Use of fractal analysis in dental images for osteoporosis detection: a systematic review and meta-analysis.

Fractal dimension (FD) calculated on oral radiographs has been proposed as a useful tool to screen for osteoporosis. This systematic review and meta-analysis firstly aimed at assessing the reliability of FD measures in distinguishing osteoporotic patients (OP) from healthy controls (HC), and secondly, to identify a standardized procedure of FD calculation in dental radiographs for the possible use as a surrogate measure of osteoporosis. A comprehensive search was conducted up to September 2020 using PubMed, Web of Science, and SCOPUS databases. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Meta-analysis was performed on FD values calculated for HC and OP. Overall, 293 articles were identified. After a three steps screening, 19 studies were included in the qualitative appraisal and 12 were considered for meta-analysis. The methodological quality of the retrieved studies was generally low. Most of the studies included used White and Rudolph and box counting to process the images and to calculate FD, respectively. Overall, 51% of the studies found a meaningful difference between HC and OP groups. Meta-analyses showed that to date, FD measures on dental radiographs are not able to distinguish the OP from HC group significantly. From the current evidence, the use of FD for the identification of OP is not reliable, and no clear conclusion can be drawn due to the heterogeneity of studies. The present review revealed the need for further studies and provided the fundamentals to design them in order to find a standardized procedure for FD calculation (regions for FD assessment; images processing technique; methods for FD measurement). More effort should be made to identify osteoporosis using dental images which are cheap and routinely taken during periodic dental examinations.

Akinetic crisis in dementia with Lewy bodies.

BACKGROUND AND PURPOSE: Dementia with Lewy bodies (DLB) is characterised by neuroleptic hypersensitivity. It is unclear, however, whether the neuroleptic hypersensitivity implies an increased incidence of neuroleptic malignant syndrome (NMS) or of akinetic crisis (AC), which are expressions of the same possibly lethal clinical event, and whether AC in DLB can appear independently of neuroleptic treatment. In our prospective study, we assessed the incidence of AC in a cohort of DLB as compared with that in patients with Parkinson disease (PD). METHODS: In total, 614 patients with PD and 236 DLB were recruited and followed during 2005-2013. AC was diagnosed as sudden akinetic state unresponsive to dopaminergic rescue drugs, dysphagia and serological alterations without recovery for 48 h or more requiring hospital admission. Exposure to neuroleptics was specifically evaluated, because of the high implicit risk in DLB. RESULTS: 24 patients with PD (3.9%) and 16 patients with DLB (6.8%) developed AC. 77 (32.6%) DLB and 32 (5.2%) PD were exposed to typical neuroleptics, but only 8 DLB and 3 PD presented with AC. Disease duration before AC was lower in DLB than in PD group (p<0.01). Outcome was fatal in 8 patients with (50%) DLB and 3 (12.5%) PD (p=0.05). When age and use of neuroleptics were adjusted for into a Cox proportional hazards model predicting time to AC, the HR of patients with DLB was 13.0 (95% CI 4.23 to 39.9; p<0.001). CONCLUSIONS: AC in DLB can appear independently of neuroleptic treatment, occurs earlier and is more frequently fatal than in PD.

Hemispheric lateralization in top-down attention during spatial relation processing: a Granger causal model approach.

Magnetoencephalography was recorded during a matching-to-sample plus cueing paradigm, in which participants judged the occurrence of changes in either categorical (CAT) or coordinate (COO) spatial relations. Previously, parietal and frontal lobes were identified as key areas in processing spatial relations and it was shown that each hemisphere was differently involved and modulated by the scope of the attention window (e.g. a large and small cue). In this study, Granger analysis highlighted the patterns of causality among involved brain areas--the direction of information transfer ran from the frontal to the visual cortex in the right hemisphere, whereas it ran in the opposite direction in the left side. Thus, the right frontal area seems to exert top-down influence, supporting the idea that, in this task, top-down signals are selectively related to the right side. Additionally, for CAT change preceded by a small cue, the right frontal gyrus was not involved in the information transfer, indicating a selective specialization of the left hemisphere for this condition. The present findings strengthen the conclusion of the presence of a remarkable hemispheric specialization for spatial relation processing and illustrate the complex interactions between the lateralized parts of the neural network. Moreover, they illustrate how focusing attention over large or small regions of the visual field engages these lateralized networks differently, particularly in the frontal regions of each hemisphere, consistent with the theory that spatial relation judgements require a fronto-parietal network in the left hemisphere for categorical relations and on the right hemisphere for coordinate spatial processing.

Magnetoencephalographic and electroencephalographic evaluation in patients with cryptogenetic partial epilepsy.

UNLABELLED: Magnetoencephalography (MEG) has been applied for more than 20 years to the localization of the epileptic focus in partial epilepsies, but correlation with electroencephalographic (EEG) data in homogeneous groups of patients is scarce. OBJECTIVE: The aim of our work was to use EEG and MEG for the study of a group of adults and children affected by cryptogenetic partial epilepsy. METHODS: We analyzed the traces obtained from electroencephalographic and magnetoencephalographic recordings of 10 patients of ages ranging from 7 to 38 years affected by cryptogenetic partial epilepsy. We evaluated the presence of commonly detected or uniquely detected spikes, and, whenever possible, we used MEG for localization of the epileptic focus. RESULTS: Three patients showed no epileptic activity during the EEG and MEG sessions. Overall agreement between EEG and MEG (presence of concordant spikes with the same localization shown by both techniques) was obtained in five patients. In one patient the spikes detected by EEG and MEG were different, and in another patient interictal activity was demonstrated exclusively by EEG. CONCLUSIONS: EEG in this series was not inferior to MEG in terms of spike detection. Combination of EEG and MEG is feasible, better than each technique alone, and may be useful for non-invasive diagnosis and monitoring of pediatric and adult patients with partial epilepsies.

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 Parkinson's 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.

Combined rehabilitation program for postural instability in progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is an atypical parkinsonism clinically characterized by prominent axial extrapyramidal motor symptoms with frequent falls. The clinical response to L-dopa is poor and there is strong need for alternative treatment strategies. METHODS: We tested the efficacy of a rehabilitative program combining a dynamic antigravity postural system (SPAD) and a vibration sound system (ViSS) on postural instability of 10 patients affected by PSP. The patients underwent SPAD and VISS treatments with a 3 sessions/week schedule for 2 months. Patients were clinically examined at baseline, every week during the 2-months treatment, and at 1 month after the end of treatment for the following parameters: baropodometry static, baropodometry dynamic and stabilometry. PSP rating scale and PD36 quality of life scale were also administered. RESULTS: The combined rehabilitative program produced improvement of all the parameters explored (p = 0.01-0.05) at the end of treatment as compared to baseline. Baropodometric dynamics improvement lasted until the end of follow-up. CONCLUSION: Our results suggest that a specific rehabilitation program could improve postural instability in PSP patients. A more continuous treatment protocol would allow stabilizations of results.

Neuromagnetic responses reveal the cortical timing of audiovisual synchrony.

Multisensory processing involving visual and auditory inputs is modulated by their relative temporal offsets. In order to assess whether multisensory integration alters the activation timing of primary visual and auditory cortices as a function of the temporal offsets between auditory and visual stimuli, a task was designed in which subjects had to judge the perceptual simultaneity of the onset of visual stimuli and brief acoustic tones. These were presented repeatedly with three different inter-stimulus intervals that were chosen to meet three perceptual conditions: (1) physical synchrony perceived as synchrony by subjects (SYNC); (2) physical asynchrony perceived as asynchrony (ASYNC); (3) physical asynchrony perceived ambiguously (AMB, i.e. 50% perceived as synchrony, 50% as asynchrony). Magnetoencephalographic activity was recorded during crossmodal sessions and unimodal control sessions. The activation of primary visual and auditory cortices peaked at a longer latency for the crossmodal conditions as compared to the unimodal conditions. Moreover, the latency in the auditory cortex was longer in the SYNC than in the ASYNC condition, whereas in the visual cortex the latency in the AMB condition was longer than in the ASYNC condition. These findings suggest that multisensory processing affects temporal dynamics already in primary cortices, that such activity can differ regionally and can be sensitive to the temporal offsets of multisensory inputs. In addition, in the AMB condition the conscious awareness of asynchrony might be associated to a later activation of the primary auditory cortex.

Persistent genital arousal disorder associated with functional hyperconnectivity of an epileptic focus.

Persistent Genital Arousal Disorder (PGAD) refers to the experience of persistent sensations of genital arousal that are felt to be unprovoked, intrusive and unrelieved by one or several orgasms. It is often mistaken for hypersexuality since PGAD often results in a high frequency of sexual behaviour. At present little is known with certainty about the etiology of this condition. We described a woman with typical PGAD symptoms and orgasmic seizures that we found to be related to a specific epileptic focus. We performed a EEG/MEG and fMRI spontaneous activity study during genital arousal symptoms and after the chronic administration of 300 mg/day of topiramate. From MEG data an epileptic focus was localized in the left posterior insular gyrus (LPIG). FMRI data evidenced that sexual excitation symptoms with PGAD could be correlated with an increased functional connectivity (FC) between different brain areas: LPIG (epileptic focus), left middle frontal gyrus, left inferior and superior temporal gyrus and left inferior parietal lobe. The reduction of the FC observed after antiepileptic therapy was more marked in the left than in the right hemisphere in agreement with the lateralization identified by MEG results. Treatment completely abolished PGAD symptoms and functional hyperconnectivity. The functional hyperconnectivity found in the neuronal network including the epileptic focus could suggest a possible central mechanism for PGAD.

Revisiting P300 cognitive studies for dementia diagnosis: Early dementia with Lewy bodies (DLB) and Alzheimer disease (AD).

AIMS OF THE STUDY: Earlier P300 studies were conducted when the prevalence of dementia with Lewy Bodies (DLB) was unknown. Our study aims to examine whether P300 abnormalities are present in DLB and to evidence possible differences between DLB and Alzheimer's disease (AD). A second aim of this study is to look for correlations between P300 recordings and EEG, as abnormal EEG variability has been described in DLB. PATIENTS AND METHODS: Auditory P300 responses were recorded by a classic oddball paradigm in 50 controls, in 36 DLB patients, and in 40 AD patients with MMSE>20. RESULTS: Reliable auditory P300 responses were obtained in 26 DLB (72%), 33 AD (82.5%), and 46 controls (92%). P300 was more delayed and had lower amplitude in DLB compared to AD groups. P300 topography was also different as the anterior-to-posterior scalp amplitude gradient was reversed in DLB. P300 latency correlated with neuropsychological test scores and with EEG variables. Gradient inversion and delayed P300 responses in frontal derivations evidenced differences between DLB and AD patients with a sensitivity of 70% and a specificity of 97%. CONCLUSIONS: P300 recordings are abnormal in DLB and can be useful to distinguish DLB from AD.

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.

Conditioning transcutaneous electrical nerve stimulation induces delayed gating effects on cortical response: a magnetoencephalographic study.

The present study was undertaken to investigate after-effects of 7 Hz non-painful prolonged stimulation of the median nerve on somatosensory-evoked fields (SEFs). The working hypothesis that conditioning peripheral stimulations might produce delayed interfering ("gating") effects on the response of somatosensory cortex to test stimuli was evaluated. In the control condition, electrical thumb stimulation induced SEFs in ten subjects. In the experimental protocol, a conditioning median nerve stimulation at wrist preceded 6 electrical thumb stimulations. Equivalent current dipoles fitting SEFs modeled responses of contralateral primary area (SI) and bilateral secondary somatosensory areas (SII) following control and experimental conditions. Compared to the control condition, conditioning stimulation induced no amplitude modulation of SI response at the initial stimulus-related peak (20 ms). In contrast, later response from SI (35 ms) and response from SII were significantly weakened in amplitude. Gradual but fast recovery towards control amplitude levels was observed for the response from SI-P35, while a slightly slower cycle was featured from SII. These findings point to a delayed "gating" effect on the synchronization of somatosensory cortex after peripheral conditioning stimulations. This effect was found to be more lasting in SII area, as a possible reflection of its integrative role in sensory processing.

Low- and high-frequency evoked responses following pattern reversal stimuli: a MEG study supported by fMRI constraint.

We investigated the neural generators of N1 and P1 components of visual magnetic responses through the concomitant study of low (1-15 Hz)- and high (15-30 Hz)-frequency brain activities phase-locked to stimulus and elicited by pattern reversal visual stimuli. Whole helmet magnetic recordings and dipole modeling technique with support of functional magnetic resonance imaging (fMRI) were used to characterize locations and orientations of N1 and P1 sources as a function of four stimulated visual field quadrants. A comparison between low- and high-frequency activities revealed fundamental differences among orientations of the quadrants dipoles thus suggesting partly distinct neural populations underlying low- and high-frequency responses to transient contrast visual stimuli. Moreover, for both low- and high-frequency bands the specific study of locations and orientations of N1 and P1 sources indicated V1/V2 cortex as the neural substrate generating the two components. In summary, we provided strong support for a cortical genesis of human oscillatory mass activity following transient contrast stimuli with specific neural districts active in the low- and high-frequency bands. The converging results obtained from the concomitant investigation of probably different brain activities provided new evidences for a striate genesis of N1 and P1 components of the broadband visual-evoked responses following pattern reversal.

A cartesian time--frequency approach to reveal brain interaction dynamics.

The study of large-scale interactions from magnetoencephalographic data based on the magnitude of the complex coherence computed at channel level is a widely used method to track the coupling between neural signals. Traditionally, a measure based on the magnitude of the complex coherence estimated by Fourier analysis, has been used under the assumption that the neural signals are stationary. Here, we split the complex coherence in its real and imaginary parts and focus on the latter with the advantage that the imaginary part is insensitive to spurious connectivity resulting from volume conducted "self interaction". Furthermore, interacting sources alone contribute to a non-vanishing imaginary part of the complex coherence whereas the contribute of non-interacting sources is also mapped from the magnitude of the complex coherence. Since it has been extensively shown that non-stationary stochastic processes contribute to the generation of neural signals, it is fundamental to be able to define interaction measures that are able to follow the temporal variations in the coupling between neural signals. To this purpose time-frequency domain techniques to estimate the magnitude of the complex coherence have been developed in the past decades. Similarly, we extend the analysis of the imaginary part of complex coherence to the time-frequency domain, by using the short-time Fourier transform to analyze the complex coherence as a function of time. In this way, it is possible to get an indication about the dynamic of the underlying source interaction pattern by looking at channel level interactions without the bias introduced by artifactual self-interaction by volume conduction or by the contribute of non-interacting sources. Furthermore, the corresponding imaginary part of the cross-spectrogram can be used to estimate interactions on a source level by localizing pools of sources interacting at a given frequency and by characterizing their dynamics. The method has been applied to magnetoencephalographic data from a cross-modal visual auditory stimulation and provided evidence for the involvement of temporal and occipital areas in the integrated information processing for simultaneous audio-visual stimulation. Furthermore, the source interaction pattern shows a variation in time that reflects a dynamical synchronization of the involved brain sources in the frequency bands of interest.

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

The present study evaluated the reactivity of cortical rhythms in 15 Alzheimer's 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.

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.

"Gating" effects of simultaneous peripheral electrical stimulations on human secondary somatosensory cortex: a whole-head MEG study.

The secondary somatosensory cortex (SII) is strongly involved in the processing of somatosensory tactile and nociceptive sensations. We investigated the effect on SII responses of simultaneous painful and nonpainful electrical stimulations delivered to the thumb and little finger. According to the "bimodal" (i.e., nociceptive, tactile) organization of SII, it was expected that simultaneous painful and nonpainful stimulations would lead to modality interference with a marked reduction ("gating") of somatosensory evoked fields (SEFs) generated in SII. Eight different stimulus conditions were studied. Two conditions were simultaneous "unimodal" (thumb and little finger nonpainful; thumb and little finger painful) and two conditions were simultaneous "bimodal" (thumb nonpainful and little finger painful; thumb painful and little finger nonpainful). As a reference, four conditions included stimulations at single sites (thumb nonpainful, little finger nonpainful, thumb painful, little finger painful). The gating phenomenon was defined as the percentage of difference between the intensities of SII activation after simultaneous compared to the sum of the separate stimulations. Results showed that simultaneous stimulations induced gating effects on SEFs generated by SII. No significant gating differences were observed after the two unimodal stimulations, suggesting a negligible effect of global energy on gating. Instead, the gating effects on bilateral SII activity were stronger after simultaneous bimodal when compared to unimodal stimulations. Our findings hint that there could be a greater level of integration/convergence of painful and nonpainful stimuli in SII with respect to SI. Future studies should explore if it could have an important role in exploring pain relief.

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.

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.