Paolo Cecchi

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex. We aimed to investigate the cortical motor circuitries in ALS patients by a combined structural and functional approach. Twenty patients with definite ALS and 16 healthy subjects underwent a structural examination with acquisition of a 3D T1-weighted sequence and fMRI examination during a maximal force handgrip task executed with the right-hand, the left-hand and with both hands simultaneously. The T1-weighted images were analyzed with Voxel-Based Morphometry (VBM) that showed several clusters of reduced cortical GM in ALS patients compared to controls including the pre and postcentral gyri, the superior, middle and inferior frontal gyri, the supplementary motor area, the superior and inferior parietal cortices and the temporal lobe, bilaterally but more extensive on the right side. In ALS patients a significant hypoactivation of the primary sensory motor cortex and frontal dorsal premotor areas as compared to controls was observed. The hypoactivated areas matched with foci of cortical atrophy demonstrated by VBM. The fMRI analysis also showed an enhanced activation in the ventral premotor frontal areas and in the parietal cortex pertaining to the fronto-parietal motor circuit which paralleled with disease progression rate and matched with cortical regions of atrophy. The hyperactivation of the fronto-parietal circuit was asymmetric and prevalent in the left hemisphere. VBM and fMRI identified structural and functional markers of an extended cortical damage within the motor circuit of ALS patients. The functional changes in non-primary motor cortices pertaining to fronto-parietal circuit suggest an over-recruitment of a pre-existing physiological sensory-motor network. However, the concomitant fronto-parietal cortical atrophy arises the possibility that such a hyper-activation reflects cortical hyper-excitability due to loss of inhibitory inter-neurons.

Comparison of 3T and 7T Susceptibility-Weighted Angiography of the Substantia Nigra in Diagnosing Parkinson Disease

BACKGROUND AND PURPOSE: Standard neuroimaging fails in defining the anatomy of the substantia nigra and has a marginal role in the diagnosis of Parkinson disease. Recently 7T MR target imaging of the substantia nigra has been useful in diagnosing Parkinson disease. We performed a comparative study to evaluate whether susceptibility-weighted angiography can diagnose Parkinson disease with a 3T scanner. MATERIALS AND METHODS: Fourteen patients with Parkinson disease and 13 healthy subjects underwent MR imaging examination at 3T and 7T by using susceptibility-weighted angiography. Two expert blinded observers and 1 neuroradiology fellow evaluated the 3T and 7T images of the sample to identify substantia nigra abnormalities indicative of Parkinson disease. Diagnostic accuracy and intra- and interobserver agreement were calculated separately for 3T and 7T acquisitions. RESULTS: Susceptibility-weighted angiography 7T MR imaging can diagnose Parkinson disease with a mean sensitivity of 93%, specificity of 100%, and diagnostic accuracy of 96%. 3T MR imaging diagnosed Parkinson disease with a mean sensitivity of 79%, specificity of 94%, and diagnostic accuracy of 86%. Intraobserver and interobserver agreement was excellent at 7T. At 3T, intraobserver agreement was excellent for experts, and interobserver agreement ranged between good and excellent. The less expert reader obtained a diagnostic accuracy of 89% at 3T. CONCLUSIONS: Susceptibility-weighted angiography images obtained at 3T and 7T differentiate controls from patients with Parkinson disease with a higher diagnostic accuracy at 7T. The capability of 3T in diagnosing Parkinson disease might encourage its use in clinical practice. The use of the more accurate 7T should be supported by a dedicated cost-effectiveness study.

Decreased and increased cortical activation coexist in de novo Parkinson's disease

Previous fMRI studies using motor tasks yielded conflicting results concerning the activation pattern in Parkinsons disease (PD) patients. Possible explanations of these discrepancies include differences in the clinical features of the examined patients and in the executed tasks and incomplete task monitoring. We evaluated with fMRI 20 patients with untreated de-novo PD and 11 healthy controls with a simple motor task consisting of self-paced continuous right hand-tapping. The task was monitored on-line with a dedicated device which measures the strength and frequency of the tapping. Fifteen patients performed the task correctly. The frequency was not significantly different, whereas force was slightly different between patients (26.4+/-3.0 N) and controls (28.5+/-2.4 N) (p=0.046, Mann-Whitney U-test). After insertion of the subjects frequency and force as covariate variables in the model, PD patients compared to controls showed areas of significantly [Z statistic image>5.1 and p< or =0.05 (corrected) cluster significance] lower activation in the left primary sensorimotor (SM1) cortex and cerebellum and higher activation in the left temporal-parietal cortex adjacent to the SM1 and in right SM1. Furthermore in PD patients the disease severity evaluated with the Hoehn and Yahr staging system correlated significantly [Z statistic image>2.3 and p< or =0.05 (corrected) cluster significance] with activation of left SM1 and supplementary motor area and cingulum, bilaterally. The mixed pattern of decreased and increased cortical activation in de novo PD patients possibly reflects the coexistence of cortical deafferentation, and compensatory phenomena by cortico-cortical circuits.

The burden of microstructural damage modulates cortical activation in elderly subjects with MCI and leuko-araiosis. A DTI and fMRI study

The term leuko‐araiosis (LA) describes a common chronic affection of the cerebral white matter (WM) in the elderly due to small vessel disease with variable clinical correlates. To explore whether severity of LA entails some adaptive reorganization in the cerebral cortex we evaluated with functional MRI (fMRI) the cortical activation pattern during a simple motor task in 60 subjects with mild cognitive impairment and moderate or severe (moderate‐to‐severe LA group, n = 46) and mild (mild LA group, n = 14) LA extension on visual rating. The microstructural damage associated with LA was measured on diffusion tensor data by computation of the mean diffusivity (MD) of the cerebral WM and by applying tract based spatial statistics (TBSS). Subjects were examined with fMRI during continuous tapping of the right dominant hand with task performance measurement. Moderate‐to‐severe LA group showed hyperactivation of left primary sensorimotor cortex (SM1) and right cerebellum. Regression analyses using the individual median of WM MD as explanatory variable revealed a posterior shift of activation within the left SM1 and hyperactivation of the left SMA and paracentral lobule and of the bilateral cerebellar crus. These data indicate that brain activation is modulated by increasing severity of LA with a local remapping within the SM1 and increased activity in ipsilateral nonprimary sensorimotor cortex and bilateral cerebellum. These potentially adaptive changes as well lack of contralateral cerebral hemisphere hyperactivation are in line with sparing of the U fibers and brainstem and cerebellar WM tracts and the emerging microstructual damage of the corpus callosum revealed by TBSS with increasing severity of LA. Hum Brain Mapp 35:819–830, 2014.

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease : a motor fMRI study under controlled conditions.

IntroductionNuclear medicine studies in Parkinson’s disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this “functional deafferentation” phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions.MethodsNineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of “8” figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the “8”s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system.ResultsFifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage.ConclusionsIn line with the “deafferentation hypothesis”, fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD.

Neurodegeneration in friedreich's ataxia is associated with a mixed activation pattern of the brain. A fMRI study.

Friedreichs ataxia (FRDA) is associated with a distributed pattern of neurodegeneration in the spinal cord and the brain secondary to selective neuronal loss. We used functional MR Imaging (fMRI) to explore brain activation in FRDA patients during two motor‐sensory tasks of different complexity, i.e. continuous hand tapping and writing of “8” figure, with the right dominant hand and without visual feedback. Seventeen FRDA patients and two groups of age‐matched healthy controls were recruited. Task execution was monitored and recorded using MR‐compatible devices. Hand tapping was correctly performed by 11 (65%) patients and writing of the “8” by 7 (41%) patients. After correction for behavioral variables, FRDA patients showed in both tasks areas of significantly lower activation in the left primary sensory‐motor cortex and right cerebellum. Also left thalamus and right dorsolateral prefrontal cortex showed hypo‐activation during hand tapping. During writing of the “8” task FRDA patients showed areas of higher activation in the right parietal and precentral cortex, globus pallidus, and putamen. Activation of right parietal cortex, anterior cingulum, globus pallidus, and putamen during writing of the “8” increased with severity of the neurological deficit. In conclusion fMRI demonstrates in FRDA a mixed pattern constituted by areas of decreased activation and areas of increased activation. The decreased activation in the primary motor cortex and cerebellum presumably reflects a regional neuronal damage, the decreased activation of the left thalamus and primary sensory cortex could be secondary to deafferentation phenomena, and the increased activation of right parietal cortex and striatum might have a possible compensatory significance. Hum Brain Mapp, 2012.

Self-paced frequency of a simple motor task and brain activation. An fMRI study in healthy subjects using an on-line monitor device.

Application of fMRI to clinical neurology implies the selection of a simple task and control of the task performance. The capability to objectively monitor variables related to task execution is, therefore, important and could improve accuracy of clinical fMRI studies. We assessed the influence of different self-paced frequencies of a simple motor task on brain activation in healthy subjects. A device was developed to measure the force exerted by a subject in pressing an air-filled rubber bulb with the last four fingers of the dominant hand. The task frequency was determined by analysis of the force signal. Nine healthy subjects performed twice the task with self-paced slow (0.35+/-0.09 Hz), intermediate (0.58+/-0.21 Hz) or fast (0.98+/-0.32 Hz) frequency. The device revealed impaired task execution in 1 subject. The coefficient of variation of frequency was 8.7% for slow, 12.2% for intermediate and 15.8% for fast paced task. No significant differences were found comparing the activation maps obtained at slow, intermediate and fast frequencies in the contralateral sensorimotor cortex and ipsilateral cerebellum. Cluster reproducibility was good for location (standard deviation<or=7.3 mm), but poor for signal intensity (coefficient of variation 0-176.8%) and extent (coefficient of variation 1.9-140.6%). In conclusion, self-paced frequency variations of a simple motor task in the 0.2-2 Hz range are not a relevant source of the variability of the fMRI results in healthy subjects. Use of the device for evaluation of the neurologically impaired patients might broaden the clinical applications of fMRI.

Mapping Cortical Degeneration in ALS with Magnetization Transfer Ratio and Voxel-Based Morphometry.

Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1 weighted spoiled gradient recalled sequence with and without MT saturation pulse. A voxel-based analysis (VBA) was adopted in order to automatically compute the regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By using a multimodal image analysis MTr was adjusted for local gray matter (GM) atrophy to investigate if MTr changes can be independent of atrophy of the cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr decrease in motor-related areas and extra-motor frontotemporal cortex. The multimodal image analysis identified areas of isolated MTr decrease in premotor and extra-motor frontotemporal areas. VBM and MTr are capable to detect the distribution of neurodegenerative alterations in the cortical GM of ALS patients, supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging changes exist beyond volume loss in frontotemporal cortices.

Operationalizing mild cognitive impairment criteria in small vessel disease: The VMCI-Tuscany Study

Mild cognitive impairment (MCI) prodromic of vascular dementia is expected to have a multidomain profile.

Abnormal response to photic stimulation in juvenile myoclonic epilepsy: an EEG-fMRI study.

Juvenile myoclonic epilepsy (JME) is a young‐onset electroclinical syndrome, characterized by myoclonic, generalized tonic–clonic, and possibly typical absence seizures. Interictal electroencephalography (EEG) displays 3–6 Hz spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to explore the blood oxygen level–dependent (BOLD) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena seen in patients with photosensitive JME.