S. Della Penna

The Human Connectome Project: A data acquisition perspective

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Human brain activation during passive listening to sounds from different locations: An fMRI and MEG study

Recent animal and human studies indicate the existence of a neural pathway for sound localization, which is similar to the “where” pathway of the visual system and distinct from the sound identification pathway. This study sought to highlight this pathway using a passive listening protocol. We employed fMRI to study cortical areas, activated during the processing of sounds coming from different locations, and MEG to disclose the temporal dynamics of these areas. In addition, the hypothesis of different activation levels in the right and in the left hemispheres, due to hemispheric specialization of the human brain, was investigated. The fMRI results indicate that the processing of sound, coming from different locations, activates a complex neuronal circuit, similar to the sound localization system described in monkeys known as the auditory “where” pathway. This system includes Heschls gyrus, the superior temporal gyrus, the supramarginal gyrus, and the inferior and middle frontal lobe. The MEG analysis allowed assessment of the timing of this circuit: the activation of Heschls gyrus was observed 139 ms after the auditory stimulus, the peak latency of the source located in the superior temporal gyrus was at 156 ms, and the inferior parietal lobule and the supramarginal gyrus peaked at 162 ms. Both hemispheres were found to be involved in the processing of sounds coming from different locations, but a stronger activation was observed in the right hemisphere. Hum. Brain Mapping, 2005.

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.

Frequency specific interactions of MEG resting state activity within and across brain networks as revealed by the multivariate interaction measure.

Resting state networks (RSNs) are sets of brain regions exhibiting temporally coherent activity fluctuations in the absence of imposed task structure. RSNs have been extensively studied with fMRI in the infra-slow frequency range (nominally <10(-1)Hz). The topography of fMRI RSNs reflects stationary temporal correlation over minutes. However, neuronal communication occurs on a much faster time scale, at frequencies nominally in the range of 10(0)-10(2)Hz. We examined phase-shifted interactions in the delta (2-3.5 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (13-30 Hz) frequency bands of resting-state source space MEG signals. These analyses were conducted between nodes of the dorsal attention network (DAN), one of the most robust RSNs, and between the DAN and other networks. Phase shifted interactions were mapped by the multivariate interaction measure (MIM), a measure of true interaction constructed from the maximization of imaginary coherency in the virtual channels comprised of voxel signals in source space. Non-zero-phase interactions occurred between homologous left and right hemisphere regions of the DAN in the delta and alpha frequency bands. Even stronger non-zero-phase interactions were detected between networks. Visual regions bilaterally showed phase-shifted interactions in the alpha band with regions of the DAN. Bilateral somatomotor regions interacted with DAN nodes in the beta band. These results demonstrate the existence of consistent, frequency specific phase-shifted interactions on a millisecond time scale between cortical regions within RSN as well as across RSNs.

Adding dynamics to the Human Connectome Project with MEG

The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.

A Dynamic Core Network and Global Efficiency in the Resting Human Brain

Spontaneous brain activity is spatially and temporally organized in the absence of any stimulation or task in networks of cortical and subcortical regions that appear largely segregated when imaged at slow temporal resolution with functional magnetic resonance imaging (fMRI). When imaged at high temporal resolution with magneto-encephalography (MEG), these resting-state networks (RSNs) show correlated fluctuations of band-limited power in the beta frequency band (14-25 Hz) that alternate between epochs of strong and weak internal coupling. This study presents 2 novel findings on the fundamental issue of how different brain regions or networks interact in the resting state. First, we demonstrate the existence of multiple dynamic hubs that allow for across-network coupling. Second, dynamic network coupling and related variations in hub centrality correspond to increased global efficiency. These findings suggest that the dynamic organization of across-network interactions represents a property of the brain aimed at optimizing the efficiency of communication between distinct functional domains (memory, sensory-attention, motor). They also support the hypothesis of a dynamic core network model in which a set of network hubs alternating over time ensure efficient global communication in the whole brain.

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.

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.

Detection and counting of specific cell populations by means of magnetic markers linked to monoclonal antibodies

We report on experiments aimed at the assessment of a new method for cell marking. This method combines superparamagnetic particles, commonly used for cell separation, linked to monoclonal antibodies, and biomagnetic instrumentation featuring an extremely high magnetic field sensitivity. The final goal of the method is to locate and estimate specific cell populations in the human body. In this experiment, quantitative features of the method are evaluated in vitro with lymphocytes and carcinoma cells. Comparison between estimation and direct counting of cells is quite satisfactory and motivates further development of the technique.