Reduced visual context effects in global motion processing in depression.

Research supports abnormal inhibitory visual motion processing in adults with remitted and current depression, but all studies to date have used paradigms with simple grating stimuli. Global motion processing, where multiple motion signals must be integrated, has not been explored in depression, nor have inhibitory processes within that domain. Depressed participants (n = 46) and healthy controls (n = 28) completed a direction discrimination task featuring a random dot pattern stimulus. Various signal (rightward or leftward dots) to noise (dots with randomly assigned directions) ratios modulated task difficulty. Metrics of global center surround suppression and facilitation were calculated. Accuracy in the baseline condition (i.e., no surrounding annulus) was not significantly different between depressed and healthy participants. Global center surround suppression and facilitation were not significantly different between healthy and depressed participants overall. When limiting the sample to unmedicated individuals, depressed participants (n = 27) showed a reduced global center surround suppression effect compared to controls, and there was no difference in global center surround facilitation. While global motion processing is intact in depression, abnormal center surround suppression effects in depression do extend to global motion stimuli. These alterations may be mitigated by the psychotropic medications taken by some subjects in our depressed sample. Future studies should explore the mechanisms underlying these effects.

The role of health systems factors in facilitating access to psychotropic medicines: a cross-sectional analysis of the WHO-AIMS in 63 low- and middle-income countries.

BACKGROUND: Neuropsychiatric conditions comprise 14% of the global burden of disease and 30% of all noncommunicable disease. Despite the existence of cost-effective interventions, including administration of psychotropic medicines, the number of persons who remain untreated is as high as 85% in low- and middle-income countries (LAMICs). While access to psychotropic medicines varies substantially across countries, no studies to date have empirically investigated potential health systems factors underlying this issue. METHODS AND FINDINGS: This study uses a cross-sectional sample of 63 LAMICs and country regions to identify key health systems components associated with access to psychotropic medicines. Data from countries that completed the World Health Organization Assessment Instrument for Mental Health Systems (WHO-AIMS) were included in multiple regression analyses to investigate the role of five major mental health systems domains in shaping medicine availability and affordability. These domains are: mental health legislation, human rights implementations, mental health care financing, human resources, and the role of advocacy groups. Availability of psychotropic medicines was associated with features of all five mental health systems domains. Most notably, within the domain of mental health legislation, a comprehensive national mental health plan was associated with 15% greater availability; and in terms of advocacy groups, the participation of family-based organizations in the development of mental health legislation was associated with 17% greater availability. Only three measures were related with affordability of medicines to consumers: level of human resources, percentage of countries' health budget dedicated to mental health, and availability of mental health care in prisons. Controlling for country development, as measured by the Human Development Index, health systems features were associated with medicine availability but not affordability. CONCLUSIONS: Results suggest that strengthening particular facets of mental health systems might improve availability of psychotropic medicines and that overall country development is associated with affordability.

Reduced cognitive control of a visually bistable image in schizophrenia.

Schizophrenia is associated with the inability to control and coordinate thoughts, actions, and perceptions. In conventional assessments of cognitive control, multiple sensory features of stimuli are concomitantly manipulated, introducing a confounding role of bottom-up perceptual information. To overcome this difficulty, we used an ambiguous visual stimulus (Necker cube), which allowed measurement of cognitive control with constant sensory input. Subjects (20 patients, 20 controls) were asked to control their perception of a transparent Necker cube by keeping a designated plane at the front or back of the stimulus, the position of which is perceptually bistable. Patients were highly deficient at controlling their perception of the cube. When a visual feature (the luminance contrast between a designated cube plane and the other planes) was systematically manipulated, an interaction was found whereby schizophrenia patients no longer under-performed on the highest contrast condition. These results show patients' impairment of controlling perception in the absence of visual modulation and suggest the potential utility of perceptually based approaches to cognitive remediation in schizophrenia.

Perceptual training strongly improves visual motion perception in schizophrenia.

Schizophrenia patients exhibit perceptual and cognitive deficits, including in visual motion processing. Given that cognitive systems depend upon perceptual inputs, improving patients' perceptual abilities may be an effective means of cognitive intervention. In healthy people, motion perception can be enhanced through perceptual learning, but it is unknown whether this perceptual plasticity remains in schizophrenia patients. The present study examined the degree to which patients' performance on visual motion discrimination can be improved, using a perceptual learning procedure. While both schizophrenia patients and healthy controls showed decreased direction discrimination thresholds (improved performance) with training, the magnitude of the improvement was greater in patients (47% improvement) than in controls (21% improvement). Both groups also improved moderately but non-significantly on an untrained task-speed discrimination. The large perceptual training effect in patients on the trained task suggests that perceptual plasticity is robust in schizophrenia and can be applied to develop bottom-up behavioral interventions.

Visual attention toward emotional stimuli: Anxiety symptoms correspond to distinct gaze patterns.

Decades of research have established a link between emotional disorders and attentional biases for emotional stimuli, but the relationship between symptom severity and visual attention is still not fully understood. Depression has been associated with increased attention towards dysphoric stimuli and decreased attention on positive stimuli ("negativity bias"), and some studies have also shown this trend in anxiety disorders. We examined eye fixation variables in 47 participants with emotional disorders completing an emotion recognition task. Results showed that depression severity was not associated with increased fixations on dysphoric stimuli, however, higher levels of generalized anxiety predicted increased fixations in the mouth region of sad and happy faces. Higher levels of social interaction anxiety predicted reduced fixations in the eye region of happy faces. While we did not replicate the negativity bias that has been shown in prior studies, our sample was highly comorbid, indicating the need to consider comorbidity, disorder severity, and the task itself when conducting research on visual attention in clinical samples. Additionally, more attention should be paid to the mouth region of emotional faces, as it may provide more specific information regarding the visual processing of emotions.

Normal Face Detection Over a Range of Luminance Contrasts in Adolescents With Autism Spectrum Disorder.

Face recognition is impaired in autism spectrum disorders (ASDs), but the reason for this remains unclear. One possibility is that impairments in the ability to visually detect faces might be a factor. As a preliminary study in this vein, we measured face detection ability as a function of visual contrast level in 13 individuals with ASD, aged 13-18, and 18 neurotypical controls (NCs) in the same age range. We also measured contrast sensitivity, using sinusoidal grating stimuli, as a control task. Individuals with ASD did not differ from controls in face detection (p > 0.9) or contrast detection (p > 0.2) ability. Performance on contrast and face detection was significantly correlated in ASD but not in NC. Results suggest that the ability to visually detect faces is not altered in ASD overall, but that alterations in basic visual processing may affect face detection ability in some individuals with ASD.

Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer's disease.

BACKGROUND: Over the past decade, visual short-term memory (VSTM) binding tests have been shown to be one of the most sensitive behavioral indicators of Alzheimer's disease (AD), especially when they require the binding of multiple features (e.g., color and shape). Recently, it has become possible to directly measure amyloid and tau levels in vivo via positron emission tomography (PET). To this point, these behavioral and neurochemical markers have not been compared in humans with AD or at risk for it. METHODS: In a cross-sectional study, we compared VSTM performance to tau and amyloid concentrations, measured by PET, in individuals certain to develop AD by virtue of their inheritance of the presenilin-1 E280A mutation. These included 21 clinically unimpaired subjects and 7 subjects with early mild cognitive impairment (MCI), as well as 30 family members who were not carriers of the mutation. RESULTS: We found that VSTM performance correlated strongly with tau in entorhinal cortex and inferior temporal lobe, and also with amyloid when examining asymptomatic carriers only. The condition requiring binding was not preferentially linked to tau-in fact, the non-binding "shape only" condition showed a stronger relationship. CONCLUSIONS: The results confirm VSTM's status as an early marker of AD pathology and raise interesting questions as to the course of binding-specific versus non-binding aspects of VSTM in early AD.

A Double-Blind Placebo Controlled Study of Intranasal Oxytocin's Effect on Emotion Recognition and Visual Attention in Outpatients with Emotional Disorders.

The current study used double-blind, placebo-controlled design to examine the effect of intranasal oxytocin (OT) on emotion recognition (ER) and visual attention in 60 outpatients presenting for assessment and treatment of emotional disorders. Our primary hypothesis was that OT would improve recognition of happy faces in depressed participants. The main effect of OT on ER accuracy, speed, and proportion of fixations in the eye region was not significant. Diagnostic group (i.e., presence/absence of a depressive disorder) moderated the effect of OT on ER, but not as expected: OT significantly slowed ER speed for all emotions in participants with anxiety disorders, but did not affect performance in participants with depressive disorders. Depressed participants fixated significantly less in the eye region of sad faces than anxious participants. Before OT can be used to target ER biases, additional research is needed to explicate the differential impact of OT on ER speed in patients with anxiety versus mood disorders.

Striatal amyloid is associated with tauopathy and memory decline in familial Alzheimer's disease.

BACKGROUND: Autosomal dominant Alzheimer's disease (ADAD) is distinguished from late-onset AD by early striatal amyloid-ß deposition. To determine whether striatal Pittsburgh compound B (PiB)-PET measurements of amyloid-ß can help predict disease severity in ADAD, we compared relationships of striatal and neocortical PiB-PET to age, tau-PET, and memory performance in the Colombian Presenilin 1 E280A kindred. METHODS: Fourteen carriers (age = 28-42, Mini-Mental State Examination = 26-30) and 20 age-matched non-carriers were evaluated using PiB, flortaucipir (FTP; tau), and memory testing (CERAD Word List Learning). PiB-PET signal was measured in neocortical and striatal aggregates. FTP-PET signal was measured in entorhinal cortex. RESULTS: Compared to non-carriers, mutation carriers had age-related elevations in both neocortical and striatal PiB binding. The PiB elevation in carriers was significantly greater in the striatum than in the neocortex. In mutation carriers, PiB binding in both the neocortex and the striatum is related to entorhinal FTP; however, the association was stronger with the striatum. Only striatal PiB was associated with worse memory. Remarkably, PiB binding in the striatum, but not in the neocortex, predicted entorhinal FTP and lower memory scores after adjusting for age, indicating that striatal PiB identified the carriers with the most severe disease. CONCLUSIONS: Based on these preliminary cross-sectional findings, striatal PiB-PET measurements may offer particular value in the detection and tracking of preclinical ADAD, informing a mutation carrier's prognosis and evaluating amyloid-ß-modifying ADAD treatments.

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

A Three-Factor Structure of Cognitive Functioning Among Unimpaired Carriers and Non-Carriers of Autosomal-Dominant Alzheimer's Disease.

BACKGROUND: There is a need to find cognitive markers that can help identify individuals at risk for Alzheimer's disease (AD), and that can be used to reliably measure cognitive decline. OBJECTIVE: We tested whether a theoretically driven three-factor structure would characterize cognitive functioning in individuals who are genetically-determined to develop AD due to a mutation in Presenilin-1 (PSEN1) gene. We also examined whether these factors could distinguish cognitively unimpaired PSEN1 mutation carriers from age-matched non-carrier family members. METHODS: 1,395 cognitively unimpaired members of a Colombian kindred with the PSEN1 E280A mutation were included in the study. A confirmatory factor analysis examined the fit of the three-factor model comprising episodic memory (MMSE memory recall, CERAD-COL Word list recall, and Constructional praxis recall), executive function (Phonemic fluency and WCST perseverative errors), and psychomotor processing speed (TMT-A and WAIS-III Digit Symbol). RESULTS: The three-factor model provided an excellent fit for all participants (p = 0.24; RMSEA = 0.01). Further, the episodic memory (p = 0.0004, d = 0.25) and executive functioning (p = 0.001, d = 0.18) factors distinguished cognitively unimpaired carriers from non-carriers. The episodic memory factor provided the earliest indication of preclinical cognitive decline at 35 years of age, nine years before individuals' estimated age of clinical onset. CONCLUSIONS: The three theoretically derived cognitive factors provide a reliable measure of cognition and may be useful for the early detection of AD, as well as for measuring disease progression. However, longitudinal studies are needed to confirm that these factors can be used to track the progression of cognitive decline in preclinical AD.

Association Between Amyloid and Tau Accumulation in Young Adults With Autosomal Dominant Alzheimer Disease.

Importance: It is critically important to improve our ability to diagnose and track Alzheimer disease (AD) as early as possible. Individuals with autosomal dominant forms of AD can provide clues as to which and when biological changes are reliably present prior to the onset of clinical symptoms. Objective: To characterize the associations between amyloid and tau deposits in the brains of cognitively unimpaired and impaired carriers of presenilin 1 (PSEN1) E280A mutation. Design, Setting, and Participants: In this cross-sectional imaging study, we leveraged data from a homogeneous autosomal dominant AD kindred, which allowed us to examine measurable tau deposition as a function of individuals' proximity to the expected onset of dementia. Cross-sectional measures of carbon 11-labeled Pittsburgh Compound B positron emission tomography (PET) and flortaucipir F 18 (previously known as AV 1451, T807) PET imaging were assessed in 24 PSEN1 E280A kindred members (age range, 28-55 years), including 12 carriers, 9 of whom were cognitively unimpaired and 3 of whom had mild cognitive impairment, and 12 cognitively unimpaired noncarriers. Main Outcomes and Measures: We compared carbon 11-labeled Pittsburgh Compound B PET cerebral with cerebellar distribution volume ratios as well as flortaucipir F 18 PET cerebral with cerebellar standardized uptake value ratios in mutation carriers and noncarriers. Spearman correlations characterized the associations between age and mean cortical Pittsburgh Compound B distribution volume ratio levels or regional flortaucipir standardized uptake value ratio levels in both groups. Results: Of the 24 individuals, the mean (SD) age was 38.0 (7.4) years, or approximately 6 years younger than the expected onset of clinical symptoms in carriers. Compared with noncarriers, cognitively unimpaired mutation carriers had elevated mean cortical Pittsburgh Compound B distribution volume ratio levels in their late 20s, and 7 of 9 carriers older than 30 years reached the threshold for amyloidosis (distribution volume ratio level > 1.2). Elevated levels of tau deposition were seen within medial temporal lobe regions in amyloid-positive mutation carriers 6 years before clinical onset of AD in this kindred. Substantial tau deposition in the neocortex was only observed in 1 unimpaired carrier and in those with mild cognitive impairment. ß-Amyloid uptake levels were diffusely elevated in unimpaired carriers approximately 15 years prior to expected onset of mild cognitive impairment. In carriers, higher levels of tau deposition were associated with worse performance on the Mini-Mental State Examination (entorhinal cortex: r = -0.60; P = .04; inferior temporal lobe: r = -0.54; P = .06) and the Consortium to Establish a Registry for Alzheimer Disease Word List Delayed Recall (entorhinal cortex: r = -0.86; P < .001; inferior temporal lobe: r = -0.70; P = .01). Conclusions and Relevance: The present findings add to the growing evidence that molecular markers can characterize biological changes associated with AD in individuals who are still cognitively unimpaired. The findings also suggest that tau PET imaging may be useful as a biomarker to distinguish individuals at high risk to develop the clinical symptoms of AD and to track disease progression.

Subjective memory complaints in preclinical autosomal dominant Alzheimer disease.

OBJECTIVE: To cross-sectionally study subjective memory complaints (SMC) in autosomal dominant Alzheimer disease (ADAD). METHODS: We examined self-reported and study partner-based SMC in 52 young, cognitively unimpaired individuals from a Colombian kindred with early-onset ADAD. Twenty-six carried the PSEN-1 E280A mutation, averaging 7 years of age younger than the kindred's expected clinical onset. Twenty-six were age-matched noncarriers. Participants also underwent structural MRI and cognitive testing. RESULTS: Self-reported SMC were greater in carriers than noncarriers (p = 0.02). Study partner-based SMC did not differ between groups (p = 0.21), but in carriers increased with age (r = 0.66, p < 0.001) and decreased with hippocampal volume (r = -0.35, p = 0.08). CONCLUSIONS: Cognitively unimpaired PSEN-1 carriers have elevated SMC. Self-reported SMC may be a relatively early indicator of preclinical AD, while partner- reported SMC increases later in preclinical AD, closer to clinical onset.

Dysregulation of visual motion inhibition in major depression.

Individuals with depression show depleted concentrations of the inhibitory neurotransmitter GABA in occipital (visual) cortex, predicting weakened inhibition within their visual systems. Yet, visual inhibition in depression remains largely unexplored. To fill this gap, we examined the inhibitory process of center-surround suppression (CSS) of visual motion in depressed individuals. Perceptual performance in discriminating the direction of motion was measured as a function of stimulus presentation time and contrast in depressed individuals (n=27) and controls (n=22). CSS was operationalized as the accuracy difference between conditions using large (7.5°) and small (1.5°) grating stimuli. Both depressed and control participants displayed the expected advantage in accuracy for small stimuli at high contrast. A significant interaction emerged between subject group, contrast level and presentation time, indicating that alterations of CSS in depression were modulated by stimulus conditions. At high contrast, depressed individuals showed significantly greater CSS than controls at the 66ms presentation time (where the effect peaked in both groups). The results' specificity and dependence on stimulus features such as contrast, size and presentation time suggest that they arise from changes in early visual processing, and are not the results of a generalized deficit or cognitive bias.

Visuospatial Attention to Single and Multiple Objects Is Independently Impaired in Parkinson's Disease.

Parkinson's disease (PD) is associated with deficits in visuospatial attention. It is as yet unknown whether these attentional deficits begin at a perceptual level or instead reflect disruptions in oculomotor or higher-order processes. In the present study, non-demented individuals with PD and matched normal control adults (NC) participated in two tasks requiring sustained visuospatial attention, both based on a multiple object tracking paradigm. Eye tracking was used to ensure central fixation. In Experiment 1 (26 PD, 21 NC), a pair of identical red dots (one target, one distractor) rotated randomly for three seconds at varied speeds. The task was to maintain the identity of the sole target, which was labeled prior to each trial. PD were less accurate than NC overall (p = .049). When considering only trials where fixation was maintained, however, there was no significant group difference, suggesting that the deficit's origin is closely related to oculomotor processing. To determine whether PD had additional impairment in multifocal attention, in Experiment 2 (25 PD, 15 NC), two targets were presented along with distractors at a moderate speed, along with a control condition in which dots remained stationary. PD were less accurate than NC for moving (p = 0.02) but not stationary targets. This group difference remained significant when considering only trials where fixation was maintained, suggesting the source of the PD deficit was independent from oculomotor processing. Taken together, the results implicate separate mechanisms for single vs. multiple object tracking deficits in PD.

Normal discrimination of spatial frequency and contrast across visual hemifields in left-onset Parkinson's disease: evidence against perceptual hemifield biases.

Individuals with Parkinson's disease (PD) with symptom onset on the left side of the body (LPD) show a mild type of left-sided visuospatial neglect, whereas those with right-onset (RPD) generally do not. The functional mechanisms underlying these observations are unknown. Two hypotheses are that the representation of left-space in LPD is either compressed or reduced in salience. We tested these hypotheses psychophysically. Participants were 31 non-demented adults with PD (15 LPD, 16 RPD) and 17 normal control adults (NC). The spatial compression hypothesis was tested by showing two sinusoidal gratings, side by side. One grating's spatial frequency (SF) was varied across trials, following a staircase procedure, whereas the comparison grating was held at a constant SF. While fixating on a central target, participants estimated the point at which they perceived the two gratings to be equal in SF. The reduced salience hypothesis was tested in a similar way, but by manipulating the contrast of the test grating rather than its SF. There were no significant differences between groups in the degree of bias across hemifields for SF discrimination or for contrast discrimination. Results did not support either the spatial compression hypothesis or the reduced salience hypothesis. Instead, they suggest that at this perceptual level, LPD do not have a systematically biased way of representing space in the left hemifield that differs from healthy individuals, nor do they perceive stimuli on the left as less salient than stimuli on the right. Neglect-like syndrome in LPD instead presumably arises from dysfunction of higher-order attention.

Perceptual, cognitive, and personality rigidity in Parkinson's disease.

Parkinson's disease (PD) is associated with motor and non-motor rigidity symptoms (e.g., cognitive and personality). The question is raised as to whether rigidity in PD also extends to perception, and if so, whether perceptual, cognitive, and personality rigidities are correlated. Bistable stimuli were presented to 28 non-demented individuals with PD and 26 normal control adults (NC). Necker cube perception and binocular rivalry were examined during passive viewing, and the Necker cube was additionally used for two volitional-control conditions: Hold one percept in front, and Switch between the two percepts. Relative to passive viewing, PD were significantly less able than NC to reduce dominance durations in the Switch condition, indicating perceptual rigidity. Tests of cognitive flexibility and a personality questionnaire were administered to explore the association with perceptual rigidity. Cognitive flexibility was not correlated with perceptual rigidity for either group. Personality (novelty seeking) correlated with dominance durations on Necker passive viewing for PD but not NC. The results indicate the presence in mild-moderate PD of perceptual rigidity and suggest shared neural substrates with novelty seeking, but functional divergence from those supporting cognitive flexibility. The possibility is raised that perceptual rigidity may be a harbinger of cognitive inflexibility later in the disease course.

Speaking from ignorance: not agreeing with others we believe are correct.

Values-pragmatics theory (Hodges & Geyer, 2006) predicts that people will sometimes disagree with others they believe are correct, for reasons similar to those explaining agreement with incorrect answers in an Asch (1956) situation. In 3 experiments, we found evidence that people in a position of ignorance sometimes do not agree with the correct answers of others in positions of knowledge. Experiments 1a and 1b found this speaking-from-ignorance (SFI) effect occurred 27% of the time. Experiment 2 introduced experimental controls and self-report data indicating that the SFI effect (30%) was generated by realizing values (e.g., truth, social solidarity) and pragmatic constraints to act cooperatively, rather than by a wide array of alternatives (e.g., normative pressure, reactance). Experiment 3 experimentally manipulated concern for truthfulness, yielding 49% nonagreeing answers, even though there were monetary incentives to give correct, agreeing answers. The overall pattern suggests that people are not so much conformists or independents as they are cooperative truth tellers under social and moral constraints. Results, while surprising for social influence theories, illustrate the dynamics of divergence and convergence that appear across studies in cultural anthropology and developmental psychology, as well as in social psychology.

Functional correlates of optic flow motion processing in Parkinson's disease.

The visual input created by the relative motion between an individual and the environment, also called optic flow, influences the sense of self-motion, postural orientation, veering of gait, and visuospatial cognition. An optic flow network comprising visual motion areas V6, V3A, and MT+, as well as visuo-vestibular areas including posterior insula vestibular cortex (PIVC) and cingulate sulcus visual area (CSv), has been described as uniquely selective for parsing egomotion depth cues in humans. Individuals with Parkinson's disease (PD) have known behavioral deficits in optic flow perception and visuospatial cognition compared to age- and education-matched control adults (MC). The present study used functional magnetic resonance imaging (fMRI) to investigate neural correlates related to impaired optic flow perception in PD. We conducted fMRI on 40 non-demented participants (23 PD and 17 MC) during passive viewing of simulated optic flow motion and random motion. We hypothesized that compared to the MC group, PD participants would show abnormal neural activity in regions comprising this optic flow network. MC participants showed robust activation across all regions in the optic flow network, consistent with studies in young adults, suggesting intact optic flow perception at the neural level in healthy aging. PD participants showed diminished activity compared to MC particularly within visual motion area MT+ and the visuo-vestibular region CSv. Further, activation in visuo-vestibular region CSv was associated with disease severity. These findings suggest that behavioral reports of impaired optic flow perception and visuospatial performance may be a result of impaired neural processing within visual motion and visuo-vestibular regions in PD.