Neural ensemble dynamics in trunk and hindlimb sensorimotor cortex encode for the control of postural stability.

The cortex has a disputed role in monitoring postural equilibrium and intervening in cases of major postural disturbances. Here, we investigate the patterns of neural activity in the cortex that underlie neural dynamics during unexpected perturbations. In both the primary sensory (S1) and motor (M1) cortices of the rat, unique neuronal classes differentially covary their responses to distinguish different characteristics of applied postural perturbations; however, there is substantial information gain in M1, demonstrating a role for higher-order computations in motor control. A dynamical systems model of M1 activity and forces generated by the limbs reveals that these neuronal classes contribute to a low-dimensional manifold comprised of separate subspaces enabled by congruent and incongruent neural firing patterns that define different computations depending on the postural responses. These results inform how the cortex engages in postural control, directing work aiming to understand postural instability after neurological disease.

Exercise therapy guides cortical reorganization after midthoracic spinal contusion to enhance control of lower thoracic muscles, supporting functional recovery.

Postural control is critical for locomotion, allowing for gait changes, obstacle avoidance and navigation of rough terrain. A major problem after spinal cord injury (SCI) is regaining the control of balance to prevent falls and further injury. While the circuits for locomotor pattern generation reside in the spinal cord, postural control consists of multiple, complex networks that interact at the spinal, brainstem and cortical levels. After complete SCI, cortical reorganization establishes novel control of trunk musculature that is required for weight-supported stepping. In this study, we examined the impact of exercise therapy on cortical reorganization in the more clinically relevant models of both moderate and severe midthoracic contusion injury in the rat. Results demonstrate that both spontaneous recovery and therapy induced recovery of weight-supported stepping utilize cortical reorganization. Moreover, exercise therapy further improves outcome by enhancing cortical control of lower thoracic muscles enabling improvements in interlimb coordination associated with improved balance that increases weight-supported stepping. The outcome of this study suggest that cortical control of posture is key to functional improvement in locomotion. This information can be used to improve the timing and type of therapy after SCI by considering changes along the entire neural axis.

Effect of spinal cord injury on neural encoding of spontaneous postural perturbations in the hindlimb sensorimotor cortex.

Supraspinal signals play a significant role in compensatory responses to postural perturbations. Although the cortex is not necessary for basic postural tasks in intact animals, its role in responding to unexpected postural perturbations after spinal cord injury (SCI) has not been studied. To better understand how SCI impacts cortical encoding of postural perturbations, the activity of single neurons in the hindlimb sensorimotor cortex (HLSMC) was recorded in the rat during unexpected tilts before and after a complete midthoracic spinal transection. In a subset of animals, limb ground reaction forces were also collected. HLSMC activity was strongly modulated in response to different tilt profiles. As the velocity of the tilt increased, more information was conveyed by the HLSMC neurons about the perturbation due to increases in both the number of recruited neurons and the magnitude of their responses. SCI led to attenuated and delayed hindlimb ground reaction forces. However, HLSMC neurons remained responsive to tilts after injury but with increased latencies and decreased tuning to slower tilts. Information conveyed by cortical neurons about the tilts was therefore reduced after SCI, requiring more cells to convey the same amount of information as before the transection. Given that reorganization of the hindlimb sensorimotor cortex in response to therapy after complete midthoracic SCI is necessary for behavioral recovery, this sustained encoding of information after SCI could be a substrate for the reorganization that uses sensory information from above the lesion to control trunk muscles that permit weight-supported stepping and postural control.NEW & NOTEWORTHY The role of cortical circuits in the encoding of posture and balance is of interest for developing therapies for spinal cord injury. This work demonstrated that unexpected postural perturbations are encoded in the hindlimb sensorimotor cortex even in the absence of hindlimb sensory feedback. In fact, the hindlimb sensorimotor cortex continues to encode for postural perturbations after complete spinal transection.

Antidepressant treatment history and drug-placebo separation in a placebo-controlled trial in major depressive disorder.

RATIONALE: A history of antidepressant treatment may predispose subjects toward placebo nonresponse in randomized controlled trials (RCTs) in major depressive disorder (MDD). OBJECTIVE: The objective of this study is to examine self-reported prior antidepressant treatment and response in relationship to clinical outcome in an 8-week randomized trial of reuptake inhibitor antidepressant medication (MED) versus placebo (PBO) administered along with limited supportive care. METHODS: Chi-square and MMRM analyses examined MED vs. PBO outcomes in antidepressant-naïve vs. antidepressant-experienced subjects. Linear regression models examined treatment history along with covariates as predictors of clinical improvement. RESULTS: Among completers (n = 56), there was no significant difference in response rate between MED (53.3 %) and PBO (42.3 %) (χ (2) = 0.33, p = 0.28, 1-tailed). The antidepressant-experienced subgroup (n = 37), however, showed a significantly greater response rate to MED (52.4 %) than PBO (25.0 %) (χ (2) = 2.82, p = 0.047, 1-tailed). The full intent-to-treat (ITT) sample (n = 69) did not show a significant difference between MED and PBO group improvement over time, but in the treatment-experienced subgroup (n = 46), MED showed significantly greater improvement than PBO (coefficient = .39, SE = .23, p = .045, 1-tailed). A history of prior antidepressant treatment predicted poorer overall response independent of pretreatment symptom severity, number or length of previous episodes, subject expectations, or family history of MDD. CONCLUSIONS: Treatment history appears to constitute a factor that is distinct from other commonly studied illness characteristics or expectancy measures, and that impacts overall response as well as drug-placebo separation in RCTs.