Background and Purpose—Injury-induced cortical reorganization is a widely recognized phenomenon. In contrast, there is almost no information on treatment-induced plastic changes in the human brain. The aim of the present study was to evaluate reorganization in the motor cortex of stroke patients that was induced with an efficacious rehabilitation treatment. Methods—We used focal transcranial magnetic stimulation to map the cortical motor output area of a hand muscle on both sides in 13 stroke patients in the chronic stage of their illness before and after a 12-day-period of constraint-induced movement therapy. Results—Before treatment, the cortical representation area of the affected hand muscle was significantly smaller than the contralateral side. After treatment, the muscle output area size in the affected hemisphere was significantly enlarged, corresponding to a greatly improved motor performance of the paretic limb. Shifts of the center of the output map in the affected hemisphere suggested the recru...

https://www.ahajournals.org/doi/pdf/10.1161/01.STR.31.6.1210

Treatment-Induced Cortical Reorganization After Stroke in Humans

Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins

Movement of an affected hand after stroke is associated with increased activation of ipsilateral motor cortical areas, suggesting that these motor areas in the undamaged hemisphere may adaptively compensate for damaged or disconnected regions. However, this adaptive compensation has not yet been demonstrated directly. Here we used transcranial magnetic stimulation (TMS) to interfere transiently with processing in the ipsilateral primary motor or dorsal premotor cortex (PMd) during finger movements. TMS had a greater effect on patients than controls in a manner that depended on the site, hemisphere, and time of stimulation. In patients with right hemiparesis (but not in healthy controls), TMS applied to PMd early (100 ms) after the cue to move slowed simple reaction-time finger movements by 12% compared with controls. The relative slowing of movements with ipsilateral PMd stimulation in patients correlated with the degree of motor impairment, suggesting that functional recruitment of ipsilateral motor areas was greatest in the more impaired patients. We also used functional magnetic resonance imaging to monitor brain activity in these subjects as they performed the same movements. Slowing of reaction time after premotor cortex TMS in the patients correlated inversely with the relative hemispheric lateralization of functional magnetic resonance imaging activation in PMd. This inverse correlation suggests that the increased activation in ipsilateral cortical motor areas during movements of a paretic hand, shown in this and previous functional imaging studies, represents a functionally relevant, adaptive response to the associated brain injury.

https://www.pnas.org/content/pnas/99/22/14518.full.pdf

The role of ipsilateral premotor cortex in hand movement after stroke

Although spontaneous regeneration of lesioned fibres is limited in the adult central nervous system, many people that suffer from incomplete spinal cord injuries show significant functional recovery. This recovery process can go on for several years after the injury and probably depends on the reorganization of circuits that have been spared by the lesion. Synaptic plasticity in pre-existing pathways and the formation of new circuits through collateral sprouting of lesioned and unlesioned fibres are important components of this recovery process. These reorganization processes might occur in cortical and subcortical motor centres, in the spinal cord below the lesion, and in the spared fibre tracts that connect these centres. Functional and anatomical evidence exists that spontaneous plasticity can be potentiated by activity, as well as by specific experimental manipulations. These studies prepare the way to a better understanding of rehabilitation treatments and to the development of new approaches to treat spinal cord injury.

Plasticity of motor systems after incomplete spinal cord injury

The neurons of the cochlear ganglion transmit acoustic information between the inner ear and the brain. These placodally derived neurons must produce a topographically precise pattern of connections in both the inner ear and the brain. In this review, we consider the current state of knowledge concerning the development of these neurons, their peripheral and central connections, and their influences on peripheral and central target cells. Relatively little is known about the cellular and molecular regulation of migration or the establishment of precise topographic connection to the hair cells or cochlear nucleus (CN) neurons. Studies of mice with neurotrophin deletions are beginning to yield increasing understanding of variations in ganglion cell survival and resulting innervation patterns, however. Finally, existing evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain. Ganglion cell innervation and synaptic activity are essential for normal development of neurons in the cochlear nucleus.

http://depts.washington.edu/rubelab/personnel/Rubel%20and%20Fritzsch,%202002.pdf

AUDITORY SYSTEM DEVELOPMENT: Primary Auditory Neurons and Their Targets

Infant monkeys were subjected to unilateral lesions of the motor cortex (mainly its hand representation). After maturation, they showed normal use of the contralateral hand for global grip movements. However, as compared with the ipsilateral hand, precision grip tasks requiring relatively independent finger movements were performed with less dexterity, particularly if adjustments of the wrist position were necessary. The purpose of this study was to investigate mechanisms which may be responsible for the rather well, although not complete, preservation of manipulative behaviour of these adult monkeys. To this end, the hand representations were mapped bilaterally with intracortical microstimulation in the mature monkeys, and the dexterity of both hands assessed quantitatively in a precision grip task. The behavioural effects of reversible inactivations of the primary (M1) and supplementary (SMA) motor cortical areas were then tested. The following were found. (i) The hand contralateral to the lesion exhibited subtle but significant dexterity deficits, as compared with the ipsilateral hand; the deficit was essentially for complex movements requiring dissociation of the thumb-index finger pinch from the other digits, involving also an arm rotation. (ii) Reversible inactivation of the M1 hand representation in the intact hemisphere dramatically impaired dexterity of the opposite hand without affecting the ipsilateral hand (contralateral to the early lesion). (iii) A relatively complete hand representation was found to occupy a new territory, medial to the old lesion. (iv) The role of this new displaced representation was crucial for the preserved dexterity of the opposite hand, as evidenced by its functional inactivation. In contrast, inactivation of both SMA cortices did not interfere with the manipulative behaviour. It is thus concluded that the preserved functional capacity of manipulations with the hand opposite the early lesion can be essentially attributed to a cortical reorganization around the old lesion. Under the present experimental conditions, contributions from either the SMA or the intact M1 appear not to be crucial.

Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion

Electrically induced Fos-like immunoreactivity in the auditory pathway of the rat: Effects of survival time, duration, and intensity of stimulation

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Dexterity in adult monkeys following early lesion of the motor cortical hand area: the role of cortex adjacent to the lesion

Electrically induced Fos-like immunoreactivity in the auditory pathway of the rat: Effects of survival time, duration, and intensity of stimulation