I. INTRODUCCIÓN
1.3. Teorías Relacionadas al tema
activated imaging
rTMS is a non-invasive procedure to create electric currents in discrete brain areas which, depending on frequency, intensity, and duration, can lead to transi-ent increases and decreases in excitability of the affected cortex. Low frequencies of rTMS (below 5 Hz) can suppress excitability of the cortex, while higher-frequency stimulation (5–20 Hz) leads to an increase in cortical excitability [85]. Increases in relative CBV in contralateral homologous language regions during overt propositional speech fMRI in chronic, non-fluent aphasia patients indicated over-activation of right language homologs. This right hemisphere over-activation may represent a maladap-tive strategy and can be interpreted as a result of
Figure 4.7. Activation patterns in patients with left hemispheric stroke 2 and 8 weeks after stroke. In the case of subcortical and frontal infarction, the left temporal areas are reactivated correlating to better recovery of language function. Used with permission from Heiss et al. [81].
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decreased transcallosal inhibition due to damage of the specialized and lateralized speech areas. TMS studies with blockade of this contralateral over-activation by a series of 1 Hz rTMS [86] have improved picture-naming ability in chronic non-fluent aphasia patients. Collateral ipsilateral as well as transcallosal contralateral inhibition can be dem-onstrated by simultaneous rTMS and PET activation studies [87]: at rest, rTMS decreased blood flow ipsi-laterally and contraipsi-laterally. During verb generation, regional CBF was decreased ipsilaterally under the coil during rTMS, but increased ipsilaterally outside the coil and in the contralateral homologous area (Figure 4.8). The effect of rTMS was accompanied by a prolongation of reaction time latencies to verbal stimuli.
The role of activation in the right hemisphere for residual language performance can be investi-gated by combining rTMS with functional imaging, e.g. PET. In patients in whom verb generation acti-vated predominantly the right inferior frontal gyrus, this response could be blocked by rTMS over this region. These patients had lower performance in verbal fluency tasks than patients with effects of rTMS only over the left inferior frontal gyrus, sug-gesting a less effective compensatory potential of right-sided network areas. These results indicate a
potential for rTMS in the treatment of post-stroke aphasia [88].
The activation studies in the course of recovery of post-stroke aphasia suggest various mechanisms for the compensation of the lesion within the functional network. Despite differences among the activation and stimulation paradigms and the heterogeneity of patients included in different imaging studies, a hierarchy for effective recovery might be deduced:
Best, even complete, recovery can only be achieved by restoration of the original activation pattern after small brain damage outside primary centers.
If primary functional centers are damaged, reduction of collateral inhibition leads to activation of areas around the lesion (intrahemispheric compensation).
If the ipsilateral network is severely damaged, reduction of transcallosal inhibition causes activation of contralateral homotopic areas, which is usually not as efficient as intrahemispheric compensation. In some patients with slowly developing brain damage the language function can be completely shifted to the right hemisphere.
In most instances the disinhibition of homotopic areas contralateral to the lesion impairs the capacity for recovery – a mechanism which might be
Figure 4.8. Effect of repetitive transcranial magnetic stimulation (rTMS) on activation pattern by verb generation. The coil position is shown in the 3D rendering. (A) shows inferior frontal gyrus activation during simple verb generation. (B) clearly shows the decreased activation on the left (blue arrow) and increased activity on the right side (yellow arrow) during rTMS interference. Modified from Thiel et al. [87].
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counteracted by rTMS of these contralateral active areas. This approach might open a new therapeutic strategy for post-stroke aphasia.
The role of activation in the right hemisphere for residual language performance can be investigated by combining rTMS with functional imaging, e.g. PET.
Counteraction by rTMS of contralateral active areas might open a new therapeutic strategy for post-stroke aphasia.
Chapter summary
Neuroimaging modalities may help to assess func-tional outcome and to predict the efficacy of rehabili-tation in individual patients additionally to functional assessment scales such as NIHSS and others.
CT:the most widely used imaging procedure in acute stroke is CT, especially for differentiation between hemorrhagic and ischemic stroke, for local-ization of the lesion, and for decision-making regarding administration of potentially risky stroke therapies as thrombolysis. ASPECTS (the Alberta Stroke Program Early Computed Tomography Score) is a measure to quantify ischemic changes on CT within the territory of the middle cerebral artery (MCA) and can help select patients for acute intravascular treatment.
MRI:with diffusion-weighted imaging (DWI), the size of the lesion can be outlined early and DWI lesion volume significantly increased the power of prediction models. Diffusion tensor imaging (DTI) measures may also be used to predict outcome.
The connectivity in networks as assessed by DTI is more important for outcome and recovery than the extent of the primary structural lesion.
Assessment of brain blood supply and cerebral perfusion
Inclusion of information from CT angiography con-tributed significantly more to outcome prediction than the ASPECTS score. Evidence of large-vessel occlusion is crucial for improving outcome by early endovascular interventions.
The final size of an infarct is also influenced by the extent and quality of collateral circulation to the affected brain area. The presence of robust collateral flow is best visualized by conventional angiography, but CT angiography as a non-invasive alternative has better spatial resolution than transcranial Doppler or MR angiography and can depict leptomeningeal collaterals.
The visualization of disturbed interaction in functional networks and of their reorganization in the recovery after focal brain damage is the domain of functional imaging modalities such as PET and fMRI.
PET: mapping of neuronal activity in the brain can be primarily achieved by quantitation of the regional cerebral metabolic rate for glucose (CMRGlc). Quantitative imaging of cerebral blood flow (CBF) is based on the principle of diffusible tracer exchange, using15O-labeled water.
PET detects and, if required, can quantify changes in CBF and CMRGlc accompanying different activation states of brain tissue. The regional values of CBF or CMRGlc represent the brain activity due to a specific state, task, or stimulus in comparison with the resting condition, and color-coded maps can be analyzed or correlated to morphological images.
fMRI measures signals that depend on the differential magnetic properties of oxygenated and deoxygenated hemoglobin, termed the blood-oxygen-level-dependent (BOLD) signal, which gives an estimate of changes in oxygen availability. The amount of deoxyhemoglobin in small blood vessels depends on the flow of well-oxygenated arterial blood (CBF), on the outflow of oxygen to the tissue (CMRO2), and on the cerebral blood volume (CBV).
fMRI images map changes in brain function and can be superimposed on the anatomical image.
Motor and somatosensory deficits
In most fMRI or PET studies involving active or pas-sive movements, a widespread network of neurons was activated in both hemispheres. During recovery from hemiparesis, a dynamic bihemispheric reorgan-ization of motor networks takes place. Ipsilateral cortical recruitment seems to be a compensatory cortical process related to the lesion of the contra-lateral primary motor cortex. The unaffected hemi-sphere actually inhibits the generation of a voluntary movement by the paretic hand. This effect of trans-callosal inhibition can be reduced by repetitive transcranial magnetic stimulation (rTMS).
Post-stroke aphasia
Studies of glucose metabolism in aphasia after stroke have shown metabolic disturbances in the ipsilateral hemisphere caused by the lesion and contralateral hemisphere caused by functional deactivation (dia-schisis). Patients with an eventual good recovery predominantly activated structures in the ipsilateral hemisphere.
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Combination of repetitive transcranial magnetic stimulation (rTMS) with activated imaging
Activation studies in the course of recovery of post-stroke aphasia suggest various mechanisms for the compensation of the lesion within the functional network: restoration of the original activation pattern, activation of areas around the lesion (intra-hemispheric compensation), and reduction of trans-callosal inhibition causing activation of contralateral homotopic areas. rTMS is a non-invasive procedure for creating electric currents in discrete brain areas which, depending on frequency, intensity, and dur-ation, can lead to transient increases (with higher frequencies) and decreases (with lower frequencies) in excitability of the affected cortex. The role of activation in the right hemisphere for residual language performance can be investigated by combining rTMS with functional imaging, e.g. PET.
Counteraction by rTMS of contralateral active areas might open a new therapeutic strategy for post-stroke aphasia.
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