Contraction intensity modulates spinal excitability during transcranial magnetic stimulation-evoked silent period in rectus femoris muscle.

PURPOSE: Reduced spinal excitability during the transcranial magnetic stimulation (TMS) silent period (SP) has recently been shown to last longer than previously thought in the upper limbs, as assessed via spinal electrical stimulation. Further, there is reason to expect that contraction intensity affects the duration of the reduced spinal excitability. METHODS: This study investigated spinal excitability at different time delays within the TMS-evoked SP in m.rectus femoris. Fifteen participants performed non-fatiguing isometric knee extensions at 25%, 50% and 75% of maximum voluntary contraction (MVC). Lumbar stimulation (LS) induced a lumbar-evoked potential (LEP) of 50% resting M-max. TMS stimulator output induced a SP lasting ~ 200 ms. In each contraction, a LEP (unconditioned) was delivered ~ 2-3 s prior to TMS, which was followed by a second LEP (conditioned) 60, 90, 120 or 150 ms into the silent period. Five contractions were performed at each contraction intensity and for each time delay in random order. RESULTS: Compared to the unconditioned LEP, the conditioned LEP amplitude was reduced (- 28 ± 34%, p = 0.007) only at 60 ms during 25% of MVC. Conditioned LEP amplitudes during 50% and 75% of MVC were reduced at 60 ms (- 37 ± 47%, p = 0.009 and - 37 ± 42%, p = 0.005, respectively) and 150 ms (- 30% ± 37%, p = 0.0083 and - 37 ± 43%, p = 0.005, respectively). LEP amplitude at 90 ms during 50% of MVC also reduced (- 25 ± 35%, p = 0.013). CONCLUSION: Reduced spinal excitability is extended during 50% and 75% of MVC. In future, paired TMS-LS could be a potential method to understand changes in spinal excitability during SP (at different contraction intensities) when testing various neurophysiological phenomena.

Increased myelination plays a central role in white matter neuroplasticity.

White matter (WM) neuroplasticity in the human brain has been tracked non-invasively using advanced magnetic resonance imaging techniques, with increasing evidence for improved axonal transmission efficiency as a central mechanism. The current study is the culmination of a series of studies, which characterized the structure-function relationship of WM transmission efficiency in the cortico-spinal tract (CST) during motor learning. Here, we test the hypothesis that increased transmission efficiency is linked directly to increased myelination using myelin water imaging (MWI). MWI was used to evaluate neuroplasticity-related improvements in the CST. The MWI findings were then compared to diffusion tensor imaging (DTI) results, with the secondary hypothesis that radial diffusivity (RD) would have a stronger relationship than axial diffusivity (AD) if the changes were due to increased myelination. Both MWI and RD data showed the predicted pattern of significant results, strongly supporting that increased myelination plays a central role in WM neuroplasticity.

Integrity of the cortico-spinal tract is associated with physical activity.

Background and purpose: Despite the primary motor efferent role of the cortico-spinal tract (CST), it is hardly understood whether the amount of physical activity is associated with the integrity of the CST.Materials and methods: We examined the association between the amount of physical activity and the integrity of the CST, using Diffusion Tensor Imaging (DTI) data from 465 individuals. The CST was segmented by probabilistic tractography and the association of the fractional anisotropy (FA) within was tested against physical activity (PA) assessed by moderate-intensity physical activity of the International Physical Activity Questionnaire.Results: The FA and PA showed a positive association. Post-hoc analyses showed that the radial diffusivity (RD) of the CST was negatively associated with PA, suggesting a potential association with preserved myelination with PA.Conclusion: This study shows that the integrity of the CST is associated with its traffic in the general population.

Minimisation of Signal Intensity Differences in Distortion Correction Approaches of Brain Magnetic Resonance Diffusion Tensor Imaging.

OBJECTIVES: To evaluate the effects of signal intensity differences between the b0 image and diffusion tensor imaging (DTI) in the image registration process. METHODS: To correct signal intensity differences between the b0 image and DTI data, a simple image intensity compensation (SIMIC) method, which is a b0 image re-calculation process from DTI data, was applied before the image registration. The re-calculated b0 image (b0ext) from each diffusion direction was registered to the b0 image acquired through the MR scanning (b0nd) with two types of cost functions and their transformation matrices were acquired. These transformation matrices were then used to register the DTI data. For quantifications, the dice similarity coefficient (DSC) values, diffusion scalar matrix, and quantified fibre numbers and lengths were calculated. RESULTS: The combined SIMIC method with two cost functions showed the highest DSC value (0.802 ± 0.007). Regarding diffusion scalar values and numbers and lengths of fibres from the corpus callosum, superior longitudinal fasciculus, and cortico-spinal tract, only using normalised cross correlation (NCC) showed a specific tendency toward lower values in the brain regions. CONCLUSION: Image-based distortion correction with SIMIC for DTI data would help in image analysis by accounting for signal intensity differences as one additional option for DTI analysis. KEY POINTS: • We evaluated the effects of signal intensity differences at DTI registration. • The non-diffusion-weighted image re-calculation process from DTI data was applied. • SIMIC can minimise the signal intensity differences at DTI registration.

Does stroke location predict walk speed response to gait rehabilitation?

OBJECTIVES: Recovery of independent ambulation after stroke is a major goal. However, which rehabilitation regimen best benefits each individual is unknown and decisions are currently made on a subjective basis. Predictors of response to specific therapies would guide the type of therapy most appropriate for each patient. Although lesion topography is a strong predictor of upper limb response, walking involves more distributed functions. Earlier studies that assessed the cortico-spinal tract (CST) were negative, suggesting other structures may be important. EXPERIMENTAL DESIGN: The relationship between lesion topography and response of walking speed to standard rehabilitation was assessed in 50 adult-onset patients using both volumetric measurement of CST lesion load and voxel-based lesion-symptom mapping (VLSM) to assess non-CST structures. Two functional mobility scales, the functional ambulation category (FAC) and the modified rivermead mobility index (MRMI) were also administered. Performance measures were obtained both at entry into the study (3-42 days post-stroke) and at the end of a 6-week course of therapy. Baseline score, age, time since stroke onset and white matter hyperintensities score were included as nuisance covariates in regression models. PRINCIPAL OBSERVATIONS: CST damage independently predicted response to therapy for FAC and MRMI, but not for walk speed. However, using VLSM the latter was predicted by damage to the putamen, insula, external capsule and neighbouring white matter. CONCLUSIONS: Walk speed response to rehabilitation was affected by damage involving the putamen and neighbouring structures but not the CST, while the latter had modest but significant impact on everyday functions of general mobility and gait. Hum Brain Mapp 37:689-703, 2016. © 2015 Wiley Periodicals, Inc.

Localization of function-specific segments of the primary motor pathway in children with Sturge-Weber syndrome: a multimodal imaging analysis.

PURPOSE: To explore whether diffusion-weighted imaging (DWI) can localize specific segments of primary motor areas in children with Sturge-Weber syndrome (SWS), this study investigated the corticospinal tract (CST) between precentral gyrus (PCG) and posterior limb of internal capsule (PIC). MATERIALS AND METHODS: DWI was performed on 32 healthy children and seven children with unilateral SWS affecting the sensorimotor area variably. A hierarchical dendrogram was applied to find PCG-segments uniquely connected to PIC-segments. The resulting PCG-clusters were used to image primary motor pathways in DWI and find metabolic abnormalities of primary motor areas in positron emission tomography (PET) scans. RESULTS: In healthy children, five PCG-clusters were found to have unique CST courses, corresponding to CST segments of mouth/lip, fingers, and leg/ankle primary motor areas determined by functional magnetic resonance imaging (fMRI). In children with SWS, reduced streamlines in these PCG clusters were highly correlated with glucose-hypometabolism on PET (R(2) = 0.2312, P = 0.0032). Impaired CST segment corresponding to finger movements correlated with severity of hand motor deficit. CONCLUSION: The presented method can detect impaired CST segments corresponding to specific motor functions in young children who cannot cooperate for fMRI. This approach can be clinically useful for a noninvasive presurgical evaluation of cortical motor areas in such children.

Correlation of Immune-Inflammatory Response System (IRS)/Compensatory Immune-Regulatory Reflex System (CIRS) with White Matter Integrity in First-Episode Patients with Schizophrenia.

Several studies have reported compromised white matter integrity, and that some inflammatory mediators may underlie this functional dysconnectivity in the brain of patients with schizophrenia. The immune-inflammatory response system and compensatory immune-regulatory reflex system (IRS/CIRS) are novel biomarkers for exploring the role of immune imbalance in the pathophysiological mechanism of schizophrenia. This study aimed to explore the little-known area regarding the composite score of peripheral cytokines, the IRS/CIRS, and its correlation with white matter integrity and the specific microstructures most affected in schizophrenia. First-episode patients with schizophrenia (FEPS, n = 94) and age- and sex-matched healthy controls (HCs, n = 50) were enrolled in this study. Plasma cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). The whole brain white matter integrity was measured by fractional anisotropy (FA) from diffusion tensor imaging (DTI) using a 3-T Prisma MRI scanner. The IRS/CIRS in FEPS was significantly higher than that in HCs (p = 1.5 × 10-5) and Cohen's d effect size was d = 0.74. FEPS had a significantly lower whole-brain white matter average FA (p = 0.032), which was negatively associated with IRS/CIRS (p = 0.029, adjusting for age, sex, years of education, BMI, and total intracranial volume), but not in the HCs (p > 0.05). Among the white matter microstructures, only the cortico-spinal tract was significantly correlated with IRS/CIRS in FEPS (r = - 0.543, p = 0.0009). Therefore, elevated IRS/CIRS may affect the white matter in FEPS.

Test-retest reliability of cortico-spinal measurements in the rectus femoris at different contraction levels.

Single-pulse Transcranial Magnetic Stimulation (TMS) and, very recently, lumbar stimulation (LS) have been used to measure cortico-spinal excitability from various interventions using maximal or submaximal contractions in the lower limbs. However, reliability studies have overlooked a wide range of contraction intensities for MEPs, and no reliability data is available for LEPs. This study investigated the reliability of motor evoked potentials and lumbar evoked potentials at different stimulation intensities and contraction levels in m.rectus femoris. Twenty-two participants performed non-fatiguing isometric knee extensions at 20 and 60% of maximum voluntary contraction (MVC). LS induced a lumbar-evoked potential (LEP) of 25 and 50% resting maximal compound action potential (M-max). TMS stimulator output was adjusted to 120, 140, and 160% of active motor threshold (aMT). In each contraction, a single MEP or LEP was delivered. Ten contractions were performed at each stimulator intensity and contraction level in random order. Moderate-to-good reliability was found when LEP was normalized to M-max/Root Mean Square in all conditions (ICC:0.74-0.85). Excellent reliability was found when MEP was normalized to Mmax for all conditions (ICC > 0.90) at 60% of MVC. Good reliability was found for the rest of the TMS conditions. Moderate-to-good reliability was found for silent period (SP) elicited by LS (ICC: 0.71-0.83). Good-to-excellent reliability was found for SP elicited by TMS (ICC > 0.82). MEPs and LEPs elicited in m.rectus femoris appear to be reliable to assess changes at different segments of the cortico-spinal tract during different contraction levels and stimulator output intensities. Furthermore, the TMS- and LS- elicited SP was a reliable tool considered to reflect inhibitory processes at spinal and cortical levels.

Increased intensity of unintended mirror muscle contractions after cervical spinal cord injury is associated with changes in interhemispheric and corticomuscular coherences.

Mirror contractions refer to unintended contractions of the contralateral homologous muscles during voluntary unilateral contractions or movements. Exaggerated mirror contractions have been found in several neurological diseases and indicate dysfunction or lesion of the cortico-spinal pathway. The present study investigates mirror contractions and the associated interhemispheric and corticomuscular interactions in adults with spinal cord injury (SCI) - who present a lesion of the cortico-spinal tract - compared to able-bodied participants (AB). Eight right-handed adults with chronic cervical SCI and ten age-matched right-handed able-bodied volunteers performed sets of right elbow extensions at 20% of maximal voluntary contraction. Electromyographic activity (EMG) of the right and left elbow extensors, interhemispheric coherence over cerebral sensorimotor regions evaluated by electroencephalography (EEG) and corticomuscular coherence between signals over the cerebral sensorimotor regions and each extensor were quantified. Overall, results revealed that participants with SCI exhibited (1) increased EMG activity of both active and unintended active limbs, suggesting more mirror contractions, (2) reduced corticomuscular coherence between signals over the left sensorimotor region and the right active limb and increased corticomuscular coherence between the right sensorimotor region and the left unintended active limb, (3) decreased interhemispheric coherence between signals over the two sensorimotor regions. The increased corticomuscular communication and decreased interhemispheric communication may reflect a reduced inhibition leading to increased communication with the unintended active limb, possibly resulting to exacerbated mirror contractions in SCI. Finally, mirror contractions could represent changes of neural and neuromuscular communication after SCI.

Mutation of Tyrosine Sites in the Human Alpha-Synuclein Gene Induces Neurotoxicity in Transgenic Mice with Soluble Alpha-Synuclein Oligomer Formation.

Overexpression of α-synuclein with tyrosine mutated to phenylalanine at position 125 leads to a severe phenotype with motor impairment and neuropathology in Drosophila. Here, we hypothesized that tyrosine mutations would similarly lead to impaired motor performance with neuropathology in a rodent model. In transgenic mice (ASO), tyrosines at positions 125, 133, and 136 in human α-synuclein were mutated to phenylalanine and cloned into a Thy1.2 expression vector, which was used to create transgenic mouse lines on a mixed genetic background TgN(Thy-1-SNCA-YF)4Emfu (YF). The YF mice had a decreased lifespan and displayed a dramatic motor phenotype with paralysis of both hind- and forelegs. Post-translational modification of α-synuclein due to phosphorylation of serine 129 is often seen in inclusions in the brains of patients with α-synucleinopathies. We observed a slight but significant increase in phosphorylation of serine 129 in the cytosol in YF mice compared to age-matched human α-synuclein transgenic mice (ASO). Conversely, significantly decreased phosphorylation of serine 129 was seen in synaptosomes of YF mice that also contained higher amounts of soluble oligomers. YF mice deposited full-length α-synuclein aggregates in neurons widespread in the CNS with the main occurrence in the forebrain structures of the cerebral cortex, the basal ganglia, and limbic structures. Full-length α-synuclein labeling was also prominent in many nuclear regions of the brain stem, deep cerebellar nuclei, and cerebellar cortex. The study shows that the substitution of tyrosines to phenylalanine in α-synuclein at positions 125, 133, and 136 leads to severe toxicity in vivo. An insignificant change upon tyrosine substitution suggests that the phosphorylation of serine 129 is not the cause of the toxicity.

Tracking the Re-organization of Motor Functions After Disconnective Surgery: A Longitudinal fMRI and DTI Study.

Objective: Mechanisms of motor plasticity are critical to maintain motor functions after cerebral damage. This study explores the mechanisms of motor reorganization occurring before and after surgery in four patients with drug-refractory epilepsy candidate to disconnective surgery. Methods: We studied four patients with early damage, who underwent tailored hemispheric surgery in adulthood, removing the cortical motor areas and disconnecting the corticospinal tract (CST) from the affected hemisphere. Motor functions were assessed clinically, with functional MRI (fMRI) tasks of arm and leg movement and Diffusion Tensor Imaging (DTI) before and after surgery with assessments of up to 3 years. Quantifications of fMRI motor activations and DTI fractional anisotropy (FA) color maps were performed to assess the lateralization of motor network. We hypothesized that lateralization of motor circuits assessed preoperatively with fMRI and DTI was useful to evaluate the motor outcome in these patients. Results: In two cases preoperative DTI-tractography did not reconstruct the CST, and FA-maps were strongly asymmetric. In the other two cases, the affected CST appeared reduced compared to the contralateral one, with modest asymmetry in the FA-maps. fMRI showed different degrees of lateralization of the motor network and the SMA of the intact hemisphere was mostly engaged in all cases. After surgery, patients with a strongly lateralized motor network showed a stable performance. By contrast, a patient with a more bilateral pattern showed worsening of the upper limb function. For all cases, fMRI activations shifted to the intact hemisphere. Structural alterations of motor circuits, observed with FA values, continued beyond 1 year after surgery. Conclusion: In our case series fMRI and DTI could track the longitudinal reorganization of motor functions. In these four patients the more the paretic limbs recruited the intact hemisphere in primary motor and associative areas, the greater the chances were of maintaining elementary motor functions after adult surgery. In particular, DTI-tractography and quantification of FA-maps were useful to assess the lateralization of motor network. In these cases reorganization of motor connectivity continued for long time periods after surgery.

3D microsurgical anatomy of the cortico-spinal tract and lemniscal pathway based on fiber microdissection and demonstration with tractography. / Anatomía microquirúrgica en 3D del tracto corticoespinal y de la vía del lemnisco basada en microdisección de fibras y demostración a través de tractografía.

OBJECTIVE: To demonstrate tridimensionally the anatomy of the cortico-spinal tract and the medial lemniscus, based on fiber microdissection and diffusion tensor tractography (DTT). MATERIAL AND METHODS: Ten brain hemispheres and brain-stem human specimens were dissected and studied under the operating microscope with microsurgical instruments by applying the fiber microdissection technique. Brain magnetic resonance imaging was obtained from 15 healthy subjects using diffusion-weighted images, in order to reproduce the cortico-spinal tract and the lemniscal pathway on DTT images. RESULTS: The main bundles of the cortico-spinal tract and medial lemniscus were demonstrated and delineated throughout most of their trajectories, noticing their gross anatomical relation to one another and with other white matter tracts and gray matter nuclei the surround them, specially in the brain-stem; together with their corresponding representation on DTT images. CONCLUSIONS: Using the fiber microdissection technique we were able to distinguish the disposition, architecture and general topography of the cortico-spinal tract and medial lemniscus. This knowledge has provided a unique and profound anatomical perspective, supporting the correct representation and interpretation of DTT images. This information should be incorporated in the clinical scenario in order to assist surgeons in the detailed and critic analysis of lesions located inside the brain-stem, and therefore, improve the surgical indications and planning, including the preoperative selection of optimal surgical strategies and possible corridors to enter the brainstem, to achieve safer and more precise microsurgical technique.

Investigating structure and function in the healthy human brain: validity of acute versus chronic lesion-symptom mapping.

Modern voxel-based lesion-symptom mapping (VLSM) analyses techniques provide powerful tools to examine the relationship between structure and function of the healthy human brain. However, there is still uncertainty on the type of and the appropriate time point of imaging and of behavioral testing for such analyses. Here we tested the validity of the three most common combinations of structural imaging data and behavioral scores used in VLSM analyses. Given the established knowledge about the neural substrate of the primary motor system in humans, we asked the mundane question of where the motor system is represented in the normal human brain, analyzing individual arm motor function of 60 unselected stroke patients. Only the combination of acute behavioral scores and acute structural imaging precisely identified the principal brain area for the emergence of hemiparesis after stroke, i.e., the corticospinal tract (CST). In contrast, VLSM analyses based on chronic behavior-in combination with either chronic or acute imaging-required the exclusion of patients who had recovered from an initial paresis to reveal valid anatomical results. Thus, if the primary research aim of a VLSM lesion analysis is to uncover the neural substrates of a certain function in the healthy human brain and if no longitudinal designs with repeated evaluations are planned, the combination of acute imaging and behavior represents the ideal dataset.

DTI measures identify mild and moderate TBI cases among patients with complex health problems: A receiver operating characteristic analysis of U.S. veterans.

Standard MRI methods are often inadequate for identifying mild traumatic brain injury (TBI). Advances in diffusion tensor imaging now provide potential biomarkers of TBI among white matter fascicles (tracts). However, it is still unclear which tracts are most pertinent to TBI diagnosis. This study ranked fiber tracts on their ability to discriminate patients with and without TBI. We acquired diffusion tensor imaging data from military veterans admitted to a polytrauma clinic (Overall n = 109; Age: M = 47.2, SD = 11.3; Male: 88%; TBI: 67%). TBI diagnosis was based on self-report and neurological examination. Fiber tractography analysis produced 20 fiber tracts per patient. Each tract yielded four clinically relevant measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity). We applied receiver operating characteristic (ROC) analyses to identify the most diagnostic tract for each measure. The analyses produced an optimal cutpoint for each tract. We then used kappa coefficients to rate the agreement of each cutpoint with the neurologist's diagnosis. The tract with the highest kappa was most diagnostic. As a check on the ROC results, we performed a stepwise logistic regression on each measure using all 20 tracts as predictors. We also bootstrapped the ROC analyses to compute the 95% confidence intervals for sensitivity, specificity, and the highest kappa coefficients. The ROC analyses identified two fiber tracts as most diagnostic of TBI: the left cingulum (LCG) and the left inferior fronto-occipital fasciculus (LIF). Like ROC, logistic regression identified LCG as most predictive for the FA measure but identified the right anterior thalamic tract (RAT) for the MD, RD, and AD measures. These findings are potentially relevant to the development of TBI biomarkers. Our methods also demonstrate how ROC analysis may be used to identify clinically relevant variables in the TBI population.

Acupuncture Increases the Excitability of the Cortico-Spinal System in Patients with Chronic Disorders of Consciousness Following Traumatic Brain Injury.

OBJECTIVE: To evaluate the immediate effect of acupuncture on cortico spinal tract (CST) activity in patients with chronic disorders of consciousness (DOC) after traumatic brain injury (TBI) by measuring motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS). DESIGN: Changes in several variables in the acupuncture session were compared with those in the control session without acupuncture in the same patients. SETTING: Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Gifu, Japan. PATIENTS: Fourteen patients (mean age ± standard deviation, 39 ± 17 years; 12 men) with chronic DOC (5 in a vegetative state and 9 in a minimally conscious state) following severe TBI. INTERVENTION: Acupuncture treatment was performed at GV 26, Ex-HN 3, bilateral LI 4, and ST 36 for 10 minutes. OUTCOME MEASURES: Main outcome measure was MEP amplitude. MEP amplitude, measured by using TMS on the primary motor cortex, was recorded from the abductor pollicis brevis muscle. MEP recordings were performed before acupuncture (baseline), 10 minutes after needle insertion (phase 1), and 10 minutes after needle removal (phase 2). As a control, the same procedure without acupuncture was performed on another day with the order randomized. MEP amplitude and latency were calculated. Evoked F-wave measurements were also performed to calculate maximum M-wave amplitude (Mmax), M-wave latency, and F-wave latency in the same muscle. Central motor conduction time (CMCT) and MEP/Mmax ratio were also calculated from the MEP and F-wave measurement data. RESULTS: MEP amplitude and MEP/Mmax were increased significantly in the acupuncture session at phases 1 and 2 compared with the control session (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). CMCTs were reduced at phases 1 and 2 in the acupuncture session compared with the control session, and the change at phase 1 was statistically significant (P = 0.002). CONCLUSIONS: Acupuncture treatment increased the CST activity of patients with chronic DOC after severe TBI.

A majority rule approach for region-of-interest-guided streamline fiber tractography.

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.