Behavioral and Neural Signatures of Visual Imagery Vividness Extremes: Aphantasia versus Hyperphantasia.

Although Galton recognized in the 1880s that some individuals lack visual imagery, this phenomenon was mostly neglected over the following century. We recently coined the terms "aphantasia" and "hyperphantasia" to describe visual imagery vividness extremes, unlocking a sustained surge of public interest. Aphantasia is associated with subjective impairment of face recognition and autobiographical memory. Here we report the first systematic, wide-ranging neuropsychological and brain imaging study of people with aphantasia (n = 24), hyperphantasia (n = 25), and midrange imagery vividness (n = 20). Despite equivalent performance on standard memory tests, marked group differences were measured in autobiographical memory and imagination, participants with hyperphantasia outperforming controls who outperformed participants with aphantasia. Face recognition difficulties and autistic spectrum traits were reported more commonly in aphantasia. The Revised NEO Personality Inventory highlighted reduced extraversion in the aphantasia group and increased openness in the hyperphantasia group. Resting state fMRI revealed stronger connectivity between prefrontal cortices and the visual network among hyperphantasic than aphantasic participants. In an active fMRI paradigm, there was greater anterior parietal activation among hyperphantasic and control than aphantasic participants when comparing visualization of famous faces and places with perception. These behavioral and neural signatures of visual imagery vividness extremes validate and illuminate this significant but neglected dimension of individual difference.

Phantasia-The psychological significance of lifelong visual imagery vividness extremes.

Visual imagery typically enables us to see absent items in the mind's eye. It plays a role in memory, day-dreaming and creativity. Since coining the terms aphantasia and hyperphantasia to describe the absence and abundance of visual imagery, we have been contacted by many thousands of people with extreme imagery abilities. Questionnaire data from 2000 participants with aphantasia and 200 with hyperphantasia indicate that aphantasia is associated with scientific and mathematical occupations, whereas hyperphantasia is associated with 'creative' professions. Participants with aphantasia report an elevated rate of difficulty with face recognition and autobiographical memory, whereas participants with hyperphantasia report an elevated rate of synaesthesia. Around half those with aphantasia describe an absence of wakeful imagery in all sense modalities, while a majority dream visually. Aphantasia appears to run within families more often than would be expected by chance. Aphantasia and hyperphantasia appear to be widespread but neglected features of human experience with informative psychological associations.

Tracking down a solution: exploring the acceptability and value of wearable GPS devices for older persons, individuals with a disability and their support persons.

PURPOSE: To explore the acceptability and value of three wearable GPS devices for older persons and individuals with a disability and safety concerns when accessing the community. METHODS: This pilot study explored six wearers' and their support persons' experience of using three different wearable GPS devices (a pendant, watch, and mini GPS phone), each for a two-week period. RESULTS: Participants identified safety as the main value of using a wearable GPS device. The acceptability and value of these devices was strongly influenced by device features, ease of use, cost, appearance, the reliability of the GPS coordinates, the wearer's health condition and the users familiarity with technology. Overall, participants indicated that they preferred the pendant. CONCLUSIONS: Wearable GPS devices are potentially useful in providing individuals who have safety concerns with reassurance and access to assistance as required. To ensure successful utilization, future device design and device selection should consider the user's familiarity with technology and their health condition. This study also revealed that not all wearable GPS devices provide continuous location tracking. It is therefore critical to ensure that the device's location tracking functions address the wearer's requirements and reason for using the device. Implications for Rehabilitation The acceptability and usability of wearable GPS devices is strongly influenced by the device features, ease of use, cost, appearance, the reliability of the device to provide accurate and timely GPS coordinates, as well as the health condition of the wearer and their familiarity with technology. Wearable GPS devices need to be simple to use and support and training is essential to ensure they are successfully utilized. Not all wearable GPS devices provide continuous location tracking and accuracy of location is impacted by line of sight to satellites. Therefore, care needs to be taken when choosing a suitable device, to ensure that the device's location tracking features are based on the wearer's requirements and value behind using the device.

Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.

Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG.

hERG quality control and the long QT syndrome.

Long-QT syndrome type-2 (LQT2) is characterized by reduced functional expression of the human ether-à-go-go related (hERG) gene product, resulting in impaired cardiac repolarization and predisposition to fatal arrhythmia. Previous studies have implicated abnormal trafficking of misfolded hERG as the primary mechanism of LQT2, with misfolding being caused by mutations in the hERG gene (inherited) or drug treatment (acquired). More generally, environmental and metabolic stresses present a constant challenge to the folding of proteins, including hERG, and must be countered by robust protein quality control (QC) systems. Disposal of partially unfolded yet functional plasma membrane (PM) proteins by protein QC contributes to the loss-of-function phenotype in various conformational diseases including cystic fibrosis (CF) and long-QT syndrome type-2 (LQT2). The prevalent view has been that the loss of PM expression of hERG is attributed to biosynthetic block by endoplasmic reticulum (ER) QC pathways. However, there is a growing appreciation for protein QC pathways acting at post-ER cellular compartments, which may contribute to conformational disease pathogenesis. This article will provide a background on the structure and cellular trafficking of hERG as well as inherited and acquired LQT2. We will review previous work on hERG ER QC and introduce the more novel view that there is a significant peripheral QC at the PM and peripheral cellular compartments. Particular attention is drawn to the unique role of the peripheral QC system in acquired LQT2. Understanding the QC process and players may provide targets for therapeutic intervention in dealing with LQT2.

Self-report tool for recognizing mania (SToRM): a new scale for aiding in the diagnosis of bipolar disorder.

OBJECTIVE: Bipolar disorder is a disabling disease that is difficult to diagnose. Primary care physicians share in the burden of diagnosing and caring for significant mental illness, including bipolar disorder, but they lack an adequate screening and diagnostic tool that can fit into use in a primary care practice. Modeling after the Patient Health Questionnaire-9, we created the Self-report Tool for Recognizing Mania (SToRM) to aid primary care physicians in the screening and diagnosis of bipolar disorder. METHODS: A 13-question tool was created and distributed to returning patients over an 11-month time period at the psychiatric clinic of a university health center. Each completed questionnaire was scored as positive or negative and then compared to the preexisting psychiatric diagnosis for that respondent, as shown on the problem list of the respondent's electronic medical record. RESULTS: A total of 102 subjects completed and returned their questionnaires. Twenty-eight surveys were scored as positive for bipolar disorder while 25 subjects carried this diagnosis on their problem list, giving a sensitivity of 72% and a specificity of 87% (CI at 95%). When alternative scoring was used, sensitivity increased to 96% with only a slight decrease in specificity to 84%. CONCLUSIONS: In this pilot study, we find that the SToRM shows potential in the pursuit of a highly reliable, self-report tool which could help primary care providers screen and diagnose bipolar disorder. As such, the SToRM deserves further study.