Epilepsy affects approximately 50 million people worldwide, and 20–30% of these cases are refractory to antiepileptic drugs. Many patients with intractable epilepsy can benefit from surgical resection of the tissue generating the seizures; however, difficulty in precisely localising seizure foci has limited the number of patients undergoing surgery as well as potentially lowered its effectiveness. Here we demonstrate a novel imaging method for monitoring rapid changes in cerebral tissue impedance occurring during interictal and ictal activity, and show that it can reveal the propagation of pathological activity in the cortex. Cortical impedance was recorded simultaneously to ECoG using a 30-contact electrode mat placed on the exposed cortex of anaesthetised rats, in which interictal spikes (IISs) and seizures were induced by cortical injection of 4-aminopyridine (4-AP), picrotoxin or penicillin. We characterised the tissue impedance responses during IISs and seizures, and imaged these responses in the cortex using Electrical Impedance Tomography (EIT). We found a fast, transient drop in impedance occurring as early as 12 ms prior to the IISs, followed by a steep rise in impedance within ~ 120 ms of the IIS. EIT images of these impedance changes showed that they were co-localised and centred at a depth of 1 mm in the cortex, and that they closely followed the activity propagation observed in the surface ECoG signals. The fast, pre-IIS impedance drop most likely reflects synchronised depolarisation in a localised network of neurons, and the post-IIS impedance increase reflects the subsequent shrinkage of extracellular space caused by the intense activity. EIT could also be used to picture a steady rise in tissue impedance during seizure activity, which has been previously described. Thus, our results demonstrate that EIT can detect and localise different physiological changes during interictal and ictal activity and, in conjunction with ECoG, may in future improve the localisation of seizure foci in the clinical setting.
Does a conflict between inborn motor preferences and educational standards during childhood impact the structure of the adult human brain? To examine this issue, we acquired high-resolution T1-weighted magnetic resonance scans of the whole brain in adult "converted" left-handers who had been forced as children to become dextral writers. Analysis of sulcal surfaces revealed that consistent right-and left-handers showed an interhemispheric asymmetry in the surface area of the central sulcus with a greater surface contralateral to the dominant hand. This pattern was reversed in the converted group who showed a larger surface of the central sulcus in their left, nondominant hemisphere, indicating plasticity of the primary sensorimotor cortex caused by forced use of the nondominant hand. Voxel-based morphometry showed a reduction of gray matter volume in the middle part of the left putamen in converted left-handers relative to both consistently handed groups. A similar trend was found in the right putamen. Converted subjects with at least one left-handed first-degree relative showed a correlation between the acquired right-hand advantage for writing and the structural changes in putamen and pericentral cortex. Our results show that a specific environmental challenge during childhood can shape the macroscopic structure of the human basal ganglia. The smaller than normal putaminal volume differs markedly from previously reported enlargement of cortical gray matter associated with skill acquisition. This indicates a differential response of the basal ganglia to early environmental challenges, possibly related to processes of pruning during motor development.
"Converted" left-handers are innately left-handed individuals forced as children to write with the right nondominant hand. We asked how a left-to-right handwriting switch shapes cortical sensorimotor representations of finger movements. In 16 adult converted lefthanders and age-matched groups of 16 consistent right-handers and 16 left-handers, we studied movement-related neuronal activity with functional magnetic resonance imaging while participants performed simple unimanual and bimanual movements with right and left index fingers. In converted left-handers, movement-related activity in the primary sensorimotor hand area (SM1) and caudal dorsal premotor cortex (PMd) of the nondominant left hemisphere correlated with the left-to-right shift in handedness. The more right-handed converted left-handers had become, the greater the sensorimotor activation in these areas. Between-group comparisons showed that the switch from left to right hand also reinforced movement representations in the dominant right hemisphere. In converted left-handers, the right inferior parietal cortex and lateral PMd were more active relative to consistent right or left-handers in all motor tasks. These results suggest two distinct neuronal correlates of handedness in human sensorimotor cortex. Although those in executive sensorimotor cortex (i.e., SM1 and adjacent PMd) depend on the hand used throughout life, those in higher-order sensorimotor areas (i.e., inferior parietal cortex and rostrolateral PMd) are invariant and thus cannot be switched to the nondominant hemisphere by educational training.
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