Ethical Considerations in Communicating Alzheimer's Disease Neuroimaging Biomarker Test Results to Symptomatic Individuals.

This article examines ethical issues associated with the return of AD neuroimaging results to cognitively symptomatic individuals. Following a review of research on patient and study partner reactions to learning the results of biomarker testing for AD, we examine ethical issues that will be of increasing significance as the field transitions to an era wherein disease-modifying treatments for AD become available. We first review the ethical justification for returning AD biomarker results to individuals who desire them. We then address a more novel question: whether, and to what extent, clinicians or clinical researchers should influence the decisions of individuals who are potentially reluctant to learn their AD imaging results. We argue that in many cases, it is ethically correct to explore, and sometimes alter, factors that may be inhibiting one's desire to know these test results. Our argument is grounded in the premise that having more complete information about changes that may be happening in one's brain will generally yield more informed participation in decisions about one's own care, thereby promoting autonomy. Finally, on the assumption that we have established that it is frequently ethically correct to try to communicate testing information, we examine considerations regarding (not whether but) how this is best accomplished, discussing the concept of responsible transparency. We suggest that both (1) explorations of why one may or may not want to learn results of AD biomarker imaging and (2) the responsible return of such test results is best accomplished using a transactional model of communication.

Mid- and Late-Life Leisure-Time Physical Activity and Global Brain Amyloid Burden: The Atherosclerosis Risk in Communities (ARIC)-PET Study.

BACKGROUND: Physical activity (PA) may slow the development of dementia by reducing the accumulation of amyloid. OBJECTIVE: We tested the hypothesis that higher levels of leisure-time PA in mid- or late-life were associated with lower brain amyloid burden in late-life among 326 non-demented participants from the Atherosclerosis Risk in Communities Study of brain florbetapir positron emission tomography (ARIC-PET) ancillary. METHODS: Self-reported PA was quantified using a past-year recall, interviewer-administered questionnaire in mid-life (1987-1989, aged 45-64 years) and late-life (2011-2013, aged 67-89 years). Continuous PA estimates were classified as 1) any leisure-time PA participation (yes/no); 2) meeting the 2018 United States' PA guidelines (yes/no); and 3) per 1 standard deviation (SD) higher metabolic equivalent of task (MET) minutes per week (MET·min·wk-1). A brain magnetic resonance imaging scan with Florbetapir PET was performed in late-life. Adjusted odds ratios (OR) of elevated amyloid burden, defined as a global cortical standardized uptake value ratio (>1.2), compared to no elevated amyloid burden were estimated according to PA measures. RESULTS: Among the 326 participants (mean age: 76 years, 42% male, 41% Black), 52% had elevated brain amyloid burden. Mid-life leisure-time PA did not show a statistically significant lower odds of elevated late-life amyloid burden (OR = 0.71, 95% CI: 0.43-1.18). A 1 SD (970 MET. min. wk-1) higher PA level in mid-life was also not significantly associated withelevated amyloid burden (OR = 0.89, 95% CI: 0.69-1.15). Similar estimates were observed for meeting versus not meeting PA guidelines in both mid- and late-life. CONCLUSION: Self-reported higher mid- and late-life leisure-time PA were not significantly associated with lower amyloid burden. Data show a trend of an association, which is, however, imprecise, suggesting replication in larger studies.

How Accurately Do Patients and Their Care Partners Report Results of Amyloid-ß PET Scans for Alzheimer's Disease Assessment?

BACKGROUND: Amyloid-ß PET scans will likely become an integral part of the diagnostic evaluation for Alzheimer's disease if Medicare approves reimbursement for the scans. However, little is known about patients' and their care partners' interpretation of scan results. OBJECTIVE: This study seeks to understand how accurately patients with mild cognitive impairment (MCI) or dementia and their care partners report results of amyloid-ß PET scans and factors related to correct reporting. METHODS: A mixed-methods approach was used to analyze survey data from 1,845 patient-care partner dyads and responses to open-ended questions about interpretation of scan results from a sub-sample of 200 dyads. RESULTS: Eighty-three percent of patients and 85% of care partners correctly reported amyloid-ß PET scan results. Patients' higher cognitive function was associated with a small but significant decrease in the predicted probability of not only patients accurately reporting scan results (ME: -0.004, 95% CI: -0.007, -0.000), but also care partners accurately reporting scan results (ME: -0.006, 95% CI: -0.007, -0.001), as well as decreased concordance between patient and care partner reports (ME: -0.004, 95% CI: -0.007, -0.001). Content analysis of open-ended responses found that participants who reported the scan results incorrectly exhibited more confusion about diagnostic terminology than those who correctly reported the scan results. CONCLUSION: Overall, patients with MCI or dementia showed high rates of accurate reporting of amyloid-ß PET scan results. However, responses to questions about the meaning of the scan results highlight the need for improved provider communication, including providing written explanations and better prognostic information.

Patient and caregiver reactions to clinical amyloid imaging.

INTRODUCTION: Amyloid imaging is a tool that has recently become available to dementia specialists evaluating patients with possible Alzheimer's disease. Studies have assessed the impact of amyloid imaging on diagnostic and treatment decisions, but patient and family perspectives have received less attention. METHODS: To examine how amyloid imaging affects the diagnostic experience of patients and families, we interviewed members of 26 patient-caregiver dyads with whom a neurologist discussed the option of amyloid positron emission tomography. RESULTS: Most participants who chose to undergo amyloid imaging would choose to do so again. Regardless of the scan outcome, patients and caregivers commonly expressed relief on learning the scan results. Some participants expressed expectations that were beyond scan capabilities. DISCUSSION: Amyloid imaging may provide information that patients and their families find useful. Clinicians must set correct expectations and ensure that families understand the limitations of amyloid imaging.

[Acceptance of dementia diagnostics by getriatric hospital patients : Comparison of various investigation methods with emphasis on FDG-PET imaging]. / Akzeptanz der Demenzdiagnostik bei stationären, geriatrischen Patienten : Vergleich verschiedener Untersuchungsmethoden mit Fokus auf der FDG-PET-Untersuchung.

BACKGROUND: The number of people with dementia is continuously rising, in hospitals as well. For the diagnostics novel methods are available but the attitude of the patients to these methods is yet unknown. OBJECTIVE: The aim of the study was to evaluatethe opinion of geriatric hospital patients with suspected dementia on the various possible methods of diagnosing dementia, especially fluorodeoxyglucose positron emission tomography (FDG-PET). Additionally, it was assessed if there are differences in toleration between imaging of the brain and conventional diagnostics by neuropsychological testing and if information on the diagnostic methods and the patient's physical or cognitive status influence their opinion. METHOD: Within the framework of the iDSS001 clinical trial 90 geriatric hospital patients with suspected dementia were interviewed with respect to examinations performed for diagnosing dementia, e.g. anamnesis including physical and neurological examinations, neuropsychological testing, cerebrospinal fluid analysis, magnetic resonance imaging (MRI) and FDG-PET imaging. RESULTS: Imaging of the brain was tolerated less than anamnesis including physical and neurological examinations, neuropsychological testing and cerebrospinal fluid analysis and patients also felt they were less informed about these procedures. The generally well-accepted FDG-PET imaging procedure was received slightly better than MRI. Cognitively impaired and less depressed patients were less willing to allow repeat MRI examinations. CONCLUSION: The results suggest that imaging of the brain is perceived by cognitively impaired hospital patients as being more burdensome than conventional diagnostics, such as neuropsychological testing. Improved care during the investigations as well as physical and organizational adjustments could increase the acceptance.

Meditative music listening to reduce state anxiety in patients during the uptake phase before positron emission tomography (PET) scans.

OBJECTIVE: This study examines the effects of listening to meditative music on state anxiety and heart rate variability (HRV) of patients during the uptake phase before positron emission tomography (PET) scans. METHODS: A two-group randomized experimental design was used. Eligible patients were randomly assigned to either the experimental or control group. All patients received baseline assessments of state anxiety using Spielberger State-Trait Anxiety Inventory (STAI-S) and HRV before receiving an intravenous injection of radiopharmaceutical fluorine-18 fludeoxyglucose in the uptake room. The experimental group (n = 35) listened individually to 30 min of meditative music, integrating Chinese "Chi" and western frequency resonation in the uptake room. The control group (n = 37) lay on bed quietly for 40 min in the uptake room without music. All patients were assessed for their anxiety level and HRV again, before receiving PET scanning as post-test. RESULTS: The results indicated that patients in the experimental group showed a significant reduction in state anxiety and heart rate, and increase on high frequency norm of HRV (p < 0.001). There was a statistically significant reduction on anxiety level (p < 0.001), heart rate (p < 0.001) and high frequency norm (p = 0.001) in the experimental group compared with those of the control group. CONCLUSION: Listening to meditative music as a non-invasive and cost-effective strategy can help maximize efforts to promote comfort and relaxation for patients awaiting stressful procedures, such as PET scans. Meditative music can be effective in alleviating state anxiety of patients during the uptake phase before PET scans. Advances in knowledge: The study provides scientific evidence of the effects of listening to meditative music for reducing state anxiety in patients during the uptake phase before PET scans. It may have the potential to lower the risk of unwanted false-positive fluorine-18 fludeoxyglucose uptake in normal organs and to further improve image quality and image interpretation. Listening to meditative music is a safe and inexpensive intervention which can be incorporated into routine procedures to reduce anxiety of patients undergoing PET scans.

Testing and disclosures related to amyloid imaging and Alzheimer's disease: Common questions and fact sheet summary.

Alzheimer's disease research has often focused on the molecular brain changes that promote memory loss and other dementia-related cognitive impairments. Many studies, for example, have used positron emission tomography (PET) imaging to measure brain levels of the beta-amyloid protein, a key molecular suspect in Alzheimer's. In recent years, PET scans have become more prominent in clinical settings. Clinicians may use a positive PET scan-that is, a significant presence of beta-amyloid plaques in the brain-to help determine a diagnosis of Alzheimer's disease. Yet, because beta-amyloid PET remains a fairly new diagnostic tool, physicians and patients still have many basic questions about how and why it is used. This article addresses some of those questions. It explains what PET scans actually show, how they are employed in research and clinical trials, and when they should and should not be used to help diagnose Alzheimer's in everyday patients. The article also discusses whether cognitively healthy people should request PET scans to assess their risk for developing dementia. Information in the text will be updated in future years, as diagnostic imaging techniques for Alzheimer's disease continue to evolve.

Do Beliefs about the Pathogenetic Role of Amyloid Affect the Interpretation of Amyloid PET in the Clinic.

BACKGROUND: Beliefs of dementia experts about the pathogenic role of amyloid in Alzheimer's disease (AD) may affect the use of amyloid positron emission tomography (PET). OBJECTIVE: To assess the role attributed to amyloid in AD pathogenesis by Italian dementia experts, and whether this modulates the impact of amyloid PET results in their diagnostic workup. METHODS: 22 dementia experts rated their beliefs about the pathogenic role of amyloid. Then, we asked them to rate the probability of change in diagnosis based on the result of amyloid PET for 7 case vignettes, depicting patients who initially received a diagnosis based on a comprehensive workup and later received amyloid PET results consistent or inconsistent with the clinical picture. RESULTS: 55% of the experts assigned a dominant role to amyloid, and 32% attributed a similar role to amyloid and tau in AD pathogenesis. The probability of change in diagnosis ranged from 17% (SD = 21.6) for cases with consistent to 51% (SD = 34) for cases with inconsistent PET versus clinical data. Diagnostic change was not biased by the clinicians' beliefs about AD pathogenesis. CONCLUSIONS: This work supports an unbiased interpretation of amyloid PET across different beliefs about the pathogenic role of amyloid, and a belief-independent reluctance to change diagnosis in cases where change is expected and recommended.

Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study.

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

A comparison of the psychological burden of PET/MRI and PET/CT scans and association to initial state anxiety and previous imaging experiences.

OBJECTIVE: To investigate the level of psychological burden experienced by patients undergoing positron emission tomography (PET)/MRI scanning compared with PET/CT. METHODS: 100 adult patients referred for PET/CT and underwent PET/MRI scanning were eligible. Initial state, psychological burden of PET/CT and PET/MRI, scan satisfaction and preference were assessed using a purpose-designed questionnaire, comprising 61 five-point Likert scale questions and a three-point tick box question indicating preference between PET/CT and PET/MRI. State anxiety was assessed using the state portion of the State Trait Anxiety Inventory. Wilcoxon signed-rank tests compared psychological burden experienced by participants following PET/CT and PET/MRI scan. RESULTS: A greater level of psychological burden was experienced by patients during PET/MRI than PET/CT p ≤ 0.001, consistent with patients' preference for PET/CT over PET/MRI (p = 0.013). There was a significant relationship between PET/CT psychological burden and initial state (r = 0.386, p ≤ 0.001). No significant relationship was identified between Initial state and psychological burden of PET MRI (r = -0.089; p = 217). There was a significant relationship between psychological burden of PET/CT and PET/MRI (r = 0.354; p = 0.001). CONCLUSION: Patients' experience increased psychological burden during PET/MRI compared with PET/CT. Previous scanning experiences and patients' interactions prior to and during PET/MRI improved patient satisfaction. Interventions could be implemented to improve imaging outcome. ADVANCES IN KNOWLEDGE: This study provides evidence for the increased psychological burden of PET/MRI compared with PET/CT, and that people prefer the PET/CT procedure. We have shown that the patients who expressed a preference for PET/MRI demonstrated significantly lower psychological burden for that procedure than those that preferred PET/CT, which indicates that the benefit of reduced psychological burden could be facilitated by an appropriate intervention.

Reduction of patient anxiety in PET/CT imaging by improving communication between patient and technologist.

UNLABELLED: Patients experience anxiety during imaging procedures because of the confined space, uncertainty about the procedure, worry about the results, and other concerns. When a patient experiences anxiety during PET/CT imaging, the quality of the scan can be affected in several ways. Current patient-technologist communication is limited in PET/CT because the technologist must be separated from the patient during the course of the imaging workflow. This study investigated the use of a call device enabling rapid communication to reduce patient anxiety. METHODS: Clinical patients with various oncologic indications and undergoing (18)F-FDG PET/CT imaging were asked to participate in anxiety surveys under several conditions. Metrics were tracked regarding the survey results for comparison between groups and survey conditions. During the course of this study, 2 patient surveys were used. One of the patient populations was asked to fill out a survey on personal perceptions of the use of such a device, with questions related to their comfort with the device and the degree to which they perceived the device to reduce their anxiety. The 2 remaining populations were given a standard Spielberger State Anxiety survey for anxiety assessments against control populations. RESULTS: Perception survey results indicated that 75% of the respondents experienced a reduction in anxiety and that 84% would request this type of device for other procedures. A correlation was observed between improved patient-technologist communication and perceived feelings of safety, with identical percentages of positive responses. Although responses were mostly positive, 18.8% did not perceive any reduction in anxiety, and the same number indicated they would not use the system in the future. For those patients given the standard Spielberger State Anxiety survey, a statistically significant reduction in anxiety was observed (P < 0.05) in those patients given a call device. Reductions in anxiety were observed for all patient populations, including first-time and repeated-imaging patients. CONCLUSION: Patient anxiety can be reduced through the use of a tangible device that improves communication between the patient and the imaging staff. Reducing anxiety may have a positive effect on imaging, because involuntary motion may be reduced and there may be improvement in the patients' comfort and in their overall experience with the imaging procedure.

Increased metabotropic glutamate receptor subtype 5 availability in human brain after one night without sleep.

BACKGROUND: Sleep deprivation (wake therapy) provides rapid clinical relief in many patients with major depressive disorder (MDD). Changes in glutamatergic neurotransmission may contribute to the antidepressant response, yet the exact underlying mechanisms are unknown. Metabotropic glutamate receptors of subtype 5 (mGluR5) are importantly involved in modulating glutamatergic neurotransmission and neuronal plasticity. The density of these receptors is reduced in the brain of patients with MDD, particularly in brain structures involved in regulating wakefulness and sleep. We hypothesized that prolonged wakefulness would increase mGluR5 availability in human brain. METHODS: Metabotropic glutamate receptor subtype 5 binding was quantified with positron emission tomography in 22 young healthy men who completed two experimental blocks separated by 1 week. Two positron emission tomography examinations were conducted in randomized, crossover fashion with the highly selective radioligand, ¹¹C-ABP688, once after 9 hours (sleep control) and once after 33 hours (sleep deprivation) of controlled wakefulness. ¹¹C-ABP688 uptake was quantified in 13 volumes of interest with high mGluR5 expression and presumed involvement in sleep-wake regulation. RESULTS: Sleep deprivation induced a global increase in mGluR5 binding when compared with sleep control (p<.006). In anterior cingulate cortex, insula, medial temporal lobe, parahippocampal gyrus, striatum, and amygdala, this increase correlated significantly with the sleep deprivation-induced increase in subjective sleepiness. CONCLUSIONS: This molecular imaging study demonstrates that cerebral functional mGluR5 availability is increased after a single night without sleep. Given that mGluR5 density is reduced in MDD, further research is warranted to examine whether this mechanism is involved in the potent antidepressant effect of wake therapy.

Degenerative jargon aphasia: unusual progression of logopenic/phonological progressive aphasia?

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction.

Nonfluent/agrammatic PPA with in-vivo cortical amyloidosis and Pick's disease pathology.

The role of biomarkers in predicting pathological findings in the frontotemporal dementia (FTD) clinical spectrum disorders is still being explored. We present comprehensive, prospective longitudinal data for a 66 year old, right-handed female who met current criteria for the nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA). She first presented with a 3-year history of progressive speech and language impairment mainly characterized by severe apraxia of speech. Neuropsychological and general motor functions remained relatively spared throughout the clinical course. Voxel-based morphometry (VBM) showed selective cortical atrophy of the left posterior inferior frontal gyrus (IFG) and underlying insula that worsened over time, extending along the left premotor strip. Five years after her first evaluation, she developed mild memory impairment and underwent PET-FDG and PiB scans that showed left frontal hypometabolism and cortical amyloidosis. Three years later (11 years from first symptom), post-mortem histopathological evaluation revealed Pick's disease, with severe degeneration of left IFG, mid-insula, and precentral gyrus. Alzheimer's disease (AD) (CERAD frequent/Braak Stage V) was also detected. This patient demonstrates that biomarkers indicating brain amyloidosis should not be considered conclusive evidence that AD pathology accounts for a typical FTD clinical/anatomical syndrome.

A neuroimaging proof of principle study of Down's syndrome and dementia: ethical and methodological challenges in intrusive research.

BACKGROUND: Research into specific illnesses and the development of new treatments may only become possible as new technologies become available. When used for research, such technologies may best be described as 'intrusive', in that they require a considerable willingness and commitment on the part of the participants. This has increasingly been the case for brain disorders and illnesses where novel neuroimaging techniques, often combined with clinical and psychological assessments, have the potential to result in new understanding. People with intellectual disabilities (ID) have a history of under-representation as participants in research using such technologies and are therefore at risk of not receiving equal access to state-of-the-art treatments. We propose that 'intrusive' biomedical research is both possible and ethical in ID, and explore some of the methodological challenges by reference to a recent proof of principle study that used a relatively new ligand-based brain scanning technique in a group of volunteers with Down's syndrome. METHODS: Five overlapping stages of the study methodology were identified and evaluated for their acceptability to volunteers with mild to moderate ID through discussion, reflection, and analysis of structured feedback in the context of key policy documents, ethical guidelines and relevant legislation. RESULTS: Identification of key ethical and methodological challenges from reflective practice and participant feedback facilitated the emergence of strategies that permitted continual refinement of the study design. Important areas considered included (1) being clear about the purpose and scientific justification for the study; (2) reconciling the potential risks and benefits with relevant ethical guidelines and legislation; (3) identifying and implementing effective recruitment strategies; (4) optimising and assessing capacity to consent; and (5) making the 'intrusive' procedures as acceptable as possible to people with ID. CONCLUSION: We were able to demonstrate that a proof of principle study incorporating a novel brain scanning technique in a group of volunteers with ID was feasible, safe and well tolerated, despite the vulnerabilities of the study cohort and the intrusive nature of the research. We consider the study within an ethical and historical discourse about the principles that define current 'best practice' in ID research and propose a number of key recommendations for making intrusive research acceptable in people with ID.

Early deficits in declarative and procedural memory dependent behavioral function in a transgenic rat model of Huntington's disease.

In Huntington's disease (HD) cognitive deficits co-exist with motor impairments, both contributing to the overall disease symptomology. Despite short-term and working memory impairments, learning and other non-motoric behavioral deficits arising from the damage to frontostriatal loop being common in HD patients, most of the experimental work with transgenic animals focuses on motor symptoms. The transgenic rat model (tgHD) recapitulates many hallmark HD-like symptoms, such as huntingtin aggregates, cellular loss and dysfunction, and motor, and some cognitive deficits. In the current study we tested tgHD rats in two different cognitive, water maze competition paradigms to learn more about the impact of the transgene on learning and memory processing using hippocampal- and striatal-based memory systems. The tgHD rats had early and robust cognitive deficits in learning and memory function in both paradigms. Specifically, the transgenic animals were impaired in task acquisition and committed more procedural errors with the strongest phenotype amongst the homozygote tgHD. Although the transgenic animals were capable of using both procedural and declarative memory, their response patterns were distinct from wild-type animals. Wide spread huntingtin aggregates were observed at 13 months, but neither PET nor autoradiography indicated neuronal loss or dysfunction in striatal dopamine receptor population. In summary, the homozygote tgHD showed a robust learning and memory impairment prior to any clear motor deficits, or striatal dysfunction. However, the data were not conclusive regarding how the memory systems were compromised and the precise nature and underlying mechanism of the cognitive deficit in the tgHD model requires further investigation.

Multiple subregions in superior temporal cortex are differentially sensitive to vocal expressions: a quantitative meta-analysis.

Vocal expressions of emotions consistently activate regions in the superior temporal cortex (STC), including regions in the primary and secondary auditory cortex (AC). Studies usually report broadly extended functional activations in response to vocal expressions, with considerable variation in peak locations across several auditory subregions. This might suggest different and distributed functional roles across these subregions instead of a uniform role for the decoding of vocal emotions. We reviewed recent studies and conducted an activation likelihood estimation meta-analysis summarizing recent fMRI and PET studies dealing with the processing of vocal expressions in the STC and AC. We included two stimulus-specific factors (paraverbal/nonverbal expression, stimulus valence) and one task-specific factor (attentional focus) in the analysis. These factors considerably influenced whether functional activity was located in the AC or STC (influence of valence and attentional focus), the laterality of activations (influence of paraverbal/nonverbal expressions), and the anterior-posterior location of STC activity (influence of valence). These data suggest distributed functional roles and a differentiated network of auditory subregions in response to vocal expressions.

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.

OBJECTIVE: To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia. METHODS: In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition and 11 met criteria for PD-MCI at study baseline. All subjects underwent standardized neurologic and neuropsychological examinations and PiB PET at baseline, and clinical examinations were conducted annually for up to 5 years. RESULTS: At baseline, precuneus PiB retention did not distinguish PD-MCI from PD-nl. Subjects with PD-MCI declined more rapidly than PD-nl subjects on cognitive tests of memory, executive function, and activation retrieval. Of the 35 PD-nl subjects, 8 progressed to PD-MCI and 1 to dementia; of the 11 PD-MCI subjects, 5 converted to dementia. Both higher PiB retention and a diagnosis of PD-MCI predicted a greater hazard of conversion to a more severe diagnosis. Baseline PiB retention predicted worsening in executive function over time. The APOE ε4 allele also related to worsening in executive function, as well as visuospatial function, activation retrieval, and performance on the Mini-Mental State Examination. In contrast to its relation to cognitive decline, PiB retention did not affect progression of motor impairment. CONCLUSIONS: At baseline measurements, amyloid burden does not distinguish between cognitively impaired and unimpaired subjects with PD without dementia, but our data suggest that amyloid contributes to cognitive, but not motor, decline over time.

5-HT2 receptor distribution shown by [18F] setoperone PET in high-functioning autistic adults.

The serotonergic system is implicated in disordered emotional behavior. Autism is characterized by impaired processing of emotional information. The serotonergic (5-HT) system is also critically involved in brain development, and abnormal brain synthesis of serotonin is observed in autism. Furthermore, whole blood and platelet serotonin have been reported to be elevated in autism. The authors examined the CNS serotonin system in autism in vivo. 5-HT2 receptors were visualized by PET imaging of [18F]setoperone-binding in this pilot study of 6 high-functioning autistic adults and 10 matched-control participants. Autism subjects had less thalamic [18F]setoperone binding than controls, when covaried for age, but no difference reached significance in other areas. A negative relationship between thalamic binding and history of language impairment was also observed. Further studies will be needed to gain a clearer picture of the role of the 5-HT system in autism.

Aging-related increases in behavioral variability: relations to losses of dopamine D1 receptors.

Intraindividual variability (IIV) reflects within-person changes in performance, such as trial-by-trial fluctuations on a reaction-time (RT) task. The neural underpinnings of IIV remain largely unknown. The neurotransmitter dopamine (DA) is of particular interest here, as human populations that exhibit DA alterations, such as the elderly, attention deficit hyperactivity disorder children, persons with schizophrenia, and Parkinson patients, also show increased behavioral IIV. We examined links between DA D(1) binding potential (BP) in multiple brain regions and IIV for the control and interference conditions of the Multi-Source Interference Task (MSIT), tapping the cingulo-fronto-parietal attention network. Participants were 18 young and 20 healthy old adults. PET and the radioligand [(11)C]SCH23390 were used to determine D(1) BP. The intraindividual standard deviation (ISD) was computed across successful latency trials of the MSIT conditions, independent of mean RT differences due to age, trial, and condition. Increasing ISDs were associated with increasing age and diminished D(1) binding in several brain regions (anterior cingulate gyrus, dorsolateral prefrontal cortex, and parietal cortex) for the interference, but not control, condition. Analyses of partial associations indicate that the association between age and IIV in the interference condition was linked to D(1) receptor losses in task-relevant brain regions. These findings suggest that dysfunctional DA modulation may contribute to increased variability in cognitive performance among older adults.