrupt small amplitude joint stretches and Pseudorandom Binary Sequence (PRBS) perturbations to both paretic and non-paretic elbow and ankle joints of stroke survivors. Using advanced system identification techniques, we quantified the dynamic stiffness of these joints, and separated its muscular (intrinsic) and reflex components. The correlations between these quantitative measures and the MAS were investigated. RESULTS: We showed that our system identification technique is valid in characterizing the intrinsic and reflex stiffness and predicting the overall net torque. Conversely, our results reveal that there is no significant correlation between muscular and reflex torque/stiffness and the MAS magnitude. We also demonstrate that the slope and intercept of reflex and intrinsic stiffnesses plotted against the joint angle are not correlated with the MAS. CONCLUSION: Lack of significant correlation between our quantitative measures of stroke effects on spastic joints and the clinical assessment of muscle tone, as reflected in the MAS suggests that the MAS does not provide reliable information about the origins of the torque change associated with spasticity, or about its contributing components.

Muscle and reflex changes with varying joint angle in hemiparetic stroke.

BACKGROUND: Despite intensive investigation, the origins of the neuromuscular abnormalities associated with spasticity are not well understood. In particular, the mechanical properties induced by stretch reflex activity have been especially difficult to study because of a lack of accurate tools separating reflex torque from torque generated by musculo-tendinous structures. The present study addresses this deficit by characterizing the contribution of neural and muscular components to the abnormally high stiffness of the spastic joint. METHODS: Using system identification techniques, we characterized the neuromuscular abnormalities associated with spasticity of ankle muscles in chronic hemiparetic stroke survivors. In particular, we systematically tracked changes in muscle mechanical properties and in stretch reflex activity during changes in ankle joint angle. Modulation of mechanical properties was assessed by applying perturbations at different initial angles, over the entire range of motion (ROM). Experiments were performed on both paretic and non-paretic sides of stroke survivors, and in healthy controls. RESULTS: Both reflex and intrinsic muscle stiffnesses were significantly greater in the spastic/paretic ankle than on the non-paretic side, and these changes were strongly position dependent. The major reflex contributions were observed over the central portion of the angular range, while the intrinsic contributions were most pronounced with the ankle in the dorsiflexed position. CONCLUSION: In spastic ankle muscles, the abnormalities in intrinsic and reflex components of joint torque varied systematically with changing position over the full angular range of motion, indicating that clinical perceptions of increased tone may have quite different origins depending upon the angle where the tests are initiated.Furthermore, reflex stiffness was considerably larger in the non-paretic limb of stroke patients than in healthy control subjects, suggesting that the non-paretic limb may not be a suitable control for studying neuromuscular properties of the ankle joint. Our findings will help elucidate the origins of the neuromuscular abnormalities associated with stroke-induced spasticity.

Therapeutic Effects of repetitive Transcranial Magnetic Stimulation on Corticospinal Tract Activities and Neuromuscular Properties in Children with Cerebral Palsy.

The objective of this research was to study the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) on corticospinal tract (CST) activities, reflex hyper-excitability, muscle stiffness, and the clinical status of children with spastic hemiplegic cerebral palsy (CP). Three children participated in this study. The treatment lasted for 6 weeks. Two of the patients, the experimental group, received rTMS therapy 4 days a week during the first 3 weeks, and then received typical occupational therapy (OT) after each rTMS session during the second 3 weeks. One patient, the control group, received the same treatment except that a sham coil was used. Each rTMS session lasted for 20 minutes and each OT session lasted for 45 minutes. We evaluated CST activities by transcranial magnetic stimulation (TMS), reflex hyperexcitability by H-reflex response, and muscle stiffness by sonoelastography images. The tests were taken before and after the treatment. Major TMS parameters (i.e., motor evoked potential (MEP) latency, MEP p-p amplitude, cortical silent period (cSP), and intensity of pulse) for experimental patients were improved in comparison with the control patient. H response latency and max H response on max M-wave (H/M) were improved for the experimental group compared to the control group. Two parameters of texture analysis of the sonoelastography images (i.e., entropy and contrast) were improved for the experimental group. Clinical evaluations such as 10 meter walk test (10MWT), timed up and go (TUG), and 6 minute walk test (6MWT) were performed before and after the course of treatment and were improved for the experimental group compared to the control group. These results indicated that rTMS therapy can improve CST activities, reflexes, muscle stiffness, and walking capacity of spastic hemiplegic CP. Therefore, it can be considered as an effective therapeutic tool for enhancing neuromuscular abnormalities resulting from CP.

The Impact of Repetitive Transcranial Magnetic Stimulation on Affected and Unaffected Sides of a Child with Hemiplegic Cerebral Palsy.

The purpose of this study was to investigate the therapeutic effects of neuro-navigated repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy (OT) on gait impairment of a child (male, age: 13.2) with spastic hemiplegic cerebral palsy (CP). The treatment included 4 days a week of rTMS sessions for 3 weeks and 4 days of rTMS and OT sessions per week for 3 weeks. Transcranial magnetic stimulation (TMS) was used to evaluate corticospinal tract (CST) activities and H-reflex test was used to assess reflex hyper-excitability. Common clinical tests demonstrate the clinical status of the patient. Evaluations were performed in 4 time steps: baseline, 3 weeks after the beginning of the treatment, at the end of the treatment, and 1 month after the end of the treatment. The patient did not receive any specific treatment after the end of the treatment up to the follow up evaluations. The tests' results were compared between the affected and unaffected legs of the patient. Four parameters of the TMS test were calculated (motor evoked potential (MEP) latency, MEP peak-to-peak amplitude, cortical silent period (cSP), and stimulation intensity). These parameters were all improved for the affected side and cSP improved for the unaffected side, but MEP p-p amplitude and intensity got worse slightly for the unaffected side. Recruitment curves of H response and M-wave of the H-reflex test for both sides were obtained. Improvements could be seen after the treatment for both sides. Max H response on max M-wave (H/M) and H response latency got better after the treatment for both sides. Walking speed for self and fast velocity, timed up and go, and walking endurance improved during and after the treatment. All the improvements persisted after one month of the end of the treatment in the follow up evaluations. These findings indicate that rTMS combined with OT can have effective and long-lasting impact on neuromuscular impairments in spastic CP children.

Upper limb impairments associated with spasticity in neurological disorders.

BACKGROUND: While upper-extremity movement in individuals with neurological disorders such as stroke and spinal cord injury (SCI) has been studied for many years, the effects of spasticity on arm movement have been poorly quantified. The present study is designed to characterize the nature of impaired arm movements associated with spasticity in these two clinical populations. By comparing impaired voluntary movements between these two groups, we will gain a greater understanding of the effects of the type of spasticity on these movements and, potentially a better understanding of the underlying impairment mechanisms. METHODS: We characterized the kinematics and kinetics of rapid arm movement in SCI and neurologically intact subjects and in both the paretic and non-paretic limbs in stroke subjects. The kinematics of rapid elbow extension over the entire range of motion were quantified by measuring movement trajectory and its derivatives; i.e. movement velocity and acceleration. The kinetics were quantified by measuring maximum isometric voluntary contractions of elbow flexors and extensors. The movement smoothness was estimated using two different computational techniques. RESULTS: Most kinematic and kinetic and movement smoothness parameters changed significantly in paretic as compared to normal arms in stroke subjects (p < 0.003). Surprisingly, there were no significant differences in these parameters between SCI and stroke subjects, except for the movement smoothness (p < or = 0.02). Extension was significantly less smooth in the paretic compared to the non-paretic arm in the stroke group (p < 0.003), whereas it was within the normal range in the SCI group. There was also no significant difference in these parameters between the non-paretic arm in stroke subjects and the normal arm in healthy subjects. CONCLUSION: The findings suggest that although the cause and location of injury are different in spastic stroke and SCI subjects, the impairments in arm voluntary movement were similar in the two spastic groups. Our results also suggest that the non-paretic arm in stroke subjects was not distinguishable from the normal, and might therefore be used as an appropriate control for studying movement of the paretic arm.

Differences in white matter microstructure between Parkinson's disease patients with and without REM sleep behavior disorder.

REM sleep behavior disorder (RBD) is characterized by increased muscle tone and violent limb movements and usually occurs during the early stages of Parkinson disease (PD). PD patients with RBD represent faster motor progression and cognitive dysfunction. We used diffusion imaging to assess which regions are involved in this phenomenon. In the current study, we computed Quantitative Anisotropic (QA), which is based on spin distribution function (SDF) that quantifies the density of diffusing water and is more sensitive to psychological differences between groups and also diffusion MRI connectometry to conduct group analysis between age and gender matched PD patients with and without RBD. The major regions with significantly reduced QA in PD patients with RBD were left and right cingulum and left and left inferior occipital fasciculus.

Structural brain network analysis in schizophrenia using minimum spanning tree.

Schizophrenia is a mental disorder in which functional and structural brain networks are disrupted. Classical network analysis has been used by many researchers to quantify brain networks and to study the network changes in schizophrenia, but unfortunately metrics used in this classical method highly depend on the networks' density and weight; the comparisons made by this method are biased. The minimum spanning tree (MST) is an alternative method to solve this problem, but its usefulness in studying the schizophrenic brain network has not been examined yet. In the present study, we quantified structural brain networks using MST metrics to conduct group analysis between age and sex matched schizophrenic patients and healthy controls. Many MST metrics including Kappa, gamma, max, Betweenness centrality (BC), leaf number, and diameter were found to have significantly changed between two groups that implied a disruption in the whole brain integrity. This was unlike the brain segregation, which was not altered in the schizophrenia group. These results have consistency with Classical network analysis works and demonstrate the MST potential as a powerful method to be used in researches, studying schizophrenic brain connectome.

Comparison between the therapeutic effects of robotic-assisted locomotor training and an anti-spastic medication on spasticity.

We studied the effects of robotic-assisted locomotor (LOKOMAT) training or an anti-spastic medication (tizanidine) on neuromuscular abnormality associated with spasticity in persons with incomplete Spinal Cord Injury (SCI). Subjects were randomly divided to three groups: Lok, Tiz, and Cont. LOKOMAT training was performed 3 days/week for 4 weeks, with up to 45 minutes of training per session. Tizanidine (2mg) was administered (4\day), for 4 weeks. Subjects in Cont group received no intervention. The participants were evaluated before and after 4 weeks of training, and the effects of training on the intrinsic (muscular) and reflexive components of the neuromuscular properties were quantified over the ankle range-of-motion. A parallel-cascade system identification technique was used to determine the reflex and intrinsic stiffness of the ankle joint as a function of ankle position at each time point. The intercept and slope of the stiffness vs. joint angle curve were then calculated and tracked over the four-week period. The number of subjects that achieved the minimally important difference (MID) for the intercepts and slopes, and levels of changes were compared. Both Lokomat and tizanidine resulted in significant reduction in both intercept and slope of reflex and intrinsic stiffness. However, a higher proportion of subjects in Lok group achieved the MID for the reflex (>90%) and intrinsic (65-78%) parameters compared with Tiz group (up to 63% and 25% for reflex and intrinsic parameters, respectively). The levels of reduction were also higher in the Lok than the Tiz group. No one in the Cont group achieved the MID. Our findings demonstrate that LOKOMAT training can be more efficient in modifying neuromuscular abnormalities associated with spasticity than tizanidine.