Episodic memory retrieval, parietal cortex, and the default mode network: Functional and topographic analyses

The default mode network (DMN) is often considered a functionally homogeneous system that is broadly associated with internally directed cognition (e.g., episodic memory, theory of mind, self-evaluation). However, few studies have examined how this network interacts with other networks during putative default processes such as episodic memory retrieval. Using functional magnetic resonance imaging, we investigated the topography and response profile of human parietal regions inside and outside the DMN, independently defined using task-evoked deactivations and resting-state functional connectivity, during episodic memory retrieval. Memory retrieval activated posterior nodes of the DMN, particularly the angular gyrus, but also more anterior and dorsal parietal regions that were anatomically separate from the DMN. The two sets of parietal regions showed different resting-state functional connectivity and response profiles. During memory retrieval, responses in DMN regions peaked sooner than non-DMN regions, which in turn showed responses that were sustained until a final memory judgment was reached. Moreover, a parahippocampal region that showed strong resting-state connectivity with parietal DMN regions also exhibited a pattern of task-evoked activity similar to that exhibited by DMN regions. These results suggest that DMN parietal regions directly supported memory retrieval, whereas non-DMN parietal regions were more involved in postretrieval processes such as memory-based decision making. Finally, a robust functional dissociation within the DMN was observed. Whereas angular gyrus and posterior cingulate/precuneus were significantly activated during memory retrieval, an anterior DMN node in medial prefrontal cortex was strongly deactivated. This latter finding demonstrates functional heterogeneity rather than homogeneity within the DMN during episodic memory retrieval

Attention to memory and the environment: functional specialization and dynamic competition in human posterior parietal cortex

none3siPosterior parietal cortex has been traditionally associated with perceptual attention and sensory-motor processing, but recent studies also indicate a potential role in episodic memory retrieval. Here, we developed a new paradigm to isolate top-down attention-related activity directed to either memory or perceptual information. We demonstrated a robust topographic separation in human posterior parietal cortex associated with searching for task-relevant information in episodic memory or in the environment. Control analyses confirmed that this difference was not dependent on differences in sensory stimulation or eye movements across tasks. Notably, we observed in memory-and perception-related regions a mechanism of reciprocal dynamic competition that was related to behavioral performance. These results provide the first evidence for a double dissociation between parietal networks involved in top-down attention to memory and the environment and support the idea of neural competition between perception and memory.openSestieri, Carlo; Shulman, Gordon L.; Corbetta, MaurizioSestieri, Carlo; Shulman, Gordon L.; Corbetta, Maurizi

Commentary. Common criteria among States for storage and use of dried blood spot specimens after newborn screening

Biological samples collected in biobanks are a resource with significant research potential. The Italian Joint Group cNB - cNBBSV (National committee of Bioethics - National committee for Biosecurity, Biotechnologies and Life Sciences) published a document reporting recommendations on storage and use of dried blood spot (DBS) and on the development of a National Network of Regional Newborn Screening Repositories for collection of residual DBS. Several ethical questions (about consent, possible use of genetic information, unanticipated possible usages for research purposes) rise from residual newborn screening specimens collections. Moreover, legal and ethical controversies are accentuated by the conflicts between the interests of sample donors, biobank holders, researchers and the public. To overcome these difficulties the identification of a few criteria for storage and research usage of DBS is crucial

Sequential Activation of Human Oculomotor Centers During Planning of Visually-Guided Eye Movements: A Combined fMRI-MEG Study

We used magneto-encephalography (MEG) to measure visually evoked activity in healthy volunteers performing saccadic eye movements to visual targets. The neuromagnetic activity was analyzed from regions of cortical activation identified in separate functional magnetic resonance imaging (fMRI) studies. The latency of visual responses significantly increased from the Middle Temporal region (MT+) to the Intraparietal Sulcus (IPS) to the Frontal Eye Field (FEF), and their amplitude was greater in the hemisphere contralateral to the visual target. Trial-to-trial variability of oculomotor reaction times correlated with visual response latency across cortical areas. These results support a feedforward recruitment of oculomotor cortical centers by visual information, and a model in which behavioral variability depends on variability at different neural stages of processing

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

A new targeted CFTR mutation panel based on next-generation sequencing technology

Searching for mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) is a key step in the diagnosis of and neonatal and carrier screening for cystic fibrosis (CF), and it has implications for prognosis and personalized therapy. The large number of mutations and genetic and phenotypic variability make this search a complex task. Herein, we developed, validated, and tested a laboratory assay for an extended search for mutations in CFTR using a next-generation sequencing based method, with a panel of 188 CFTR mutations customized for the Italian population. Overall, 1426 dried blood spots from neonatal screening, 402 genomic DNA samples from various origins, and 1138 genomic DNA samples from patients with CF were analyzed. The assay showed excellent analytical and diagnostic operative characteristics. We identified and experimentally validated 159 (of 188) CFTR mutations. The assay achieved detection rates of 95.0% and 95.6% in two large-scale case series of CF patients from central and northern Italy, respectively. These detection rates are among the highest reported so far with a genetic test for CF based on a mutation panel. This assay appears to be well suited for diagnostics, neonatal and carrier screening, and assisted reproduction, and it represents a considerable advantage in CF genetic counseling

The Candoglia Marble and the “Veneranda Fabbrica del Duomo di Milano”: A Renowned Georesource to Be Potentially Designed as Global Heritage Stone

Marbles from Alpine area have been widely employed to build and decorate masterpieces and buildings which often represent the cultural heritage of an area (statuary, historic buildings and sculptures). Candoglia marble, object of the present research, is one of the most famous and appreciated marbles from Alpine area; it has been quarried since Roman times in the Verbano-Cusio-Ossola (VCO; Piemonte—NW Italy) extractive area. Candoglia Marble outcrops are present as lenses within the high-grade paragneisses of the Ivrea Zone, a visible section of deep continental crust characterised by amphibolite- to granulite-facies metamorphism (Palaeozoic period). Candoglia calcitic marble (80–85% CaCO3 and the 15–20% other minerals) shows a characteristic pink to gray colour and a coarse-grained texture (>3 mm): frequent centimetre-thick dark-greenish silicate layers (mainly represented by diopside and tremolite) characterize the texture of the marble. It has been largely used in local rural constructions and historical buildings, but its most famous application has been (and still is) for the “Duomo di Milano” construction (fourteenth century). The Veneranda Fabbrica del Duomo di Milano carried out the anthropogenic activities dealing with the Candoglia marble exploitation; it has to be highlighted that the company have managed the Marble exploitation during the last seven centuries and that the quarry itself is a tangible sign of the development of extraction and heritage in the VCO area. Candoglia marble can be recognized as a significant example of a “Global Heritage Stone Resource”: its exploitation from quarry to building (the Duomo di Milano) well represents the close correlation between stone and cultural heritage, between georesources and humankind development

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