Domain-general signals in the cingulo-opercular network for visuospatial attention and episodic memory

We investigated the functional properties of a previously described cingulo-opercular network (CON) putatively involved in cognitive control. Analyses of common fMRI task-evoked activity during perceptual and episodic memory search tasks that differently recruited the dorsal attention (DAN) and default mode network (DMN) established the generality of this network. Regions within the CON (anterior insula/frontal operculum and anterior cingulate/presupplementary cortex) displayed sustained signals during extended periods in which participants searched for behaviorally relevant information in a dynamically changing environment or from episodic memory in the absence of sensory stimulation. The CON was activated during all phases of both tasks, which involved trial initiation, target detection, decision, and response, indicating its consistent involvement in a broad range of cognitive processes. Functional connectivity analyses showed that the CON flexibly linked with the DAN or DMN regions during perceptual or memory search, respectively. Aside from the CON, only a limited number of regions, including the lateral pFC, showed evidence of domain-general sustained activity, although in some cases the common activations may have reflected the functional-anatomical variability of domain-specific regions rather than a true domain generality. These additional regions also showed task-dependent functional connectivity with the DMN and DAN, suggesting that this feature is not a specific marker of cognitive control. Finally, multivariate clustering analyses separated the CON from other frontoparietal regions previously associated with cognitive control, indicating a unique fingerprint. We conclude that the CON's functional properties and interactions with other brain regions support a broad role in cognition, consistent with its characterization as a task control network

Absence of Rac1 and Rac3 GTPases in the nervous system hinders thymic, splenic and immune-competence development

The nervous system influences organ development by direct innervation and the action of hormones. We recently showed that the specific absence of Rac1 in neurons (Rac1N) in a Rac3-deficient (Rac3KO) background causes motor behavioural defects, epilepsy, and premature mouse death around postnatal day 13. We report here that Rac1N/Rac3KO mice display a progressive loss of immune-competence. Comparative longitudinal analysis of lymphoid organs from control, single Rac1N or Rac3KO, and double Rac1N/Rac3KO mutant animals showed that thymus development is preserved up to postnatal day 9 in all animals, but is impaired in Rac1N/Rac3KO mice at later times. This is evidenced by a drastic reduction in thymic cell numbers. Cell numbers were also reduced in the spleen, leading to splenic tissue disarray. Organ involution occurs in spite of unaltered thymocyte and lymphocyte subset composition, and proper mature T-cell responses to polyclonal stimuli in vitro. Suboptimal thymus innervation by tau-positive neuronal terminals possibly explains the suboptimal thymic output and arrested thymic development, which is accompanied by higher apoptotic rates. Our results support a role for neuronal Rac1 and Rac3 in dictating proper lymphoid organ development, and suggest the existence of lymphoid-extrinsic mechanisms linking neural defects to the loss of immune-competence

Dynamics of EEG rhythms support distinct visual selection mechanisms in parietal cortex: A simultaneous transcranial magnetic stimulation and EEG study

Using repetitive transcranial magnetic stimulation (rTMS), we have recently shown a functional anatomical distinction in human parietal cortex between regions involved in maintaining attention to a location [ventral intraparietal sulcus (vIPS)] and a region involved in shifting attention between locations [medial superior parietal lobule (mSPL)]. In particular, while rTMS interference over vIPS impaired target discrimination at contralateral attended locations, interference over mSPL affected performance following shifts of attention regardless of the visual field (Capotosto et al., 2013). Here, using rTMS interference in conjunction with EEG recordings of brain rhythms during the presentation of cues that indicate to either shift or maintain spatial attention, we tested whether this functional anatomical segregation involves different mechanisms of rhythm synchronization. The transient inactivation of vIPS reduced the amplitude of the expected parieto-occipital low-alpha (8 - 10 Hz) desynchronization contralateral to the cued location. Conversely, the transient inactivation of mSPL, compared with vIPS, reduced the high-alpha (10 - 12 Hz) desynchronization induced by shifting attention into both visual fields. Furthermore, rTMS induced a frequency-specific delay of task-related modulation of brain rhythms. Specifically, rTMS over vIPS or mSPL during maintenance (stay cues) or shifting (shift cues) of spatial attention, respectively, caused a delay of alpha parieto-occipital desynchronization. Moreover, rTMS over vIPS during stay cues caused a delay of delta (2-4 Hz) frontocentral synchronization. These findings further support the anatomo-functional subdivision of the dorsal attention network in subsystems devoted to shifting or maintaining covert visuospatial attention and indicate that these mechanisms operate in different frequency channels linking frontal to parieto-occipital visual regions

Forecasting Visitors’ behaviour in Crowded Museums

In this paper, we tackle the issue of measuring and understanding the visitors’ dynamics in a crowded museum in order to create and calibrate a predictive mathematical model. The model is then used as a tool to manage, control and optimize the fruition of the museum. Our contribution comes with one successful use case, the Galleria Borghese in Rome, Italy

Anatomical segregation of visual selection mechanisms in human parietal cortex

none8siVisual selection requires mechanisms for representing object salience and for shifting the focus of processing to novel objects. It is not clear from computational or neural models whether these operations are performed within the same or different brain regions. Here, we use repetitive transcranial magnetic stimulation to briefly interfere with neural activity in individually localized regions of human posterior parietal cortex (PPC) that are putatively involved in attending to contralateral locations or shifting attention between locations. Stimulation over right ventral intraparietal sulcus impaired target discrimination at contralateral locations, whereas stimulation over right medial superior parietal lobule impaired target discrimination after a shift of attention regardless of its location. This double dissociation is consistent with neuroimaging studies and indicates that mechanisms of visual selection are partly anatomically segregated in human PPC.mixedCapotosto, Paolo; Tosoni, Annalisa; Spadone, Sara; Sestieri, Carlo; Perrucci, Mauro Gianni; Romani, Gian Luca; Della Penna, Stefania; Corbetta, MaurizioCapotosto, Paolo; Tosoni, Annalisa; Spadone, Sara; Sestieri, Carlo; Perrucci, Mauro Gianni; Romani, Gian Luca; Della Penna, Stefania; Corbetta, Maurizi

TMS-EEG biomarkers of amnestic mild cognitive impairment due to Alzheimer\u27s disease: A proof-of-concept six years prospective study

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge. Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD

Rac1 and Rac3 GTPases Control Synergistically the Development of Cortical and Hippocampal GABAergic Interneurons

The intracellular mechanisms driving postmitotic development of cortical γ-aminobutyric acid (GABA)ergic interneurons are poorly understood. We have addressed the function of Rac GTPases in cortical and hippocampal interneuron development. Developing neurons express both Rac1 and Rac3. Previous work has shown that Rac1 ablation does not affect the development of migrating cortical interneurons. Analysis of mice with double deletion of Rac1 and Rac3 shows that these GTPases are required during postmitotic interneuron development. The number of parvalbumin-positive cells was affected in the hippocampus and cortex of double knockout mice. Rac depletion also influences the maturation of interneurons that reach their destination, with reduction of inhibitory synapses in both hippocampal CA1 and cortical pyramidal cells. The decreased number of cortical migrating interneurons and their altered morphology indicate a role of Rac1 and Rac3 in regulating the motility of cortical interneurons, thus interfering with their final localization. While electrophysiological passive and active properties of pyramidal neurons including membrane capacity, resting potential, and spike amplitude and duration were normal, these cells showed reduced spontaneous inhibitory currents and increased excitability. Our results show that Rac1 and Rac3 contribute synergistically to postmitotic development of specific populations of GABAergic cells, suggesting that these proteins regulate their migration and differentiation

Rac1 and Rac3 GTPases Regulate the Development of Hilar Mossy Cells by Affecting the Migration of Their Precursors to the Hilus

We have previously shown that double deletion of the genes for Rac1 and Rac3 GTPases during neuronal development affects late developmental events that perturb the circuitry of the hippocampus, with ensuing epileptic phenotype. These effects include a defect in mossy cells, the major class of excitatory neurons of the hilus. Here, we have addressed the mechanisms that affect the loss of hilar mossy cells in the dorsal hippocampus of mice depleted of the two Rac GTPases. Quantification showed that the loss of mossy cells was evident already at postnatal day 8, soon after these cells become identifiable by a specific marker in the dorsal hilus. Comparative analysis of the hilar region from control and double mutant mice revealed that synaptogenesis was affected in the double mutants, with strongly reduced presynaptic input from dentate granule cells. We found that apoptosis was equally low in the hippocampus of both control and double knockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5 showed no evident difference in the proliferation of neuronal precursors in the hippocampal primordium, while differences in the number of bromodeoxyuridine-labelled cells in the developing hilus revealed a defect in the migration of immature, developing mossy cells in the brain of double knockout mice. Overall, our data show that Rac1 and Rac3 GTPases participate in the normal development of hilar mossy cells, and indicate that they are involved in the regulation of the migration of the mossy cell precursor by preventing their arrival to the dorsal hilus

Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin

Andrea Baccarelli and colleagues show that maternal exposure to a dioxin following the industrial accident in Seveso, Italy in 1976 is associated with modified neonatal thyroid function even many years later