Brain

Morrison, Karen E.

doi: 10.1093/brain/122.10.1805pmid: 10506084

DeFelipe, Javier

doi: 10.1093/brain/122.10.1807pmid: 10506085

The main goal of this article is to review certain aspects of the circuitry of the human cerebral cortex that may be particularly relevant for the development, maintenance or spread of seizures. There are a number of different structural abnormalities that are commonly found in the cortex of epileptic patients, but these abnormalities do not appear to be intrinsically epileptogenic, since some patients displaying them are epileptic (after variable delays) whereas others are not. Therefore, cortical circuits in an affected brain may undergo a series of changes that finally cause epilepsy. In this article, it is proposed that the chandelier cell, which is considered to be the most powerful cortical GABAergic inhibitory interneuron, is probably a key component of cortical circuits in the establishment of human intractable temporal lobe epilepsy. These cells (among other types) have been found to be lost or reduced at epileptic foci in both experimental animals and epileptic patients. A hypothesis is presented by which the normal variability in the number of interneurons might explain the predisposition of some individuals to develop epilepsy more than others as a result of a lesion or other precipitating factors that lead to loss of neurons. The sources of GABAergic input on dendrites and somata of cortical pyramidal cells originate from many and diverse types of interneurons but, at the level of the axon initial segment of these cells, all synapses come from a few chandelier cells (five or less). Loss of one class of interneurons ending on soma and dendrites might have relatively little impact on the inhibitory control of the pyramidal cell. However, if chandelier cells were affected, it would have serious consequences for the inhibitory control of the pyramidal cells. Evidence suggests that the loss of chandelier cells may be non-specific and that when this occurs epilepsy may develop. Therefore, these cells might represent a key component in the aetiology of human temporal lobe epilepsy.

Mallucci, G. R.; Campbell, T. A.; Dickinson, A.; Beck, J.; Holt, M.; Plant, G.; de Pauw, K. W.; Hakin, R. N.; Clarke, C. E.; Howell, S.; Davies-Jones, G. A. B.; Lawden, M.; Smith, C. M. L.; Ince, P.; Ironside, J. W.; Bridges, L. R.;

Maguire, E. A.; Frith, C. D.

doi: 10.1093/brain/122.10.1839pmid: 10506087

Stories are a common way in which humans convey and acquire new information. Their effectiveness and memorability require that they be understood which, in turn, depends on two factors—whether the story makes sense and the prior knowledge that the listener brings to bear. Comprehension requires the linking of related pieces of information, some provided within the story and some by the listener, in a process establishing coherence. In this study, we examined brain activations associated with story processing. During PET scanning, passages of prose were read twice to subjects during successive scans with the requirement to remember them. These were either standard stories that were readily comprehensible, or unusual stories for which the global theme was very difficult to extract without prior knowledge of the mental framework. This was manipulated by the provision of relevant, irrelevant or no visual cues shortly before the story. Ratings of comprehension provided by the subjects just after each scan confirmed that standard stories were more comprehensible than the unusual stories, as were unusual stories with a mental framework compared with those without. PET results showed activation of anterior and ventral parts of the medial parietal/posterior cingulate cortex in association with hearing unusual stories when subjects were given prior knowledge of what it might be about. Medial ventral orbitofrontal cortex and left temporal pole activations were found to be associated with more general aspects of comprehension. Medial parietal cortex (precuneus) and left prefrontal cortex were associated with story repetition. We suggest that while the temporal pole is involved in the linking of propositions to build a narrative, the anterior medial parietal/posterior cingulate cortex is concerned with linking this information with prior knowledge. All of this occurs in the context of a general memory processing/retrieval system that includes the posterior parietal (precuneus) and prefrontal cortex. Knowledge of how distinct brain regions contribute differentially to aspects of comprehension and memory has implications for understanding how these processes break down in conditions of brain injury or disease.

Kahane, P.; Merlet, I.; Grégoire, M. C.; Munari, C.; Perret, J.

doi: 10.1093/brain/122.10.1851pmid: 10506088

Partial epileptic seizures are known to cause a focal increase in cerebral blood flow (CBF). However, quantified studies of ictal CBF changes under intracranial EEG control are still needed to assess the relationships in time and space between CBF changes and electrical discharges. Ten patients undergoing an intracerebral stereotaxic EEG (stereo-EEG) investigation for epilepsy surgery were prospectively studied for local perfusion changes. These were measured by H 2 15 O-PET during 12 subclinical or mild symptomatic focal epileptic discharges induced by intracerebral electrical stimulation of the hippocampus (eight), amygdala (two), temporal pole (one) and fusiform gyrus (one). This study aimed to assess whether a significant focal blood flow change reflected the geographical extent of the underlying coincident epileptic discharge, as measured by this method at seizure onset. No significant CBF change was observed on test–retest at rest or during ineffective electrical stimulations outside the epileptogenic area. Compared with the resting condition, a significant focal perfusion increase of 16–55% occurred during eight discharges, there was no CBF change in three and a significant CBF decrease in one. Ictal CBF increases were mostly associated with low-voltage fast activity, but their magnitude had no obvious link with the duration of the discharge (range 8–106 s). Regional analysis of ictal PET was performed in 10 anatomical areas during each of the 12 discharges. Of all the 120 regions, 59 were not explored by intracerebral electrodes and 14 (24%) of these demonstrated ictal CBF changes. In 43 of the 61 regions explored by stereo-EEG (70.5%), PET and depth EEG findings converged, showing either a CBF change in a discharging area or no CBF change in a region unaffected by the discharge. Areas of increased CBF indicated an underlying epileptic discharge in almost 100% of the cases. Conversely, of the 18 regions showing discrepancies between intracerebral recordings and PET data, 17 were discharging regions showing no ictal CBF changes. Thus, a focal CBF increase, when detected at the seizure onset concomitantly with the initial low-voltage fast activity, was a reliable marker of an underlying epileptic discharge. It emphasizes the importance of injecting blood-flow tracers as soon as possible after detection of the discharge in routine clinical studies, even at a subclinical stage of the seizure. However, the extent of significant ictal CBF changes can be more restricted than that of the electrical discharge, thus limiting the reliability of ictal CBF images for outlining the contours of a tailored cortectomy.

Sirigu, Angela; Daprati, Elena; Pradat-Diehl, Pascale; Franck, Nicolas

doi: 10.1093/brain/122.10.1867pmid: 10506089

Three apraxic patients with lesions in the left parietal cortex were required to execute finger movements with either hand, while the visual feedback they received about the movement was manipulated systematically. We used a device which allowed us to present on a video monitor either the patient's hand or the examiner's hand simultaneously performing an identical or a different movement. In each trial, patients were required to decide whether the hand shown on the screen was their own or not. Hand movements produced in response to verbal command included simple (single-finger extension) and complex gestures (multi-finger extension). Ownership judgements were analysed and compared with those produced by six normal controls and two non-apraxic neurological patients. Apraxic patients and controls accurately recognized their own hand on the screen (own movement condition) and correctly identified the viewed hand as the examiner's when it performed a movement different from their own movement (incongruent movement condition). However, when the viewed hand was the examiner's hand executing their own movement (congruent movement condition), apraxic patients were significantly more impaired than controls. When the results were analysed as a function of gesture type, the number of correct responses was significantly lower for apraxic patients with respect to controls only for complex gestures. Interestingly, when patients executed the finger gestures inaccurately, they still failed to recognize the examiner's hand as alien, and claimed that the correct movement presented on the screen was their own. These results confirm that parietal lesions alter the representational aspects of gestures, and suggest a failure in evaluating and comparing internal and external feedback about movement. We conclude that the parietal cortex plays an important role in generating and maintaining a kinaesthetic model of ongoing movements.

Grèzes, J.; Costes, N.

doi: 10.1093/brain/122.10.1875pmid: 10506090

PET was used to explore the neural network involved in the perception of meaningless action. In two conditions, subjects observed learned and unknown meaningless actions without any purpose. In two other conditions, subjects observed the same type of stimuli for later imitation. The control condition, which consisted of the presention of stationary hands, served as a baseline. Unsurprisingly, a common network that forms part of the dorsal pathway was engaged in all conditions when compared with stationary hands, and this was interpreted as being devoted to the analysis of hand movements. One of the most striking results of the present study was that some brain areas were strongly modulated by the learning level, independent of the subject's intention. Two different effects were observed: a reduced activity in posterior regions within the common network, which correlated with specific increases in the frontopolar area 10 and in the angular gyrus during the perception of learned meaningless actions compared with the perception of unknown actions. Finally, the major effect of the subject's intention to imitate was a strong increase in the dorsal pathway extending to the lateral premotor cortex and to the dorsolateral prefrontal cortex, which reflects the information processing needed for prospective action. Overall, our results provide evidence for both an effect of the visuomotor learning level and of the subject's intention on the neural network involved during the perception of human meaningless actions.

Forss, Nina; Hietanen, Marja; Salonen, Oili

doi: 10.1093/brain/122.10.1889pmid: 10506091

To study the effects of parietal lesions on activation of the human somatosensory cortical network, we measured somatosensory evoked fields to electric median nerve stimuli, using a whole-scalp 122-channel neuromagnetometer, from six patients with cortical right-hemisphere stroke and from seven healthy control subjects. In the control subjects, unilateral stimuli elicited responses which were satisfactorily accounted for by modelled sources in the contralateral primary (SI) and bilateral secondary (SII) somatosensory cortices. In all patients, stimulation of the right median nerve also activated the SI and SII cortices of the healthy left hemisphere. However, the activation pattern was altered, suggesting diminished interhemispheric inhibition via callosal connections after right-sided stroke. Responses to left median nerve stimuli showed large interindividual variability due to the different extents of the lesions. The strength of the 20-ms response, originating in the SI cortex, roughly reflected the severity of the tactile impairment. Right SII responses were absent in patients with abnormal right SI responses, whereas the left SII was active in all patients, regardless of the responsiveness of the right SI and/or SII. Our results suggest that the human SI and SII cortices may be sequentially activated within one hemisphere, whereas SII ipsilateral to the stimulation may receive direct input from the periphery, at least when normal input from SI is interrupted.

Brunswick, N.; McCrory, E.; Price, C. J.; Frith, C. D.

doi: 10.1093/brain/122.10.1901pmid: 10506092

Two groups of male university students who had been diagnosed as dyslexic when younger, and two groups of control subjects of similar age and IQ to the dyslexics, were scanned whilst reading aloud and during a task where reading was implicit. The dyslexics performed less well than their peers on a range of literacy tasks and were strikingly impaired on phonological tasks. In the reading aloud experiment, simple words and pseudowords were presented at a slow pace so that reading accuracy was equal for dyslexics and controls. Relative to rest, both normal and dyslexic groups activated the same peri- and extra-sylvian regions of the left hemisphere that are known to be involved in reading. However, the dyslexic readers showed less activation than controls in the left posterior inferior temporal cortex (Brodmann area (BA) 37, or Wernicke's Wortschatz), left cerebellum, left thalamus and medial extrastriate cortex. In the implicit reading experiment, word and pseudoword processing was contrasted to visually matched false fonts while subjects performed a feature detection paradigm. The dyslexic readers showed reduced activation in BA 37 relative to normals suggesting that this group difference, seen in both experiments, resides in highly automated aspects of the reading process. Since BA 37 has been implicated previously in modality-independent naming, the reduced activation may indicate a specific impairment in lexical retrieval. Interestingly, during the reading aloud experiment only, there was increased activation for the dyslexics relative to the controls in a pre-motor region of Broca's area (BA 6/44). We attribute this result to the enforced use of an effortful compensatory strategy involving sublexical assembly of articulatory routines. The results confirm previous findings that dyslexic readers process written stimuli atypically, based on abnormal functioning of the left hemisphere reading system. More specifically, we localize this deficit to the neural system underlying lexical retrieval.

Ashby, P.; Kim, Y. J.; Kumar, R.; Lang, A. E.

doi: 10.1093/brain/122.10.1919pmid: 10506093

The effects of stimulation through macroelectrodes implanted in the subthalamic nucleus (STN) were studied in 14 patients with parkinsonism. Single stimuli delivered directly to the STN electrodes with an external stimulator modulated voluntary electromyography (EMG) of contralateral muscles in most patients. A short-latency facilitation (`peak') was attributed to the activation of the corticospinal system. A longer latency inhibition (`dip'), often preceded or followed by facilitations, appeared to arise from the activation of large-diameter fibres running parallel to the electrode and to be transmitted through the motor cortex. It is possible that the dip could result from the inhibition of thalamocortical neurons. With high-frequency stimulation (~100 Hz) the peaks occurred at the stimulus frequency; the dips became confluent and outlasted the duration of the stimulus train. There was no evidence that high-frequency stimulation produced `blocking'. The studies were repeated in 12 patients a mean of 5.8 months after implantation of the stimulator. The same short-latency effects were obtained. They were present on 7 out of 23 sides at the settings in use and on the majority of sides if the stimulus intensity was slightly increased. There was no clear relationship between these short-latency effects and the patients' overall clinical improvement; the effects may result from the spread of current to large-fibre systems near the STN. In five patients, high-frequency stimulation on one side immediately reduced tremor in the contralateral limbs. This effect arose from the activation of large-diameter fibres and, like the dip, had about the same threshold at each of the contacts. Frequencies as low as 70 Hz were sufficient. We conclude that the control of tremor by STN stimulation is due to the activation of a large-fibre system.