Targeted mini-strokes produce changes in interhemispheric sensory signal processing that are indicative of disinhibition within minutes
31 May 2011-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 108, Iss: 22, pp 8932-8933
TL;DR: It is suggested that acute stroke activates unique pathways that can rapidly redistribute function within the spared cortical hemisphere within 30–50 min of stroke onset, and not merely loss of activity.
Abstract: Most processing of sensation involves the cortical hemisphere opposite (contralateral) to the stimulated limb. Stroke patients can exhibit changes in the interhemispheric balance of sensory signal processing. It is unclear whether these changes are the result of poststroke rewiring and experience, or whether they could result from the immediate effect of circuit loss. We evaluated the effect of mini-strokes over short timescales (<2 h) where cortical rewiring is unlikely by monitoring sensory-evoked activity throughout much of both cortical hemispheres using voltage-sensitive dye imaging. Blockade of a single pial arteriole within the C57BL6J mouse forelimb somatosensory cortex reduced the response evoked by stimulation of the limb contralateral to the stroke. However, after stroke, the ipsilateral (uncrossed) forelimb response within the unaffected hemisphere was spared and became independent of the contralateral forelimb cortex. Within the unaffected hemisphere, mini-strokes in the opposite hemisphere significantly enhanced sensory responses produced by stimulation of either contralateral or ipsilateral pathways within 30-50 min of stroke onset. Stroke-induced enhancement of responses within the spared hemisphere was not reproduced by inhibition of either cortex or thalamus using pharmacological agents in nonischemic animals. I/LnJ acallosal mice showed similar rapid interhemispheric redistribution of sensory processing after stroke, suggesting that subcortical connections and not transcallosal projections were mediating the novel activation patterns. Thalamic inactivation before stroke prevented the bilateral rearrangement of sensory responses. These findings suggest that acute stroke, and not merely loss of activity, activates unique pathways that can rapidly redistribute function within the spared cortical hemisphere.
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Paris 12 Val de Marne University1, French Institute of Health and Medical Research2, University of Göttingen3, Ghent University4, University Hospital of Lausanne5, University of Lisbon6, university of lille7, Università Campus Bio-Medico8, University of Belgrade9, University of Hamburg10, Turku University Hospital11, Aristotle University of Thessaloniki12, University of Regensburg13, University of Bern14, Ludwig Maximilian University of Munich15, University of Siena16, The Catholic University of America17, University College London18, University of Ulm19, Copenhagen University Hospital20, University of Oxford21, University of Barcelona22, University of Tübingen23
TL;DR: There is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rT MS of the left dorsolateral prefrontal cortex (DLPFC).
1,554 citations
Cites background from "Targeted mini-strokes produce chang..."
...While there is evidence that the neural process of interhemispheric balance and rivalry can affect both M1 and S1 (Schambra et al., 2003; Mohajerani et al., 2011), this cannot be generalized to the entire cortex....
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TL;DR: The development of new imaging techniques allows a better understanding of the complexity of brain organization and it is now possible to reliably investigate a new type of diaschisis defined as the changes of structural and functional connectivity between brain areas distant to the lesion.
Abstract: After a century of false hopes, recent studies have placed the concept of diaschisis at the centre of the understanding of brain function. Originally, the term 'diaschisis' was coined by von Monakow in 1914 to describe the neurophysiological changes that occur distant to a focal brain lesion. In the following decades, this concept triggered widespread clinical interest in an attempt to describe symptoms and signs that the lesion could not fully explain. However, the first imaging studies, in the late 1970s, only partially confirmed the clinical significance of diaschisis. Focal cortical areas of diaschisis (i.e. focal diaschisis) contributed to the clinical deficits after subcortical but only rarely after cortical lesions. For this reason, the concept of diaschisis progressively disappeared from the mainstream of research in clinical neurosciences. Recent evidence has unexpectedly revitalized the notion. The development of new imaging techniques allows a better understanding of the complexity of brain organization. It is now possible to reliably investigate a new type of diaschisis defined as the changes of structural and functional connectivity between brain areas distant to the lesion (i.e. connectional diaschisis). As opposed to focal diaschisis, connectional diaschisis, focusing on determined networks, seems to relate more consistently to the clinical findings. This is particularly true after stroke in the motor and attentional networks. Furthermore, normalization of remote connectivity changes in these networks relates to a better recovery. In the future, to investigate the clinical role of diaschisis, a systematic approach has to be considered. First, emerging imaging and electrophysiological techniques should be used to precisely map and selectively model brain lesions in human and animals studies. Second, the concept of diaschisis must be applied to determine the impact of a focal lesion on new representations of the complexity of brain organization. As an example, the evaluation of remote changes in the structure of the connectome has so far mainly been tested by modelization of focal brain lesions. These changes could now be assessed in patients suffering from focal brain lesions (i.e. connectomal diaschisis). Finally, and of major significance, focal and non-focal neurophysiological changes distant to the lesion should be the target of therapeutic strategies. Neuromodulation using transcranial magnetic stimulation is one of the most promising techniques. It is when this last step will be successful that the concept of diaschisis will gain all the clinical respectability that could not be obtained in decades of research.
605 citations
Cites background from "Targeted mini-strokes produce chang..."
...…an increase in the response by guest on O ctober 7, 2016 http://brain.oxfordjournals.org/ D ow nloaded from to evoked potentials can be observed in the contralesional cortex, without concomitant alterations of metabolism ‘at rest’ in the same areas (Nakashima et al., 1985; Mohajerani et al., 2011)....
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...missures, as reported in acallosal mice (Mohajerani et al., 2011)....
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...After stroke, spreading depression and inflammation (Mohajerani et al., 2011) may also play a role in distant increase in excitability in addition to the interruption of transcallosal connections....
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...This increase in contralateral evoked potentials response is consistent with the definition of diaschisis as it occurs remotely to the lesion within minutes after stroke (Mohajerani et al., 2011), and tends to regress over time....
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...within minutes after stroke (Mohajerani et al., 2011), and tends to...
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411 citations
Cites background from "Targeted mini-strokes produce chang..."
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393 citations
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301 citations
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TL;DR: Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur, and how to optimally engage and modify surviving neuronal networks is studied.
Abstract: Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and the impairment of sensation, movement or cognition. Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur. Plasticity mechanisms include activity-dependent rewiring and synapse strengthening. The challenge for improving stroke recovery is to understand how to optimally engage and modify surviving neuronal networks, to provide new response strategies that compensate for tissue lost to injury.
1,554 citations
"Targeted mini-strokes produce chang..." refers background in this paper
...D stroke, neurons that are deprived of their normal substrates can show signs of structural damage after as little as 2 min of ischemia (1, 2)....
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...However, it is also possible to view the stroke recovery process not as a response to damaging events such as apoptosis and necrosis but as a form of compensation (homeostatic plasticity) because of loss of function (1, 65)....
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...Recovery after a small stroke may involve spared peri-infarct tissue with function similar to the infarct (1, 7)....
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TL;DR: This paper found that after the median nerve was transected and ligated in adult owl and squirrel monkeys, the cortical sectors representing it within skin surface representations in Areas 3b and 1 were completely occupied by 'new' and expanded representations of surrounding skin fields.
948 citations
TL;DR: This data set provides the first functional description of the excitatory synaptic wiring diagram of a physiologically relevant and anatomically well-defined cortical column at single-cell resolution.
871 citations
"Targeted mini-strokes produce chang..." refers background in this paper
...In addition, recent studies have shown that, although sensory-evoked activity originates mainly at the granular layer of cortex, the activity distributes rapidly among all cortical lamina (25, 26)....
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TL;DR: It is shown that the light-gated channel channelrhodopsin-2 (ChR2) is delivered to axons in pyramidal neurons in vivo, and laminar specificity may be identical for local and long-range cortical projections.
Abstract: The functions of cortical areas depend on their inputs and outputs, but the detailed circuits made by long-range projections are unknown. We show that the light-gated channel channelrhodopsin-2 (ChR2) is delivered to axons in pyramidal neurons in vivo. In brain slices from ChR2-expressing mice, photostimulation of ChR2-positive axons can be transduced reliably into single action potentials. Combining photostimulation with whole-cell recordings of synaptic currents makes it possible to map circuits between presynaptic neurons, defined by ChR2 expression, and postsynaptic neurons, defined by targeted patching. We applied this technique, ChR2-assisted circuit mapping (CRACM), to map long-range callosal projections from layer (L) 2/3 of the somatosensory cortex. L2/3 axons connect with neurons in L5, L2/3 and L6, but not L4, in both ipsilateral and contralateral cortex. In both hemispheres the L2/3-to-L5 projection is stronger than the L2/3-to-L2/3 projection. Our results suggest that laminar specificity may be identical for local and long-range cortical projections.
859 citations
"Targeted mini-strokes produce chang..." refers background in this paper
...The presence of ipsilateral responses (measured in the left hemisphere to left forepaw stimulation) in the animal with a stroke on the right side was surprising, because the contralateral (right) forelimb area was ischemic and could not relay this signal across the corpus callosumas expected innaïveanimals (28, 29, 31)....
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TL;DR: It is concluded that substantial functional reorganization occurs in primary motor cortex of adult primates following a focal ischemic infarct, but at least in the absence of postinfarct training, the movements formerly represented in the infarCTed zone do not reappear in adjacent cortical regions.
Abstract: 1. Intracortical microstimulation (ICMS) techniques were used to derive detailed maps of distal forelimb movement representations in primary motor cortex (area 4) of adult squirrel monkeys before and a few months after a focal ischemic infarct. 2. Infarcts caused a marked but transient deficit in use of the contralateral hand, as evidenced by increased use of the ipsilateral hand, and reduced performance on a task requiring skilled digit use. 3. Infarcts resulted in a widespread reduction in the areal extent of digit representations adjacent to the lesion, and apparent increases in adjacent proximal representations. 4. We conclude that substantial functional reorganization occurs in primary motor cortex of adult primates following a focal ischemic infarct, but at least in the absence of postinfarct training, the movements formerly represented in the infarcted zone do not reappear in adjacent cortical regions.
789 citations
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...The appearance of new structural connections that form over weeks during recovery from stroke is supported by data from a number of different studies (7, 14, 17, 63, 64)....
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