Rett syndrome: an eye‐tracking study of attention and recognition memory

Rose, Susan A.; Djukic, Aleksandra; Jankowski, Jeffery J.; Feldman, Judith F.; Fishman, I. I.; Valicenti-McDermott, Maria

doi:10.1111/dmcn.12085

Cited by 64 publications

(58 citation statements)

References 31 publications

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“…RTT is marked by arrested development of visual processing (33), atypical visually evoked cortical responses (34,35), deficits in visual attention and recognition, and unusual gaze intensity (36). In primary visual cortex (V1), "simple" stimuli, such as oriented gratings, and "complex" stimuli, such as natural scenes, activate local and distributed circuits that lead to well-defined responses from visual cortex neurons (37)(38)(39)(40)(41).…”

Section: Significancementioning

confidence: 99%

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Banerjee

Rikhye

Breton-Provencher

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

154

202

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Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.MeCP2 | E/I balance | parvalbumin neurons | IGF1 | chloride transporters S ynaptic excitation (E) and inhibition (I), along with the neuronal balance of excitation and inhibition (E/I), is key to the function of brain circuits, and is often disrupted in neurodevelopmental disorders, including autism spectrum disorders (ASDs) (1-3). Rett syndrome (RTT) is a severe neurodevelopmental and adult disorder that arises from sporadic loss-of-function mutations in the X-linked (Xq28) methyl-CpG binding protein 2 gene (Mecp2) encoding the protein MeCP2 (4-7). MeCP2 is a critical regulator of brain development and adult neural function (8), and arrested brain maturation due to synaptic dysfunction is one of the hallmarks of RTT (3). However, the effects of MeCP2 on excitatory and inhibitory synaptic mechanisms in vivo, and on neuronal and circuit function underlying RTT pathophysiology, are unknown.MeCP2 is ubiquitously expressed in multiple cell types and subregions of the brain (4, 6, 9), including inhibitory interneurons, and has cell-autonomous as well as non-cell-autonomous effects (10); thus, it has been particularly challenging to identify its role in cell-specific brain circuits. Anatomically diverse inhibitory interneuron subtypes with distinct physiological signatures influence different aspects of neocortical function and behavior (11,12). Soma-targeting parvalbumin-expressing (PV + ) and dendritetargeting somatostatin-expressing (SOM + ) interneurons are the two major nonoverlapping populations of interneurons in mice that target cortical pyramidal neurons (13). Inhibition by PV + and SOM + neurons powerfully influences neuronal responses and circuit computations in visual cortex (14-17). Deletion of MeCP2 from all forebrain GABAergic interneurons recapitulates key aspects of RTT (18), demonstrating that altered inhibitory function is an important facet of RTT pathophysiology. Indeed, a major phenotype of MeCP2 reduction in individuals with RTT and in mouse models is ...

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Section: Significancementioning

confidence: 99%

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Banerjee

Rikhye

Breton-Provencher

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

154

202

View full text Add to dashboard Cite

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“…Human-computer interaction, virtual and augmented reality, usability tests, e-learning, assistive technology, pilot training assistance are some of the many eye-tracking applications [8]. Medicine, psychology and neuroscience can also benefit from this technology in studies, accessing cognitive abilities, attention and recognition memory in patients [9]. Assistive technology has been helping individuals with disabilities to improve their functional capabilities, enabling them to perform activities conducted by eye movements.…”

Section: Applications Of Eye Tracking Technologymentioning

confidence: 99%

Eye-Tracking Technology for Construction Safety: A Feasibility Study

Pinheiro¹,

Pradhananga²,

Jianu³

et al. 2016

Proceedings of the International Symposium on Automation and Robotics in Construction (IAARC)

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A construction site is a harsh environment demanding entire human senses and attention, even for regular scheduled tasks. Many accidents occur on construction sites because of inability of workers to identify hazards and make timely decisions. To understand why some hazards go unseen, it is crucial to study how workers perceive the site. The objective of this research is to leverage eye-tracking technology to study workers' gazing pattern in a construction environment. A real picture from an active construction site is modified to introduce hazards and a desktop experiment is conducted, in which, subjects are asked to identify the hazards. A different group of subjects are made to make similar observations on a 2D sketch-representation of the same construction scenario. Eye-tracking data gathered from their observations is analyzed to understand when, how, and which hazards do they recognize and the pattern of recognition is studied. The results of this study will enhance our understanding on the visual factors that govern attention and help workers recognize potential hazards in a construction site. The comparison between the observation pattern in real and sketch-representation is done to assess how subjects respond to artificial images compared to real images. This comparison will test the feasibility of using virtual reality for safety training and simulations.

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“…This approach is of potentially great interest but may not avoid some important biases. Rose et al . have addressed these to evaluate attention as well as face and pattern recognition in a group of patients with Rett syndrome.…”

mentioning

confidence: 99%

“…Phenotypic Plasticity and the PACE Paradigm Bernard Dan et al 53 approach is of potentially great interest but may not avoid some important biases. Rose et al 20 have addressed these to evaluate attention as well as face and pattern recognition in a group of patients with Rett syndrome. They concluded that attention was 'less mature', with fewer and longer fixations, and restricted gaze focus tending to ignore nose and mouth.…”

mentioning

confidence: 99%

Phenotypic plasticity and the perception–action–cognition–environment paradigm in neurodevelopmental genetic disorders

Dan

Pelc

Meırleır

et al. 2015

Develop Med Child Neuro

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Careful study of the phenotype can have implications at several levels, namely clinical diagnosis, pathophysiological reasoning, management planning, and outcome measurement. Behavioural phenotypes involve cognition, communication, social skills, and motor control. They can be documented in a host of neurodevelopmental conditions and approached with the recently refined perception–action–cognition–environment (PACE) paradigm, which focuses on the neurodevelopmental processes that underlie learning and adaption to the environment through perception, action, and cognitive processing. Although this paradigm was originally developed in the context of cerebral palsy, it can be applied along developmental trajectories in several neurogenetic conditions, including Down syndrome, fragile X syndrome, Rett syndrome, Angelman syndrome, and Williams syndrome, to name but a few. It must be recognized, however, that relevant, valid tools for assessment and management strategies still need to be developed.

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Rett syndrome: an eye‐tracking study of attention and recognition memory

Cited by 64 publications

References 31 publications

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Jointly reduced inhibition and excitation underlies circuit-wide changes in cortical processing in Rett syndrome

Eye-Tracking Technology for Construction Safety: A Feasibility Study

Phenotypic plasticity and the perception–action–cognition–environment paradigm in neurodevelopmental genetic disorders

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