An attentional and working memory theory of hallucination vulnerability in frontotemporal dementia.

The rate and prevalence of hallucinations in behavioural variant frontotemporal dementia is well established. The mechanisms for underlying vulnerability however are the least well described in FTD compared with other neuropsychiatric conditions, despite the presence of these features significantly complicating the diagnostic process. As such, this present study aimed to provide a detailed characterization of the neural, cognitive and behavioural profile associated with a predisposition to hallucinatory experiences in behavioural variant frontotemporal dementia. In total, 153 patients with behavioural variant frontotemporal dementia were recruited sequentially for this study. A group of patients with well characterized hallucinations and good-quality volumetric MRI scans (n = 23) were genetically and demographically matched to a group without hallucinations (n = 23) and a healthy control cohort (n = 23). All patients were assessed at their initial visit by means of a detailed clinical interview, a comprehensive battery of neuropsychological tests and MRI. Data were analysed according to three levels: (i) the relationship between neural structures, cognition, behaviour and hallucinations in behavioural variant frontotemporal dementia; (ii) the impact of the C9orf72 expansion; and (iii) hallucination subtype on expression of hallucinations. Basic and complex attentional (including divided attention and working memory) and visual function measures differed between groups (all P < 0.001) with hallucinators demonstrating poorer performance, along with evidence of structural changes centred on the prefrontal cortex, caudate and cerebellum (corrected for False Discovery Rate at P < 0.05 with a cluster threshold of 100 contiguous voxels). Attentional processes were also implicated in C9orf72 carriers with hallucinations with structural changes selectively involving the thalamus. Patients with visual hallucinations in isolation showed a similar pattern with emphasis on cerebellar atrophy. Our findings provided novel insights that attentional and visual function subsystems and related distributed brain structures are implicated in the generation of hallucinations in behavioural variant frontotemporal dementia, that dissociate across C9orf72, sporadic behavioural variant frontotemporal dementia and for the visual subtype of hallucinations. This loading on attentional and working memory measures is in line with current mechanistic models of hallucinations that frequently suggest a failure of integration of cognitive and perceptual processes. We therefore propose a novel cognitive and neural model for hallucination predisposition in behavioural variant frontotemporal dementia that aligns with a transdiagnostic model for hallucinations across neurodegeneration and psychiatry.

A randomised controlled trial of clinician supported vs self-help delivery of online cognitive behaviour therapy for Bulimia Nervosa.

High dropout rates and poor adherence associated with digital interventions have prompted research into modifications of these treatments to improve engagement and completion rates. This trial aimed to investigate the added benefit of clinician support when paired alongside a ten-session, online cognitive behaviour therapy (CBT) self-help intervention for bulimia nervosa (BN). As part of a three-arm, phase II randomised controlled trial, 114 participants (16 years or over) with full or subthreshold BN were randomly assigned to complete the intervention in a self-help mode (with administrative researcher contact; n = 38), with adjunct clinician support (weekly 30-minute videoconferencing sessions; n = 37), or a no-treatment waitlist control (WLC; n = 39). Baseline to post-treatment (12-weeks) decreases in objective binge episode frequency were significantly greater for clinician-supported participants as compared to WLC, but not for self-help when compared to WLC. However, due to continued improvements for self-help across follow-up (24-weeks), both arms outperformed WLC when analysed as an overall rate of change across three timepoints. Clinician-supported participants outperformed self-help in regards to laxative use and dietary restraint. Our results demonstrate that good clinical outcomes can be achieved with a relatively brief online CBT-based program even in the absence of structured clinical support, indicating a possible overreliance upon clinician support as a primary adherence-facilitating mechanism.

Hemispheric contributions toward interoception and emotion recognition in left-vs right-semantic dementia.

BACKGROUND: The hemispheric contributions toward interoception, the perception of internal bodily cues, and emotion recognition remains unclear. Semantic dementia cases with either left-dominant (i.e., left-SD) or right-dominant (i.e., right-SD) anterior temporal lobe atrophy experience emotion recognition difficulties, however, little is known about interoception in these syndromes. Here, we hypothesised that right-SD would show worse interoception and emotion recognition due to right-dominant atrophy. METHODS: Thirty-five participants (8 left-SD; 6 right-SD; 21 controls) completed a monitoring task. Participants pressed a button when they: (1) felt their heartbeat, without pulse measurement (Interoception); or (2) heard a recorded heartbeat (Exteroception-control). Simultaneous ECG was recorded. Accuracy was calculated by comparing the event frequency (i.e., heartbeat or sound) to response frequency. Emotion recognition was assessed via the Facial Affect Selection Task. Voxel-based morphometry analyses identified neural correlates of interoception and emotion recognition. RESULTS: Right-SD showed worse interoception than controls and left-SD (both p's < 0.001). Both patient groups showed worse emotion recognition than controls (right-SD: p < .001; left-SD: p = .018), and right-SD showed worse emotion recognition than left-SD (p = .003). Regression analyses revealed that worse emotion recognition was predicted by right-SD (p = .002), left-SD (p = .005), and impaired interoception (p = .004). Interoception and emotion were associated with the integrity of right-lateralised structures including the insula, temporal pole, thalamus, superior temporal gyrus, and hippocampus. CONCLUSION: Our study provides the first evidence for impaired interoception in right-SD, suggesting that impaired emotion recognition in this syndrome is driven by inaccurate internal monitoring. Further we identified a common neurobiological basis for interoception and emotion in the right hemisphere.

Thinking versus feeling: How interoception and cognition influence emotion recognition in behavioural-variant frontotemporal dementia, Alzheimer's disease, and Parkinson's disease.

Disease-specific mechanisms underlying emotion recognition difficulties in behavioural-variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD) are unknown. Interoceptive accuracy, accurately detecting internal cues (e.g., one's heart beating), and cognitive abilities are candidate mechanisms underlying emotion recognition. One hundred and sixty-eight participants (52 bvFTD; 41 AD; 24 PD; 51 controls) were recruited. Emotion recognition was measured via the Facial Affect Selection Task or the Mini-Social and Emotional Assessment Emotion Recognition Task. Interoception was assessed with a heartbeat detection task. Participants pressed a button each time they: 1) felt their heartbeat (Interoception); or 2) heard a recorded heartbeat (Exteroception-control). Cognition was measured via the Addenbrooke's Cognitive Examination-III or the Montreal Cognitive Assessment. Voxel-based morphometry analyses identified neural correlates associated with emotion recognition and interoceptive accuracy. All patient groups showed worse emotion recognition and cognition than controls (all P's ≤ .008). Only the bvFTD showed worse interoceptive accuracy than controls (P < .001). Regression analyses revealed that in bvFTD worse interoceptive accuracy predicted worse emotion recognition (P = .008). Whereas worse cognition predicted worse emotion recognition overall (P < .001). Neuroimaging analyses revealed that the insula, orbitofrontal cortex, and amygdala were involved in emotion recognition and interoceptive accuracy in bvFTD. Here, we provide evidence for disease-specific mechanisms for emotion recognition difficulties. In bvFTD, emotion recognition impairment is driven by inaccurate perception of the internal milieu. Whereas, in AD and PD, cognitive impairment likely underlies emotion recognition deficits. The current study furthers our theoretical understanding of emotion and highlights the need for targeted interventions.

Examining the presence and nature of delusions in Alzheimer's disease and frontotemporal dementia syndromes.

OBJECTIVES: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach. METHODS: Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy. All patients underwent neuropsychological assessment and brain magnetic resonance imaging, and the Neuropsychiatric Inventory was conducted with an informant, by an experienced clinician. RESULTS: In our cohort, 48/487 patients (10.8%) had delusions. A diagnosis of behavioural-variant frontotemporal dementia (18.4%) and Alzheimer's disease (11.8%) were associated with increased risk of delusions. A positive gene mutation was observed in 11/27 people with delusions. Individuals with frequent delusions performed worse on the Addenbrooke's Cognitive Examination (p = 0.035), particularly on the orientation/attention (p = 0.022) and memory (p = 0.013) subtests. Voxel-based morphometry analyses found that increased delusional psychopathology was associated with reduced integrity of the right middle frontal gyrus, right planum temporale and left anterior temporal pole. CONCLUSION: Our results demonstrate that delusions are relatively common in dementia and uncover a unique cognitive and neural profile associated with the manifestation of delusions. Clinically, delusions may lead to delayed or misdiagnosis. Our results shed light on how to identify individuals at risk of neuropsychiatric features of dementia, a crucial first step to enable targeted symptom management.

Considering Hemispheric Specialization in Emotional Face Processing: An Eye Tracking Study in Left- and Right-Lateralised Semantic Dementia.

Face processing relies on a network of occipito-temporal and frontal brain regions. Temporal regions are heavily involved in looking at and processing emotional faces; however, the contribution of each hemisphere to this process remains under debate. Semantic dementia (SD) is a rare neurodegenerative brain condition characterized by anterior temporal lobe atrophy, which is either predominantly left- (left-SD) or right-lateralised (right-SD). This syndrome therefore provides a unique lesion model to understand the role of laterality in emotional face processing. Here, we investigated facial scanning patterns in 10 left-SD and 6 right-SD patients, compared to 22 healthy controls. Eye tracking was recorded via a remote EyeLink 1000 system, while participants passively viewed fearful, happy, and neutral faces over 72 trials. Analyses revealed that right-SD patients had more fixations to the eyes than controls in the Fear (p = 0.04) condition only. Right-SD patients also showed more fixations to the eyes than left-SD patients in all conditions: Fear (p = 0.01), Happy (p = 0.008), and Neutral (p = 0.04). In contrast, no differences between controls and left-SD patients were observed for any emotion. No group differences were observed for fixations to the mouth, or the whole face. This study is the first to examine patterns of facial scanning in left- versus right- SD, demonstrating more of a focus on the eyes in right-SD. Neuroimaging analyses showed that degradation of the right superior temporal sulcus was associated with increased fixations to the eyes. Together these results suggest that right lateralised brain regions of the face processing network are involved in the ability to efficiently utilise changeable cues from the face.

Healthy recovery: A stepped wedge cluster randomised controlled trial of a healthy lifestyle intervention for people attending residential alcohol and other drug treatment.

BACKGROUND: Unhealthy lifestyle behaviours contribute to the poor health of people attending alcohol and other drug (AOD) treatment. Healthy Recovery is an 8-session group-based intervention that targets smoking, diet and physical inactivity as part of an integrated healthy lifestyle approach. The current study aimed to examine the effectiveness of Healthy Recovery when delivered within residential AOD treatment settings. METHODS: The study design was a stepped-wedge cluster randomised trial. Participants were 151 current smokers attending residential AOD programs provided by the Australian Salvation Army (n = 71, Control condition; n = 80, Intervention condition). The primary outcome was number of cigarettes smoked per day. Secondary outcomes examined other smoking behaviours (7-day point prevalence, use of nicotine replacement therapy [NRT]), diet (servings and variety of fruit and vegetables), and physical activity. RESULTS: The mean number of cigarettes smoked per day was significantly lower in the Intervention condition at 2-, 5-, and 8-month follow-up. There were also significant differences in favour of the Intervention condition for number of quit attempts, use of NRT and variety of fruit. There were no other significant differences for other dietary or physical activity variables. CONCLUSIONS: Healthy Recovery had a positive impact on smoking behaviours. Future research should consider strategies to further promote smoking cessation (e.g. promoting longer-term use of NRT), as well as addressing physical activity and dietary behaviours. The introduction of broader organisational approaches (e.g. smoke free policies, organised group exercise and cooking activities) might help to enhance healthy lifestyle approaches within AOD treatment settings.

Using a second-person approach to identify disease-specific profiles of social behavior in frontotemporal dementia and Alzheimer's disease.

Changes in social behavior are recognized as potential symptoms of behavioral-variant frontotemporal dementia (bvFTD) and semantic dementia (SD), yet objective ways to assess these behaviors in natural social situations are lacking. This study takes a truly social (or second-person) approach and examines changes in real-world social behavior in different dementia syndromes, by analyzing non-scripted social interactions in bvFTD patients (n = 20) and SD patients (n = 20), compared to patients with Alzheimer's disease (AD) (n = 20). Video recordings of 10-min conversations between patients and behavioral neurologists were analyzed for the presence of socially engaging (e.g., nodding, smiling, gesturing) and disengaging behavior (e.g., avoiding eye contact, self-grooming, interrupting). Results demonstrated disease-specific profiles, with bvFTD patients showing less nodding and more looking away than AD, and SD patients showing more gesturing than AD. A principal components analysis revealed the presence of four unobserved components, showing atypical disengaging patterns of behavior. Whole-brain voxel-based morphometry analyses revealed distinct neurobiological bases for each of these components, with the brain regions identified previously associated with behavior selection, abstract mentalization and processing of multi-sensory and socially-relevant information, in mediating socially engaging and disengaging behavior. This study demonstrates the utility of systematic behavioral observation of social interactions in the differential diagnosis of dementia.

Facial expressiveness and physiological arousal in frontotemporal dementia: Phenotypic clinical profiles and neural correlates.

Early theories of emotion processing propose an interplay between autonomic function and cognitive appraisal of emotions. Patients with frontotemporal dementia show profound social cognition deficits and atrophy in regions implicated in autonomic emotional responses (insula, amygdala, prefrontal cortex), yet objective measures of facial expressiveness and physiological arousal have been relatively unexplored. We investigated psychophysiological responses (surface facial electromyography (EMG); skin conductance level (SCL)) to emotional stimuli in 25 behavioural-variant frontotemporal dementia (bvFTD) patients, 14 semantic dementia (SD) patients, and 24 healthy older controls, while viewing emotionally positive, neutral, or negative video clips. Voxel-based morphometry was conducted to identify neural correlates of responses. Unlike controls, patients with bvFTD did not show differential facial EMG responses according to emotion condition, whereas SD patients showed increased zygomaticus responses to both positive and neutral videos. Controls showed greater arousal (SCL) when viewing positive and negative videos; however, both bvFTD and SD groups showed no change in SCL across conditions. Regardless of group membership, right insula damage was associated with dampened zygomaticus responses to positive film stimuli. Change in arousal (SCL) was associated with lower integrity of the caudate, amygdala, and temporal pole. Our results demonstrate that while bvFTD patients show an overall dampening of responses, SD patients appear to show incongruous facial emotional expressions. Abnormal responding is related to cortical and subcortical brain atrophy. These results identify potential mechanisms for the abnormal social behaviour in bvFTD and SD and demonstrate that psychophysiological responses are an important mechanism underpinning normal socioemotional functioning.

Beyond the face: how context modulates emotion processing in frontotemporal dementia subtypes.

The importance of assessing social cognition to characterize dementia syndromes is increasingly recognized, with lower social cognition capacity associated with reduced functional independence and greater carer burden. Emotion recognition is impaired in both behavioural-variant frontotemporal dementia and semantic dementia, yet the social and behavioural changes observed in these syndromes in everyday situations varies. To date, most studies have investigated isolated, context-free stimuli indexing recognition of facial emotions only. Here, we aimed to investigate how contextual information (i.e. emotional body language) influences emotion recognition, within the framework of the Social Context Network Model. Thirty-one patients with frontotemporal dementia (19 behavioural-variant frontotemporal dementia; 12 semantic dementia) and 20 healthy age- and education-matched controls were assessed on three tasks which varied contextual cues: (i) face alone; (ii) context alone; and (iii) face embedded in context. Voxel-based morphometry was used to identify neural correlates of task performance. Our results demonstrated that both behavioural-variant frontotemporal dementia and semantic dementia patients performed worse than controls in recognizing emotions from face alone and context alone. Importantly, performance differed when faces were presented in context. While both behavioural-variant frontotemporal dementia and semantic dementia patients performed similarly to controls on congruent items (i.e. face emotion and body emotion are the same) (P-values > 0.05), patients with behavioural-variant frontotemporal dementia performed worse than both controls (P < 0.001) and patients with semantic dementia (P = 0.044) for incongruent items (i.e. face emotion and body emotion are different). Neuroimaging analyses revealed that abnormal contextual influence was associated with lower integrity of the right parahippocampal gyrus/amygdala and left precentral gyrus. Together, these results indicate that patients with behavioural-variant frontotemporal dementia are over-reliant on external contextual information. Conversely, in semantic dementia and controls, contextual influence varies, with the degree of contextual influence appearing to be mediated, at least in part, by the facial expression depicted. The profile in behavioural-variant frontotemporal dementia is reminiscent of the 'environmental dependency syndrome' described in frontal lesion patients. It also converges with recent evidence of abnormal face perception in this group. From a theoretical perspective, our findings demonstrate that the capacity to incorporate contextual body language is dependent on the integrity of both contextual association brain regions (i.e. parahippocampal gyrus), as well as regions necessary for processing dynamic body movements. Clinically, these results open new avenues for rehabilitation of social impairments in dementia.

Normal adult and adolescent performance on TASIT-S, a short version of The Assessment of Social Inference Test.

There is a need for short, reliable, sensitive assessment tools to measure social cognition. The Awareness of Social Inference Test (TASIT) is an ecologically valid instrument that uses videos of actors engaged in everyday conversations to assess emotion perception, the ability to detect lies, sarcasm and sincerity, and the ability to judge what others are thinking, intending, feeling, and saying. A recently developed short version of TASIT retains the structure of the original test and its clinical sensitivity. In this paper, we compare TASIT-S performance in healthy adolescents, adults, and older adults as well as the effects of country (U.S.A. and Australia), English familiarity and gender. In this study 616 Australians including 226 adolescents (13-19) and 390 adults aged 20-75 + along with 180 U.S. residents (aged 20-74) completed one, two, or three parts of TASIT-S either face to face (Australians) or on-line (US residents). Results indicated that there were minor differences in TASIT-S performance (Part 3 only) based on country of residence and no significant effects for English familiarity in adolescents (not examined in adults). There were no gender effects. Young and middle aged adults (20-59) tended to perform better than adolescents and older adults on most parts of TASIT-S. In general, TASIT-S scores decreased moderately with advancing age. In conclusion, TASIT-S is a useful screen for social cognitive impairment in English speakers that is appropriate for use from adolescence through to older age. It produces comparable scores in the U.S.A. and Australia.

Assessing the "social brain" in dementia: Applying TASIT-S.

The ability to recognise how other people are feeling and make judgements based on their inferred thoughts is essential for successful social interactions, and is thought to depend on a complex network of brain regions, commonly referred to as the "social brain". These abilities, together referred to as social cognition, are increasingly recognised as being compromised in some dementia syndromes, particularly in behavioural-variant frontotemporal dementia (bvFTD), which is characterised by changes in personality and social conduct. Whether social cognition is impaired in other dementia syndromes, such as Alzheimer's disease (AD), or whether lower performance reflects general cognitive impairment, is less well established. Furthermore, ecologically valid tests with known neurobiological correlates are currently lacking. Here, we investigated performance on a newly devised short version of The Awareness of Social Inference Test (TASIT-S) and associated neural correlates in 25 bvFTD patients, 23 AD patients and 25 healthy controls. On Part 1-Emotion Evaluation, only bvFTD were impaired (p = .033) (AD vs. CONTROLS: p = .475) after controlling for cognitive impairment and education. On Part 2-Social Inference, both bvFTD and AD showed intact ability to interpret sincere exchanges (p values > .05). Importantly, however, bvFTD patients were impaired in interpreting sarcasm (p = .008), whereas AD performed within normal limits (p = .477). Voxel-based morphometry analyses demonstrated correlations between TASIT-S Part 1 performance and integrity of emotion processing brain regions (amygdala, insula, fusiform) and Part 2 performance with theory of mind brain regions (precuneus, temporal pole). These results demonstrate the utility of TASIT-S in identifying social cognition impairment in dementia and reveal that TASIT-S taps into integrity of key regions within the "social brain".