The Symbol Digit Modalities Test (SDMT) is sensitive but non-specific in MS: Lexical access speed, memory, and information processing speed independently contribute to SDMT performance.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is the most sensitive metric of neurocognitive function in multiple sclerosis (MS), and is consistently interpreted as a measure of information processing speed (IPS). OBJECTIVE: To evaluate the cognitive psychometric profile captured by the SDMT to identify whether different cognitive processes independently underlie performance. METHODS: Three samples of MS patients (total n=661; 185 research patients at MS center; 370 clinical patients at MS center; 106 persons with MS from the community) completed objective assessments of neuropsychological function across cognitive domains. Exploratory factor analysis (EFA) was used to derive latent cognitive factor scores, and operationalize cognitive domain composite scores, to understand the unique, shared and redundant contribution of different cognitive domains to SDMT performance using hierarchical multiple regression and commonality analysis. RESULTS: Across three independent samples we provide converging strong evidence that the cognitive domains of Memory, IPS and Rapid Automatized Naming (lexical access speed) jointly and uniquely contribute to SDMT performance. CONCLUSION: The SDMT measures multiple cognitive processes, which likely explains the high degree of sensitivity to cognitive change in MS. Researchers and clinicians should interpret the SDMT as a multifarious measure of general cognition rather than a specific test of IPS.

Brief, prior, exposure to red decreases categorical and coordinate spatial task performance.

Location information is processed through two types of spatial processing; categorical and coordinate processing. Categorical spatial relations indicate where an object is relative to another object, without regard to the metric distance between the two objects. Coordinate spatial relations indicate metric distance without regard to relative location. In human behavioral studies, the magnocellular pathway of the lateral geniculate nucleus has been implicated in coordinate spatial processing abilities. Magnocellular pathway cells (type IV) have a center surround organization, such that red light inhibits neuronal firing. In these behavioral studies, red stimuli decreases coordinate spatial processing accuracy. Prior studies also show that there is a lag between the time of visual stimulus presentation and the time of observing a neural response in the magnocellular pathway. We sought to understand whether prior presentation of red stimuli decreases coordinate spatial performance, and also examined its effects on categorical spatial performance. The results indicate that prior presentation of red stimuli decreases accuracy and perceived confidence on both the categorical and coordinate tasks. These results confirm prior findings of the association between magnocellular pathway function and coordinate spatial processing. Implications for categorical task results and associated neural pathways are discussed.

Categorical and coordinate spatial task performance in inconsistent-handers versus consistent-right-handers: part II.

A previous study reported superior categorical and coordinate spatial task performance in inconsistent-versus consistent-right-handers (ICH versus CRH). Propper et al. used a three-dimensional (3D) computer-based task wherein individuals navigated to 21 locations within a realistic cityscape. During testing, participants were queried on their categorical and coordinate spatial knowledge of the map. In that study, the categorical and coordinate tasks may have inadvertently encouraged language coding of learned spatial information, potentially confounding spatial processing with recall ability for language-based information. Also, that study used a between-subjects design, which precludes examination of relationships between spatial knowledge as a function of handedness. The present study duplicated the learning task in Propper et al. using test stimuli that more faithfully represent spatial, and not language-based, information, as well as a within-subjects design. Results did not significantly replicate the previous study. Possible reasons for this finding are discussed.

Independent replication of motor cortex and cervical spinal cord electrical stimulation to promote forelimb motor function after spinal cord injury in rats.

Cervical spinal cord injury (SCI) impairs arm and hand function largely by interrupting descending tracts. Most SCI spare some axons at the lesion, including the corticospinal tract (CST), which is critical for voluntary movement. We targeted descending motor connections with paired electrical stimulation of motor cortex and cervical spinal cord in the rat. We sought to replicate the previously published effects of intermittent theta burst stimulation of forelimb motor cortex combined with trans-spinal direct current stimulation placed on the skin over the neck to target the cervical enlargement. We hypothesized that paired stimulation would improve performance in skilled walking and food manipulation (IBB) tasks. Rats received a moderate C4 spinal cord contusion injury (200 kDynes), which ablates the main CST. They were randomized to receive paired stimulation for 10 consecutive days starting 11 days after injury, or no stimulation. Behavior was assessed weekly from weeks 4-7 after injury, and then CST axons were traced. Rats with paired cortical and spinal stimulation achieved significantly better forelimb motor function recovery, as measured by fewer stepping errors on the horizontal ladder task (34 ±â€¯9% in stimulation group vs. 51 ±â€¯18% in control, p = .013) and higher scores on the food manipulation task (IBB, 0-9 score; 7.2 ±â€¯0.8 in stimulated rats vs. 5.2 ±â€¯2.6 in controls, p = .025). The effect size for both tasks was large (Cohen's d = 1.0 and 0.92, respectively). The CST axon length in the cervical spinal cord did not differ significantly between the groups, but there was denser and broader ipsilateral axons distribution distal to the spinal cord injury. The large behavioral effect and replication in an independent laboratory validate this approach, which will be trialed in cats before being tested in people using non-invasive methods.

Corrigendum: Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

[This corrects the article DOI: 10.3389/fncir.2018.00028.].

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.