Establishing the link between motivational disturbances and behavioural rigidity in frontotemporal dementia.

BACKGROUND: Rigid and inflexible behaviours are common in frontotemporal dementia (FTD), manifesting in compulsive pursuit of specific interests, routines, and rituals. Paradoxically, these changes occur alongside profound motivational disturbances including apathy and anhedonia. While posited to be related, no study to date has explored the link between motivational changes and behavioural rigidity in FTD. METHODS: Carer ratings for 71 FTD participants (26 semantic dementia [SD], 45 behavioural variant [bvFTD]) were obtained on the Dimensional Apathy Scale (apathy), the Snaith-Hamilton Pleasure Scale (hedonic tone) and the Cambridge Behavioural Inventory-Revised (CBI-R; behavioural changes). A rigidity index was created from existing items on the CBI-R. Whole-brain voxel-based morphometry was used to explore associations between rigidity and grey matter intensity in the combined FTD group. RESULTS: Behavioural rigidity was significantly related to apathy severity (r = 0.57) and decreased hedonic tone (r = -0.36) in the combined FTD group. Multiple linear regression revealed a significant diagnosis × hedonic tone interaction (ß = -1.40), whereby lower hedonic tone predicted rigidity in SD (r = -0.65) but not in bvFTD (r = -0.18). In contrast, the relationship between rigidity and apathy did not differ between the groups (ß = -0.42). At the neural level, rigidity correlated with degeneration of predominantly right-sided frontostriatal structures including, notably, the nucleus accumbens. CONCLUSIONS: As the first study to demonstrate a link between motivational changes and behavioural rigidity in FTD, our findings have important clinical implications. By identifying candidate mechanisms of behavioural rigidity, our findings can inform targeted interventions to manage inflexible patterns of thought and behaviour in daily life.

Scene construction in healthy aging - Exploring the interplay between task complexity and oculomotor behaviour.

Mounting evidence indicates a close correspondence between episodic memory, mental imagery, and oculomotor behaviour. It remains unclear, however, how oculomotor variables support endogenously driven forms of mental imagery and how this relationship changes across the adult lifespan. In this study we investigated age-related changes in oculomotor signatures during scene construction and explored how task complexity impacts these processes. Younger and cognitively healthy older participants completed a guided scene construction paradigm where scene complexity was manipulated according to the number of elements to be sequentially integrated. We recorded participants' eye movements and collected subjective ratings regarding their phenomenological experience. Overall, older adults rated their constructions as more vivid and more spatially integrated, while also generating more fixations and saccades relative to the younger group, specifically on control trials. Analyses of participants' total scan paths revealed that, in the early stages of scene construction, oculomotor behaviour changed as a function of task complexity within each group. Following the introduction of a second stimulus, older but not younger adults showed a significant decrease in the production of eye movements. Whether this shift in oculomotor behaviour serves a compensatory function to bolster task performance represents an important question for future research.

Exploring Information Flow from Posteromedial Cortex during Visuospatial Working Memory: A Magnetoencephalography Study.

The posteromedial cortex (PMC) is a major hub of the brain's default mode network, and is implicated in a broad range of internally driven cognitions, including visuospatial working memory. However, its precise contribution to these cognitive processes remains unclear. Using MEG, we measured PMC activity in healthy human participants (young adults of both sexes) while they performed a visuospatial working memory task. Multivariate pattern classification analyses revealed stimulus-related information during encoding and retrieval in a set of a priori defined cortical ROIs, including prefrontal, occipital, and ventrotemporal cortices, in addition to PMC. We measured the extent to which this stimulus information was exchanged between areas in an information flow analysis, measuring Granger-causal relationships between areas over time. Consistent with the visual nature of the task, information from occipital cortex shaped other regions across most epochs. However, the PMC shaped object representations in occipital and prefrontal cortices during visuospatial working memory, influencing occipital cortex during retrieval and PFC across all task epochs. Our findings are consistent with a proposed role for the PMC in the representation of internal content, including remembered information, and in the comparison of external stimuli with remembered material.SIGNIFICANCE STATEMENT The human brain operates as a collection of highly interconnected regions. Mapping the function of this interconnectivity, as well as the specializations within different regions, is central to understanding the neural processes underlying cognition. The posteromedial cortex (PMC) is a highly connected cortical region, implicated in visuospatial working memory, although its precise contribution remains unclear. We measured the activity of PMC during a visuospatial working memory task, testing how different regions represented the stimuli, and whether these representations were driven by other cortical regions. We found that PMC influenced stimulus information in other regions across all task phases, suggesting that PMC plays a key role in shaping stimulus representations during visuospatial working memory.

Altered reward processing underpins emotional apathy in dementia.

INTRODUCTION: While apathy is broadly defined as a loss of motivation, it is increasingly recognised as a multidimensional syndrome spanning executive, emotional, and initiation domains. Emotional apathy is purportedly driven by deficits in using socioemotional rewards to guide behaviour, yet the link between these symptoms and reward processing, and their common neural correlates, has not been directly examined. METHODS: Sixty-four patients (33 behavioural-variant frontotemporal dementia, 14 Alzheimer's disease, 8 semantic dementia, 6 progressive nonfluent aphasia, 3 logopenic progressive aphasia) were classified into high (HEA; n = 36) and low (LEA; n = 28) emotional apathy groups based on emotional apathy subscale scores on the Dimensional Apathy Scale. Patients and age-matched healthy controls (n = 27) performed an instrumental reward learning task where they learned to associate cues with either social or monetary outcomes. RESULTS: HEA patients showed impaired learning on both the social and monetary reward conditions, relative to LEA patients (p = 0.016) and controls (p = 0.005). Conversely, the LEA group did not differ from controls (p = 0.925). Importantly, multiple regression analyses indicated that social reward learning significantly predicted emotional apathy. Voxel-based morphometry analyses revealed that emotional apathy and social reward learning were both associated with orbitofrontal cortex, ventral striatum, and insula atrophy. DISCUSSION: Our results demonstrate a unique link between impaired social reward learning and emotional apathy in dementia and reveal a shared neurobiological basis. Greater understanding of these neurocognitive mechanisms of reward processing will help improve the identification of emotional apathy in dementia and inform the development of novel interventions to address these symptoms.

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia.

The logopenic variant of primary progressive aphasia is characterized by early deficits in language production and phonological short-term memory, attributed to left-lateralized temporoparietal, inferior parietal and posterior temporal neurodegeneration. Despite patients primarily complaining of language difficulties, emerging evidence points to performance deficits in non-linguistic domains. Temporoparietal cortex, and functional brain networks anchored to this region, are implicated as putative neural substrates of non-linguistic cognitive deficits in logopenic variant primary progressive aphasia, suggesting that degeneration of a shared set of brain regions may result in co-occurring linguistic and non-linguistic dysfunction early in the disease course. Here, we provide a Review aimed at broadening the understanding of logopenic variant primary progressive aphasia beyond the lens of an exclusive language disorder. By considering behavioural and neuroimaging research on non-linguistic dysfunction in logopenic variant primary progressive aphasia, we propose that a significant portion of multidimensional cognitive features can be explained by degeneration of temporal/inferior parietal cortices and connected regions. Drawing on insights from normative cognitive neuroscience, we propose that these regions underpin a combination of domain-general and domain-selective cognitive processes, whose disruption results in multifaceted cognitive deficits including aphasia. This account explains the common emergence of linguistic and non-linguistic cognitive difficulties in logopenic variant primary progressive aphasia, and predicts phenotypic diversification associated with progression of pathology in posterior neocortex.

Deconstructing spontaneous expressions of memory in dementia.

Dementia syndromes offer a unique opportunity to clarify some of the component processes of spontaneous expressions of memory proposed by the Barzykowski and Moulin model. By considering the model through the lens of memory disorders, I outline several important extensions to progress our understanding of these spontaneous cognitive phenomena.

Longitudinal changes in behaviour, mood and functional capacity in the primary progressive aphasia variants.

Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterised by a progressive decline in speech and language functions. Deficits in behaviour, mood and functional capacity are reported in PPA but are less well understood. This study examined the PPA variants' profiles on these domains at initial presentation and over time and evaluated their relations to overall cognitive ability. Behaviour, mood and functional capacity were measured annually (over ~6 years) in 145 individuals diagnosed with PPA (41 logopenic [lv-PPA], 44 non-fluent [nfv-PPA] and 60 semantic variants [sv-PPA]) using the Cambridge Behavioural Inventory-Revised (CBI-R) carer questionnaire. Overall cognition was assessed annually with the Addenbrooke's Cognitive Examination-III. Distinct profiles were observed across PPA syndromes. Notably, sv-PPA carers reported greater behavioural, eating and motivational disturbances than the other PPA variants throughout the disease course. Reported memory problems were also greater in sv-PPA and lv-PPA than in nfv-PPA across all time points. These disturbances occurred in the context of the sv-PPA group demonstrating a slower rate of cognitive decline than the lv-PPA group and a parallel rate to that found in the nfv-PPA group. Associations between overall cognition and the CBI-R domains were trivial at baseline assessment; however, distinct profiles emerged when mapping each syndrome's overall cognitive decline with their behavioural, mood and functional trajectories. Our findings demonstrate that the evolving behaviour, mood and functional capacity profiles of the PPA variants are distinct and extend beyond the primary disorder of language. These findings have important implications for clinical management and caregiver education in PPA.

Distinct disease trajectories in frontotemporal dementia-motor neuron disease and behavioural variant frontotemporal dementia: A longitudinal study.

BACKGROUND AND PURPOSE: The heterogeneity of cognitive and behavioural disturbances in frontotemporal dementia-motor neuron disease (FTD-MND), and clinical differences between FTD-MND and FTD subtypes, have been illustrated cross-sectionally. This study aimed to examine the FTD-MND disease trajectory by comparing clinical features of FTD-MND and the behavioural variant FTD (bvFTD) longitudinally. METHODS: Neuropsychological and disease severity assessments were conducted in a cohort of FTD-MND (baseline, n = 42; follow-up, n = 18) and bvFTD (baseline, n = 116; follow-up, n = 111) using a longitudinal, case-control design. Age-, sex-, and education-matched controls (n = 52) were recruited. Predictors of clinical progression were analyzed. Voxel-based morphometry analysis was undertaken to investigate the progression of brain atrophy. RESULTS: At baseline, FTD-MND was characterized by semantic and general cognition deficits, whereas bvFTD had greater behavioural disturbances. General cognition and language deteriorated in FTD-MND when followed longitudinally. Language deficits at baseline predicted cognitive deterioration and disease progression and correlated with progressive atrophy of language regions. Further deterioration in behaviour was evident in bvFTD over time. The rate of disease progression (i.e., general cognition, semantic association, and disease severity) was significantly faster in FTD-MND than in bvFTD. CONCLUSIONS: FTD-MND and bvFTD appear to have distinct disease trajectories, with more rapid progression in FTD-MND. Language impairments should be closely monitored in FTD-MND as potential predictors of cognitive deterioration and disease progression.

The interplay of emotional and social conceptual processes during moral reasoning in frontotemporal dementia.

Cooperative social behaviour in humans hinges upon our unique ability to make appropriate moral decisions in accordance with our ethical values. The complexity of the neurocognitive mechanisms underlying moral reasoning is revealed when this capacity breaks down. Patients with the behavioural variant of frontotemporal dementia (bvFTD) display striking moral transgressions in the context of atrophy to frontotemporal regions supporting affective and social conceptual processing. Developmental studies have highlighted the importance of social knowledge to moral decision making in children, yet the role of social knowledge in relation to moral reasoning impairments in neurodegeneration has largely been overlooked. Here, we sought to examine the role of affective and social conceptual processes in personal moral reasoning in bvFTD, and their relationship to the integrity and structural connectivity of frontotemporal brain regions. Personal moral reasoning across varying degrees of conflict was assessed in 26 bvFTD patients and compared with demographically matched Alzheimer's disease patients (n = 14), and healthy older adults (n = 22). Following each moral decision, we directly probed participants' subjective emotional experience as an index of their affective response, while social norm knowledge was assessed via an independent task. While groups did not differ significantly in terms of their moral decisions, bvFTD patients reported feeling 'better' about their decisions than healthy control subjects. In other words, although bvFTD patients could adjudicate between different courses of action in the moral scenarios, their affective responses to these decisions were highly irregular. This blunted emotional reaction was exclusive to the personal high-conflict condition, with 61.5% of bvFTD patients reporting feeling 'extremely good' about their decisions, and was correlated with reduced knowledge of socially acceptable behaviour. Voxel-based morphometry analyses revealed a distributed network of frontal, subcortical, and lateral temporal grey matter regions involved in the attenuated affective response to moral conflict in bvFTD. Crucially, diffusion-tensor imaging implicated the uncinate fasciculus as the pathway by which social conceptual knowledge may influence emotional reactions to personal high-conflict moral dilemmas in bvFTD. Our findings suggest that altered moral behaviour in bvFTD reflects the dynamic interplay between degraded social conceptual knowledge and blunted affective responsiveness, attributable to atrophy of, and impaired information transfer between, frontal and temporal cortices. Delineating the mechanisms of impaired morality in bvFTD provides crucial clinical information for understanding and treating this challenging symptom, which may help pave the way for targeted behavioural interventions.

Uncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia.

Much of human behaviour is motivated by the drive to experience pleasure. The capacity to envisage pleasurable outcomes and to engage in goal-directed behaviour to secure these outcomes depends upon the integrity of frontostriatal circuits in the brain. Anhedonia refers to the diminished ability to experience, and to pursue, pleasurable outcomes, and represents a prominent motivational disturbance in neuropsychiatric disorders. Despite increasing evidence of motivational disturbances in frontotemporal dementia (FTD), no study to date has explored the hedonic experience in these syndromes. Here, we present the first study to document the prevalence and neural correlates of anhedonia in FTD in comparison with Alzheimer's disease, and its potential overlap with related motivational symptoms including apathy and depression. A total of 172 participants were recruited, including 87 FTD, 34 Alzheimer's disease, and 51 healthy older control participants. Within the FTD group, 55 cases were diagnosed with clinically probable behavioural variant FTD, 24 presented with semantic dementia, and eight cases had progressive non-fluent aphasia (PNFA). Premorbid and current anhedonia was measured using the Snaith-Hamilton Pleasure Scale, while apathy was assessed using the Dimensional Apathy Scale, and depression was indexed via the Depression, Anxiety and Stress Scale. Whole-brain voxel-based morphometry analysis was used to examine associations between grey matter atrophy and levels of anhedonia, apathy, and depression in patients. Relative to controls, behavioural variant FTD and semantic dementia, but not PNFA or Alzheimer's disease, patients showed clinically significant anhedonia, representing a clear departure from pre-morbid levels. Voxel-based morphometry analyses revealed that anhedonia was associated with atrophy in an extended frontostriatal network including orbitofrontal and medial prefrontal, paracingulate and insular cortices, as well as the putamen. Although correlated on the behavioural level, the neural correlates of anhedonia were largely dissociable from that of apathy, with only a small region of overlap detected in the right orbitofrontal cortices whilst no overlapping regions were found between anhedonia and depression. This is the first study, to our knowledge, to demonstrate profound anhedonia in FTD syndromes, reflecting atrophy of predominantly frontostriatal brain regions specialized for hedonic tone. Our findings point to the importance of considering anhedonia as a primary presenting feature of behavioural variant FTD and semantic dementia, with distinct neural drivers to that of apathy or depression. Future studies will be essential to address the impact of anhedonia on everyday activities, and to inform the development of targeted interventions to improve quality of life in patients and their families.

Try to see it my way - Examining the relationship between visual perspective taking and theory of mind in frontotemporal dementia.

The behavioural variant of frontotemporal dementia (bvFTD) is characterised by pronounced alterations in social functioning, including the understanding of others' thoughts and feelings via theory of mind. The emergence of such impairments in other social disorders such as autism and schizophrenia is suggested to reflect an inability to imagine the other person's visual perspective of the world. To our knowledge, relationships between visual perspective taking and theory of mind have not previously been explored in bvFTD. Here, we sought to examine the capacity for visual perspective taking and theory of mind in bvFTD, and to establish their inter-relationships and underlying neural correlates. Fifteen bvFTD patients and 15 healthy Controls completed a comprehensive battery of perspective taking measures, comprising Level 1 ('what') and Level 2 ('how') visual perspective taking tasks, a cartoon task capturing theory of mind, and a questionnaire assessing subjective perspective taking in daily life. Compared with Controls, bvFTD patients displayed significant impairments across all perspective taking measures. These perspective taking impairments, however, were not correlated with one another in bvFTD. Region-of-interest voxel-based morphometry analyses suggested distinct neural correlates for visual perspective taking (inferior frontal gyrus) versus theory of mind (medial prefrontal cortex, precuneus), which appeared to partially overlap with those implicated in subjective perspective taking (inferior frontal gyrus, precuneus, temporoparietal junction). Despite pervasive impairments in all aspects of perspective taking in bvFTD, these did not appear to relate to one another at the behavioural or neural level in our study. Future large-scale studies manipulating discrete aspects of the tasks will help to clarify the neurocognitive mechanisms of, and relationships between, visual perspective taking and theory of mind in bvFTD, along with their real-world implications.

Rethinking the distinction between episodic and semantic memory: Insights from the past, present, and future.

On the 50th anniversary of Tulving's introduction of the celebrated distinction between episodic and semantic memory, it seems more than fitting to revisit his proposal in light of recent conceptual and methodological advances in the field. This Special Issue of Memory & Cognition brings together researchers doing cutting-edge work at the intersection between episodic and semantic memory to showcase studies directly probing this psychological distinction, as well as articles that seek to provide conceptual and theoretical accounts to understand their interaction. The 14 articles presented here highlight the need to critically examine the way in which we conceptualize not only the relationship between episodic and semantic memory, but also the interplay between declarative and non-declarative memory, and the myriad implications of such conceptual changes. In many ways, we suggest this Special Issue might serve as a call to action for our field, inspiring future work to challenge pre-existing conceptions and stimulate new directions in this fast-moving field.

Exploring episodic and semantic contributions to past and future thinking performance in Korsakoff's syndrome.

Korsakoff's syndrome (KS) is a neuropsychiatric disorder characterized by severe declarative memory disruption. While episodic memory deficits and confabulation are well documented, it remains unclear to what extent semantic memory is compromised in this syndrome. Moreover, how such impairments relate to the capacity for future-oriented thinking remains unknown. Here, we sought to determine the extent to which episodic and semantic forms of past and future thinking are impacted in KS and the interrelationship between different classes of memory in this syndrome. Twenty patients with KS and 17 matched healthy controls took part in this study. We included well-established indices of past and future thinking capacity, enabling us to compare episodic (event-based) versus semantic (nonpersonal knowledge) across past and future conditions. We also included a novel event generation task to probe implausible event simulation (i.e., spending a day on the moon). Our findings revealed marked impairments in KS across all forms of past and future thinking, as well as the generation of episodic details on the implausible event simulation task. Correlation analyses revealed significant associations between implausible event construction and episodic and semantic future thinking in KS; however, no significant associations were found between future thinking performance and confabulation. This study is the first, to our knowledge, to reveal striking impairments in the capacity for past and future thinking across episodic and semantic domains in KS. Our findings resonate with current theoretical perspectives in which the lines between episodic and semantic memory systems are viewed as increasingly blurred.

Examining the episodic-semantic interaction during future thinking - A reanalysis of external details.

While traditional analyses of autobiographical construction tend to focus on the 'internal' or episodic details of the narrative, contemporary studies employing fine-grained scoring measures reveal the 'external' component to contain important information relevant to the individual's life story. Here, we used the recently developed NExt scoring protocol to explore profiles of external details generated by patients with Alzheimer's disease (AD) (n = 11) and semantic dementia (SD) (n = 13) on a future thinking task. Overall, distinct NExt profiles were observed for future events in AD and SD. Specifically, AD patients provided significantly more Specific Episode external details compared with Controls. Using voxel-based morphometry, these increased external details within future narratives related to grey matter intensity in medial and lateral frontal regions in AD. By contrast, SD patients displayed an elevation of Specific Episode, Extended Episode, and General Semantic details during future simulation relative to Controls, which related to grey matter intensity of medial and lateral parietal regions. Our findings suggest that the compensatory external details generated during future simulation comprise an array of episodic and semantic details that vary in terms of specificity and self-relevance, which may be differentially affected depending on the locus of underlying neuropathology in dementia. Adopting a fine-grained approach to external details helps to characterise the interplay between episodic and semantic content during future stimulation and suggests potentially differential vulnerability and preservation of distinct components of the constructed narrative in clinical disorders.

Hippocampal atrophy and intrinsic brain network dysfunction relate to alterations in mind wandering in neurodegeneration.

Mind wandering represents the human capacity for internally focused thought and relies upon the brain's default network and its interactions with attentional networks. Studies have characterized mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. This paper used a validated thought-sampling task to probe mind wandering capacity in two neurodegenerative disorders: behavioral variant frontotemporal dementia [(bvFTD); n = 35] and Alzheimer's disease [(AD); n = 24], compared with older controls (n = 37). These patient groups were selected due to canonical structural and functional changes across sites of the default and frontoparietal networks and well-defined impairments in cognitive processes that support mind wandering. Relative to the controls, bvFTD patients displayed significantly reduced mind wandering capacity, offset by a significant increase in stimulus-bound thought. In contrast, AD patients demonstrated comparable levels of mind wandering to controls, in the context of a relatively subtle shift toward stimulus-/task-related forms of thought. In the patient groups, mind wandering was associated with gray matter integrity in the hippocampus/parahippocampus, striatum, insula, and orbitofrontal cortex. Resting-state functional connectivity revealed associations between mind wandering capacity and connectivity within and between regions of the frontoparietal and default networks with distinct patterns evident in patients vs. controls. These findings support a relationship between altered mind wandering capacity in neurodegenerative disorders and structural and functional integrity of the default and frontoparietal networks. This paper highlights a dimension of cognitive dysfunction not well documented in neurodegenerative disorders and validates current models of mind wandering in a clinical population.

The Box Task: A novel tool to differentiate the primary progressive aphasias.

OBJECTIVE: Differentiating the primary progressive aphasia (PPA) variants in clinical settings remains complex and challenging, especially for the logopenic (lv-PPA) and non-fluent variants (nfv-PPA). Recent studies suggest that visuospatial memory is more compromised in lv-PPA than in nfv-PPA and is relatively spared in the semantic variant (sv-PPA). Accordingly, assessment of visuospatial memory performance may assist in the differential diagnosis of PPA variants. Here, we investigated the utility of a novel computerised visuospatial working memory test-the Box Task-to differentiate the three PPA variants and typical Alzheimer's disease (AD). METHODS: Eighteen lv-PPA, 14 nfv-PPA, 23 sv-PPA, 33 AD patients, and 32 healthy controls matched for age and education were recruited. All participants completed the computerised Box Task and WMS-III Spatial Span as measures of visuospatial working memory. RESULTS: The lv-PPA group made significantly more Box Task between-search errors than nfv-PPA, sv-PPA and control groups. The AD group, however, displayed the greatest impairments on this measure relative to the PPA variants. Logistic regression analyses in lv-PPA and nfv-PPA demonstrated that the combination of Box Task between-search error variables (i.e., 4- and 6-box levels) could correctly classify 72% of lv-PPA patients and nearly 79% of nfv-PPA patients. Area under the receiver operator characteristics curve (AUC) analyses revealed the Box Task was more sensitive than Spatial Span at differentiating lv-PPA from nfv-PPA. CONCLUSIONS: Our findings suggest that a simple, computerised measure of visuospatial working memory-the Box Task-shows potential diagnostic utility in differentiating lv-PPA from the other PPA variants.

"More than words" - Longitudinal linguistic changes in the works of a writer diagnosed with semantic dementia.

Leveraging recent advances in automated language analysis and anovel statistical approach utilizing an independent control group, we explored changes in lexical output across two published works of a man diagnosed with semantic dementia. We found significant increase in adverb usage and decline in familiarity, meaningfulness, age of acquisition and co-occurrence probability over 2 years. Collectively, these indices suggest that WR's narrative structure became progressively simpler, lexically less sophisticated, and that words commonly associated together no longer appeared in close proximity. Our study illustrates how degeneration of the semantic knowledge base impacts the production, content, and quality of literary works.

The effect of semantic memory degeneration on creative thinking: A voxel-based morphometry analysis.

Increasing attention is being directed towards explicating the neurocognitive mechanisms of divergent thinking. While neuroimaging studies have tended to dominate the contemporary creativity literature, lesion studies provide important converging evidence by revealing the regions that are not only implicated in, but essential for, task performance. Here we explored the capacity for divergent thinking in semantic dementia (SD), a neurodegenerative disorder characterised by the progressive degeneration of the conceptual knowledge base. The performance of 10 SD patients on a divergent thinking task was contrasted with that of 15 patients with the behavioural variant of frontotemporal dementia (bvFTD) and 20 healthy control participants. In addition, all participants underwent neuropsychological testing and structural MRI. Relative to controls, both patient groups generated significantly fewer responses on the divergent thinking task, with disproportionate impairment in the SD group. Further, the responses generated by patient groups were less original and reflected less flexible thinking when compared with controls. For SD patients, fluency of responses correlated with performance on a measure of semantic association, and originality of responses correlated with semantic naming and comprehension ability. In bvFTD, originality of ideas correlated with letter fluency and response inhibition. Voxel-based morphometry analyses revealed two grey matter clusters consistently associated with diminished Fluency of ideas, namely a left medial temporal lobe cluster centred on the left anterior hippocampus, and a left middle frontal gyrus cluster. Our study highlights the importance of distinct temporal and prefrontal contributions to divergent thinking via a lesion approach, and underscores the pivotal role of semantic processes in creative cognition.

The other side of the coin: Semantic dementia as a lesion model for understanding recollection and familiarity.

The syndrome of semantic dementia represents the "other side of the coin" to Alzheimer's disease, offering convergent evidence to help refine Bastin et al.'s integrative memory model. By considering the integrative memory model through the lens of semantic dementia, we propose a number of important extensions to the framework, to help clarify the complex neurocognitive mechanisms underlying recollection and familiarity.

Fronto-parietal contributions to episodic retrieval-evidence from neurodegenerative disorders.

Converging evidence suggests a critical role for the parietal cortices in episodic memory retrieval. Here, we examined episodic memory performance in Corticobasal Syndrome (CBS), a rare neurodegenerative disorder presenting with early parietal atrophy in the context of variable medial temporal lobe damage. Forty-four CBS patients were contrasted with 29 typical Alzheimer's disease (AD), 29 healthy Controls, and 20 progressive supranuclear palsy patients presenting with brainstem atrophy as a disease control group. Participants completed standardized assessments of verbal episodic memory (learning, delayed recall, and recognition), and underwent structural and diffusion-weighted MRI. Selective delayed recall deficits were evident in the CBS group relative to Controls, at an intermediate level to the stark amnesia displayed by AD, and Control-level performance noted in progressive supranuclear palsy. Considerable variability within the CBS group on delayed recall performance led to the identification of memory-spared (N = 19) and memory-impaired (N = 25) subgroups. Whereas CBS-Spared showed no significant memory deficits, the CBS-Impaired subgroup were indistinguishable from typical AD across all episodic memory measures. Whole-brain voxel-based morphometry analyses implicated fronto-parietal and medial temporal regions in delayed recall performance in both the CBS-Impaired and AD groups. Furthermore, diffusion tensor imaging analyses revealed correlations between delayed recall performance and altered structural connectivity between fronto-parietal and frontotemporal regions in the CBS-Impaired group. Our findings underscore the importance of a distributed brain network including frontal, medial temporal, and parietal brain regions in supporting the capacity for successful episodic memory retrieval.