Dhakshin S. Ramanathan

The Role of Spatial Attention in the Selection of Real and Illusory Objects

Selective attention may be flexibly directed toward particular locations in the visual field (spatial attention) or to entire object configurations (object-based attention). A key question is whether spatial attention plays a direct role in the selection of objects, perhaps by spreading its facilitatory influence throughout the boundaries of an object. We studied the relationship between spatial and object-based attention in a design in which subjects attended to brief offsets of one corner of a real or illusory square form. Object-selective attention was indexed by differences in event-related potential (ERP) amplitudes and blood oxygen level-dependent (BOLD) activations to unattended corner offsets in conditions in which the objects were intact versus fragmented or absent. This design ensured that object-based attention effects were not an artifact of attention being guided by simple directional cues such as parallel lines, which may have occurred in previous studies. Both space-based and object-based attention were associated with enhanced negative ERPs (N1 component at 140–180 ms) that were colocalized with BOLD activations in lateral occipital cortex (LOC). These results provide physiological evidence that directing spatial attention to one part of an object (whether real or illusory) facilitates the processing of the entire object at the level of the LOC and thus contributes directly to object-based selective attention.

The basal forebrain cholinergic system is required specifically for behaviorally mediated cortical map plasticity.

The basal forebrain cholinergic system has been implicated in the reorganization of adult cortical sensory and motor representations under many, but not all, experimental conditions. It is still not fully understood which types of plasticity require the cholinergic system and which do not. In this study, we examine the hypothesis that the basal forebrain cholinergic system is required for eliciting plasticity associated with complex cognitive processing (e.g., behavioral experiences that drive cortical reorganization) but is not required for plasticity mediated under behaviorally independent conditions. We used established experimental manipulations to elicit two distinct forms of plasticity within the motor cortex: facial nerve transections evoke reorganization of cortical motor representations independent of behavioral experience, and skilled forelimb training induces behaviorally dependent expansion of forelimb motor representations. In animals that underwent skilled forelimb training in conjunction with a facial nerve lesion, cholinergic mechanisms were required for mediating the behaviorally dependent plasticity associated with the skilled motor training but were not necessary for mediating plasticity associated with the facial nerve transection. These results dissociate the contribution of cholinergic mechanisms to distinct forms of cortical plasticity and support the hypothesis that the forebrain cholinergic system is selectively required for modulating complex forms of cortical plasticity driven by behavioral experience.

Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation

Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep, the underlying neural mechanisms remain poorly understood. To investigate the neurophysiological basis for offline gains, we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb task. We found that sleep improved movement speed with preservation of accuracy. These offline improvements were linked to both replay of task-related ensembles during non-rapid eye movement (NREM) sleep and temporal shifts that more tightly bound motor cortical ensembles to movements; such offline gains and temporal shifts were not evident with sleep restriction. Interestingly, replay was linked to the coincidence of slow-wave events and bursts of spindle activity. Neurons that experienced the most consistent replay also underwent the most significant temporal shift and binding to the motor task. Significantly, replay and the associated performance gains after sleep only occurred when animals first learned the skill; continued practice during later stages of learning (i.e., after motor kinematics had stabilized) did not show evidence of replay. Our results highlight how replay of synchronous neural activity during sleep mediates large-scale neural plasticity and stabilizes kinematics during early motor learning.

Robust Neuroprosthetic Control from the Stroke Perilesional Cortex

Intracortical brain–machine interfaces (BMIs) may eventually restore function in those with motor disability after stroke. However, current research into the development of intracortical BMIs has focused on subjects with largely intact cortical structures, such as those with spinal cord injury. Although the stroke perilesional cortex (PLC) has been hypothesized as a potential site for a BMI, it remains unclear whether the injured motor cortical network can support neuroprosthetic control directly. Using chronic electrophysiological recordings in a rat stroke model, we demonstrate here the PLCs capacity for neuroprosthetic control and physiological plasticity. We initially found that the perilesional network demonstrated abnormally increased slow oscillations that also modulated neural firing. Despite these striking abnormalities, neurons in the perilesional network could be modulated volitionally to learn neuroprosthetic control. The rate of learning was surprisingly similar regardless of the electrode distance from the stroke site and was not significantly different from intact animals. Moreover, neurons achieved similar task-related modulation and, as an ensemble, formed cell assemblies with learning. Such control was even achieved in animals with poor motor recovery, suggesting that neuroprosthetic control is possible even in the absence of motor recovery. Interestingly, achieving successful control also reduced locking to abnormal oscillations significantly. Our results thus suggest that, despite the disrupted connectivity in the PLC, it may serve as an effective target for neuroprosthetic control in those with poor motor recovery after stroke.

An automated behavioral box to assess forelimb function in rats

BACKGROUND Rodent forelimb reaching behaviors are commonly assessed using a single-pellet reach-to-grasp task. While the task is widely recognized as a very sensitive measure of distal limb function, it is also known to be very labor-intensive, both for initial training and the daily assessment of function. NEW METHOD Using components developed by open-source electronics platforms, we have designed and tested a low-cost automated behavioral box to measure forelimb function in rats. Our apparatus, made primarily of acrylic, was equipped with multiple sensors to control the duration and difficulty of the task, detect reach outcomes, and dispense pellets. Our control software, developed in MATLAB, was also used to control a camera in order to capture and process video during reaches. Importantly, such processing could monitor task performance in near real-time. RESULTS We further demonstrate that the automated apparatus can be used to expedite skill acquisition, thereby increasing throughput as well as facilitating studies of early versus late motor learning. The setup is also readily compatible with chronic electrophysiological monitoring. COMPARISON WITH EXISTING METHODS Compared to a previous version of this task, our setup provides a more efficient method to train and test rodents for studies of motor learning and recovery of function after stroke. The unbiased delivery of behavioral cues and outcomes also facilitates electrophysiological studies. CONCLUSIONS In summary, our automated behavioral box will allow high-throughput and efficient monitoring of rat forelimb function in both healthy and injured animals.

Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia.

Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation.Recovery of skilled motor function in rodents after stroke correlates with the restoration of low-frequency quasi-oscillatory activity in the motor cortex, and neuromodulatory electrical stimulation targeting this activity can further accelerate recovery.