Can Anything Good Ever Come From Bearing Migraine Attacks? Suggestions for a Comprehensive Concept of Gain in Migraine.

PURPOSE OF REVIEW: The purpose of this review is to summarise the current state of knowledge concerning known types of gain, the reasons why patients might seek it, as well as implications for headache disorders. RECENT FINDINGS: Even though the subject has been studied in the past, it received less attention in recent years. There is no doubt that migraine is a highly disabling disorder. However, attacks sometimes may be beneficial for the migraine brain as a time-out from the daily routine. On the other hand, patients are often stigmatised as trying to satisfy other needs through their disease. These "other needs" may be the exaggerated seeking for attention and affection or an undue official sickness certificate and were named secondary gain. Striving for secondary gain denotes a behaviour that aims at benefiting from a disease in a way that is seen as inappropriate by others. The fact that the term has persisted in doctors' vocabulary for decades probably indicates that it designates a concept considered relevant by many. However, its usage is complicated by its usually imprecise definition. We found in a literature search that the strive for secondary gain is not limited to neurosis, might both occur consciously and unconsciously, sometimes may aim at financial gain and sometimes at social gain, and can either be potentially expected or readily obtained. This behaviour mainly seems to aim at shaping one's interactions with the environment. Its causes have not been elucidated completely, though, but "unrequited demands for love, attention and affection" have been postulated. The desire for social gain can be influenced by approaches based upon behavioural psychology. Broaching the issue of secondary gain may be beneficial in the daily clinical routine.

Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

A robotic platform to assess, guide and perturb rat forelimb movements.

Animal models are widely used to explore the mechanisms underlying sensorimotor control and learning. However, current experimental paradigms allow only limited control over task difficulty and cannot provide detailed information on forelimb kinematics and dynamics. Here we propose a novel robotic device for use in motor learning investigations with rats. The compact, highly transparent, three degree-of-freedom manipulandum is capable of rendering nominal forces of 2 N to guide or perturb rat forelimb movements, while providing objective and quantitative assessments of endpoint motor performance in a 50×30 mm(2) planar workspace. Preliminary experiments with six healthy rats show that the animals can be familiarized with the experimental setup and are able to grasp and manipulate the end-effector of the robot. Further, dynamic perturbations and guiding force fields (i.e., haptic tunnels) rendered by the device had significant influence on rat motor behavior (ANOVA, ). This approach opens up new research avenues for future characterizations of motor learning stages, both in healthy and in stroke models.

A small-scale robotic manipulandum for motor training in stroke rats.

The investigation and characterization of sensori-motor learning and execution represents a key objective for the design of optimal rehabilitation therapies following stroke. By supplying new tools to investigate sensorimotor learning and objectively assess recovery, robot assisted techniques have opened new lines of research in neurorehabilitation aiming to complement current clinical strategies. Human studies, however, are limited by the complex logistics, heterogeneous patient populations and large dropout rates. Rat models may provide a substitute to explore the mechanisms underlying these processes in humans with larger and more homogeneous populations. This paper describes the development and evaluation of a three-degrees-of-freedom robotic manipulandum to train and assess precision forelimb movement in rats before and after stroke. The mechanical design is presented based on the requirements of interaction with rat kinematics and kinetics. The characterization of the robot exhibits a compact, low friction device, with a sufficient bandwidth suitable for motor training studies with rodents. The manipulandum was integrated with an existing training environment for rodent experiments and a first study is currently underway.

Dopamine in motor cortex is necessary for skill learning and synaptic plasticity.

Preliminary evidence indicates that dopamine given by mouth facilitates the learning of motor skills and improves the recovery of movement after stroke. The mechanism of these phenomena is unknown. Here, we describe a mechanism by demonstrating in rat that dopaminergic terminals and receptors in primary motor cortex (M1) enable motor skill learning and enhance M1 synaptic plasticity. Elimination of dopaminergic terminals in M1 specifically impaired motor skill acquisition, which was restored upon DA substitution. Execution of a previously acquired skill was unaffected. Reversible blockade of M1 D1 and D2 receptors temporarily impaired skill acquisition but not execution, and reduced long-term potentiation (LTP) within M1, a form of synaptic plasticity critically involved in skill learning. These findings identify a behavioral and functional role of dopaminergic signaling in M1. DA in M1 optimizes the learning of a novel motor skill.

Speed of motor re-learning after experimental stroke depends on prior skill.

Many motor rehabilitation therapies are based on principles of motor learning. Motor learning depends on preliminary knowledge of the trained and other (similar) skills. This study sought to investigate the influence of prior skill knowledge on re-learning of a precision reaching skill after a cortical lesion in rat. One group of animals recovered a previously known skill (skill training, followed by stroke and re-learning training, TST, n = 8). A second group learned the skill for the first time after stroke (ST, n = 6). A control group received prolonged training without stroke (n = 6). Unilateral partial motor cortex lesions were induced photothrombotically after identifying the forelimb representation using epidural stimulation mapping. In TST animals, re-learning after stroke was slower than learning before stroke (post hoc repeated measures ANOVA P = 0.039) and learning in the control group (P = 0.033). De novo learning after stroke (ST group) was not different from healthy learning. These findings show that skill learning can be performed if the motor cortex is partially lesioned; re-learning of a skill after stroke is slowed by prior knowledge of the skill. It remains to be tested in humans whether task novelty positively influences rehabilitation therapy.