Digitally enabled asynchronous remote medical management of anxiety and depression: A cohort study.

OBJECTIVE: To evaluate the clinical outcomes of a remote mental health program for managing anxiety and depression, primarily using asynchronous digital communication. METHODS: This retrospective cohort study examined U.S. adults seeking remote care for anxiety and depression from January 2021 to May 2022. The program involves clinician-led assessment, patient education, medication management, and ongoing monitoring, primarily via text. Anxiety and depression were measured using Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) scores. Outcomes examined were changes in scores, 50% score improvement rate, and remission rate (score <5) at 1, 3, and 6 months. RESULTS: During the period evaluated, 11,844 program participants met the inclusion criteria. Most were female (n = 8328, 70.3%); their age ranged from 18-82 years (median 31 years). At baseline, median PHQ-9 and GAD-7 scores were 13 (IQR 9-17); 67% and 69% met score criteria for depression and anxiety, respectively. Most participants (80%) were prescribed a selective serotonin reuptake inhibitor (SSRI). By one month, average PHQ-9 and GAD-7 scores decreased significantly by 9.2 and 9.1 points (both p < .01). At 1-month follow-up, the 50% score improvement rate was 66% for PHQ-9 and 69% GAD-7 (p < .01). Scores continued to decrease with follow-up. At 3 months, over half achieved remission (percent [95% CI]: 52% [51-54] for anxiety, 53% [52-55] for depression). Similar improvement was observed at 6 months and in sensitivity analyses accounting for loss to follow-up. CONCLUSIONS: Use of a remote mental health program with digital tools was associated with significant clinical improvement in anxiety and depression. Challenges remain in maintaining patient engagement and ensuring appropriate care quality monitoring in digital mental health programs. Additional research comparing remote digital care to traditional in-person models is warranted. Studies should examine long-term outcomes, optimal care protocols, and the challenges to integrating these programs into existing healthcare systems and ensuring equitable access.

The Impact of Surgical Expertise on the Cost-Effectiveness of Stapes Surgery.

INTRODUCTION: Otosclerosis is the primary cause of conductive hearing loss with normal otoscopy. As the condition worsens, certain patients may develop a sensorineural component. Patients with successful surgeries may still need hearing aids, which creates a dilemma for health professionals as there are insufficient data to make informed decisions. This study investigated the influence of the surgeon's proficiency level, individual patient factors (e.g., age at the time of intervention and survival rates), and surgery costs on the cost-effectiveness of stapes surgery. METHODS: We performed a cost-effectiveness analysis using an adapted Markov model incorporating annual all-cause mortalities. In addition, we introduced sensitivity analyses to address the effects of surgical expertise on adults with bilateral conductive hearing loss due to otosclerosis. A model was developed based on a decision tree with treatment options and complication scenarios for otosclerosis patients undergoing stapes surgery or receiving hearing aids. Annual all-cause mortality was considered. A sensitivity analysis was performed assigned to different training levels ("experts" and "less experienced") to simulate the effects of surgical experience on the cost-effectiveness of surgical outcomes. Successful surgery was defined as closing of the air-bone gap to 10 dB or less. Based on published data, "experts" were simulated with a 93.7% success rate, and "less experienced" were manufactured with a 68.9% success rate. RESULTS: Stapes surgery provides improved quality of life (QoL) compared to hearing aids with lower cumulative costs up to 87 years of age in the case of "expert" surgeons and up to 78 years of age, when performed by "less experienced" surgeons. CONCLUSIONS: Primary stapes surgery is highly cost-effective and delivers improved QoL compared to hearing aids with lower cumulative costs. Additionally, undergoing stapes surgical training remains highly cost-effective.

Cost-Effectiveness of Septorhinoplasty.

Importance: Septorhinoplasties are performed for functional, aesthetic, or a combination of these indications. As a nonvital intervention, cost-effectiveness may be questioned. Objective: To determine the cost-effectiveness of septorhinoplasty. Design and Setting: The literature was reviewed for revision rates (RRs) and health utility values (HUVs) for both septorhinoplasty and revision septorhinoplasty. Age-specific mortality rates and life expectancies were used. Costs were gathered from international settings and analyzed in an adapted Markov model. Intervention: Septorhinoplasty versus no intervention. Main Outcomes and Measures: Cost-efficiency was calculated for different willingness-to-pay thresholds in a probabilistic sensitivity analysis. The effect of different parameters (costs, RRs, HUVs, age, gender) were reviewed and addressed in a sensitivity analysis for an incremental cost-effectiveness ratio (ICER) willingness-to-pay threshold of $50,000/quality-adjusted life year (QALY). Results: The ICER for septorhinoplasty for a 40-year-old woman ranges from $1216 to $3509/QALY (depending on the country) in comparison with no intervention. Septorhinoplasty is cost-effective in 98.8% (for a $50,000/QALY threshold). The sensitivity analysis showed high robustness of the cost-effectiveness for various scenarios. Conclusions and Relevance: Septorhinoplasty is a highly cost-effective treatment.

Cost Effectiveness of Cochlear Implantation in Single-Sided Deafness.

OBJECTIVE: To analyze the cost effectiveness of cochlear implantation (CI) for the treatment of single-sided deafness (SSD). STUDY DESIGN: Cost-utility analysis in an adapted Markov model. SETTING: Adults with single-sided deafness in a high-income country. INTERVENTION: Unilateral CI was compared with no intervention. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratios were compared with different cost-effectiveness thresholds ($10,000 to $150,000) for different age, sex, and cost combinations. The calculations were based on the quality-adjusted life year (QALY), national life expectancy tables, and different cost settings. The health utility values for the QALY were either directly collected from published data, or, derived from published data using a regression model of multiple utility indices (regression estimate). RESULTS: The regression estimate showed an increase of the health utility value from 0.62 to 0.74 for SSD patients who underwent CI. CI for SSD was cost effective for women up to 64 years ($50,000 per-QALY threshold), 80 years ($100,000 per-QALY threshold), and 86 years ($150,000 per-QALY threshold). For men, these values were 58, 77, and 84, respectively. Changing the discount rate by up to 5% further increased the cutoff ages up to 5 years. A detailed cost and age sensitivity analysis is presented and allows testing for cost effectiveness in local settings worldwide. CONCLUSIONS: CI is a cost-effective option to treat patients with SSD.

Characteristics and Symptoms of App Users Seeking COVID-19-Related Digital Health Information and Remote Services: Retrospective Cohort Study.

BACKGROUND: Patient-facing digital health tools have been promoted to help patients manage concerns related to COVID-19 and to enable remote care and self-care during the COVID-19 pandemic. It has also been suggested that these tools can help further our understanding of the clinical characteristics of this new disease. However, there is limited information on the characteristics and use patterns of these tools in practice. OBJECTIVE: The aims of this study are to describe the characteristics of people who use digital health tools to address COVID-19-related concerns; explore their self-reported symptoms and characterize the association of these symptoms with COVID-19; and characterize the recommendations provided by digital health tools. METHODS: This study used data from three digital health tools on the K Health app: a protocol-based COVID-19 self-assessment, an artificial intelligence (AI)-driven symptom checker, and communication with remote physicians. Deidentified data were extracted on the demographic and clinical characteristics of adults seeking COVID-19-related health information between April 8 and June 20, 2020. Analyses included exploring features associated with COVID-19 positivity and features associated with the choice to communicate with a remote physician. RESULTS: During the period assessed, 71,619 individuals completed the COVID-19 self-assessment, 41,425 also used the AI-driven symptom checker, and 2523 consulted with remote physicians. Individuals who used the COVID-19 self-assessment were predominantly female (51,845/71,619, 72.4%), with a mean age of 34.5 years (SD 13.9). Testing for COVID-19 was reported by 2901 users, of whom 433 (14.9%) reported testing positive. Users who tested positive for COVID-19 were more likely to have reported loss of smell or taste (relative rate [RR] 6.66, 95% CI 5.53-7.94) and other established COVID-19 symptoms as well as ocular symptoms. Users communicating with a remote physician were more likely to have been recommended by the self-assessment to undergo immediate medical evaluation due to the presence of severe symptoms (RR 1.19, 95% CI 1.02-1.32). Most consultations with remote physicians (1940/2523, 76.9%) were resolved without need for referral to an in-person visit or to the emergency department. CONCLUSIONS: Our results suggest that digital health tools can help support remote care and self-management of COVID-19 and that self-reported symptoms from digital interactions can extend our understanding of the symptoms associated with COVID-19.

Distinct and similar patterns of emotional development in adolescents and young adults.

Adolescence is a developmental period of increased sensitivity to social emotional cues, but it is less known whether young adults demonstrate similar social emotional sensitivity. The current study tested variation in reaction times to emotional face cues during different phases of emotional development. Ex-Gaussian parameters mu, sigma, and tau were computed, in addition to mean, median and standard deviation (SD) in reaction times (RT) during an emotional go/nogo-paradigm with fearful, happy, and calm facial expressions in 377 participants, 6-30 years of age. Across development, mean RT showed slowing to fearful facial expressions relative to both calm and happy facial cues, but mu revealed that this pattern was specific to adolescence. In young adulthood, increased variability to fearful expressions relative to both happy and calm ones was captured by SD and tau. The findings that adolescents had longer response latencies to fearful faces, whereas young adults demonstrated greater response variability to fearful faces, together reflect how social emotional processing continues to evolve from adolescence into early adulthood. The findings suggest that young adulthood is also a vulnerable period for processing social emotional cues that ultimately may be important to better understand why different psychopathologies emerge in early adulthood.

Age Dependent Cost-Effectiveness of Cochlear Implantation in Adults. Is There an Age Related Cut-off?

OBJECTIVE: To analyze the impact of age at implantation on the cost-effectiveness of cochlear implantation (CI). STUDY DESIGN: Cost-utility analysis in an adapted Markov model. SETTING: Adults with profound postlingual hearing loss in a "high income" country. INTERVENTION: Unilateral and sequential CI were compared with hearing aids (HA). MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio (ICER), calculated as costs per quality adjusted life year (QALY) gained (in CHF/QALY), for individual age and sex combinations in relation to two different willingness to pay thresholds. 1 CHF (Swiss franc) is equivalent to 1.01 USD. RESULTS: When a threshold of 50,000 CHF per QALY is applied, unilateral CI in comparison to HA is cost-effective up to an age of 91 for women and 89 for men. Sequential CI in comparison to HA is cost-effective up to an age of 87 for women and 85 for men. If a more contemporary threshold of 100,000 CHF per QALY is applied, sequential CI in comparison to unilateral CI is cost-effective up to an age of 80 for women and 78 for men. CONCLUSIONS: Performing both sequential and unilateral CI is cost-effective up to very advanced ages when compared with hearing aids.

Patients with bulimia nervosa do not show typical neurodevelopment of cognitive control under emotional influences.

Bulimia nervosa (BN) emerges in the late teen years and is characterized by binge eating and related compensatory behaviors. These behaviors often co-occur with periods of negative affect suggesting an association between emotions and control over eating behavior. In the current study, we examined how cognitive control and neural processes change under emotional states of arousal in 46 participants with (n=19) and without (n=27) BN from the ages of 18-33 years. Participants performed a go/nogo task consisting of brief negative, positive and neutral emotional cues and sustained negative, positive and neutral emotional states of arousal during functional magnetic resonance imaging (fMRI). Overall task performance improved with age for healthy participants, but not for patients with BN. These age-dependent behavioral effects were paralleled by diminished recruitment of prefrontal control circuitry in patients with BN with age. Although patients with BN showed no difference in performance on the experimental manipulations of negative emotions, sustained positive emotions related to improved performance among patients with BN. Together the findings highlight a neurodevelopmental approach towards understanding markers of psychopathology and suggest that sustained positive affect may have potential therapeutic effects on maintaining behavioral control in BN.

Changes in cortico-subcortical and subcortico-subcortical connectivity impact cognitive control to emotional cues across development.

The capacity to suppress inappropriate thoughts, emotions and actions in favor of appropriate ones shows marked changes throughout childhood and adolescence. Most research has focused on pre-frontal circuit development to explain these changes. Yet, subcortical circuitry involving the amygdala and ventral striatum (VS) has been shown to modulate cue-triggered motivated behaviors in rodents. The nature of the interaction between these two subcortical regions in humans is less well understood, especially during development when there appears to be heightened sensitivity to emotional cues. In the current study, we tested how task-based cortico-subcortical and subcortico-subcortical functional connectivity in 155 participants ages from 5 to 32 impacted cognitive control performance on an emotional go/nogo task. Functional connectivity between the amygdala and VS was inversely correlated with age and predicted cognitive control to emotional cues, when controlling for performance to neutral cues. In contrast, increased medial pre-frontal-amygdala connectivity was associated with better cognitive control to emotional cues and this cortical-subcortical connectivity mediated the association between amygdala-VS connectivity and emotional cognitive control. These findings suggest a dissociation in how subcortical-subcortical and cortical-subcortical connectivity impact cognitive control across development.

Probing behavioral responses to food: development of a food-specific go/no-go task.

The ability to exert self-control in the face of appetitive, alluring cues is a critical component of healthy development. The development of behavioral measures that use disease-relevant stimuli can greatly improve our understanding of cue-specific impairments in self-control. To produce such a tool relevant to the study of eating and weight disorders, we modified the traditional go/no-go task to include food and non-food targets. To confirm that performance on this new task was consistent with other go/no-go tasks, it was given to 147 healthy, normal weight volunteers between the ages of 5 and 30. High-resolution photos of food or toys were used as the target and nontarget stimuli. Consistent with expectations, overall improvements in accuracy were seen from childhood to adulthood. Participants responded more quickly and made more commission errors to food cues compared to nonfood cues (F(1,140)=21.76, P<0.001), although no behavioral differences were seen between low- and high-calorie food cues for this non-obese, healthy developmental sample. This novel food-specific go/no-go task may be used to track the development of self-control in the context of food cues and to evaluate deviations or deficits in the development of this ability in individuals at risk for eating problem behaviors and disorders.

Teens impulsively react rather than retreat from threat.

There is a significant inflection in risk taking and criminal behavior during adolescence, but the basis for this increase remains largely unknown. An increased sensitivity to rewards has been suggested to explain these behaviors, yet juvenile offences often occur in emotionally charged situations of negative valence. How behavior is altered by changes in negative emotional processes during adolescence has received less attention than changes in positive emotional processes. The current study uses a measure of impulsivity in combination with cues that signal threat or safety to assess developmental changes in emotional responses to threat cues. We show that adolescents, especially males, impulsively react to threat cues relative to neutral ones more than adults or children, even when instructed not to respond. This adolescent-specific behavioral pattern is paralleled by enhanced activity in limbic cortical regions implicated in the detection and assignment of emotional value to inputs and in the subsequent regulation of responses to them when successfully suppressing impulsive responses to threat cues. In contrast, prefrontal control regions implicated in detecting and resolving competing responses show an adolescent-emergent pattern (i.e. greater activity in adolescents and adults relative to children) during successful suppression of a response regardless of emotion. Our findings suggest that adolescence is a period of heightened sensitivity to social and emotional cues that results in diminished regulation of behavior in their presence.

Impairment of script comprehension in Lewy body spectrum disorders.

A disabling impairment of higher-order language function can be seen in patients with Lewy body spectrum disorders such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). We focus on script comprehension in patients with Lewy body spectrum disorders. While scripts unfold sequentially, constituent events are thought to contain an internal organization. Executive dysfunction in patients with Lewy body spectrum disorders may interfere with comprehension of this internal structure. We examined 42 patients (30 non-demented PD and 12 mildly demented PDD/DLB patients) and 12 healthy seniors. We presented 22 scripts (e.g., "going fishing"), each consisting of six events. Pilot data from young controls provided the basis for organizing associated events into clusters and arranging them hierarchically into scripts. We measured accuracy and latency to judge the order of adjacent events in the same cluster versus adjacent events in different clusters. PDD/DLB patients were less accurate in their ordering judgments than PD patients and controls. Healthy seniors and PD patients were significantly faster to judge correctly the order of highly associated within-cluster event pairs relative to less closely associated different-cluster event pairs, while PDD/DLB patients did not consistently distinguish between these event-pair types. This relative insensitivity to the clustered-hierarchical organization of events was related to executive impairment and to frontal atrophy as measured by volumetric MRI. These findings extend prior work on script processing to patients with Lewy body spectrum disorders and highlight the potential impact of frontal/executive dysfunction on the daily lives of affected patients.

Self-appraisal in behavioural variant frontotemporal degeneration.

OBJECTIVE: Previous work investigating deficits in self-appraisal in behavioural-variant frontotemporal degeneration (bvFTD) has focused on a single domain: social/behavioural processes. We examined whether a domain-specific versus multi-domain model best explains degraded self-appraisal in bvFTD. METHODS: 49 patients with bvFTD and 73 patients with Alzheimer's disease (AD) were administered quantitative assessments of episodic memory, naming and grammatical comprehension. Self-appraisal of cognitive test performance was assessed by asking patients to rate their performance immediately after completing each neuropsychological test. A discrepancy score was created to reflect the difference between patient performance on neuropsychological tests and self-appraisal of their test performance. Self-appraisal for each neuropsychological measure was related to grey matter (GM) density in each group using voxel-based morphometry. RESULTS: bvFTD patients were poor at evaluating their own performance on all cognitive tests, with no significant correlations between self-appraisal and actual performance. By contrast, poor self-appraisal in AD was restricted to episodic memory performance. Poor self-appraisal on each task in bvFTD and AD was related to reduced GM density in several ventral and rostral medial prefrontal regions. Crucially, poor self-appraisal for all domains in bvFTD was related to a specific area of reduced GM density in the subgenual cingulate (BA 25). CONCLUSION: Poor self-appraisal in bvFTD affects multiple domains, and this multi-domain impairment pattern is associated with frontal disease in the subgenual cingulate.

Category-specific semantic memory: converging evidence from bold fMRI and Alzheimer's disease.

Patients with Alzheimer's disease have category-specific semantic memory difficulty for natural relative to manufactured objects. We assessed the basis for this deficit by asking healthy adults and patients to judge whether pairs of words share a feature (e.g. "banana:lemon-COLOR"). In an fMRI study, healthy adults showed gray matter (GM) activation of temporal-occipital cortex (TOC) where visual-perceptual features may be represented, and prefrontal cortex (PFC) which may contribute to feature selection. Tractography revealed dorsal and ventral stream white matter (WM) projections between PFC and TOC. Patients had greater difficulty with natural than manufactured objects. This was associated with greater overlap between diseased GM areas correlated with natural kinds in patients and fMRI activation in healthy adults for natural kinds. The dorsal WM projection between PFC and TOC in patients correlated only with judgments of natural kinds. Patients thus remained dependent on the same neural network as controls during judgments of natural kinds, despite disease in these areas. For manufactured objects, patients' judgments showed limited correlations with PFC and TOC GM areas activated by controls, and did not correlate with the PFC-TOC dorsal WM tract. Regions outside of the PFC-TOC network thus may help support patients' judgments of manufactured objects. We conclude that a large-scale neural network for semantic memory implicates both feature knowledge representations in modality-specific association cortex and heteromodal regions important for accessing this knowledge, and that patients' relative deficit for natural kinds is due in part to their dependence on this network despite disease in these areas.

The organization and anatomy of narrative comprehension and expression in Lewy body spectrum disorders.

OBJECTIVE: Patients with Lewy body spectrum disorders (LBSD) such as Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies exhibit deficits in both narrative comprehension and narrative expression. The present research examines the hypothesis that these impairments are due to a material-neutral deficit in organizational executive resources rather than to impairments of language per se. We predicted that comprehension and expression of narrative would be similarly affected and that deficits in both expression and comprehension of narrative would be related to the same anatomic distribution of prefrontal disease. METHOD: We examined 29 LBSD patients and 26 healthy seniors on their comprehension and expression of narrative discourse. For comprehension, we measured accuracy and latency in judging events with high and low associativity from familiar scripts such as "going fishing." The expression task involved maintaining the connectedness of events while narrating a story from a wordless picture book. RESULTS: LBSD patients were impaired on measures of narrative organization during both comprehension and expression relative to healthy seniors. Measures of organization during narrative expression and comprehension were significantly correlated with each other. These measures both correlated with executive measures but not with neuropsychological measures of lexical semantics or grammar. Voxel-based morphometry revealed overlapping regressions relating frontal atrophy to narrative comprehension, narrative expression, and measures of executive control. CONCLUSIONS: Difficulty with narrative discourse in LBSD stems in part from a deficit of organization common to comprehension and expression. This deficit is related to prefrontal cortical atrophy in LBSD.

Sentence processing in Lewy body spectrum disorder: the role of working memory.

Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body spectrum disorder (LBSD). Thirty-three patients with LBSD were given a two-alternative, forced-choice sentence-picture matching task. Sentence type, working memory, and grammatical structure were systematically manipulated in the sentences. We found that patients with PDD and DLB were significantly impaired relative to non-demented PD patients and healthy controls. The deficit in PDD/DLB was most pronounced for sentences lengthened by the strategic placement of an additional prepositional phrase and for sentences with an additional proposition due to a center-embedded clause. However, there was no effect for subject-relative versus object-relative grammatical structure. An MRI voxel-based morphometry analysis in a subset of patients showed significant gray matter thinning in the frontal lobe bilaterally, and this extended to temporal, parietal and occipital regions. A regression analysis related sentence processing difficulty in LBSD to frontal neocortex, including inferior prefrontal, premotor, and dorsolateral prefrontal regions, as well as right superior temporal cortex. These findings are consistent with the hypothesis that patients with PDD and DLB have difficulty processing sentences with increased working memory demands and that this deficit is related in part to their frontal disease.

Difficulty processing temporary syntactic ambiguities in Lewy body spectrum disorder.

While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an on-line word detection procedure, patients heard sentences with a syntactic structure that has high-compatibility or low-compatibility with the main verb's statistically preferred syntactic structure, and half of the sentences were lengthened strategically between the onset of the ambiguity and its resolution. We found selectively slowed processing of lengthened ambiguous sentences in the PDD/DLB subgroup. This correlated with impairments on measures of executive control. Regression analyses related the working memory deficit during ambiguous sentence processing to significant cortical thinning in frontal and parietal regions. These findings emphasize the role of prefrontal disease in the executive limitations that interfere with processing ambiguous sentences in LBSD.

The Philadelphia Brief Assessment of Cognition (PBAC): a validated screening measure for dementia.

The Philadelphia Brief Assessment of the Cognition (PBAC) is a brief dementia-screening instrument. The PBAC assesses five cognitive domains: working memory/executive control; lexical retrieval/language; visuospatial/visuoconstructional operations; verbal/visual episodic memory; and behavior/social comportment. A revised version of the PBAC was administered to 198 participants including patients with Alzheimer's disease (AD) (n=46) and four groups of patients with frontotemporal dementia (FTD) syndromes: behavioral-variant FTD (bvFTD; n=65), semantic-variant primary progressive aphasia (PPA) (svPPA; n=22), non-fluent/agrammatic-variant PPA (nfaPPA; n=23), and corticobasal syndrome (CBS; n=42), and a group of normal controls (n=15). The total PBAC score was highly correlated with the MMSE. The criterion validity of the PBAC was assessed relative to standard neuropsychological test performance. Using standard neuropsychological test performance as a criterion, the total PBAC score accurately identified the presence and severity of dementia. Intra-class correlations between PBAC subscales and standard neuropsychological tests were highly significant. PBAC subscales demonstrated good clinical utility in distinguishing AD and FTD subtypes using receiver operating characteristic analysis and standard diagnostic performance statistics to determine optimal subscale cut scores. The PBAC is a valid tool and able to assesses differential patterns neuropsychological/behavioral impairment in a broad range of neurodegenerative conditions.

Some is not enough: quantifier comprehension in corticobasal syndrome and behavioral variant frontotemporal dementia.

Quantifiers are very common in everyday speech, but we know little about their cognitive basis or neural representation. The present study examined comprehension of three classes of quantifiers that depend on different cognitive components in patients with focal neurodegenerative diseases. Patients evaluated the truth-value of a sentence containing a quantifier relative to a picture illustrating a small number of familiar objects, and performance was related to MRI grey matter atrophy using voxel-based morphometry. We found that patients with corticobasal syndrome (CBS) and posterior cortical atrophy (PCA) are significantly impaired in their comprehension of cardinal quantifiers (e.g. "At least three birds are on the branch"), due in part to their deficit in quantity knowledge. MRI analyses related this deficit to temporal-parietal atrophy found in CBS/PCA. We also found that patients with behavioral variant frontotemporal dementia (bvFTD) are significantly impaired in their comprehension of logical quantifiers (e.g. "Some of the birds are on the branch"), associated with a simple form of perceptual logic, and this correlated with their deficit on executive measures. This deficit was related to disease in rostral prefrontal cortex in bvFTD. These patients were also impaired in their comprehension of majority quantifiers (e.g. "At least half of the birds are on the branch"), and this too was correlated with their deficit on executive measures. This was related to disease in the basal ganglia interrupting a frontal-striatal loop critical for executive functioning. These findings suggest that a large-scale frontal-parietal neural network plays a crucial role in quantifier comprehension, and that comprehension of specific classes of quantifiers may be selectively impaired in patients with focal neurodegenerative conditions in these areas.

The organization of narrative discourse in Lewy body spectrum disorder.

Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB.