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Objective: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. Methods: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. Results: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. Conclusions: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction. (c) 2006 Elsevier Inc. All rights reserved.

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.

As a central fear processor of the brain, the amygdala initiates a cascade of critical physiological and behavioral responses. Neuroimaging studies have shown that the human amygdala responds not only to fearful and angry facial expressions but also to fearful and threatening scenes such as attacks, explosions, and mutilations. Given the relative importance of facial expressions in adaptive social behavior, we hypothesized that the human amygdala would exhibit a stronger response to angry and fearful facial expressions in comparison to other fearful and threatening stimuli. Twelve subjects completed two tasks while undergoing fMRI: matching angry or fearful facial expressions, and matching scenes depicting fearful or threatening situations derived from the International Affective Picture System (IAPS). While there was an amygdala response to both facial expressions and IAPS stimuli, direct comparison revealed that the amygdala response to facial expressions was significantly greater than that to IAPS stimuli. Autonomic reactivity, measured by skin conductance responses, was also greater to facial expressions. These results suggest that the human amygdala shows a stronger response to affective facial expressions than to scenes, a bias that should be considered in the design of experimental paradigms interested in probing amygdala function.

We reviewed the brain MRI of 66 patients with the adult form of myotonic dystrophy type 1 (DM1) to evaluate the extent and significance of white matter involvement and to look for a pattern of MRI abnormalities suggestive of DM1. White matter lesions (WMLs) and large Virchow Robin spaces (VRSs) were rated by semiquantitative methods and the signal intensity of white matter superior and posterior to the trigones (WMPST) by reference to standard images. Disease duration was correlated positively with WML and negatively with VRS scores. Patients were divided into four groups according to increasing severity of WMPST involvement: group A with mild WMPST hyperintensity, group B with large VRSs and mild or moderate WMPST hyperintensity, group C with moderate WMPST hyperintensity or mild WMPST hyperintensity with small WMLs, group D with severe WMPST hyperintensity or moderate WMPST hyperintensity with small WMLs. Disease duration, muscular impairment, lobar WMLs and brain atrophy significantly increased from groups A and B (not significantly different) to C and from C to D, while convexity VRSs significantly decreased from group B to C and from C to D. Lobar white matter involvement in DM1 seems progressive during the disease and may be characterized initially by large VRSs or mild WMPST hyperintensity, then by small WMLs or moderate WMPST hyperintensity, and finally by more extensive and confluent WMLs or diffuse white matter hyperintensity and by brain atrophy.

BACKGROUND: There are well-defined and characteristic age-related deficits in motor abilities that may reflect structural and chemical changes in the aging brain. OBJECTIVE: To delineate age-related changes in the physiology of brain systems subserving simple motor behavior. METHODS: Ten strongly right-handed young (50 years of age) subjects with no evidence of cognitive or motor deficits participated in the study. Whole-brain functional imaging was performed on a 1.5-T MRI scanner using a spiral pulse sequence while the subjects performed a visually paced "button-press" motor task with their dominant right hand alternating with a rest state. RESULTS: Although the groups did not differ in accuracy, there was an increase in reaction time in the elderly subjects (mean score plus minus SD, young subjects = 547 +/- 97 ms, elderly subjects = 794 +/- 280 ms, p < 0.03). There was a greater extent of activation in the contralateral sensorimotor cortex, lateral premotor area, supplementary motor area, and ipsilateral cerebellum in the elderly subjects relative to the young subjects (p < 0.001). Additional areas of activation, absent in the young subjects, were seen in the ipsilateral sensorimotor cortex, putamen (left > right), and contralateral cerebellum of the elderly subjects. CONCLUSIONS: The results of this study show that elderly subjects recruit additional cortical and subcortical areas even for the performance of a simple motor task. These changes may represent compensatory mechanisms invoked by the aging brain, such as reorganization and redistribution of functional networks to compensate for age-related structural and neurochemical changes.

The human brain is a network of a large number of different brain regions characterized by specific task and function, but which are continuously sharing information with each other. Functional communication between brain regions is likely to play a key role in complex brain processes, thriving on the continuous integration of information across different regions of the brain. This makes the examination of brain functional connectivity (FC) of high importance, providing new insights in the human brain organization. In the context of functional neuroimaging, FC is related to the relationship between the neuronal activation patterns of anatomically separated brain regions, reflecting the level of functional communication between regions. During resting-state (RS) studies, volunteers were instructed to relax while their level of spontaneous brain activity was measured throughout the period of the experiment. Biswal and colleagues were the first to demonstrate that during rest the left and right hemispheric regions of the primary motor network are not silent, but show a high correlation between their fMRI BOLD time-series, suggesting ongoing information processing and ongoing FC between these regions during rest. Several studies have replicated these pioneering results, showing a high level of FC also between regions of other known functional networks. In fact, the spontaneous BOLD signal fluctuations are topographically organized in highly reproducible functional networks, called RS networks (RSNs). The most commonly reported RSNs are the default mode network (DMN), the fronto-parietal (or executive) network (FPN), the sensorimotor network (SMN) and the visual and auditory networks. Several RS-fMRI studies have recently demonstrated disrupted RSNs FC in patients suffering from chronic pain conditions suggesting that pain has a widespread impact on overall brain FC. More recently, RS-fMRI has been applied in studies focused on migraine, to assess alterations of baseline intrinsic brain activity, likely related to long term migraine attacks. Along this research line, several studies have analysed the alteration of baseline FC within different RSNs in both patients with migraine without aura and migraine with aura. All this body of scientific data has to be interpreted with caution because of small sample sizes, patients’ clinical heterogeneity and sometimes lack of consistent methodological approach. However, the interpretation of the biological significance of these various FC changes could remain incomplete without a combination of expanding genomic information about neurochemical pathways and genetic polymorphisms linked to specific migraine phenotypes or subtypes.

Background Despite the fact that the clinical features of migraine are well described, the relationship between migraine and cognitive performance is still poorly understood. Indeed, some authors have reported the presence of cognitive deficits in patients with migraine without aura (MwoA) and with aura (MwA) whereas others have not confirmed these findings. Although neuropsychological studies in migraine are not conclusive, the most likely pattern of neuropsychological impairment would relate to the cognitive domain of executive functions (EF) [1]. Recent imaging studies have shown a significant functional connectivity decrease within the fronto-parietal networks (FPN), known to be associated with EF, in patients with MwoA in absence of significant executive dysfunction [2]. Objective To further explore FPN functional connectivity in patients with MwA and patients with MwoA, in the interictal period. Methods Using resting-state functional magnetic resonance imaging (RS-fMRI), we compared functional connectivity within the FPN in 20 patients with MwA, versus 20 sex- and agematched healthy controls (HC). To examine the specificity of any observed differences in FPN functional connectivity between patients and HC, we further studied 20 age- and sex-matched patients with MwoA. Furthermore, we assessed the correlation between functional connectivity within FPN and EF in both migraine groups. Finally, we used voxel-based morphometry to assess whether between-group differences in functional connectivity were dependent on structural differences. Results Neuropsychological data revealed no significant executive dysfunction in both migraine groups compared to HC. RS-fMRI showed that both MwA and MwoA patients, compared to HC, had a significant functional connectivity decrease within the right FPN and specifically in the middle frontal gyrus and the dorsal anterior cingulate cortex. There were no structural differences between the three groups. Conclusions Our data demonstrate that, even in the absence of clinically evident EF deficits, MwA and MwoA are associated with reduced FPN functional connectivity. We suggest that disrupted FPN functional connectivity might be only a part of a complex cascade that terminates in a migraine attack. In this context, FPN abnormalities may be the neuronal substrate on which biological, genetic and environmental factors could induce, and in turn correlate with, migraine attacks mostly characterized by high pain intensity in patients with MwoA and aura phenomenon in patients with MwA. In other terms, observed FPN connectivity changes may represent a migraine biomarker, probably related to well-known maladaptive stress response in migraine patients. Written informed consent to publish was obtained from the patient(s).

Vestibular migraine (VM) has been increasingly recognized as a possible cause of episodic vertigo [1], but its pathophysiology is still unclear. In our previous fMRI study, we had observed a significantly increased thalamic activation in patients with vestibular migraine (VM) during vestibular stimulation in comparison with patients with migraine without aura (MwoA) and healthy controls (HC) [2]. Recently, a voxel based morphometry (VBM) study has shown gray matter volume reduction in brain areas involved in pain and vestibular processing [3]. However, no studies have yet investigated white matter (WM) microstructural abnormalities in patients with VM.