Stroke has long been regarded as focal disease with circumscribed damage leading to neurological deficits. However, advances in methods for assessing the human brain and in statistics have enabled new tools for the examination of the consequences of stroke on brain structure and function. Thereby, it has become clear that stroke has impact on the entire brain and its network properties and can therefore be considered as a network disease. The present review first gives an overview of current methodological opportunities and pitfalls for assessing stroke-induced changes and reorganization in the human brain. We then summarize principles of plasticity after stroke that have emerged from the assessment of networks. Thereby, it is shown that neurological deficits do not only arise from focal tissue damage but also from local and remote changes in white-matter tracts and in neural interactions among widespread networks. Similarly, plasticity and clinical improvements are associated with specific compensatory structural and functional patterns of neural network interactions. Innovative treatment approaches have started to target such network patterns to enhance recovery. Network assessments to predict treatment response and to individualize rehabilitation is a promising way to enhance specific treatment effects and overall outcome after stroke.

Identification of optimal treatment strategies to improve recovery is limited by the incomplete understanding of the neurobiological principles of recovery. Motor cortex (M1) reorganization of the lesioned hemisphere (ipsilesional M1) plays a major role in post-stroke motor recovery and is a primary target for rehabilitation therapy. Reorganization of M1 in the hemisphere contralateral to the stroke (contralesional M1) may, however, serve as an additional source of cortical reorganization and related recovery. The extent and outcome of such reorganization depends on many factors, including lesion size and time since stroke. In the chronic phase post-stroke, contralesional M1 seems to interfere with motor function of the paretic limb in a subset of patients, possibly through abnormally increased inhibition of lesioned M1 by the contralesional M1. In such patients, decreasing contralesional M1 excitability by cortical stimulation results in improved performance of the paretic limb. However, emerging evidence suggests a potentially supportive role of contralesional M1. After infarction of M1 or its corticospinal projections, there is abnormally increased excitatory neural activity and activation in contralesional M1 that correlates with favorable motor recovery. Decreasing contralesional M1 excitability in these patients may result in deterioration of paretic limb performance. In animal stroke models, reorganizational changes in contralesional M1 depend on the lesion size and rehabilitation treatment and include long-term changes in neurotransmitter systems, dendritic growth, and synapse formation. While there is, therefore, some evidence that activity in contralesional M1 will impact the extent of motor function of the paretic limb in the subacute and chronic phase post-stroke and may serve as a new target for rehabilitation treatment strategies, the precise factors that specifically influence its role in the recovery process remain to be defined.

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Integration of sensory and motor information is one-step, among others, that underlies the successful production of goal-directed hand movements necessary for interacting with our environment. Disruption of sensorimotor integration is prevalent in many neurologic disorders, including stroke. In most stroke survivors, persistent paresis of the hand reduces function and overall quality of life. Current rehabilitative methods are based on neuroplastic principles to promote motor learning that focuses on regaining motor function lost due to paresis, but the sensory contributions to motor control and learning are often overlooked and currently understudied. There is a need to evaluate and understand the contribution of both sensory and motor function in the rehabilitation of skilled hand movements after stroke. Here, we will highlight the importance of integration of sensory and motor information to produce skilled hand movements in healthy individuals and individuals after stroke. We will then discuss how compromised sensorimotor integration influences relearning of skilled hand movements after stroke. Finally, we will propose an approach to target sensorimotor integration through manipulation of sensory input and motor output that may have therapeutic implications.

The role of ipsilateral primary motor cortex (M1) in hand motor control during complex task performance remains controversial. Bilateral M1 activation is inconsistently observed in functional (f)MRI studies of unilateral hand performance. Two factors limit the interpretation of these data. As the motor tasks differ qualitatively in these studies, it is conceivable that M1 contributions differ with the demand on skillfulness. Second, most studies lack the verification of a strictly unilateral execution of the motor task during the acquisition of imaging data. Here, we use fMRI to determine whether ipsilateral M1 activity depends on the demand for precision in a pointing task where precision varied quantitatively while movement trajectories remained equal. Thirteen healthy participants used an MRI-compatible joystick to point to targets of four different sizes in a block design. A clustered acquisition technique allowed simultaneous fMRI/EMG data collection and confirmed that movements were strictly unilateral. Accuracy of performance increased with target size. Overall, the pointing task revealed activation in contralateral and ipsilateral M1, extending into contralateral somatosensory and parietal areas. Target size-dependent activation differences were found in ipsilateral M1 extending into the temporal/parietal junction, where activation increased with increasing demand on accuracy. The results suggest that ipsilateral M1 is active during the execution of a unilateral motor task and that its activity is modulated by the demand on precision.

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Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.

Hebbian-type stimulation is feasible in patients poststroke and induces map reorganization and associated decreases in GABAergic inhibition. However, because TMS protocols have a different effect on motor reorganization in the injured brain and may depend on location of the lesion, protocols need to be tailored to the patient's pathology.