Focal Cortical Injuries Research Articles

Comparison of motor recovery after neonatal and adult hemidecortication

Hemidecortication produces a wide range of cognitive and motor symptoms in both children and lab animals that are generally far greater than smaller bilateral focal lesions of cerebral cortex. Although there have been many studies of motor functions after hemidecortication, the analyses largely have been of general motor functions rather than of more skilled motor functions such as forelimb reaching. The objective of the present experiment was to analyze the sensorimotor forelimb function of rats after infant or adult hemidecortication by utilizing multiple motor analyses. Rats were given hemidecortications either on postnatal day 10 (P10) or day 90 (P90). Both groups were then tested on a number of behavioural tasks (two tests of skilled reaching, forelimb placing during spontaneous vertical exploration, and a sunflower seed opening task) beginning at P 120. In a portion of the P10 female animals, topographic movement representations were derived in the hemisphere contralateral to lesion using Intracortical Microstimulation (ICMS). The brains of the male animals were prepared for Golgi-Cox staining and subsequent analysis of dendritic arborisation and spine density. There were three main findings. 1) Both groups of hemidecorticate animals were impaired when tested on the motor tasks, but the impairments were qualitatively different in the neonatal and adult operates. For example, the P 10 hemidecorticate animals displayed simultaneous bilateral forelimb movement, or “mirror movements.” 2) Hemidecortication at P90 but not P10, led to increased dendritic arborisation of Layer III pyramidal cells in the intact parietal cortex but whereas P90 animals showed a decrease in cortical thickness in the intact hemisphere, the P10 animals do not, even though there are no callosal connections. 3) P10 hemidecortication altered the details of the ICMS-delineated motor maps in a small group of female hemidecorticates that were studied. In conclusion, there was postinjury compensation for motor impairments in both P10 and P90 rats but the mechanisms were different. Furthermore, comparisons of postinjury behavioral and anatomical compensation in rats with focal cortical injuries at those ages in our previous studies showed marked differences. These results suggest that there is a fundamental difference in the way that the brain compensates from hemidecortication and focal injury in development.

Local sleep-like cortical reactivity in the awake brain after focal injury.

The functional consequences of focal brain injury are thought to be contingent on neuronal alterations extending beyond the area of structural damage. This phenomenon, also known as diaschisis, has clinical and metabolic correlates but lacks a clear electrophysiological counterpart, except for the long-standing evidence of a relative EEG slowing over the injured hemisphere. Here, we aim at testing whether this EEG slowing is linked to the pathological intrusion of sleep-like cortical dynamics within an awake brain. We used a combination of transcranial magnetic stimulation and electroencephalography (TMS/EEG) to study cortical reactivity in a cohort of 30 conscious awake patients with chronic focal and multifocal brain injuries of ischaemic, haemorrhagic and traumatic aetiology. We found that different patterns of cortical reactivity typically associated with different brain states (coma, sleep, wakefulness) can coexist within the same brain. Specifically, we detected the occurrence of prominent sleep-like TMS-evoked slow waves and off-periods-reflecting transient suppressions of neuronal activity-in the area surrounding focal cortical injuries. These perilesional sleep-like responses were associated with a local disruption of signal complexity whereas complex responses typical of the awake brain were present when stimulating the contralesional hemisphere. These results shed light on the electrophysiological properties of the tissue surrounding focal brain injuries in humans. Perilesional sleep-like off-periods can disrupt network activity but are potentially reversible, thus representing a principled read-out for the neurophysiological assessment of stroke patients, as well as an interesting target for rehabilitation.

Deficits in Behavioral Functions of Intact Barrel Cortex Following Lesions of Homotopic Contralateral Cortex.

Focal unilateral injuries to the somatosensory whisker barrel cortex have been shown cause long-lasting deficits in the activity and experience-dependent plasticity of neurons in the intact contralateral barrel cortex. However, the long-term effect of these deficits on behavioral functions of the intact contralesional cortex is not clear. In this study, we used the “Gap-crossing task” a barrel cortex-dependent, whisker-sensitive, tactile behavior to test the hypothesis that unilateral lesions of the somatosensory cortex would affect behavioral functions of the intact somatosensory cortex and degrade the execution of a bilaterally learnt behavior. Adult rats were trained to perform the Gap-crossing task using whiskers on both sides of the face. The barrel cortex was then lesioned unilaterally by subpial aspiration. As observed in other studies, when rats used whiskers that directly projected to the lesioned hemisphere the performance of Gap-crossing was drastically compromised, perhaps due to direct effect of lesion. Significant and persistent deficits were present when the lesioned rats performed Gap-crossing task using whiskers that projected to the intact cortex. The deficits were specific to performance of the task at the highest levels of sensitivity. Comparable deficits were seen when normal, bilaterally trained, rats performed the Gap-crossing task with only the whiskers on one side of the face or when they used only two rows of whiskers (D row and E row) intact on both side of the face. These findings indicate that the prolonged impairment in execution of the learnt task by rats with unilateral lesions of somatosensory cortex could be because sensory inputs from one set of whiskers to the intact cortex is insufficient to provide adequate sensory information at higher thresholds of detection. Our data suggest that optimal performance of somatosensory behavior requires dynamic activity-driven interhemispheric interactions from the entire somatosensory inputs between homotopic areas of the cerebral cortex. These results imply that focal unilateral cortical injuries, including those in humans, are likely to have widespread bilateral effects on information processing including in intact areas of the cortex.

Neuronal mechanisms underlying transhemispheric diaschisis following focal cortical injuries

Unilateral cortical lesions cause disturbances often spreading into the hemisphere contralateral to the injury. The functional alteration affecting the contralesional cortex is called transhemispheric diaschisis and is believed to contribute to neurological deficits and to processes of functional reorganization post-lesion. Despite the profound implications for recovery, little is known about the cellular mechanisms that underlie this phenomenon. In the present study, transhemispheric diaschisis was investigated with an in vivo-ex vivo model of unilateral lesions, induced by an infrared laser in rat visual cortex. Visually evoked cortical activity was evaluated by the expression level of the cellular activity marker zif268, which showed an elevation in the cortex contralateral to the lesion. In vitro patch-clamp recordings from layer 2/3 pyramidal neurons revealed a shift in the excitatory–inhibitory balance in favor of excitability, particularly expressed in the undamaged hemisphere. Layer 5 principal neurons displayed an increased spontaneous firing rate contralateral to the lesion, while cells of the injured cortex displayed a reduced firing upon somatic current injection. These data suggest that a cortical lesion triggers an enhanced neuronal activity in the hemisphere contralateral to the damage. Our findings constitute an important step toward the understanding of transhemispheric diaschisis on the cellular level.

Alterations in membrane and firing properties of layer 2/3 pyramidal neurons following focal laser lesions in rat visual cortex

Focal cortical injuries are well known to cause changes in function and excitability of the surviving cortical areas but the cellular correlates of these physiological alterations are not fully understood. In the present study we employed a well established ex vivo–in vitro model of focal laser lesions in the rat visual cortex and we studied membrane and firing properties of the surviving layer 2/3 pyramidal neurons. Patch-clamp recordings, performed in the first week post-injury, revealed an increased input resistance, a depolarized spike threshold as well as alterations in the firing pattern of neurons in the cortex ipsilateral to the lesion. Notably, the reported lesion-induced alterations emerged or became more evident when an exciting perfusing solution, known as modified artificial cerebrospinal fluid, was used to increase the ongoing synaptic activity in cortical slices. Conversely, application of glutamatergic or GABAA receptor blockers reduced the observed alterations and GABAB receptor blockers abolished the differences completely. All together the present findings suggest that changes in synaptic receptors function, following focal cortical injuries, can modulate membrane and firing properties of layer 2/3 pyramidal neurons. This previously unknown functional interplay between synaptic and membrane properties may constitute a novel cellular mechanism to explain alterations in neuronal network function and excitability following focal cortical injuries.

Recovery from medial prefrontal cortex injury during adolescence: Implications for age-dependent plasticity

Focal cortical injuries generate various behavioral deficits associated with different morphological changes. The age and the area of the injury determine the nature and extent of recovery represented by the level of performance in various behavioral tasks. Previously, we have shown that motor cortex injury in early (but not late) adolescence leads to behavioral deficits that do not recover spontaneously with time. Considering the fact that the pace of brain maturation differs in different brain areas, we undertook to examine the pattern of spontaneous recovery following medial prefrontal cortex (mPFC) lesion in early or late adolescence. A battery of motor tasks (postural asymmetry, skilled reaching, sunflower seed manipulation, forepaw inhibition in swimming) was used to investigate the pattern of behavioral recovery following mPFC lesions. Golgi–Cox analysis was used to examine dendritic reorganization of the relevant brain areas. The results indicated that rats perform poorly when receiving mPFC injuries in late adolescence in contrast to when they receive the lesion in early adolescence. Almost opposite pattern of recovery following motor cortex and medial prefrontal injuries in early and late adolescence will be discussed as an age–area dependent model for prognosis of brain injury during adolescence.

Metaplasticity of horizontal connections in the vicinity of focal laser lesions in rat visual cortex

Focal cortical injuries are accompanied by a reorganization of the adjacent neuronal networks. An increased synaptic plasticity has been suggested to mediate, at least in part, this functional reorganization. Previous studies showed an increased long-term potentiation (LTP) at synapses formed by ascending fibres projecting onto layers 2/3 pyramidal cells following lesions in rat visual cortex. This could be important to establish new functional connections within a vertical cortical column. Importantly, horizontal intracortical connections constitute an optimal substrate to mediate the functional reorganization across different cortical columns. However, so far little is known about their potential implication in the functional rewiring post-lesion. Here, we investigated possible alterations of synaptic plasticity of horizontal connections in layers 2/3 in an 'ex vivo-in vitro' model of focal laser lesion in rat visual cortex. LTP at these synapses was found to be enhanced post-lesion, whereas long-term depression (LTD) was impaired, revealing a metaplastic shift toward strengthening of these synapses. Furthermore, we disclosed a prolonged decay-time constant of NMDAR-dependent currents, which can contribute to the enhanced LTP. Taken together these data revealed that a laser lesion-induced focal damage of the visual cortex is accompanied by a facilitated potentiation of horizontal synaptic connections in the vicinity of the focal injury. This specific strengthening of synaptic plasticity at horizontal connections in layers 2/3 might be one important cellular mechanism to compensate focal injury-mediated dysfunction in the cerebral cortex.

Focal cortical infarcts alter intrinsic excitability and synaptic excitation in the reticular thalamic nucleus.

Focal cortical injuries result in death of cortical neurons and their efferents and ultimately in death or damage of thalamocortical relay (TCR) neurons that project to the affected cortical area. Neurons of the inhibitory reticular thalamic nucleus (nRT) receive excitatory inputs from corticothalamic and thalamocortical axons and are thus denervated by such injuries, yet nRT cells generally survive these insults to a greater degree than TCR cells. nRT cells inhibit TCR cells, regulate thalamocortical transmission, and generate cerebral rhythms including those involved in thalamocortical epilepsies. The survival and reorganization of nRT after cortical injury would determine recovery of thalamocortical circuits after injury. However, the physiological properties and connectivity of the survivors remain unknown. To study possible alterations in nRT neurons, we used the rat photothrombosis model of cortical stroke. Using in vitro patch-clamp recordings at various times after the photothrombotic injury, we show that localized strokes in the somatosensory cortex induce long-term reductions in intrinsic excitability and evoked synaptic excitation of nRT cells by the end of the first week after the injury. We find that nRT neurons in injured rats show (1) decreased membrane input resistance, (2) reduced low-threshold calcium burst responses, and (3) weaker evoked excitatory synaptic responses. Such alterations in nRT cellular excitability could lead to loss of nRT-mediated inhibition in relay nuclei, increased output of surviving TCR cells, and enhanced thalamocortical excitation, which may facilitate recovery of thalamic and cortical sensory circuits. In addition, such changes could be maladaptive, leading to injury-induced epilepsy.