Raffaella Franciotti

Topographic organization of the human primary and secondary somatosensory cortices: comparison of fMRI and MEG findings

We studied MEG and fMRI responses to electric median and tibial nerve stimulation in five healthy volunteers. The aim was to compare the results with those of a previous study using only fMRI on the primary and secondary somatosensory cortices in which the somatotopic organization of SII was observed with fMRI. In the present work we focus on the comparison between fMRI activation and MEG equivalent current dipole (ECD) localizations in the SII area. The somatotopic organization of SII was confirmed by MEG, with the upper limb areas located more anteriorly and more inferiorly than the lower limb areas. In addition a substantial consistency of the ECD locations with the areas of fMRI activation was observed, with an average mismatch of about 1 cm. MEG ECDs and fMRI activation areas showed comparable differences in SI.

Cortical rhythms reactivity in AD, LBD and normal subjects: A quantitative MEG study

The present study evaluated the reactivity of cortical rhythms in 15 Alzheimers disease (AD) patients, 7 Lewy body dementia (LBD) patients and 9 control subjects using a 165 SQUID whole-head MEG system. The absolute power values of the rhythms recorded over different areas over the brain (frontal, parietal, temporal, occipital) were analysed in the 3-47Hz frequency range. The cortical reactivity of the alpha (9-14Hz) and pre-alpha rhythms (7-9Hz) during open and closed eyes conditions differentiated the control group from the patient groups and moderate AD from severe AD and LBD groups, respectively. The cortical reactivity of the slow-band (3-7Hz) obtained by comparing a simple mental task and the rest discriminated the severe AD group from the other groups. In addition, spectral coherence analysis in the alpha band showed that the loss of coherence in AD and LBD patients mainly involved long connections. These results suggest that investigations on rhythms reactivity and spectral coherence might help on the study of the dementias with different etiology.

Comparison between SI and SII responses as a function of stimulus intensity.

In this MEG study we investigated the differences in responses to somatosensory electrical stimuli between primary (SI) and secondary (SII) sensory cortices using 10 different levels of stimulus intensity, starting from below the sensory threshold up to a weak painful level. SI dipole source linearly increased in amplitude as the stimulus intensity raised up to a strong motor level and then saturated at higher stimulation levels. The contralateral and ipsilateral SII dipole source strengths followed the stimulus intensity growing up to the motor threshold, but showed a decrease at the strong motor level, followed by an increase as the stimulus intensity raised towards the weak painful threshold. These results suggest different responses of SI and SII cortices as the intensity of stimulation rises from non-painful to painful values.

Effects of Transcranial Direct Current Stimulation on episodic memory related to emotional visual stimuli.

The present study investigated emotional memory following bilateral transcranial electrical stimulation (direct current of 1 mA, for 20 minutes) over fronto-temporal cortical areas of healthy participants during the encoding of images that differed in affective arousal and valence. The main result was a significant interaction between the side of anodal stimulation and image emotional valence. Specifically, right anodal/left cathodal stimulation selectively facilitated the recall of pleasant images with respect to both unpleasant and neutral images whereas left anodal/right cathodal stimulation selectively facilitated the recall of unpleasant images with respect to both pleasant and neutral images. From a theoretical perspective, this double dissociation between the side of anodal stimulation and the advantage in the memory performance for a specific type of stimulus depending on its pleasantness supported the specific-valence hypothesis of emotional processes, which assumes a specialization of the right hemisphere in processing unpleasant stimuli and a specialization of the left hemisphere in processing pleasant stimuli. From a methodological point of view, first we found tDCS effects strictly dependent on the stimulus category, and second a pattern of results in line with an interfering and inhibitory account of anodal stimulation on memory performance. These findings need to be carefully considered in applied contexts, such as the rehabilitation of altered emotional processing or eye-witness memory, and deserve to be further investigated in order to understand their underlying mechanisms of action.

Improving MEG source localizations: an automated method for complete artifact removal based on independent component analysis.

The major limitation for the acquisition of high-quality magnetoencephalography (MEG) recordings is the presence of disturbances of physiological and technical origins: eye movements, cardiac signals, muscular contractions, and environmental noise are serious problems for MEG signal analysis. In the last years, multi-channel MEG systems have undergone rapid technological developments in terms of noise reduction, and many processing methods have been proposed for artifact rejection. Independent component analysis (ICA) has already shown to be an effective and generally applicable technique for concurrently removing artifacts and noise from the MEG recordings. However, no standardized automated system based on ICA has become available so far, because of the intrinsic difficulty in the reliable categorization of the source signals obtained with this technique. In this work, approximate entropy (ApEn), a measure of data regularity, is successfully used for the classification of the signals produced by ICA, allowing for an automated artifact rejection. The proposed method has been tested using MEG data sets collected during somatosensory, auditory and visual stimulation. It was demonstrated to be effective in attenuating both biological artifacts and environmental noise, in order to reconstruct clear signals that can be used for improving brain source localizations.

Default network is not hypoactive in dementia with fluctuating cognition: an Alzheimer disease/dementia with Lewy bodies comparison.

Default mode network resting state activity in posterior cingulate cortex is abnormally reduced in Alzheimer disease (AD) patients. Fluctuating cognition and electroencephalogram abnormalities are established core and supportive elements respectively for the diagnosis of dementia with Lewy bodies (DLB). Our aim was to assess whether patients with DLB with both of these features have different default mode network patterns during resting state functional magnetic resonance imaging compared with AD. Eighteen patients with DLB, 18 AD patients without fluctuating cognition, and 15 control subjects were selected after appropriate matching and followed for 2-5 years to confirm diagnosis. Independent component analysis with functional connectivity (FC) and Granger causality approaches were applied to isolate and characterize resting state networks. FC was reduced in AD and DLB patients compared with control subjects. Posterior cingulate cortex activity was lower in AD than in control subjects and DLB patients (p < 0.05). Right hemisphere FC was reduced in DLB patients in comparison with control subjects but not in patients with AD, and was correlated with severity of fluctuations (ρ = -0.69; p < 0.01). Causal flow analysis showed differences between patients with DLB and AD and control subjects.

Visual hallucinations in PD and Lewy body dementias: old and new hypotheses.

Visual Hallucinations (VH) are a common non-motor symptom of Parkinson’s Disease (PD) and the Lewy body dementias (LBD) of Parkinsons disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH.

Temporal dynamics of alpha and beta rhythms in human SI and SII after galvanic median nerve stimulation. A MEG study.

In this MEG study, we investigated cortical alpha/sigma and beta ERD/ERS induced by median nerve stimulation to extend previous evidence on different resonant and oscillatory behavior of SI and SII (NeuroImage 13 [2001] 662). Here, we tested whether simple somatosensory stimulation could induce a distinctive sequence of alpha/sigma and beta ERD/ERS over SII compared to SI. We found that for both alpha/sigma (around 10 Hz) and beta (around 20 Hz) rhythms, the latencies of ERD and ERS were larger in bilateral SII than in contralateral SI. In addition, the peak amplitude of alpha/sigma and beta ERS was smaller in bilateral SII than in contralateral SI. These results indicate a delayed and prolonged activation of SII responses, reflecting a protracted information elaboration possibly related to SII higher order role in the processing of somatosensory information. This temporal dynamics of alpha/sigma and beta rhythms may be related to a sequential activation scheme of SI and SII during the somatosensory information processes. Future studies should evaluate in SII the possible different functional significance of alpha/sigma with respect to beta rhythms during somatosensory processing.

Quantitative electroencephalogram utility in predicting conversion of mild cognitive impairment to dementia with Lewy bodies

Mild cognitive impairment (MCI) as a precursor of dementia with Lewy bodies (DLB) is the focus of recent research, trying to explore the early mechanisms and possible biomarkers of DLB. Quantitative electroencephalogram (QEEG) methods are able to differentiate early DLB from Alzheimers disease (AD). The aim of the present study was to assess whether QEEG abnormalities, characterized by dominant frequency <8 Hz and dominant frequency variability >1.5 Hz, typical of early DLB, are already present at the stage of MCI and to evaluate whether EEG abnormalities can predict the development of DLB. Forty-seven MCI subjects were followed for 3 years. EEG recordings were obtained at admission and at the end of the study. At the end of follow-up, 20 subjects had developed probable DLB (MCI-DLB), 14 had probable AD (MCI-AD), 8 did not convert to dementia, 5 developed a non-AD/DLB dementia. One hundred percent of MCI-DLB showed EEG abnormalities at admission. Ninety three percent of MCI-AD maintained a normal EEG throughout the study. QEEG may represent a powerful tool to predict the progression from MCI to DLB with a sensitivity and specificity close to 100%.

Nociceptive and non-nociceptive sub-regions in the human secondary somatosensory cortex: An MEG study using fMRI constraints

Previous evidence from functional magnetic resonance imaging (fMRI) has shown that a painful galvanic stimulation mainly activates a posterior sub-region in the secondary somatosensory cortex (SII), whereas a non-painful sensory stimulation mainly activates an anterior sub-region of SII [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625-1638.]. The present study, combining fMRI with magnetoencephalographic (MEG) findings, assessed the working hypothesis that the activity of such a posterior SII sub-region is characterized by an amplitude and temporal evolution in line with the bilateral functional organization of nociceptive systems. Somatosensory evoked magnetic fields (SEFs) recordings after alvanic median nerve stimulation were obtained from the same sample of subjects previously examined with fMRI [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625-1638.]. Constraints for dipole source localizations obtained from MEG recordings were applied according to fMRI activations, namely, at the posterior and the anterior SII sub-regions. It was shown that, after painful stimulation, the two posterior SII sub-regions of the contralateral and ipsilateral hemispheres were characterized by dipole sources with similar amplitudes and latencies. In contrast, the activity of anterior SII sub-regions showed statistically significant differences in amplitude and latency during both non-painful and painful stimulation conditions. In the contralateral hemisphere, the source activity was greater in amplitude and shorter in latency with respect to the ipsilateral. Finally, painful stimuli evoked a response from the posterior sub-regions peaking significantly earlier than from the anterior sub-regions. These results suggested that both ipsi and contra posterior SII sub-regions process painful stimuli in parallel, while the anterior SII sub-regions might play an integrative role in the processing of somatosensory stimuli.