Functional Evaluation of Awareness in Vegetative and Minimally Conscious State.

OBJECTIVE: The aim of this study was to assess differences in brain activation in a large sample of Vegetative State (VS) and Minimally Conscious State (MCS) patients, using functional magnetic resonance imaging (fMRI). METHODS: We studied 50 patients four to seven months after brain injury. By using international clinical criteria and validated behavioural scales such as the Glasgow Coma Scale and the Clinical Unawareness Assessment Scale, the patients were grouped into VS (n=23) and MCS (n=27). All patients underwent to fMRI examination. After 6 months, the patients were reassessed using Glasgow Outcome Scale and Revised Coma Recovery Scale. RESULTS: fMRI showed significant (p<0.01, cluster-corrected) brain activation in the primary auditory cortex bilaterally during the acoustic stimuli in patients with both VS and MCS. However, ten patients clinically classified as VS, showed a pattern of brain activation very similar to that of MCS patients. Six months later, these ten VS patients had significant clinical improvement, evolving into MCS, whereas the other VS patients and patients with MCS remained clinically stable. CONCLUSION: Brain activity could help in discerning whether the status of wakefulness in VS is also accompanied by partial awareness, as occurs in MCS. This may have very important prognostic implications.

Functional cortical and cerebellar reorganization in a case of moyamoya disease.

BACKGROUND: Functional studies have been previous reported in stroke patients, but no studies of functional magnetic resonance imaging have been performed in Moyamoya disease. OBJECTIVE: To assess the cortical and cerebellar reorganization in a moyamoya patient. METHODS: We reported a case of a patient suffering from moyamoya disease, undergoing a neuropsychological assessment, a neurocognitive rehabilitative treatment, an electroencephalogram evaluation, and a functional magnetic resonance imaging examination. RESULTS: The subject showed a cognitive impairment, a slow electroencephalogram activity, and the ipsi- and controlateral motor cortex and cerebellar functional magnetic resonance imaging activation. CONCLUSIONS: This is the first functional magnetic resonance imaging case study reported in moyamoya disease. We showed a cortical reorganization, which could play an important role in clinical evaluation and motor recovery. The cerebellar activation, showed after cognitive and motor rehabilitation, could support the idea that the cerebellum contains several cognitive-related subregions involved in different functional networks in moyamoya disease.

Basal ganglia network by constrained spherical deconvolution: a possible cortico-pallidal pathway?

In the recent past, basal ganglia circuitry was simplified as represented by the direct and indirect pathways and by hyperdirect pathways. Based on data from animal studies, we hypothesized a fourth pathway, the cortico-pallidal, pathway, that complements the hyperdirect pathway to the subthalamus. Ten normal brains were analyzed by using the high angular resolution diffusion imaging-constrained spherical deconvolution (CSD)-based technique. The study was performed with a 3T magnetic resonance imaging (MRI) scanner (Achieva, Philips Healthcare, Best, Netherlands); by using a 32-channel SENSE head coil. We showed that CSD is a powerful technique that allows a fine evaluation of both the long and small tracts between cortex and basal ganglia, including direct, indirect, and hyperdirect pathways. In addition, a pathway directly connecting the cortex to the globus pallidus was seen. Our results confirm that the CSD tractography is a valuable technique allowing a reliable reconstruction of small- and long-fiber pathways in brain regions with multiple fiber orientations, such as basal ganglia. This could open a future scenario in which CSD could be used to focally target with deep brain stimulation (DBS) the small bundles within the basal ganglia loops.

The Italian Alzheimer's Disease Neuroimaging Initiative (I-ADNI): validation of structural MR imaging.

BACKGROUND: The North American Alzheimer's Disease Neuroimaging Initiative (NA-ADNI) was the first program to develop standardized procedures for Alzheimer's disease (AD) imaging biomarker collection. OBJECTIVE: We describe the validation of acquisition and processing of structural magnetic resonance imaging (MRI) in different Italian academic AD clinics following NA-ADNI procedures. METHODS: 373 patients with subjective memory impairment (n = 12), mild cognitive impairment (n = 92), Alzheimer's dementia (n = 253), and frontotemporal dementia (n = 16) were enrolled in 9 Italian centers. 22 cognitively healthy elderly controls were also included. MRI site qualification and MP-RAGE quality assessment was applied following the NA-ADNI procedures. Indices of validity were: (i) NA-ADNI phantom's signal-to-noise and contrast-to-noise ratio, (ii) proportion of images passing quality control, (iii) comparability of automated intracranial volume (ICV) estimates across scanners, and (iv) known-group validity of manual hippocampal volumetry. RESULTS: Results on Phantom and Volunteers scans showed that I-ADNI acquisition parameters were comparable with those one of the ranked-A ADNI scans. Eighty-seven percent of I-ADNI MPRAGE images were ranked of high quality in comparison of 69% of NA-ADNI. ICV showed homogeneous variances across scanners except for Siemens scanners at 3.0 Tesla (p = 0.039). A significant difference in hippocampal volume was found between AD and controls on 1.5 Tesla scans (p < 0.001), confirming known group validity test. CONCLUSION: This study has provided standardization of MRI acquisition and imaging marker collection across different Italian clinical units and equipment. This is a mandatory step to the implementation of imaging biomarkers in clinical routine for early and differential diagnosis.

Cortical sources of resting state electroencephalographic alpha rhythms deteriorate across time in subjects with amnesic mild cognitive impairment.

Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with mild cognitive impairment (MCI). Here, we tested the hypothesis that these sources in amnesic MCI subjects further deteriorate over 1 year. To this aim, the resting state eyes-closed EEG data were recorded in 54 MCI subjects at baseline (Mini Mental State Examination I = 26.9; standard error [SE], 0.2) and at approximately 1-year follow-up (13.8 months; SE, 0.5; Mini Mental State Examination II = 25.8; SE, 0.2). As a control, EEG recordings were also performed in 45 normal elderly and in 50 mild Alzheimer's disease subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Cortical EEG sources were estimated using low-resolution brain electromagnetic tomography. Compared with the normal elderly and mild Alzheimer's disease subjects, the MCI subjects were characterized by an intermediate power of posterior alpha1 sources. In the MCI subjects, the follow-up EEG recordings showed a decreased power of posterior alpha1 and alpha2 sources. These results suggest that the resting state EEG alpha sources were sensitive-at least at the group level-to the cognitive decline occurring in the amnesic MCI group over 1 year, and might represent cost-effective, noninvasive and widely available markers to follow amnesic MCI populations in large clinical trials.

The in vivo topography of cortical changes in healthy aging and prodromal Alzheimer's disease.

BACKGROUND: Gray matter atrophy is regarded as a valid marker of neurodegeneration in Alzheimer's disease (AD), but few studies have investigated in detail the topographic changes associated with normal aging. In addition, few studies have compared the changes in the earliest clinical stage of AD (prodromal AD (pAD)) with those of healthy aging. Here we aimed to investigate the topographical distribution of age-related cortical atrophy and to compare it with that associated with prodromal and estabilished AD. METHODS: Structural T1-weighted high-resolution brain magnetic resonance imaging scans were acquired from 60 healthy volunteers (20 young adults, YA: age 32.7 +/- 4.5 years; 40 elderly subjects, HE: age 71.3 +/- 6.2 years), 16 mild cognitive impairment subjects who converted to AD within 2 years (prodromal AD, pAD: age 72.8 +/- 5.4), and 20 mild to moderate AD patients (mAD, age 72.5 +/- 10.3). Cortical gray matter differences were investigated using a surface-based anatomical mesh modeling technique (cortical pattern matching) and region-of-interest (ROI) analyses based on hypothesized brain networks taught to have a functional and a structural link to each other. Differences in cortical atrophy were assessed between groups, as well as the effect of age within groups. RESULTS: HE compared to YA showed a 10-30% deficit in cortical gray matter in widespread frontal, temporal, and parietal regions (p = 0.0001 by permutation testing), 6-13% loss in the visual and sensorimotor cortices (p < 0.01) and up to 13% loss in the direct hippocampal pathway ROIs (p < 0.001). pAD patients showed on average 8-9% cortical loss compared to HE (p < 0.0001), mainly in the left (up to 6% loss, p = 0.06) and right polysynaptic hippocampal pathway ROIs (up to 8% loss, p = 0.01), and in the left and right olfactory/orbitofrontal cortex (up to 12-15% loss, p < 0.001). The pattern of cortical atrophy in mAD versus HE was similar to that in pAD, but was more severe in the direct hippocampal pathway ROIs and sensorimotor, visual and temporal cortices (13-15% loss compared with HE, p < 0.0001). CONCLUSION: Gray matter loss occurs during aging with rates of atrophy even more severe than that observed during the course of AD. These changes may be caused by normal mechanisms. In pAD, cortical atrophy due to disease is milder than that due to aging, maybe resulting from a slowed down velocity of cell loss, but affects specific brain areas. These findings are consistent with the view that AD is not merely accelerated aging.

Is high oral dose L-arginine intake effective in leukoaraiosis? Preliminary data, study protocol and expert's opinion.

BACKGROUND: Leukoraraiosis is worldwide considered as a part of the normal aging process, although it is strongly associated with dementia and other disabilities. The pathogenesis of leukoaraiosis still has not been thoroughly acknowledged, even though chronic ischemia with consequent arteriolosclerosis probably due to endothelial dysfunction has been suggested. Treatment focuses on prevention of lesion formation and progression by aggressive control of risk factors, which should begin at an early age and continue on regular basis. Aim of our protocol is to evaluate the effect of long-term oral administration of high-dose L-arginine (6 g/day at least for 24 months) on white matter lesions and neurological and cognitive functions. MATERIALS AND METHODS: Patients affected by mild to moderate leukoaraiosis will be enrolled in the study. After a complete neurovascular assessment (i.e. accurate blood test examinations, Echocardiography, Doppler ultrasound of the neck and peripheral arteries), they will undergo MRI, specific neuropsychological tests and gait analysis. Patients will be evaluated at baseline, at 6, 12, 18 and 24 month-follow up. Statistical Analysis will be performed using the software R. A significant level of P<0.05 will be set for all the tests. PRELIMINARY DATA: Two of the 4 patients currently enrolled in the study presented a mild improvement in cognitive function. DISCUSSION: Because of its high prevalence in over-65-year-old subjects, we hypothesized that treatment with 6 gr of Larginine, as supplementary dietary option, could be helpful in patients affected by leukoaraiosis to improve the cognitive and gait impairment often observed in these subjects (as demonstrated by the LADIS study).

Resting state cortical electroencephalographic rhythms are related to gray matter volume in subjects with mild cognitive impairment and Alzheimer's disease.

Cortical gray matter volume and resting state cortical electroencephalographic rhythms are typically abnormal in subjects with amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here we tested the hypothesis that in amnesic MCI and AD subjects, abnormalities of EEG rhythms are a functional reflection of cortical atrophy across the disease. Eyes-closed resting state EEG data were recorded in 57 healthy elderly (Nold), 102 amnesic MCI, and 108 AD patients. Cortical gray matter volume was indexed by magnetic resonance imaging recorded in the MCI and AD subjects according to Alzheimer's disease neuroimaging initiative project (http://www.adni-info.org/). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). These rhythms were indexed by LORETA. Compared with the Nold, the MCI showed a decrease in amplitude of alpha 1 sources. With respect to the Nold and MCI, the AD showed an amplitude increase of delta sources, along with a strong amplitude reduction of alpha 1 sources. In the MCI and AD subjects as a whole group, the lower the cortical gray matter volume, the higher the delta sources, the lower the alpha 1 sources. The better the score to cognitive tests the higher the gray matter volume, the lower the pathological delta sources, and the higher the alpha sources. These results suggest that in amnesic MCI and AD subjects, abnormalities of resting state cortical EEG rhythms are not epiphenomena but are strictly related to neurodegeneration (atrophy of cortical gray matter) and cognition.

Neurofunctional assessment in a stroke patient with musical hallucinations.

We reported a case of an elderly female patient affected by musical hallucinations (MHs) as the unique symptom of a right temporal ischemic stroke. A functional magnetic resonance imaging examination was performed in the patient and in five age- and sex-matched normal controls (NC) to detect the complex neural substrate subserving MHs in such a context. Although an activation pattern involving the primary auditory cortex and the temporal associative areas bilaterally was found in the patient and NC, a significant increased activation mostly located in right temporal cortex (in the ischemic area), was observed in the patient. Further functional neuroimaging studies should be performed to detect the complex neural pathways underlying MHs and to find out differences between these hallucinations and real music perception.

Resting state cortical electroencephalographic rhythms and white matter vascular lesions in subjects with Alzheimer's disease: an Italian multicenter study.

Resting state electroencephalographic (EEG) rhythms do not deteriorate with the increase of white matter vascular lesion in amnesic mild cognitive impairment (MCI) subjects [1], although white matter is impaired along Alzheimer's disease (AD). Here we tested whether this is true even in AD subjects. Closed-eye resting state EEG data were recorded in 40 healthy elderly (Nold), 96 amnesic MCI, and 83 AD subjects. White matter vascular lesions were indexed by magnetic resonance imaging recorded in the MCI and AD subjects (about 42% of cases following ADNI standards). The MCI subjects were divided into two sub-groups based on the median of the white matter lesion, namely MCI+ (people with highest vascular load; n = 48) and MCI- (people with lowest vascular load; n = 48). The same was true for the AD subjects (AD+, n = 42; AD-, n = 41). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), beta2 (20-30 Hz), and gamma (30-40 Hz). LORETA software estimated cortical EEG sources. When compared to Nold group, MCI and AD groups showed well known abnormalities of delta and alpha sources. Furthermore, amplitude of occipital, temporal, and limbic alpha 1 sources were higher in MCI+ than MCI- group. As a novelty, amplitude of occipital delta sources was lower in AD+ than AD- group. Furthermore, central, parietal, occipital, temporal, and limbic alpha sources were higher in amplitude in AD+ than AD- group. Amplitude of these sources was correlated to global cognitive status (i.e., Mini Mental State Evaluation score). These results suggest that in amnesic MCI and AD subjects, resting state posterior delta and alpha EEG rhythms do not deteriorate with the increase of white-matter vascular lesion. These rhythms might be more sensitive to AD neurodegenerative processes and cognitive status rather than to concomitant lesions to white matter.