Neural correlates of distress and comfort in individuals with avoidant, anxious and secure attachment style: an fMRI study.

Despite a growing literature, experiments directly related to attachment are still needed. We explored brain processes involved in two aspects of attachment, distress and comfort. Seventy-eight healthy adult males with different attachment styles (secure, avoidant, and anxious) viewed distress, comfort, complicity-joy and neutral images (picture database BAPS-Adult) in an fMRI block design. ROIs from the modules described in the functional Neuro-Anatomical Model of Attachment (Long et al. 2020) were studied. Secure participants used more co- and self-regulation strategies and exhibited a higher activation of the reward network in distress and comfort viewing, than insecure participants. Avoidant participants showed the lower brain activations. Their approach and reward modules were the least activated in distress and comfort. Anxious participants presented both higher activations of the approach and aversion modules during complicity-joy. In addition, comfort and complicity-joy were processed differently according to attachment styles and should be differentiated among positive stimuli to disentangle attachment processes.

Don't forget the lyrics! Spatiotemporal dynamics of neural mechanisms spontaneously evoked by gaps of silence in familiar and newly learned songs.

The vast majority of people experience musical imagery, the sensation of reliving a song in absence of any external stimulation. Internal perception of a song can be deliberate and effortful, but also may occur involuntarily and spontaneously. Moreover, musical imagery is also involuntarily used for automatically completing missing parts of music or lyrics from a familiar song. The aim of our study was to explore the onset of musical imagery dynamics that leads to the automatic completion of missing lyrics. High-density electroencephalography was used to record the cerebral activity of twenty healthy volunteers while they were passively listening to unfamiliar songs, very familiar songs, and songs previously listened to for two weeks. Silent gaps inserted into these songs elicited a series of neural activations encompassing perceptual, attentional and cognitive mechanisms (range 100-500ms). Familiarity and learning effects emerged as early as 100ms and lasted 400ms after silence occurred. Although participants reported more easily mentally imagining lyrics in familiar rather than passively learnt songs, the onset of neural mechanisms and the power spectrum underlying musical imagery were similar for both types of songs. This study offers new insights into the musical imagery dynamics evoked by gaps of silence and on the role of familiarity and learning processes in the generation of these dynamics. The automatic and effortless method presented here is a potentially useful tool to understand failure in the familiarity and learning processes of pathological populations.

Left Prefrontal Repetitive Transcranial Magnetic Stimulation in a Logopenic Variant of Primary Progressive Aphasia: A Case Report.

BACKGROUND/AIMS: High frequency repetitive transcranial magnetic stimulation (hf-rTMS) improves language skills in Alzheimer's disease (AD). We report the use of hf-rTMS in a patient with logopenic primary progressive aphasia (LPPA) due to AD. METHOD: hf-rTMS was applied to the left dorsolateral prefrontal cortex of a LPPA patient. Cerebral perfusion, neuropsychological and linguistic performances were evaluated before and 1 month after hf-rTMS. RESULTS: The tolerance was good. Improvements on linguistic (fluency, naming, lesser paraphasia) and cognitive skills (Mini Mental State Examination, verbal memory free recall, speed processing) and cerebral perfusion were observed. CONCLUSION: hf-rTMS can be used in LPPA patients. A procognitive effect persisting several weeks after stimulation in LPPA patients was suggested and should therefore be evaluated in a clinical trial as an adjunctive therapeutic tool.

Visual scanning behavior during processing of emotional faces in older adults with major depression.

OBJECTIVES: Although several reported studies have suggested that younger adults with depression display depression-related biases during the processing of emotional faces, there remains a lack of data concerning these biases in older adults. The aim of our study was to assess scanning behavior during the processing of emotional faces in depressed older adults. METHOD: Older adults with and without depression viewed happy, neutral or sad portraits during an eye movement recording. RESULTS: Depressed older adults spent less time with fewer fixations on emotional features than healthy older adults, but only for sad and neutral portraits, with no significant difference for happy portraits. CONCLUSION: These results suggest disengagement from sad and neutral faces in depressed older adults, which is not consistent with standard theoretical proposals on congruence biases in depression. Also, aging and associated emotional regulation change may explain the expression of depression-related biases. Our preliminary results suggest that information processing in depression consists of a more complex phenomenon than merely a general searching for mood-congruent stimuli or general disengagement from all kinds of stimuli. These findings underline that care must be used when evaluating potential variables, such as aging, which interact with depression and selectively influence the choice of relevant stimulus dimensions.

Nestin expression in the retina of rats with inherited retinal degeneration.

Nestin is found in radial glia and neuronal/glial progenitor cells during retinal development, and is re-expressed after acute damage in the retina of adult mammals. We have investigated nestin expression in the retina of the Royal College of Surgeons (RCS) rat model of human inherited blindness, Retinitis pigmentosa (RP). During the first postnatal week, nestin immunoreactivity was located in elongated processes resembling radial glia in both control and dystrophic animals. During the second postnatal week, the density of nestin immunoreactive radial processes decreased progressively starting in the outer retina. At postnatal day 20 (PNd20), Nestin immunoreactive radial processes were no longer visible, with immunoreactivity restricted to structures resembling Müller end-feet and/or astrocytes located in the ganglion cell layer (GCL) in both control and dystrophic rats. These morphological results were confirmed by Western blotting and qPCR analysis. The level of nestin remained low in control animals at different time points up to 1 year, but we observed a re-expression of this protein from PNd30 in the dystrophic animals. The morphology of cells re-expressing nestin resembled that of radial glia and/or Muller cells, but co-localization of nestin and glutamine synthetase (GS: a marker of mature Müller cells) was only partial. Interestingly, whereas Western blot analysis confirmed the increase in protein levels from PNd30 onwards, mRNA levels remained low in dystrophic rats. Additional studies demonstrated that the discrepancy between protein and mRNA contents could be due to a dysfunction in proteasome activity as often observed in neurodegenerative pathologies. In conclusion, because of its localization in astrocytes and in radial processes resembling radial glia in the pathologic adult retina, nestin may be involved in mechanisms such as cell migration, generation of new neurons or glial cells and/or in retinal (re)modeling in dystrophic adult animals. The lack of concomitant up-regulation of mRNAs in adult dystrophic animals suggests that the pathology could lead to transcriptional and/or metabolic changes involving the stabilization of the half-life and/or dysregulation of degradation processes of nestin protein.

Anxiety and hospitalization in adolescence: relations to attachment style and parental support.

This exploratory study examined attachment style and state/trait anxiety in adolescents - 30 recently hospitalized psychiatric patients, and 49 school controls. All were aged 13-18, with the majority (67%) female. The attachment style interview (ASI, Bifulco et al. 2002) was administered, together with the Recent Life Events questionnaire (Brugha & Cragg 1990) and the STAI anxiety questionnaire (Spielberger et al. 1983). Results showed the hospitalised group to have significantly more negative interactions with parents and poorer support than the comparison group. They had significantly more insecure attachment style (96% s 37%). Among the hospitalized adolescents, both the Anxious and the Avoidant attachment style group had higher anxiety scores on the STAI-trait scores than on the STAI-state scores assessed during the first days of hospitalisation. This suggests adolescents, even those with Avoidant attachment feel less anxious after admission. Implications for assessing attachment style in adolescent patients to aid with care planning is discussed.

Resting motor threshold changes and clinical response to prefrontal repetitive transcranial magnetic stimulation in depressed patients.

AIMS: Several variables are able to influence the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS), particularly the intensity of stimulation, which is generally expressed according to the resting motor threshold (RMT). The aim of our study was to investigate whether or not RMT changes during the treatment of resistant depression by rTMS and whether these fluctuations could alter treatment outcome. METHODS: Seventy-five inpatients suffering from unipolar or bipolar treatment-resistant depression and who had been antidepressant-free or taking a stable antidepressant drug and a daily dose of benzodiazepine for at least a month received a left prefrontal rTMS session once a day for 10 days at 10 Hz and 95% RMT. RESULTS: For the whole group, no significant fluctuation of RMT was observed between the first and the second week of rTMS treatment. However, RMT increased, decreased or remained constant throughout treatment depending on the patient. These RMT changes influenced the outcome of the 10 sessions concerning the severity of depressive and anxiety symptoms, measured by the Beck Depression Inventory and State Trait Anxiety, respectively. CONCLUSIONS: Our results justify calculating RMT regularly, and suggest that its variations play a role in treatment outcome.

Massively multiplayer online role-playing games: comparing characteristics of addict vs non-addict online recruited gamers in a French adult population.

BACKGROUND: Massively Multiplayer Online Role-Playing Games (MMORPGs) are a very popular and enjoyable leisure activity, and there is a lack of international validated instruments to assess excessive gaming. With the growing number of gamers worldwide, adverse effects (isolation, hospitalizations, excessive use, etc.) are observed in a minority of gamers, which is a concern for society and for the scientific community. In the present study, we focused on screening gamers at potential risk of MMORPG addiction. METHODS: In this exploratory study, we focused on characteristics, online habits and problematic overuse in adult MMORPG gamers. In addition to socio-demographical data and gamer behavioral patterns, 3 different instruments for screening addiction were used in French MMORPG gamers recruited online over 10 consecutive months: the substance dependence criteria for the Diagnostic and Statistical Manual of Mental Disorder, fourth revised edition (DSM-IV-TR) that has been adapted for MMORPG (DAS), the qualitative Goldberg Internet Addiction Disorder scale (GIAD) and the quantitative Orman Internet Stress Scale (ISS). For all scales, a score above a specific threshold defined positivity. RESULTS: The 448 participating adult gamers were mainly young adult university graduates living alone in urban areas. Participants showed high rates of both Internet addiction (44.2% for GIAD, 32.6% for ISS) and DAS positivity (27.5%). Compared to the DAS negative group, DAS positive gamers reported significantly higher rates of tolerance phenomenon (increased amount of time in online gaming to obtain the desired effect) and declared significantly more social, financial (OR: 4.85), marital (OR: 4.61), family (OR: 4.69) and/or professional difficulties (OR: 4.42) since they started online gaming. Furthermore, these gamers self-reported significantly higher rates (3 times more) of irritability, daytime sleepiness, sleep deprivation due to play, low mood and emotional changes since online gaming onset. CONCLUSIONS: The DAS appeared to be a good first-line instrument to screen MMORPG addiction in online gamers. This study found high MMORPG addiction rates, and self-reported adverse symptoms in important aspects of life, including mood and sleep. This confirms the need to set up relevant prevention programs against online game overuse.

[Neurodevelopmental disorders modify neurodegenerative diseases: a medical history to screen in memory clinic]. / Les troubles neurodéveloppementaux miment ou influencent les pathologies neurodégénératives : prise en compte des antécédents neurodéveloppementaux en consultation mémoire.

Neurodevelopmental disorders are frequent in the general population and are often lifelong conditions despite sometimes being masked by conscious or unconscious compensation and avoidance mechanisms. These conditions are often unknown or underestimated in adults, even when diagnosed in childhood. Neurodevelopmental disorders share similarities with and frequently interact in a complex way with neurodegenerative disorders. Considering these aspects during memory clinic assessments can provide a new perspective on lifelong neurocognitive trajectories. Assessing both neurodevelopmental and neurodegenerative dimensions is challenging but should improve diagnostic accuracy. It is therefore necessary to understand the lifelong specific neurocognitive trajectory of each patient in order to develop personalized and focused cognitive medicine and care.

Saccadic Eye Movements in Elderly Depressed Patients With Suicidal Behaviors: An Exploratory Eye-Tracking Study.

Suicidal behaviors (SBs) are often associated with impaired performance on neuropsychological executive functioning (EF) measures that encourage the development of more specific and reliable tools. Recent evidence could suggest that saccadic movement using eye tracking can provide reliable information on EF in depressive elderly. The aim of this study was to describe oculomotor performances in elderly depressed patients with SB. To achieve this aim, we compared saccadic eye movement (SEM) performances in elderly depressed patients (N = 24) with SB and with no SB in prosaccade (PS) and antisaccade (AS) tasks under the gap, step, and overlap conditions. All participants also underwent a complete neuropsychological battery. Performances were impaired in patients with SB who exhibited less corrected AS errors and longer time to correct them than patients with no SB. Moreover, both groups had a similar performance for PS latencies and correct AS. These preliminary results suggested higher cognitive inflexibility in suicidal patients compared to non-suicidal. This inflexibility may explain the difficulty of the depressed elderly in generating solutions to the resurgence of suicidal ideation (SI) to respond adequately to stressful environments. The assessment of eye movement parameters in depressed elderly patients may be a first step in identifying high-risk patients for suicide.

Repetitive Transcranial Magnetic Stimulation as an Add-On Treatment for Cognitive Impairment in Alzheimer's Disease and Its Impact on Self-Rated Quality of Life and Caregiver's Burden.

Alzheimer's disease (AD) is associated with progressive memory loss and decline in executive functions, as well as neuropsychiatric symptoms. Patients usually consider quality of life (QoL) and mood as more important for their health status than disease-specific physical and mental symptoms. In this open-label uncontrolled trial, 12 subjects diagnosed with AD underwent 10 sessions of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (10 Hz, 20 min, 2000 pulses/day, 110% MT). Outcomes were measured before and 30 days after treatment. Our primary objective was to test the efficacy of rTMS as an add-on treatment for AD on the global cognitive function, assessed through the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (MDRS). As secondary objectives, the detailed effect on cognitive functions, depression and anxiety symptoms, QoL, and functionality in daily life activities were evaluated, as well as correlations between QoL and cognition, depression and anxiety scores. The treatment significantly enhanced semantic memory and reduced anxiety. Improvement of these features in AD could become an important target for treatment strategies. Although limited by its design, this trial may contribute with another perspective on the analysis and the impact of rTMS on AD.

(±)-BIGI-3h: Pentatarget-Directed Ligand combining Cholinesterase, Monoamine Oxidase, and Glycogen Synthase Kinase 3ß Inhibition with Calcium Channel Antagonism and Antiaggregating Properties for Alzheimer's Disease.

Multitarget-directed ligands (MTDLs) are considered a promising therapeutic strategy to address the multifactorial nature of Alzheimer's disease (AD). Novel MTDLs have been designed as inhibitors of human acetylcholinesterases/butyrylcholinesterases, monoamine oxidase A/B, and glycogen synthase kinase 3ß and as calcium channel antagonists via the Biginelli multicomponent reaction. Among these MTDLs, (±)-BIGI-3h was identified as a promising new hit compound showing in vitro balanced activities toward the aforementioned recognized AD targets. Additional in vitro studies demonstrated antioxidant effects and brain penetration, along with the ability to inhibit the aggregation of both τ protein and ß-amyloid peptide. The in vivo studies have shown that (±)-BIGI-3h (10 mg/kg intraperitoneally) significantly reduces scopolamine-induced cognitive deficits.

Comparison of Noninvasive Imagery Methods to Observe Healthy and Degenerated Olfactory Epithelium in Mice for the Early Diagnosis of Neurodegenerative Diseases.

Olfactory dysfunction could be an early and reliable indicator for the diagnosis of neurodegenerative disorders such as Alzheimer and Parkinson's diseases. In this paper, we compare the potential of different noninvasive medical imaging modalities (optical coherence tomography, confocal microscopy, and fluorescence endomicroscopy) to distinguish how the olfactory epithelium, both at the cellular and the structural levels, is altered. Investigations were carried out on three experimental groups: two pathological groups (mice models with deliberately altered olfactory epithelium and Alzheimer's disease transgenic mice models) were compared with healthy mice models. As histological staining, the three tested noninvasive imaging tools demonstrated the general tubular organization of the olfactory epithelium on healthy mice. Contrary to OCT, confocal microscopy, and endomicroscopy allowed visualizing the inner structure of olfactory epithelium as well as its morphological or functional changes on pathological models, alterations classically observed with histological assessment. The results could lead to relevant development of imaging tools for noninvasive and early diagnosis of neurodegenerative diseases through the in situ characterization of the olfactory epithelium.

[Pharmacogenetics of depression in elderly patients]. / Pharmacogénétique de la dépression du sujet âgé

Depression is one of the leading causes of disability and is efficiently treated by antidepressant pharmacotherapy. Pharmacological treatment is still hampered by a delayed time of onset of clinical improvement and a series of side effects. In elderly, it is complicated by an increased risk of adverse drug events, associated with age-related physiological changes, individual variability in drug metabolism mainly related to polymedication, concurrent diseases and diet. Then every physician would like to predict these impairments and to prescribe a "tailored" treatment based on individual characteristics. One of the tools for this tailored medication is the use of pharmacogenetics, leading to an evaluation of the human genome implications in the treatment response (efficacy, time of onset and adverse events). Some candidate-genes have already been identified, showing encouraging results, but only a few studies focus on depressed old subjects. The existing studies have analyzed the polymorphism of the metabolizing enzyme gene CYP2D6 and the serotonin transporter genes implications. The results are promising but more researches are necessary to include pharmacogenetic studies in the clinical practice.

The Besançon affective picture set-adult (BAPS-Adult): Development and validation.

We developed and validated a new picture database of attachment-related photographs, the BAPS-Adult. Participants (N = 315) rated 256 pictures, according to dimension (valence, arousal, and dominance) using Self-Assessment Manikins (SAM), emotional category (positive, negative, mixed, and neutral) using labels, and discrete emotion (comfort, joy, complicity, distress, horror, and hate) using linear scales. Pictures were then classified into four types, depending on content (distress, comfort, complicity-joy, and neutral). Dimensional ratings of valence, arousal, and dominance, as well as discrete emotion ratings, differed significantly from each other between picture types. The BAPS-Adult is a new, highly discriminated database, allowing researchers to select from a variety of pre-rated, attachment-related pictures.

How do adolescents regulate distress according to attachment style? A combined eye-tracking and neurophysiological approach.

According to attachment theory, attachment representations influence emotion regulation (ER) across the lifespan. However, research into attachment-related ER in adolescence is still scarce. The aim of this study was to assess attachment-related ER using a multimodal approach, relying on behavioral and neurophysiological parameters. Attachment styles in eighty-one adolescents were assessed with the Attachment Style Interview (ASI). A distress-then-comfort paradigm based on visual stimuli (the Besancon Affective Picture Set-Adolescents) was employed to "activate" then "deactivate" the attachment system. Gaze and neurophysiological parameters of ER strategies were assessed using eye-tracking synchronized with a physiological device. During the first phase "distress exposure", attachment style was associated with the early stage of distress processing indexed by first fixation duration. Withdrawn adolescents fixated distress pictures less than other groups. Fearful adolescents showed a longer first fixation duration than withdrawn adolescents. During the following phase, "comfort-seeking", all groups initially fixed joy-complicity and comfort pictures earlier than neutral pictures, except for withdrawn adolescents, who fixated comfort pictures later than neutral pictures. Additionally, withdrawn adolescents explored comfort pictures less than enmeshed adolescents. Enmeshed adolescents explored neutral pictures less than comfort and joy-complicity pictures. Concerning neurophysiological parameters, first fixation duration correlated positively with Skin Conductance Response (SCR) rise time in fearful adolescents, while glance count correlated negatively with SCR latency in withdrawn adolescents. This study provides an innovative and objective evaluation of behavioral and neurophysiological parameters for attachment-related ER in adolescents, with a temporal resolution. These parameters constitute potential biomarkers that could contribute to our understanding of ER differences in insecure adolescents. This study was registered with the clinical trials database ClinicalTrials.gov on August 01, 2016, under the number NCT02851810.

Saccadic Eye Movements and Attentional Control in Alzheimer's Disease.

OBJECTIVE: Several studies have demonstrated saccadic eye movement (SEM) abnormalities in Alzheimer's disease (AD) when patients performed prosaccade (PS) and antisaccade (AS) tasks. Some studies have also showed that SEM abnormalities were correlated with dementia rating tests such as the Mini Mental State Evaluation (MMSE). Therefore, it has been suggested that SEMs could provide useful information for diagnosis. However, little is known about predictive saccades (PreS)-saccades triggered before or very quickly after stimuli appearance-and their relationships with cognition in AD. Here, we aimed to examine the relationships between our usual dementia screening tests and SEM parameters in PS, AS, and also PreS task. METHOD: We compared SEMs in 20 patients suffering from AD and in 35 healthy older adults (OA) in PS, AS, and PreS task. All participants also completed a neuropsychological evaluation. RESULTS: We showed that AD patients had higher latency and latency variability regardless the tasks, and also higher AS cost, in comparison with OA. Moreover, AD patients made more uncorrected AS and took more time-to-correct incorrect AS. In PreS task, AD patients showed higher gain and gain variability than OA when they made anticipated saccades. Close relationships were found between the majority of SEM variables in PS, AS, and PreS tasks and dementia screening tests, especially the MMSE and episodic memory measures. CONCLUSION: Our findings, in agreement with previous studies, demonstrated that AD affects several SEM parameters. SEM abnormalities may reflect selective and executive-attention impairments in AD.

Evidence for a neural signature of musical preference during silence.

One of the most basic and person-specific affective responses to music is liking. The present investigation sought to determine whether liking was preserved during spontaneous auditory imagery. To this purpose, we inserted two-second silent intervals into liked and disliked songs, a method known to automatically recreate a mental image of these songs. Neural correlates of musical preference were measured by high-density electroencephalography in twenty subjects who had to listen to a set of five pre-selected unknown songs the same number of times for two weeks. Time frequency analysis of the two most liked and the two most disliked songs confirmed the presence of neural responses related to liking. At the beginning of silent intervals (400-900 ms and 1000-1300 ms), significant differences in theta activity were originating from the inferior frontal and superior temporal gyrus. These two brain structures are known to work together to process various aspects of music and are also activated when measuring liking while listening to music. At the end of silent intervals (1400-1900 ms), significant alpha activity differences originating from the insula were observed, whose exact role remains to be explored. Although exposure was controlled for liked and disliked songs, liked songs were rated as more familiar, underlying the strong relationship that exists between liking, exposure, and familiarity.

Production of neurospheres from mammalian Müller cells in culture.

In lower vertebrates, like fishes and amphibians, retina is able to self-regenerate whereas Mammalian retina has lost this property. Nevertheless, recently, it has turned out that retinal glial Müller cells were playing a role in neuronal regeneration of the adult rodent retina, in case of acute damages, by dedifferentiating and redifferentiating in glial and neural cells. The purpose of this study was to analyse the ability of mammalian Müller cells for forming neurospheres. First of all, rats Müller cells were isolated in a primary culture. Second, these cells were resuspended in two different culture media: the cells cultures in the Neurobasal-A medium kept a typical Müller cells morphology even after 15 days of EGF treatment, and the cells plated in the DMEM-F12 medium formed neurospheres from the third day in culture. The neurosphere cells expressed nestin, cellular retinaldehyde binding protein (CRALBP) and glial fibrillary acidic protein (GFAP). These results showed our capacity to isolate and propagate Müller cells-derived progenitor cells. Moreover, it allows us to control the number of progenitor cells and, in the future, to study their differentiation capacity.

The antidepressant-like effect of tDCS in mice: A behavioral and neurobiological characterization.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive method increasingly popular for the treatment of several brain disorders, such as major depression. Despite great enthusiasm and promising results, some studies report discrepant findings and no consensus exists for the clinical use of tDCS. OBJECTIVE: The present study aims to (i) determine the most effective stimulation parameters to optimize antidepressant-like effect of tDCS in the forced-swim test in mice and (ii) identify brain regions recruited by tDCS and possibly involved in its behavioral effect using Fos immunohistochemistry. RESULTS: We reported that tDCS induced long-lasting antidepressant-like effect, which varied as a function of stimulation settings including number, duration, intensity and polarity of stimulation. Interestingly, the present study also demonstrated that tDCS reduced depressive-like behaviors induced by chronic corticosterone exposure. Furthermore, behavioral outcomes induced by a single stimulation were associated with neuronal activation in the prefrontal cortex, dorsal hippocampus, ventral tegmental area and nucleus accumbens, whereas no overexpression of c-fos was associated with 10 stimulations. CONCLUSION: The strongest behavioral response was observed with an anodal stimulation of 200 µA during 20min. The repetition of this stimulation was necessary to induce long-lasting behavioral effects that are probably associated with plastic changes in the neuronal response.