Task-phase-specific dynamics of basal forebrain neuronal ensembles.

Cortically projecting basal forebrain neurons play a critical role in learning and attention, and their degeneration accompanies age-related impairments in cognition. Despite the impressive anatomical and cell-type complexity of this system, currently available data suggest that basal forebrain neurons lack complexity in their response fields, with activity primarily reflecting only macro-level brain states such as sleep and wake, onset of relevant stimuli and/or reward obtainment. The current study examined the spiking activity of basal forebrain neuron populations across multiple phases of a selective attention task, addressing, in particular, the issue of complexity in ensemble firing patterns across time. Clustering techniques applied to the full population revealed a large number of distinct categories of task-phase-specific activity patterns. Unique population firing-rate vectors defined each task phase and most categories of task-phase-specific firing had counterparts with opposing firing patterns. An analogous set of task-phase-specific firing patterns was also observed in a population of posterior parietal cortex neurons. Thus, consistent with the known anatomical complexity, basal forebrain population dynamics are capable of differentially modulating their cortical targets according to the unique sets of environmental stimuli, motor requirements, and cognitive processes associated with different task phases

Simulation of cholinergic and noradrenergic modulation of behavior in uncertain environments

Attention is a complex neurobiological process that involves rapidly and flexibly balancing sensory input and goal-directed predictions in response to environmental changes. The cholinergic and noradrenergic systems, which have been proposed to respond to expected and unexpected environmental uncertainty, respectively, play an important role in attention by differentially modulating activity in a multitude of cortical targets. Here we develop a model of an attention task that involves expected and unexpected uncertainty. The cholinergic and noradrenergic systems track this uncertainty and, in turn, influence cortical processing in five different, experimentally verified ways: (1) nicotinic enhancement of thalamocortical input, (2) muscarinic regulation of corticocortical feedback, (3) noradrenergic mediation of a network reset, (4) locus coeruleus (LC) activation of the basal forebrain (BF), and (5) cholinergic and noradrenergic balance between sensory input and frontal cortex predictions. Our results shed light on how the noradrenergic and cholinergic systems interact with each other and a distributed set of neural areas, and how this could lead to behavioral adaptation in the face of uncertainty

Basal forebrain cholinergic lesions disrupt increments but not decrements in conditioned stimulus processing

Magnocellular neurons in the basal forebrain provide the major cholinergic innervation of cortex. Recent research suggests that this cholinergic system plays an important role in the regulation of attentional processes. The present study examined the ability of rats with selective immunotoxic lesions of these neurons (made with 192 IgG- saporin) to modulate attention within an associative learning framework. Each rat was exposed to conditioned stimuli (CS) that were either consistent or inconsistent predictors of subsequent cues. Intact control rats showed increased CS associability when that cue was an inconsistent predictor of a subsequent cue, whereas lesioned rats were impaired in increasing attention to the CS when its established relation to another cue was modified. In a separate experiment designed to test latent inhibition, it was shown that removal of the corticopetal cholinergic neurons spared a decrement in associability that occurs when rats are extensively preexposed to a CS prior to conditioning. These data indicate that the cholinergic innervation of cortex is critical for incrementing, but not for decrementing attentional processing. The specific behavioral tests used to assess the role of the basal forebrain cholinergic system in the present study were previously used to identify a role for the amygdala central nucleus in attention (Holland and Gallagher, 1993b). Those studies, together with the results in this report, indicate that regulation of attentional processes during associative learning may be mediated by projections from the amygdala to the basal forebrain cholinergic system

When rats rescue robots

Robots are increasingly being used to monitor and even participate in social interactions with animals in their own environments. Robotic animals enable social behaviors to be observed in natural environments, or specifically elicited under the control of an experimenter. It is an open question to what extent animals will form positive social connections with such robots. To test this, we familiarized rats to two rat-sized robots, one exhibiting “social” behaviors, including helping, while the other was also mobile but not helpful. When given an opportunity to release the robots from restrainers, as they do for conspecifics, we found that rats did release the robots, and moreover, were significantly more likely to release the helpful than the unhelpful robot. These findings indicate that robots can elicit helpful behavior from rats, and that rats will even discriminate between robots on the basis of their behaviors

A Clinical Practice Guideline for the Management of Patients With Degenerative Cervical Myelopathy: Recommendations for Patients With Mild, Moderate, and Severe Disease and Nonmyelopathic Patients With Evidence of Cord Compression.

Study Design: Guideline development. Objectives: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. Methods: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the management of degenerative cervical myelopathy (DCM). Results: Our recommendations were as follows: (1) "We recommend surgical intervention for patients with moderate and severe DCM." (2) "We suggest offering surgical intervention or a supervised trial of structured rehabilitation for patients with mild DCM. If initial nonoperative management is pursued, we recommend operative intervention if there is neurological deterioration and suggest operative intervention if the patient fails to improve." (3) "We suggest not offering prophylactic surgery for non-myelopathic patients with evidence of cervical cord compression without signs or symptoms of radiculopathy. We suggest that these patients be counseled as to potential risks of progression, educated about relevant signs and symptoms of myelopathy, and be followed clinically." (4) "Non-myelopathic patients with cord compression and clinical evidence of radiculopathy with or without electrophysiological confirmation are at a higher risk of developing myelopathy and should be counselled about this risk. We suggest offering either surgical intervention or nonoperative treatment consisting of close serial follow-up or a supervised trial of structured rehabilitation. In the event of myelopathic development, the patient should be managed according to the recommendations above." Conclusions: These guidelines will promote standardization of care for patients with DCM, decrease the heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions

A clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on the use of methylprednisolone sodium succinate

Introduction: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest." Results: The main conclusions from the systematic review included the following: (1) there were no differences in motor score change at any time point in patients treated with MPSS compared to those not receiving steroids; (2) when MPSS was administered within 8 hours of injury, pooled results at 6- and 12-months indicated modest improvements in mean motor scores in the MPSS group compared with the control group; and (3) there was no statistical difference between treatment groups in the risk of complications. Our recommendations were: (1) "We suggest not offering a 24-hour infusion of high-dose MPSS to adult patients who present after 8 hours with acute SCI"; (2) "We suggest a 24-hour infusion of high-dose MPSS be offered to adult patients within 8 hours of acute SCI as a treatment option"; and (3) "We suggest not offering a 48-hour infusion of high-dose MPSS to adult patients with acute SCI." Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in SCI patients

A clinical practice guideline for the management of patients with acute spinal cord injury and central cord syndrome: recommendations on the timing (<= 24 hours versus > 24 hours) of decompressive surgery

Objective: To develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome. Methods: A systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as "we recommend," whereas a weak recommendation is presented as "we suggest." Results: Conclusions from the systematic review included (1) isolated studies reported statistically significant and clinically important improvements following early decompression at 6 months and following discharge from inpatient rehabilitation; (2) in one study on acute central cord syndrome without instability, a marginally significant improvement in total motor scores was reported at 6 and 12 months in patients managed with early versus late surgery; and (3) there were no significant differences in length of acute care/rehabilitation stay or in rates of complications between treatment groups. Our recommendations were: "We suggest that early surgery be considered as a treatment option in adult patients with traumatic central cord syndrome" and "We suggest that early surgery be offered as an option for adult acute SCI patients regardless of level." Quality of evidence for both recommendations was considered low. Conclusions: These guidelines should be implemented into clinical practice to improve outcomes in patients with acute SCI and central cord syndrome by promoting standardization of care, decreasing the heterogeneity of management strategies, and encouraging clinicians to make evidence-informed decisions

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Role of Baseline Magnetic Resonance Imaging in Clinical Decision Making and Outcome Prediction

Introduction: The objective of this guideline is to outline the role of magnetic resonance imaging (MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI. This review focused on longitudinal studies that controlled for baseline neurologic status. A multidisciplinary Guideline Development Group (GDG) used this information, their clinical expertise, and patient input to develop recommendations on the use of MRI for SCI patients. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: Based on the limited available evidence and the clinical expertise of the GDG, our recommendations were: (1) “We suggest that MRI be performed in adult patients with acute SCI prior to surgical intervention, when feasible, to facilitate improved clinical decision-making” (quality of evidence, very low) and (2) “We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome” (quality of evidence, low). Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and prognostication for patients with SCI

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on the Type and Timing of Rehabilitation.

Introduction: The objective of this study is to develop guidelines that outline the appropriate type and timing of rehabilitation in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to rehabilitation in patients with acute SCI. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the type and timing of rehabilitation. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as "we recommend," whereas a weaker recommendation is indicated by "we suggest. Results: Based on the findings from the systematic review, our recommendations were: (1) We suggest rehabilitation be offered to patients with acute spinal cord injury when they are medically stable and can tolerate required rehabilitation intensity (no included studies; expert opinion); (2) We suggest body weight-supported treadmill training as an option for ambulation training in addition to conventional overground walking, dependent on resource availability, context, and local expertise (low evidence); (3) We suggest that individuals with acute and subacute cervical SCI be offered functional electrical stimulation as an option to improve hand and upper extremity function (low evidence); and (4) Based on the absence of any clear benefit, we suggest not offering additional training in unsupported sitting beyond what is currently incorporated in standard rehabilitation (low evidence). Conclusions: These guidelines should be implemented into clinical practice to improve outcomes and reduce morbidity in patients with SCI by promoting standardization of care, decreasing the heterogeneity of management strategies and encouraging clinicians to make evidence-informed decisions