Multimodal investigation of neuropathology and neurometabolites in mild cognitive impairment and late-life depression with 11C-PiB beta-amyloid PET and 7T magnetic resonance spectroscopy.

Positron emission tomography (PET) and magnetic resonance spectroscopy (1H-MRS) are complementary techniques that can be applied to study how proteinopathy and neurometabolism relate to cognitive deficits in preclinical stages of Alzheimer's disease (AD)-mild cognitive impairment (MCI) and late-life depression (LLD). We acquired beta-amyloid (Aß) PET and 7 T 1H-MRS measures of GABA, glutamate, glutathione, N-acetylaspartate, N-acetylaspartylglutamate, myo-inositol, choline, and lactate in the anterior and posterior cingulate cortices (ACC, PCC) in 13 MCI and 9 LLD patients, and 13 controls. We used linear regression to examine associations between metabolites, Aß, and cognitive scores, and whether metabolites and Aß explained cognitive scores better than Aß alone. In the ACC, higher Aß was associated with lower GABA in controls but not MCI or LLD patients, but results depended upon MRS data quality control criteria. Greater variance in California Verbal Learning Test scores was better explained by a model that combined ACC glutamate and Aß deposition than by models that only included one of these variables. These findings identify preliminary associations between Aß, neurometabolites, and cognition.

First impressions: Do faces with scars and palsies influence warmth, competence and humanization?

A glance is enough to assign psychological attributes to others. Attractiveness is associated with positive attributes ('beauty-is-good' stereotype). Here, we raise the question of a similar but negative bias. Are people with facial anomalies associated with negative personal characteristics? We hypothesized that biases against faces with anomalies arise because of negative stereotypes (less warmth and competence) and forms of dehumanization (animalistic and mechanistic). We enrolled 1493 mTurk participants (N = 1306 after exclusion) to assess 31 traits of photographed people using 60 pairs of photographs of the same person before and after plastic surgery. Half anomalous faces had a scar and the other half had a palsy. To calculate warmth and competence, we conducted a principal components analysis of the 31 attributes. Animalistic dehumanization was assessed by averaging reverse-scored ratings corresponding to moral sensibility and rationality/logic, and mechanistic dehumanization by averaging across reverse-scored ratings corresponding to emotional responsiveness and interpersonal warmth. We found that both kinds of anomalous faces were seen as less warm, competent and were dehumanized. Our findings suggest that an 'anomalous-is-bad' stereotype generalizes regardless of the aetiology of the anomaly. This effect may be related to a reverse halo effect, that is, the horn effect.

Visual Attention Toward Patients with Hemifacial Microsomia Reconstruction: A Prospective Eye-Tracking Study.

BACKGROUND: Facial areas attracting the most visual attention in Hemifacial Microsomia (HFM) are poorly understood. Further, it is not clear if and how visual attention changes from pre- to post-operatively. This study characterized layperson visual attention to pre- and post-reconstruction hemifacial microsomia (HFM) using eye-tracking technology. METHODS: Visual fixations (Tobii Pro Nano) were recorded in four areas of interest from sixty participants completing two consecutive trials of 68 total images in each hemi-face of 17 patients with HFM pre- and post- orthognathic jaw reconstruction. Linear mixed effect models evaluated if visual fixations were affected by surgical reconstruction. RESULTS: 47,354 visual fixations were captured over 120 trials within defined AOIs. Linear mixed effect models revealed significantly decreased postoperative visual fixations in the mandible and chin region [716 (54.8%) pre-reconstruction, 591 (45.2%) post reconstruction; ß = -0.198, SE = 0.056, z = -3.550, p < 0.001]. Analysis also revealed significantly increased postoperative visual fixations in the forehead and orbit region [11350 (48.6%) pre-reconstruction, 12000 (51.4%) post-reconstruction; ß = 0.086, SE = 0.015, z = 5.664, p < 0.00001]. CONCLUSIONS: Following corrective jaw surgery for HFM, laypersons demonstrated significantly less visual attention to the mandible and chin and increased visual attention to the forehead and orbit. These findings suggest postoperative improvement towards aesthetic normalcy may reduce visual attention to previously anomalous anatomy.

Visual Attention, Bias, and Social Dispositions Toward People With Facial Anomalies: A Prospective Study With Eye-Tracking Technology.

BACKGROUND: Facial attractiveness influences our perceptions of others, with beautiful faces reaping societal rewards and anomalous faces encountering penalties. The purpose of this study was to determine associations of visual attention with bias and social dispositions toward people with facial anomalies. METHODS: Sixty subjects completed tests evaluating implicit bias, explicit bias, and social dispositions before viewing publicly available images of preoperative and postoperative patients with hemifacial microsomia. Eye-tracking was used to register visual fixations. RESULTS: Participants with higher implicit bias scores fixated significantly less on the cheek and ear region preoperatively (P = 0.004). Participants with higher scores in empathic concern and perspective taking fixated more on the forehead and orbit preoperatively (P = 0.045) and nose and lips (P = 0.027) preoperativel. CONCLUSIONS: Participants with higher levels of implicit bias spent less visual attention on anomalous facial anatomy, whereas participants with higher levels of empathic concern and perspective taking spent more visual attention on normal facial anatomy. Levels of bias and social dispositions such as empathy may predict layperson gaze patterns toward those with facial anomalies and provide insights to neural mechanisms underlying the "anomalous is bad" paradigm.

Which moral exemplars inspire prosociality?

Some stories of moral exemplars motivate us to emulate their admirable attitudes and behaviors, but why do some exemplars motivate us more than others? We systematically studied how motivation to emulate is influenced by the similarity between a reader and an exemplar in social or cultural background (Relatability) and how personally costly or demanding the exemplar's actions are (Attainability). Study 1 found that university students reported more inspiration and related feelings after reading true stories about the good deeds of a recent fellow alum, compared to a famous moral exemplar from decades past. Study 2A developed a battery of short moral exemplar stories that more systematically varied Relatability and Attainability, along with a set of non-moral exemplar stories for comparison. Studies 2B and 2C examined the path from the story type to relatively low stakes altruism (donating to charity and intentions to volunteer) through perceived attainability and relatability, as well as elevation and pleasantness. Together, our studies suggest that it is primarily the relatability of the moral exemplars, not the attainability of their actions, that inspires more prosocial motivation, at least regarding acts that help others at a relatively low cost to oneself.

Facial Scars: Do Position and Orientation Matter?

BACKGROUND: This study tested the core tenets of how facial scars are perceived by characterizing layperson response to faces with scars. The authors predicted that scars closer to highly viewed structures of the face (i.e., upper lip and lower lid), scars aligned against resting facial tension lines, and scars in the middle of anatomical subunits of the face would be rated less favorably. METHODS: Volunteers aged 18 years and older from the United States were recruited through Amazon's Mechanical Turk to complete a face rating survey. Scars were digitally added in different locations and orientations for a total of 14 unique scars added to each face. Each participant rated 50 different faces on confidence, friendliness, and attractiveness. Data were analyzed using linear mixed effects models. RESULTS: A total of 88,850 ratings [82,990 scarred (93.4 percent)] for attractiveness, friendliness, and confidence were analyzed. In univariate linear mixed effects models, the presence of a facial scar did not significantly impact attractiveness (ß = 0.016, SE = 0.014, z = 1.089, p = 0.276). A second set of linear mixed effects models identified interactions between location, subunit placement, and orientation to facial tension lines. Scars located on the lower lid mid subunit perpendicular to facial tension lines were rated less attractive (ß = -0.065, SE = 0.028, z = -2.293, p = 0.022). CONCLUSIONS: On average, a single well-healed facial scar does not negatively affect first impressions of attractiveness, confidence, or friendliness. Specific scar location and orientation combinations, however, such as a perpendicular scar at the mid-lower eyelid, may result in lower perceived attractiveness, confidence, and friendliness. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Associations of Facial Proportionality, Attractiveness, and Character Traits.

BACKGROUND: Facial proportionality and symmetry are positively associated with perceived levels of facial attractiveness. OBJECTIVE: The aims of this study were to confirm and extend the association of proportionality with perceived levels of attractiveness and character traits and determine differences in attractiveness and character ratings between "anomalous" and "typical" faces using a large dataset. METHODS: Ratings of 597 unique individuals from the Chicago Face Database were used. A formula was developed as a proxy of relative horizontal proportionality, where a proportionality score of "0" indicated perfect proportionality and more negative scores indicated less proportionality. Faces were categorized as "anomalous" or "typical" by 2 independent reviewers based on physical features. RESULTS: Across the ratings for all faces, Spearman correlations revealed greater proportionality was associated with attractiveness ( ρ = 0.292, P < 0.001) and trustworthiness ( ρ = 0.193, P < 0.001), while lesser proportionality was associated with impressions of anger (ρ = 0.132, P = 0.001), dominance (ρ = 0.259, P < 0.001), and threateningness ( ρ = 0.234, P < 0.001). Mann-Whitney U tests revealed the typical cohort had significantly higher levels of proportionality (-13.98 versus -15.14, P = 0.030) and ratings of attractiveness (3.39 versus 2.99, P < 0.001) and trustworthiness (3.48 versus 3.35, P < 0.001). CONCLUSIONS: This study demonstrated that facial proportionality is not only significantly associated with higher ratings of attractiveness, but also associated with judgements of trustworthiness. Proportionality plays a role in evoking negative attributions of personality characteristics to people with facial anomalies.

Evidence against the "anomalous-is-bad" stereotype in Hadza hunter gatherers.

People have an "anomalous-is-bad" stereotype whereby they make negative inferences about the moral character of people with craniofacial anomalies like scars. This stereotype is hypothesized to be a byproduct of adaptations for avoiding pathogens. However, evidence for the anomalous-is-bad stereotype comes from studies of European and North American populations; the byproduct hypothesis would predict universality of the stereotype. We presented 123 Hadza across ten camps pairs of morphed Hadza faces-each with one face altered to include a scar-and asked who they expected to be more moral and a better forager. Hadza with minimal exposure to other cultures chose at chance for both questions. Hadza with greater exposure to other cultures, however, expected the scarred face to be less moral and a better forager. These results suggest the anomalous-is-bad stereotype may be culturally shared or learned erroneously through associations with population-level differences, providing evidence against a universal pathogen avoidance byproduct hypothesis.

Regional amyloid correlates of cognitive performance in ageing and mild cognitive impairment.

Beta-amyloid deposition is one of the earliest pathological markers associated with Alzheimer's disease. Mild cognitive impairment in the setting of beta-amyloid deposition is considered to represent a preclinical manifestation of Alzheimer's disease. In vivo imaging studies are unique in their potential to advance our understanding of the role of beta-amyloid deposition in cognitive deficits in Alzheimer's disease and in mild cognitive impairment. Previous work has shown an association between global cortical measures of beta-amyloid deposition ('amyloid positivity') in mild cognitive impairment with greater cognitive deficits and greater risk of progression to Alzheimer's disease. The focus of the present study was to examine the relationship between the regional distribution of beta-amyloid deposition and specific cognitive deficits in people with mild cognitive impairment and cognitively normal elderly individuals. Forty-seven participants with multi-domain, amnestic mild cognitive impairment (43% female, aged 57-82 years) and 37 healthy, cognitively normal comparison subjects (42% female, aged 55-82 years) underwent clinical and neuropsychological assessments and high-resolution positron emission tomography with the radiotracer 11C-labelled Pittsburgh compound B to measure beta-amyloid deposition. Brain-behaviour partial least-squares analysis was conducted to identify spatial patterns of beta-amyloid deposition that correlated with the performance on neuropsychological assessments. Partial least-squares analysis identified a single significant (P < 0.001) latent variable which accounted for 80% of the covariance between demographic and cognitive measures and beta-amyloid deposition. Performance in immediate verbal recall (R = -0.46 ± 0.07, P < 0.001), delayed verbal recall (R = -0.39 ± 0.09, P < 0.001), immediate visual-spatial recall (R = -0.39 ± 0.08, P < 0.001), delayed visual-spatial recall (R = -0.45 ± 0.08, P < 0.001) and semantic fluency (R = -0.33 ± 0.11, P = 0.002) but not phonemic fluency (R = -0.05 ± 0.12, P < 0.705) negatively covaried with beta-amyloid deposition in the identified regions. Partial least-squares analysis of the same cognitive measures with grey matter volumes showed similar associations in overlapping brain regions. These findings suggest that the regional distribution of beta-amyloid deposition and grey matter volumetric decreases is associated with deficits in executive function and memory in mild cognitive impairment. Longitudinal analysis of these relationships may advance our understanding of the role of beta-amyloid deposition in relation to grey matter volumetric decreases in cognitive decline.

Subgenual activation and the finger of blame: individual differences and depression vulnerability.

BACKGROUND: Subgenual cingulate cortex (SCC) responses to self-blaming emotion-evoking stimuli were previously found in individuals prone to self-blame with and without a history of major depressive disorder (MDD). This suggested SCC activation reflects self-blaming emotions such as guilt, which are central to models of MDD vulnerability. METHOD: Here, we re-examined these hypotheses in an independent larger sample. A total of 109 medication-free participants (70 with remitted MDD and 39 healthy controls) underwent fMRI whilst judging self- and other-blaming emotion-evoking statements. They also completed validated questionnaires of proneness to self-blaming emotions including those related to internal (autonomy) and external (sociotropy) evaluation, which were subjected to factor analysis. RESULTS: An interaction between group (remitted MDD v. Control) and condition (self- v. other-blame) was observed in the right SCC (BA24). This was due to higher SCC signal for self-blame in remitted MDD and higher other-blame-selective activation in Control participants. Across the whole sample, extracted SCC activation cluster averages for self- v. other-blame were predicted by a regression model which included the reliable components derived from our factor analysis of measures of proneness to self-blaming emotions. Interestingly, this prediction was solely driven by autonomy/self-criticism, and adaptive guilt factors, with no effect of sociotropy/dependency. CONCLUSIONS: Despite confirming the prediction of SCC activation in self-blame-prone individuals and those vulnerable to MDD, our results suggest that SCC activation reflects blame irrespective of where it is directed rather than selective for self. We speculate that self-critical individuals have more extended SCC representations for blame in the context of self-agency.

Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares.

Depression in late-life is associated with increased risk of cognitive decline and development of all-cause dementia. The neurobiology of late-life depression (LLD) may involve both neurochemical and neurodegenerative mechanisms that are common to depression and dementia. Transgenic amyloid mouse models show evidence of early degeneration of monoamine systems. Informed by these preclinical data, the hypotheses were tested that a spatial covariance pattern of higher beta-amyloid (Aß) and lower serotonin transporter availability (5-HTT) in frontal, temporal, and parietal cortical regions would distinguish LLD patients from healthy controls and the expression of this pattern would be associated with greater depressive symptoms. Twenty un-medicated LLD patients who met DSM-V criteria for major depression and 20 healthy controls underwent PET imaging with radiotracers for Aß ([11C]-PiB) and 5-HTT ([11C]-DASB). A voxel-based multi-modal partial least squares (mmPLS) algorithm was applied to the parametric PET images to determine the spatial covariance pattern between the two radiotracers. A spatial covariance pattern was identified, including higher Aß in temporal, parietal and occipital cortices associated with lower 5-HTT in putamen, thalamus, amygdala, hippocampus and raphe nuclei (dorsal, medial and pontine), which distinguished LLD patients from controls. Greater expression of this pattern, reflected in summary 5-HTT/Aß mmPLS subject scores, was associated with higher levels of depressive symptoms. The mmPLS method is a powerful approach to evaluate the synaptic changes associated with AD pathology. This spatial covariance pattern should be evaluated further to determine whether it represents a biological marker of antidepressant treatment response and/or cognitive decline in LLD patients.

The Face Image Meta-Database (fIMDb) & ChatLab Facial Anomaly Database (CFAD): Tools for research on face perception and social stigma.

Investigators increasingly need high quality face photographs that they can use in service of their scholarly pursuits-whether serving as experimental stimuli or to benchmark face recognition algorithms. Up to now, an index of known face databases, their features, and how to access them has not been available. This absence has had at least two negative repercussions: First, without alternatives, some researchers may have used face databases that are widely known but not optimal for their research. Second, a reliance on databases comprised only of young white faces will lead to science that isn't representative of all the people whose tax contributions, in many cases, make that research possible. The "Face Image Meta-Database" (fIMDb) provides researchers with the tools to find the face images best suited to their research, with filters to locate databases with people of a varied racial and ethnic backgrounds and ages. Problems of representation in face databases are not restricted to race and ethnicity or age - there is a dearth of databases with faces that have visible differences (e.g., scars, port wine stains, and cleft lip and palate). A well-characterized database is needed to support programmatic research into perceivers' attitudes, behaviors, and neural responses to anomalous faces. The "ChatLab Facial Anomaly Database" (CFAD) was constructed to fill this gap, with photographs of faces with visible differences of various types, etiologies, sizes, locations, and that depict individuals from various ethnic backgrounds and age groups. Both the fIMDb and CFAD are available from: https://cliffordworkman.com/resources/.

The effect of aging on facial attractiveness: An empirical and computational investigation.

How does aging affect facial attractiveness? We tested the hypothesis that people find older faces less attractive than younger faces, and furthermore, that these aging effects are modulated by the age and sex of the perceiver and by the specific kind of attractiveness judgment being made. Using empirical and computational network science methods, we confirmed that with increasing age, faces are perceived as less attractive. This effect was less pronounced in judgments made by older than younger and middle-aged perceivers, and more pronounced by men (especially for female faces) than women. Attractive older faces were perceived as elegant more than beautiful or gorgeous. Furthermore, network analyses revealed that older faces were more similar in attractiveness and were segregated from younger faces. These results indicate that perceivers tend to process older faces categorically when making attractiveness judgments. Attractiveness is not a monolithic construct. It varies by age, sex, and the dimensions of attractiveness being judged.

Morality is in the eye of the beholder: the neurocognitive basis of the "anomalous-is-bad" stereotype.

Are people with flawed faces regarded as having flawed moral characters? An "anomalous-is-bad" stereotype is hypothesized to facilitate negative biases against people with facial anomalies (e.g., scars), but whether and how these biases affect behavior and brain functioning remain open questions. We examined responses to anomalous faces in the brain (using a visual oddball paradigm), behavior (in economic games), and attitudes. At the level of the brain, the amygdala demonstrated a specific neural response to anomalous faces-sensitive to disgust and a lack of beauty but independent of responses to salience or arousal. At the level of behavior, people with anomalous faces were subjected to less prosociality from participants highest in socioeconomic status. At the level of attitudes, we replicated previously reported negative character evaluations made about individuals with facial anomalies, and further identified explicit biases directed against them as a group. Across these levels of organization, the specific amygdala response to facial anomalies correlated with stronger just-world beliefs (i.e., people get what they deserve), less dispositional empathic concern, and less prosociality toward people with facial anomalies. Characterizing the "anomalous-is-bad" stereotype at multiple levels of organization can reveal underappreciated psychological burdens shouldered by people who look different.

Molecular imaging of beta-amyloid deposition in late-life depression.

Late-life depression (LLD) is associated with an increased risk of all-cause dementia and may involve Alzheimer's disease pathology. Twenty-one LLD patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a current major depressive episode and 21 healthy controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes, and high-resolution positron emission tomography to measure beta-amyloid (Aß) deposition. Clinical and neuropsychological assessments were repeated after 10-12 weeks of Citalopram or Sertraline treatment (LLD patients only). LLD patients did not differ from healthy controls in baseline neuropsychological function, although patients improved in both depressive symptoms and visual-spatial memory during treatment. Greater Aß in the left parietal cortex was observed in LLD patients compared with controls. Greater Aß was correlated with greater depressive symptoms and poorer visual-spatial memory, but not with improvement with treatment. The study of LLD patients with prospective measurements of mood and cognitive responses to antidepressant treatment is an opportunity to understand early neurobiological mechanisms underlying the association between depression and subsequent cognitive decline.

Molecular imaging of the serotonin transporter availability and occupancy by antidepressant treatment in late-life depression.

Patients with late-life depression (LLD) have a more variable response to pharmacotherapy relative to patients with mid-life depression. Degeneration of the serotonergic system and lower occupancy of the initial target for antidepressant medications, the serotonin transporter (5-HTT), may contribute to variability in treatment response. The focus of this study was to test the hypotheses that lower cortical and limbic serotonin transporter (5-HTT) availability in LLD patients relative to controls and less 5-HTT occupancy by antidepressant medications would be associated with less improvement in mood and cognition with treatment in LLD patients. Twenty LLD patients meeting DSM-IV criteria for a current major depressive episode and 20 non-depressed controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes and high-resolution positron emission tomography (PET) scanning to measure 5-HTT before and after 10-12 weeks of treatment with Citalopram or Sertraline (patients only). Prior to treatment, 5-HTT was lower in LLD patients relative to controls in mainly temporal cortical and limbic (amygdala and hippocampus) regions. Gray matter volumes were not significantly different between groups. 5-HTT occupancy was detected throughout cortical, striatal, thalamic and limbic regions. The magnitude of regional 5-HTT occupancy by antidepressants was 70% or greater across cortical and sub-cortical regions, consistent with the magnitude of 5-HTT occupancy observed in mid-life depressed patients. Greater regional 5-HTT occupancy correlated with greater improvement in depressive symptoms and visual-spatial memory performance. These data support the hypothesis that serotonin degeneration and variability in 5-HTT occupancy may contribute to heterogeneity in treatment response in LLD patients.

Neurotransmitters and Neurometabolites in Late-Life Depression: A Preliminary Magnetic Resonance Spectroscopy Study at 7T.

BACKGROUND: Magnetic resonance spectroscopy (MRS) methods have quantified changes in levels of neurotransmitters and neurometabolites in patients with major depression across the lifespan. The application of 7T field strengths and greater have not been a major focus of study in patients with late-life depression (LLD). METHODS: Nine LLD patients who met DSM-IV criteria for a current major depressive episode and nine non-depressed, healthy, age-matched controls underwent clinical and neuropsychological assessment and single-voxel 7T 1H-MRS at baseline and after 10-12 weeks of antidepressant treatment (Citalopram; patients only). Spectra were acquired from two brain regions implicated in both depressive symptoms and neuropsychological deficits in LLD, the anterior (ACC) and posterior cingulate (PCC). Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr) using linear-combination modeling. RESULTS: Baseline Glu/tCr levels were not significantly different between groups. Decreased Glu/tCr levels after Citalopram treatment were observed in a subset of LLD patients. Exploratory analyses showed that LLD patients had lower NAA levels in the PCC relative to controls. Higher levels of ml in the LLD patients relative to the controls and decreases after Citalopram treatment had large effect sizes but were not statistically significant. Further, decreases in PCC Glu/tCr and increases in ACC GSH/tCr were associated with improvement in depressive symptoms. LIMITATIONS: Sample size. CONCLUSIONS: These preliminary results suggest a role of neurochemicals and neurometabolites in the neurobiology of LLD and antidepressant treatment response.

The Dark Side of Morality - Neural Mechanisms Underpinning Moral Convictions and Support for Violence.

People are motivated by shared social values that, when held with moral conviction, can serve as compelling mandates capable of facilitating support for ideological violence. The current study examined this dark side of morality by identifying specific cognitive and neural mechanisms associated with beliefs about the appropriateness of sociopolitical violence, and determining the extent to which the engagement of these mechanisms was predicted by moral convictions. Participants reported their moral convictions about a variety of sociopolitical issues prior to undergoing functional MRI scanning. During scanning, they were asked to evaluate the appropriateness of violent protests that were ostensibly congruent or incongruent with their views about sociopolitical issues. Complementary univariate and multivariate analytical strategies comparing neural responses to congruent and incongruent violence identified neural mechanisms implicated in processing salience and in the encoding of subjective value. As predicted, neuro-hemodynamic response was modulated parametrically by individuals' beliefs about the appropriateness of congruent relative to incongruent sociopolitical violence in ventromedial prefrontal cortex, and by moral conviction in ventral striatum. Overall moral conviction was predicted by neural response to congruent relative to incongruent violence in amygdala. Together, these findings indicate that moral conviction about sociopolitical issues serves to increase their subjective value, overriding natural aversion to interpersonal harm.

Neurometabolites and associations with cognitive deficits in mild cognitive impairment: a magnetic resonance spectroscopy study at 7 Tesla.

The levels of several brain metabolites were investigated in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) in 13 healthy controls (HC) and 13 patients with mild cognitive impairment (MCI) using single-voxel magnetic resonance spectroscopy at 7T. Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr). The effect of diagnosis on metabolite levels, and relationships between metabolite levels and memory and executive function, correcting for age, were investigated. MCI patients showed significantly decreased GABA/tCr (ACC, PCC), Glu/tCr (PCC), and NAA/tCr (PCC), and significantly increased mI/tCr (ACC). In the combined group, worse episodic verbal memory performance was correlated with lower Glu/tCr (PCC), lower NAA/tCr (PCC), and higher mI/tCr (ACC, PCC). Worse verbal fluency performance was correlated with lower GSH/tCr (PCC). In summary, MCI is associated with decreased GABA and Glu, most consistently in the PCC. Further studies in larger patient samples should be undertaken to determine the utility of 7T magnetic resonance spectroscopy in detecting MCI-related neurochemical changes.

Reproducibility of brain MRS in older healthy adults at 7T.

To date, the majority of MRS reproducibility studies have been conducted in healthy younger adults, with only a few conducted in older adults at 3 T. With the growing interest in applying MRS methods to study the longitudinal course and effects of treatments in neurodegenerative disease, it is important to establish reproducibility in age-matched controls, especially in older individuals. In this study, spectroscopic data were acquired using a stimulated echo acquisition mode (STEAM) localization technique in two regions (anterior and posterior cingulate cortices-ACC, PCC, respectively) in 10 healthy, cognitively normal older adults (64 ± 8.1 years). Reproducibility was assessed via mean coefficients of variation (CVs) and relative differences (RDs) calculated across two visits performed 2-3 months apart. Metabolites with high signal-to-noise ratio (SNR) such as NAA, tCho, and Glu had mean CVs of 10% or less and mean RDs of 15% or less across both regions. Metabolites with lower SNR such as GABA and Gln had slightly higher mean CVs of 22% or less and mean RDs of 27% or less across both regions. These results demonstrate the feasibility of acquiring MRS data at 7 T in older subjects, and establish that the spectroscopic data are reproducible in both the ACC and PCC in older, healthy subjects to the same extent as in previous studies in young subjects.