Fiona Kumfor

Disturbance of Emotion Processing in Frontotemporal Dementia: A Synthesis of Cognitive and Neuroimaging Findings

Accurate processing of emotional information is a critical component of appropriate social interactions and interpersonal relationships. Disturbance of emotion processing is present in frontotemporal dementia (FTD) and is a clinical feature in two of the three subtypes: behavioural-variant FTD and semantic dementia. Emotion processing in progressive nonfluent aphasia, the third FTD subtype, is thought to be mostly preserved, although current evidence is scant. This paper reviews the literature on emotion recognition, reactivity and expression in FTD subtypes, although most studies focus on emotion recognition. The relationship between patterns of emotion processing deficits and patterns of neural atrophy are considered, by integrating evidence from recent neuroimaging studies. The review findings are discussed in the context of three contemporary theories of emotion processing: the limbic system model, the right hemisphere model and a multimodal system of emotion. Results across subtypes of FTD are most consistent with the multimodal system model, and support the presence of somewhat dissociable neural correlates for basic emotions, with strongest evidence for the emotions anger and sadness. Poor emotion processing is evident in all three subtypes, although deficits are more widespread than what would be predicted based on studies in healthy cohorts. Studies that include behavioural and imaging data are limited. Future investigations combining these approaches will help improve the understanding of the neural network underlying emotion processing. Presently, longitudinal investigations of emotion processing in FTD are lacking, and studies investigating emotion processing over time are critical to understand the clinical manifestations of disease progression in FTD.

Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia

Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions. This study used voxel-based morphometry to identify discrete neural correlates involved in the recognition of basic emotions (anger, disgust, fear, sadness, surprise and happiness) in frontotemporal dementia. Forty frontotemporal dementia patients (18 behavioural-variant, 11 semantic dementia, 11 progressive nonfluent aphasia) and 27 healthy controls were tested on two facial emotion recognition tasks: The Ekman 60 and Ekman Caricatures. Although each frontotemporal dementia group showed impaired recognition of negative emotions, distinct associations between emotion-specific task performance and changes in grey matter intensity emerged. Fear recognition was associated with the right amygdala; disgust recognition with the left insula; anger recognition with the left middle and superior temporal gyrus; and sadness recognition with the left subcallosal cingulate, indicating that discrete neural substrates are necessary for emotion recognition in frontotemporal dementia. The erosion of emotion-specific neural networks in neurodegenerative disorders may produce distinct profiles of performance that are relevant to understanding the neurobiological basis of emotion processing.

Tracking the progression of social cognition in neurodegenerative disorders

Background and purpose Behavioural-variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD) patients experience behavioural and emotion recognition alterations, yet understanding of how socioemotional processing is affected with disease progression is minimal. Additionally, evidence suggests that bvFTD patients with limited brain atrophy on neuroimaging at presentation (bvFTD-la) have a more benign course than those with marked atrophy (bvFTD-ma). Longitudinal investigation of these patients, however, is lacking. Methods We investigated general cognition, emotion recognition and sarcasm detection in 20 bvFTD (8 with limited brain atrophy) and 17 AD patients longitudinally and used mixed models analyses to determine the level and rates of decline across groups over time. Results At baseline, all patient groups performed worse than controls on general cognition and emotion recognition measures. The bvFTD-ma group showed significant impairment on the sarcasm detection task compared with controls. Longitudinally, an overall effect of time was present for general cognition (p<0.001); however, the rate of decline did not differ across groups. Trends for interactions between time and diagnosis were observed for both emotion recognition tasks (p=0.055; p=0.062), with the bvFTD-ma group declining more rapidly than AD or bvFTD-la groups. On the sarcasm detection task, the bvFTD-ma and AD patients declined, whereas bvFTD-la patients remained stable over time (p=0.002). Conclusions Tasks of sarcasm detection represent a clinically useful tool to differentiate between bvFTD and AD at baseline. Furthermore, tasks of socioemotional functioning can track progression within bvFTD and identify bvFTD patients more likely to show a faster rate of decline.

The orbitofrontal cortex is involved in emotional enhancement of memory: evidence from the dementias

The enhancing effect of emotion on subsequent memory retrieval is well established. Patients with frontotemporal dementia show profound emotion processing difficulties, yet the extent to which such deficits attenuate emotional enhancement of memory remains unknown. Here, we studied the intersection between emotion and memory using a visual forced-choice recognition test for negative and neutral stimuli in 34 patients with frontotemporal dementia compared with 10 patients with Alzheimers disease and 15 control subjects. Control subjects and patients with Alzheimers disease recognized more emotional than neutral items, as demonstrated by a significant interaction between emotion and memory for true recognition. This emotional enhancement effect was notably absent in the frontotemporal dementia cohort, with comparable recognition performance regardless of emotional content. Voxel-based morphometry analyses revealed distinct neural substrates for overall memory versus emotional memory performance. Overall memory performance correlated with the hippocampus, precuneus and posterior cingulate, regions crucial for successful episodic memory performance. Emotional enhancement of memory, by contrast, was associated exclusively with the integrity of the right orbitofrontal and subcallosal cortex. Our findings demonstrate differential disruption of emotional enhancement of memory in neurodegenerative disorders, and point toward the potentially pivotal role of the orbitofrontal cortex in supporting the successful retrieval of emotionally charged negative stimuli.

On the right side? A longitudinal study of left- versus right-lateralized semantic dementia

The typical presentation of semantic dementia is associated with marked, left predominant anterior temporal lobe atrophy and with changes in language. About 30% of individuals, however, present with predominant right anterior temporal lobe atrophy, usually accompanied by behavioural changes and prosopagnosia. Here, we aimed to establish whether these initially distinct clinical presentations evolve into a similar syndrome at the neural and behavioural level. Thirty-one patients who presented with predominant anterior temporal lobe atrophy were included. Based on imaging, patients were categorized as either predominant left (n = 22) or right (n = 9) semantic dementia. Thirty-three Alzheimers disease patients and 25 healthy controls were included for comparison. Participants completed the Addenbrookes Cognitive Examination, a Face and Emotion Processing Battery and the Cambridge Behavioural Inventory, and underwent magnetic resonance imaging annually. Longitudinal neuroimaging analyses showed greater right temporal pole atrophy in left semantic dementia than Alzheimers disease, whereas right semantic dementia showed greater orbitofrontal and left temporal lobe atrophy than Alzheimers disease. Importantly, direct comparisons between semantic dementia groups revealed that over time, left semantic dementia showed progressive thinning in the right temporal pole, whereas right semantic dementia showed thinning in the orbitofrontal cortex and anterior cingulate. Behaviourally, longitudinal analyses revealed that general cognition declined in all patients. In contrast, patients with left and right semantic dementia showed greater emotion recognition decline than Alzheimers disease. In addition, left semantic dementia showed greater motivation loss than Alzheimers disease. Correlational analyses revealed that emotion recognition was associated with right temporal pole, right medial orbitofrontal and right fusiform integrity, while changes in motivation were associated with right temporal pole cortical thinning. While left and right semantic dementia show distinct profiles at presentation, both phenotypes develop deficits in emotion recognition and behaviour. These findings highlight the pervasive socio-emotional deficits in frontotemporal dementia, even in patients with an initial language presentation. These changes reflect right anterior temporal and orbitofrontal cortex degeneration, underscoring the role of these regions in social cognition and behaviour.

Degradation of emotion processing ability in corticobasal syndrome and Alzheimer’s disease

Disturbed emotion processing and difficulty with social interactions are present to variable degrees in dementia. They are characteristic features of frontotemporal dementia, whereas these deficits tend to be mild in Alzheimers disease, reflecting the different patterns of neurodegeneration seen in these disorders. Corticobasal syndrome is an atypical parkinsonian disorder clinically and pathologically related to frontotemporal dementia. Corticobasal syndrome typically presents as a motor disturbance, although cognitive and behavioural changes are now recognized. Pathological changes are found in frontoparietal cortical regions and in the basal ganglia; regions that are heavily involved in emotion processing. Despite the overlap with frontotemporal dementia and the observed regions of brain atrophy, emotion processing has not been systematically explored in corticobasal syndrome. This study aimed to (i) comprehensively examine emotion processing in corticobasal syndrome in comparison to Alzheimers disease, to determine whether emotion processing deficits exist in this syndrome, beyond those seen in Alzheimers disease; and (ii) identify the neural correlates underlying emotion processing in corticobasal syndrome and Alzheimers disease. Sixteen patients with corticobasal syndrome, 18 patients with Alzheimers disease and 22 matched healthy control subjects were assessed on a comprehensive battery of face and emotion processing tasks. Behavioural analyses revealed deficits in both basic face processing and high-level emotion processing tasks in patients with corticobasal syndrome. Notably, the emotion processing disturbance persisted even after controlling for face processing deficits. In contrast, patients with Alzheimers disease were impaired on high-level complex and cognitively demanding emotion recognition tasks (Ekman 60, The Awareness of Social Inference Test) only. Neuroimaging analyses using FreeSurfer revealed that emotion processing deficits in corticobasal syndrome were associated with basal ganglia volume loss as well as cortical thinning of the left paracentral gyrus/precuneus region. In Alzheimers disease, however, emotion processing deficits were associated with atrophy in a different set of brain regions, including the right cingulate and the bilateral insulae, as well as the hippocampi, right amygdala and nucleus accumbens bilaterally. Our results demonstrate that patients with corticobasal syndrome experience widespread deficits in emotion processing, and these deficits are related to changes in brain regions known to be crucial for emotion processing. These findings have important clinical implications for the treatment and management of these patients.

Differentiating between right-lateralised semantic dementia and behavioural-variant frontotemporal dementia: an examination of clinical characteristics and emotion processing

Background and purpose Right-lateralised semantic dementia (right SD) and behavioural-variant frontotemporal dementia (bvFTD) appear clinically similar, despite different patterns of underlying brain changes. This study aimed to elucidate distinguishing clinical and cognitive features in right SD versus bvFTD, emphasising emotion processing and its associated neural correlates. Methods 12 patients with right SD and 19 patients with bvFTD were recruited. Clinical features were documented. All patients were assessed on standardised neuropsychological tests and a facial emotion processing battery. Performance was compared to 20 age-matched and education-matched controls. Grey matter intensity was related to emotion processing performance using whole-brain voxel-based morphometry analysis. Results Patients with right SD exhibited disproportionate language dysfunction, prosopagnosia and a suggestion of increased obsessive personality/behavioural changes versus patients with bvFTD. In contrast, patients with bvFTD demonstrated pronounced deficits in attention/working memory, increased apathy and greater executive dysfunction, compared to patients with right SD. Decreased empathy, disinhibition and diet changes were common to both dementia subtypes. Emotion processing deficits were present in both FTD syndromes but were associated with divergent patterns of brain atrophy. In right SD, emotion processing dysfunction was associated with predominantly right medial and lateral temporal integrity, compared to mainly left temporal, inferior frontal and orbitofrontal and right frontal gyrus integrity in bvFTD. Conclusions This study demonstrates comparable deficits in facial emotion processing in right SD and bvFTD, in keeping with their similar clinical profiles. These deficits are attributable to divergent neural substrates in each patient group, namely, right lateralised regions in right SD, versus predominantly left lateralised regions in bvFTD.

Disease-specific patterns of cortical and subcortical degeneration in a longitudinal study of Alzheimer's disease and behavioural-variant frontotemporal dementia.

Background: Clinical differentiation between Alzheimers disease (AD) and behavioural‐variant frontotemporal dementia (bvFTD) is challenging due to overlapping clinical features at presentation. Whilst diagnostic criteria for both disorders incorporate evidence of frontal and temporal cortical atrophy, understanding of the progression of atrophy in these disorders is limited. This study aimed to elucidate common and disease‐specific progressive changes in cortical and subcortical brain structures in AD and bvFTD. Methods: Forty‐one AD, 37 bvFTD and 33 healthy controls underwent baseline MRI and of these longitudinal follow‐up was obtained for 20 AD and 20 bvFTD (1 to 4 years). A total of 87 AD and 70 bvFTD consecutive scans were included in the study. The trajectories of progression in cortical and subcortical structures were identified with FreeSurfer and linear mixed effect modelling. Results: The results uncovered cortical and subcortical disease‐specific trajectories of neurodegeneration in AD and bvFTD. Specifically, direct comparisons between patient groups revealed that over time AD showed greater cortical atrophy in the inferior parietal and posterior cingulate cortex than bvFTD. Conversely, bvFTD patients showed greater atrophy in the striatum than AD over time. Conclusions: These results indicate that atrophy in the posterior cingulate and the striatum diverges with disease progression in these dementia syndromes and may represent a potential diagnostic biomarker for tracking rates of progression of AD and bvFTD. These findings may help inform future drug trials by identifying appropriate outcome measures to quantify drug efficacy and their ability to modulate disease progression over time. HighlightsWe report divergent patterns of cortical and subcortical involvement in AD and bvFTD with disease progression.AD show more atrophy in cortical regions (e.g., posterior cingulate) than in subcortical structures over time.The reverse pattern is seen in bvFTD, with greater involvement of subcortical striatal structures with disease progression.This paper demonstrates the utility of linear mixed effects models to examine disease‐specific patterns of neurodegeneration.

Emotion processing deficits distinguish pure amyotrophic lateral sclerosis from frontotemporal dementia

Abstract Amyotrophic lateral sclerosis (ALS) is a multisystem disease that overlaps with frontotemporal dementia (FTD). Although FTD patients exhibit prominent deficits in emotion perception and social cognition, these domains have received relatively little attention in ALS. Moreover, direct comparisons between ALS and FTD on emotion processing tasks remain lacking. Twenty-nine patients with ALS (16 with coexisting FTD (FTD-ALS) and 13 without dementia), 25 behavioural variant FTD patients and 30 healthy controls completed neuropsychological and emotion tasks (Ekman Caricatures and the TASIT). Both ALS and FTD patient groups showed significant deficits on the emotion tasks compared to controls. After dividing ALS patients into those with and without FTD, only the patients with coexisting FTD (FTD-ALS) were impaired. FTD-ALS and FTD patient groups displayed similar levels of impairment, even after controlling for measures of general cognition, and demonstrated similar profiles across different types of emotions. We conclude that patients with FTD-ALS and FTD show similar, significant impairments in emotional processing. By contrast, ALS patients without dementia exhibit preserved emotion processing. Performance on emotion processing tasks may provide a useful clinical tool in identifying those with early FTD-ALS.

A tale of two hemispheres. Contrasting socioemotional dysfunction in right- versus left-lateralised semantic dementia

OBJECTIVE Semantic dementia, a subtype of frontotemporal lobar degeneration, is characterised by cross-modal loss of conceptual knowledge attributable to progressive degeneration of the left anterior temporal lobe. Much less is known regarding the clinical presentation of SD patients with predominantly right-lateralised atrophy. Recent reports emphasise marked socioemotional and behavioural disturbances in such cases. Given the importance of the right anterior temporal lobes in social cognition, we hypothesised that socioemotional functioning would be disproportionately affected in right versus left-lateralised SD cases. METHODS We assessed well-characterised cases of predominantly right (n=10) and left (n=12) SD and 20 matched healthy controls on tests of emotion processing and interpersonal functioning. RESULTS Right SD cases showed disproportionate difficulties in the recognition of positive and negative facial emotions, specifically happiness and anger, compared with left SD cases. Deficits in anger recognition persisted in right SD despite covarying for facial and semantic processing. On a contextually rich task of emotion recognition using multimodal videos, no subgroup differences were evident. Finally, empathic concern was rated as significantly lower by caregivers of right versus left SD cases. Overall, the extent of socioemotional disturbance was associated with the degree of behavioural changes in SD. CONCLUSION Our results reveal considerable overlap in the extent to which socioemotional processes are disrupted in left and right-lateralised cases of SD. Notably, however, right SD cases show disproportionate deficits for recognition of facial emotions and the capacity for empathic concern, supporting a specialised role for the right anterior temporal lobes in mediating these cognitive functions.