Functional and structural asymmetry in primary motor cortex in Asperger syndrome: a navigated TMS and imaging study.

Motor functions are frequently impaired in Asperger syndrome (AS). In this study, we examined the motor cortex structure and function using navigated transcranial magnetic stimulation (nTMS) and voxel-based morphometry (VBM) and correlated the results with the box and block test (BBT) of manual dexterity and physical activity in eight boys with AS, aged 8-11 years, and their matched controls. With nTMS, we found less focused cortical representation areas of distinct hand muscles in AS. There was hemispheric asymmetry in the motor maps, silent period duration and active MEP latency in the AS group, but not in controls. Exploratory VBM analysis revealed less gray matter in the left postcentral gyrus, especially in the face area, and less white matter in the precentral area in AS as compared to controls. On the contrary, in the right leg area, subjects with AS displayed an increased density of gray matter. The structural findings of the left hemisphere correlated negatively with BBT score in controls, whereas the structure of the right hemisphere in the AS group correlated positively with motor function as assessed by BBT. These preliminary functional (neurophysiological and behavioral) findings are indicative of asymmetry, and co-existing structural alterations may reflect the motor impairments causing the deteriorations in manual dexterity and other motor functions commonly encountered in children with AS.

Posttraumatic epilepsy - disease or comorbidity?

Traumatic brain injury (TBI) can cause a myriad of sequelae depending on its type, severity, and location of injured structures. These can include mood disorders, posttraumatic stress disorder and other anxiety disorders, personality disorders, aggressive disorders, cognitive changes, chronic pain, sleep problems, motor or sensory impairments, endocrine dysfunction, gastrointestinal disturbances, increased risk of infections, pulmonary disturbances, parkinsonism, posttraumatic epilepsy, or their combinations. The progression of individual pathologies leading to a given phenotype is variable, and some progress for months. Consequently, the different post-TBI phenotypes appear within different time windows. In parallel with morbidogenesis, spontaneous recovery occurs both in experimental models and in human TBI. A great challenge remains; how can we dissect the specific mechanisms that lead to the different endophenotypes, such as posttraumatic epileptogenesis, in order to identify treatment approaches that would not compromise recovery?

Non-invasive mapping of bilateral motor speech areas using navigated transcranial magnetic stimulation and functional magnetic resonance imaging.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a modern precise method to activate and study cortical functions noninvasively. We hypothesized that a combination of nTMS and functional magnetic resonance imaging (fMRI) could clarify the localization of functional areas involved with motor control and production of speech. NEW METHOD: Navigated repetitive TMS (rTMS) with short bursts was used to map speech areas on both hemispheres by inducing speech disruption during number recitation tasks in healthy volunteers. Two experienced video reviewers, blinded to the stimulated area, graded each trial offline according to possible speech disruption. The locations of speech disrupting nTMS trials were overlaid with fMRI activations of word generation task. COMPARISON WITH EXISTING METHODS: Speech disruptions were produced on both hemispheres by nTMS, though there were more disruptive stimulation sites on the left hemisphere. Grade of the disruptions varied from subjective sensation to mild objectively recognizable disruption up to total speech arrest. The distribution of locations in which speech disruptions could be elicited varied among individuals. On the left hemisphere the locations of disturbing rTMS bursts with reviewers' verification followed the areas of fMRI activation. Similar pattern was not observed on the right hemisphere. CONCLUSIONS: The reviewer-verified speech disruptions induced by nTMS provided clinically relevant information, and fMRI might explain further the function of the cortical area. nTMS and fMRI complement each other, and their combination should be advocated when assessing individual localization of speech network.

Locating and Outlining the Cortical Motor Representation Areas of Facial Muscles With Navigated Transcranial Magnetic Stimulation.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) has become established as an accurate noninvasive technique for mapping the functional motor cortex for the representation areas of upper and lower limb muscles but not yet for facial musculature. OBJECTIVE: To characterize the applicability and clinical impact of using nTMS to map cortical motor areas of facial muscles in healthy volunteers and neurosurgical tumor patients. METHODS: Eight healthy volunteers and 12 patients with tumor were studied. The motor threshold (MT) was determined for the abductor pollicis brevis and mentalis muscles. The lateral part of the motor cortex was mapped with suprathreshold stimulation intensity, and motor evoked potentials were recorded from several facial muscles. The patient protocol was modified according to the clinical indication. RESULTS: In all healthy subjects, motor evoked potentials were elicited in the mentalis (mean latency, 13.4 milliseconds) and orbicularis oris (mean latency, 12.6 milliseconds) muscles. At 110% of MT of the mentalis, the motor evoked potentials of facial muscles were elicited mainly in the precentral gyrus but also from one gyrus anterior and posterior to it. The cortical areas applicable for mapping were limited by an artifact attributable to direct peripheral nerve stimulation. The mapping protocol was successful in 10 of 12 tumor patients at locating the representation area of the lower facial muscles. The MT of the facial muscles was significantly higher than that of the abductor pollicis brevis. CONCLUSION: nTMS is an applicable and clinically beneficial noninvasive method to preoperatively map the cortical representation areas of the facial muscles in the lower part of the face. Instead of using the MT of the abductor pollicis brevis, the stimulus intensity during mapping should be proportioned to the MT of a facial muscle.

Projections from the amygdaloid complex to the piriform cortex: A PHA-L study in the rat.

Projections from the amygdala to the piriform cortex are proposed to provide a pathway via which the emotional system can modulate the processing of olfactory information as well as mediate the spread of seizure activity in epilepsy. To understand the details of the distribution and topography of these projections, we injected the anterograde tracer Phaseolus vulgaris-leucoagglutinin into different nuclear divisions of the amygdaloid complex in 101 rats and analyzed the distribution and density of projections in immunohistochemically processed preparations. The heaviest projections from the amygdala to the piriform cortex originated in the medial division of the lateral nucleus, the periamygdaloid and sulcal subfields of the periamygdaloid cortex, and the posterior cortical nucleus. The heaviest terminal labeling was observed in layers Ib and III of the medial aspect of the posterior piriform cortex. Lighter projections to the posterior piriform cortex originated in the dorsolateral division of the lateral nucleus, the magnocellular and parvicellular divisions of the basal and accessory basal nuclei, and the anterior cortical nucleus. The projections to the anterior piriform cortex were light and originated in the dorsolateral and medial divisions of the lateral nucleus, the magnocellular division of the basal and accessory basal nuclei, the anterior and posterior cortical nuclei, and the periamygdaloid subfield of the periamygdaloid cortex. The results indicate that only selective amygdaloid nuclei or their subdivisions project to the piriform cortex. In addition, substantial projections from several amygdaloid nuclei converge in the medial aspect of the posterior piriform cortex. Via these projections, the amygdaloid complex can modulate the processing of olfactory information in the piriform cortex. In pathologic conditions such as epilepsy, these connections might provide pathways for the spread of seizure activity from the amygdala to extra-amygdaloid regions.

Projections from the amygdaloid complex to the claustrum and the endopiriform nucleus: a Phaseolus vulgaris leucoagglutinin study in the rat.

The claustrum and the endopiriform nucleus contribute to the spread of epileptiform activity from the amygdala to other brain areas. Data of the distribution of pathways underlying the information flow between these regions are, however, incomplete and controversial. To investigate the projections from the amygdala to the claustrum and the endopiriform nucleus, we injected the anterograde tracer Phaseolus vulgaris leucoagglutinin into various divisions of the amygdaloid complex, including the lateral, basal, accessory basal, central, anterior cortical and posterior cortical nuclei, the periamygdaloid cortex, and the amygdalohippocampal area in the rat. Analysis of immunohistochemically processed sections reveal that the heaviest projections to the claustrum originate in the magnocellular division of the basal nucleus. The projection is moderate in density and mainly terminates in the dorsal aspect of the anterior part of the claustrum. Light projections from the parvicellular and intermediate divisions of the basal nucleus terminate in the same region, whereas light projections from the accessory basal nucleus and the lateral division of the amygdalohippocampal area innervate the caudal part of the claustrum. The most substantial projections from the amygdala to the endopiriform nucleus originate in the lateral division of the amygdalohippocampal area. These projections terminate in the central and caudal parts of the endopiriform nucleus. Lighter projections originate in the anterior and posterior cortical nuclei, the periamygdaloid cortex, the medial division of the amygdalohippocampal area, and the accessory basal nucleus. These data provide an anatomic basis for recent functional studies demonstrating that the claustrum and the endopiriform nucleus are strategically located to synchronize and spread epileptiform activity from the amygdala to the other brain regions. These topographically organized pathways also provide a route by means of which the claustrum and the endopiriform nucleus have access to inputs from the amygdaloid networks that process emotionally significant information.

Comparison of the distribution of calcium-binding proteins and intrinsic connectivity in the lateral nucleus of the rat, monkey, and human amygdala.

A large amount of anatomic, electrophysiologic, pharmacologic, and behavioral data published over the past decade has provided novel insight into the function of the amygdala in the rat. An important question remains as to how well the data obtained in the rat amygdala can be extrapolated to primates. To address this issue from a functional neuroanatomic point of view, we compared the recently published data on the distribution of calcium-binding proteins (parvalbumin, calbindin-D(28k), calretinin) and intrinsic connectivity in the rat, monkey, and human amygdala. The aim of our ongoing analysis is twofold: (1) to determine whether the nuclei with the "same name" in the three species are chemoarchitectonically similar and (2) to determine whether the intradivisional, interdivisional, and internuclear connectivity is similarly organized in the rat and monkey. We focused on the lateral nucleus, which is the major recipient of thalamic and cortical sensory information directed to the amygdala and provides the most widespread intraamygdaloid connections. Our analysis suggests many similarities in the organization of chemoarchitectonics and intrinsic connectivity of the different subdivisions of the lateral nucleus of the rat, monkey, and human amygdala. There are also dissimilarities, however, which might relate to differences in the function of the amygdala in rodents and primates.

Projections from the posterior cortical nucleus of the amygdala to the hippocampal formation and parahippocampal region in rat.

The posterior cortical nucleus of the amygdala is involved in the processing of pheromonal information and presumably participates in ingestive, defensive, and reproductive behaviors as a part of the vomeronasal amygdala. Recent studies suggest that the posterior cortical nucleus might also modulate memory processing via its connections to the medial temporal lobe memory system. To investigate the projections from the posterior cortical nucleus to the hippocampal formation and the parahippocampal region, as well as the intra-amygdaloid connectivity in detail, we injected the anterograde tracer phaseolus vulgaris-leucoagglutinin into different rostrocaudal levels of the posterior cortical nucleus. Within the hippocampal formation, the stratum lacunosum-moleculare of the temporal CA1 subfield and the adjacent molecular layer of the proximal temporal subiculum received a moderate projection. Within the parahippocampal region, the ventral intermediate, dorsal intermediate, and medial subfields of the entorhinal cortex received light to moderate projections. Most of the labeled terminals were in layers I, II, and III. In the ventral intermediate subfield, layers V and VI were also moderately innervated. Layers I and II of the parasubiculum received a light projection. There were no projections to the presubiculum or to the perirhinal and postrhinal cortices. The heaviest intranuclear projection was directed to the deep part of layer I and to layer II of the posterior cortical nucleus. There were moderate-to-heavy intra-amygdaloid projections terminating in the bed nucleus of the accessory olfactory tract, the central division of the medial nucleus, and the sulcal division of the periamygdaloid cortex. Our data suggest that via these topographically organized projections, pheromonal information processed within the posterior cortical nucleus can influence memory formation in the hippocampal and parahippocampal areas. Also, these pathways provide routes through which seizure activity can spread from the epileptic amygdala to the surrounding region of the temporal lobe.