This thesis describes a series of experiments to investigate the effect of thermal stimulation on corticospinal excitability using transcranial magnetic stimulation (TMS). Experiment I showed that innocuous cooling or warming of a single digit, produced short-lasting and mixed patterns of modulation only during actual thermal stimulation, with the inhibition being the most common pattern observed. In line with this finding, cooling stimulation applied to a larger area (i.e. multi-digits) produced variable but more sustained modulation in motor evoked potential (MEP) amplitude in the post-cooling phase (Exp II). Notably, the responses to cooling in terms of either suppressed or enhanced corticospinal excitability tended to be fairly consistent in a given individual with repeated applications. When examining possible sources of the observed variable MEP modulation, we found that individual characteristics such as age, sex and changes in skin temperature had no major influences. We hypothesized that the variability of responses might be related to individual differences in the excitability of intra-cortical circuits involved in sensorimotor integration. To test this hypothesis, we performed Experiment III using conditioning TMS paradigms. This experiment revealed that TMS markers of sensorimotor integration (SAI and SAF levels) were good predictors of individual variations in cooling-induced modulation in corticospinal excitability. This provided evidence supporting the role of SAI and SAF as markers to predict individual’s response to focal thermal stimulation. The identification of such predictors could enhance the therapeutic applicability of this form of stimulation in neurorehabilitation. Collectively, these findings advance our understanding of the neurophysiological basis of thermal stimulation and shed light on the development of a more rational application of neurofacilitation techniques based on afferent stimulation in clinical populations, such as stroke survivors.

No description available.

<p>Neuroimaging and neurophysiology techniques were used to study some aspects of cortical sensory and motor system reorganisation in patients in the chronic phase after stroke. Using Diffusion Tensor Imaging, we found that the degree of white matter integrity of the corticofugal tracts (CFT) was positively related to grip strength. Structural changes of the CFT were also associated with functional changes in the corticospinal pathways, measured using Transcranial Magnetic Stimulation. This suggests that structural and functional integrity of the CFT is essential for upper limb function after stroke.</p><p>Using functional magnetic resonance imaging (fMRI), to measure brain activity during slow and fast passive hand movements, we found that velocity-dependent brain activity correlated positively with neural contribution to passive movement resistance in the hand in ipsilateral primary sensory (S1) and motor (M1) cortex in both patients and controls. This suggests a cortical involvement in the hyperactive reflex response of flexor muscles upon fast passive stretch.</p><p>Effects of a four week passive-active movement training programme were evaluated in chronic stroke patients. The group improved in range of motion and upper limb function after the training. The patients also reported improvements in a variety of daily tasks requiring the use of the affected upper limb. </p><p>Finally, we used fMRI to explore if brain activity during passive hand movement is related to time after stroke, and if such activity can be affected with intense training. In patients, reduced activity over time was found in supplementary motor area (SMA), contralateral M1 and prefrontal and parietal association areas along with ipsilateral cerebellum. After training, brain activity increased in SMA, ipsilateral S1 and intraparietal sulcus, and contralateral cerebellum in parallel with functional improvements of the upper limb. The findings suggest a use-dependent modification of cortical activation patterns in the affected hand after stroke. </p>

A key issue in understanding how the brain functions is the ability to correlate functional information with anatomical localisation. Functional information can be provided by a variety of techniques like positron emission tomography (PET), functional MRI (fMRI), electroencephalography (EEG), magnetoencephalography (MEG) or transcranial magnetic stimulation (TMS). All these methods provide different, but complementary, information about the functional areas of the brain. PET and fMRI provide spatially accurate picture of brain regions involved in a given task. TMS permits to infer the contribution of the stimulated brain area to the task under investigation. EEG and MEG, which reflects brain activity directly, have temporal accuracy of the order of a millisecond. TMS, EEG and MEG are offset by their low spatial resolution. In this thesis, we propose two methods to improve the spatial accuracy of method based on TMS and EEG. The first part of this thesis presents an automatic method to improve the localisation of TMS points. The method enables real-time visualisation and registration of TMS evoked responses and MRI. A MF digitiser is used to sample approximately 200 points on the subject's head following a specific digitisation pattern. Registration is obtained by minimising the RMS point to surface distance, computed efficiently using the Euclidean distance transform. Functional maps are created from TMS evoked responses projected onto the brain surface previously segmented from MRI. The second part presents the possibilities to set up a brain-computer interface (BCI) based on reconstructed sources of EEG activity and the parameters to adjust. Reconstructed sources could improve the EEG spatial accuracy as well as add biophysical information on the origin of the signal. Both informations could improve the BCI classification step. Eight BCIs are built to enable comparison between electrode-based and reconstructed source-based BCIs. Tests on detection of laterality of upcoming hand movement demonstrate the interest of reconstructed sources.

Neuroimaging and neurophysiology techniques were used to study some aspects of cortical sensory and motor system reorganisation in patients in the chronic phase after stroke. Using Diffusion Tensor Imaging, we found that the degree of white matter integrity of the corticofugal tracts (CFT) was positively related to grip strength. Structural changes of the CFT were also associated with functional changes in the corticospinal pathways, measured using Transcranial Magnetic Stimulation. This suggests that structural and functional integrity of the CFT is essential for upper limb function after stroke. Using functional magnetic resonance imaging (fMRI), to measure brain activity during slow and fast passive hand movements, we found that velocity-dependent brain activity correlated positively with neural contribution to passive movement resistance in the hand in ipsilateral primary sensory (S1) and motor (M1) cortex in both patients and controls. This suggests a cortical involvement in the hyperactive reflex response of flexor muscles upon fast passive stretch. Effects of a four week passive-active movement training programme were evaluated in chronic stroke patients. The group improved in range of motion and upper limb function after the training. The patients also reported improvements in a variety of daily tasks requiring the use of the affected upper limb. Finally, we used fMRI to explore if brain activity during passive hand movement is related to time after stroke, and if such activity can be affected with intense training. In patients, reduced activity over time was found in supplementary motor area (SMA), contralateral M1 and prefrontal and parietal association areas along with ipsilateral cerebellum. After training, brain activity increased in SMA, ipsilateral S1 and intraparietal sulcus, and contralateral cerebellum in parallel with functional improvements of the upper limb. The findings suggest a use-dependent modification of cortical activation patterns in the affected hand after stroke.

This thesis investigated the role of CBF assessment in the management of stroke in children with sickle cell disease (SCD). It is divided into two parts. In the first part, a systematic review of CBF assessment using different imaging modalities in SCD children was designed. The prevalence of CBF abnormalities was found to be equal to or higher than those of structural MRI and transcranial Doppler (TCD) in SCD children who have not experienced stroke. Studies reviewed suggested CBF assessment in SCD could aid in addressing brain abnormalities at the tissue level. In the second part, the arterial spin labeling (ASL) technique was used to depict CBF abnormalities in SCD children. ASL demonstrated perfusion abnormalities that seem to remain invisible in TCD measurements; CBF interhemispheric asymmetries were associated with clinically silent infarctions with no corresponding flow velocity interhemispheric asymmetries assessed with TCD.

This thesis investigated the role of CBF assessment in the management of stroke in children with sickle cell disease (SCD). It is divided into two parts. In the first part, a systematic review of CBF assessment using different imaging modalities in SCD children was designed. The prevalence of CBF abnormalities was found to be equal to or higher than those of structural MRI and transcranial Doppler (TCD) in SCD children who have not experienced stroke. Studies reviewed suggested CBF assessment in SCD could aid in addressing brain abnormalities at the tissue level. In the second part, the arterial spin labeling (ASL) technique was used to depict CBF abnormalities in SCD children. ASL demonstrated perfusion abnormalities that seem to remain invisible in TCD measurements; CBF interhemispheric asymmetries were associated with clinically silent infarctions with no corresponding flow velocity interhemispheric asymmetries assessed with TCD.

Four experiments, using both humans and monkeys as participants, were conducted to investigate the similarities and differences in human and nonhuman primate numerical cognition. In Experiment 1 it was determined that both humans and monkeys display a SNARC effect, with similar symbolic distance effects for both species. In addition, both species were found to respond faster to congruent stimulus pairs. In Experiment 2 both species were found accurately to recognize quantitative stimuli when presented for durations of 150 msec in a divided visual field paradigm. Performance for humans and monkeys for numerals and dot-patterns was almost identical in terms of accuracy and response times. In Experiment 3 participants were required to make relative numerousness judgments in a divided visual field paradigm. Both species responded faster and more accurately to stimuli presented to the right visual field. Species differences appeared, with monkeys performing equally well on both trial types whereas the humans performed better on numeral trials than on dot trials. In Experiment 4 repetitive transcranial magnetic stimulation (rTMS) was combined with the divided visual field paradigm. Accuracy was significantly disrupted for both species when compared to a no stimulation condition. A facilitation effect was also evident with both species exhibiting significant decreases in response time for all trials. Right-handed participants took longer to respond to stimuli presented to the left visual field. These findings add to the body of knowledge regarding both the similarities and differences of how quantitative stimuli are processed by humans and monkeys.

Estimates of the capacity of visuospatial short-term memory (VSTM) have ranged from less than 1 item to 4 +/- 1 items. The purpose of the present study was to find the capacity of VSTM by looking at the contribution of the other working memory systems (phonological loop and central executive) and determine the factor that limits VSTM capacity (either number of objects or object complexity). In this study, the psychophysiological measure of cerebral blood flow velocity also was incorporated to determine whether changes in cerebral blood flow velocity were indicative of VSTM performance and capacity. Both performance measures and cerebral blood flow velocity indicate that capacity for random polygons is approximately one object. Complexity of the objects affected capacity, such that simple objects had higher capacities and lower cerebral blood flow velocity than complex objects. Other working memory systems were not found to have an effect on performance.

Stamning är en komplex motorisk talstörning, vars neurologisk bakgrund fortfarande inte är klarlagd. En växande mängd studier ger dock stöd för att stamning kan vara orsakat av strukturella avvikelser i den vänstra hemisfären. En studie (Sommer et al., 2003) som använde transkraniell magnetstimulering (TMS) för att undersöka kortikal inhibition hos personer som stammar (PsS) fann som ett bi-fynd att den stammande gruppen hade signifikant högre motortrösklar (MT) för vänster hemisfärs handmotorarea, det vill säga att det krävdes starkare stimulering för att väcka en muskelrespons i den kontralaterala handen. Resultat har dock inte uppmärksammats av senare forskning, och behöver verifieras. Den aktuella studien syftade till att undersöka om PsS tenderar att ha förhöjda MT, samt om det finns avvikande hemisfärsskilnader i MT hos PsS. MT mättes från båda hemisfärernas handmotorareor hos 15 PsS och 15 matchade kontollförsökspersoner med flytande tal. Resultatet visade på signifikant avvikande lateralisering av MT (p = 0,005) hos PsS; tvärtemot gruppen med flytande tal visade den stammande gruppen tendens till lägst MT i höger hemisfär, med 6 av 15 stammande som hade starkare högersidig lateralisering än någon i kontrollgruppen. Samstämmigt med resultaten från Sommer et al. (2003) var MT för vänster hemisfär signifikant högre i den stammande gruppen jämfört med kontrollgruppen (p = 0,049). Däremot fanns ingen tendens till avvikande MT i höger hemisfär (p = 0,92). Den förhöjda vänstersidiga MT kan vara relaterad till strukturella avvikelser i vänster hemisfär hos PsS.