Muireann Irish

The University of Sydney · Brain and Mind Research Institute (BMRI)

This scientific commentary refers to ‘The architecture of abnormal reward behaviour in dementia: multimodal hedonic phenotypes and brain substrate’, by Chokesuwattanaskul et al. (https://doi.org/10.1093/braincomms/fcad027).

Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic e...

Background Hypothalamic dysregulation plays an established role in eating abnormalities in behavioural variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS). Its contribution to cognitive and behavioural impairments, however, remains unexplored. Methods Correlation between hypothalamic subregion atrophy and cognitive and...

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, an...

Background: 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 behaviour...

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 pe...

The Addenbrooke’s Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the ut...

Apathy is the most common and disabling non-cognitive feature of dementia, affecting up to 90% of individuals over the disease course. Despite its prevalence, the underlying mechanisms of apathy remain elusive. This study aimed to investigate whether cognitive apathy and executive functioning have a shared cognitive and neural basis, in behavioural...

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...

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are part of the same disease spectrum. While thalamic–cerebellar degeneration has been observed in C9orf72 expansion carriers, the exact subregions involved across the clinical phenotypes of the ALS–FTD spectrum remain unclear. Using MRIs from 58 bvFTD, 41 ALS–FTD and 52 ALS pati...

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 intersect...

Background The GGGGCC hexanucleotide repeat expansion in the non-coding region of the chromosome 9 open reading frame 72 gene (C9orf72) is the most common genetic cause of familial frontotemporal dementia (FTD). This study aims to clarify the patterns of cerebellar atrophy in FTD patients with and without a C9orf72 repeat expansion compared with he...

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 re...

Scene construction refers to the process by which humans generate richly detailed and spatially cohesive scenes in the mind’s eye. The cognitive processes that underwrite this capacity remain unclear, particularly when the envisaged scene calls for the integration of various types of contextual information. Here, we explored social and non-social f...

Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logop...

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 ti...

The capacity for subjective time in humans encompasses the perception of time’s unfolding from moment to moment, as well as the ability to traverse larger temporal expanses of past- and future-oriented thought via mental time travel. Disruption in time perception can result in maladaptive outcomes—from the innocuous lapse in timing that leads to a...

Two common clinical variants of frontotemporal dementia (FTD) are the behavioural variant (bvFTD) presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia (SD) displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entiti...

The disease syndromes of amyotrophic lateral sclerosis and frontotemporal dementia display considerable clinical, genetic and pathological overlap, yet mounting evidence indicates substantial differences in progression and survival. To date, there has been limited examination of how profiles of brain atrophy might differ between clinical phenotypes...

Although characterized primarily as a language disorder, mounting evidence indicates episodic amnesia in Logopenic Progressive Aphasia (LPA). Whether such memory disturbances extend to information encoded pre-disease onset remains unclear. To address this question, we examined autobiographical memory in 10 LPA patients, contrasted with 18 typical a...

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 pro...

Impaired verbal ‘phonological’ short-term memory is considered a cardinal feature of the logopenic variant of primary progressive aphasia (lv-PPA) and is assumed to underpin most of the language deficits in this syndrome. Clinically, examination of verbal short-term memory in individuals presenting with PPA is common practice and serves two objecti...

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...

Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right tempora...

Clinical and pathological heterogeneity is common in patients with FTLD pathology. This investigated clinical or imaging characteristics that differentiate FTLD-TDP from FTLD-tau, FTLD-TDP subtypes from each other, or pathological stages of FTLD-TDP. Initial clinical, neuropsychological and neuroimaging characteristics were compared between patholo...

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...

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...

Objective The variants of primary progressive aphasia (PPA) are predominantly diagnosed on the basis of specific profiles of language impairments. Deficits in other cognitive domains and their evolution over time are less well documented. This study examined the cognitive profiles of the PPA variants over time and determined the contribution of cog...

Objective Alterations in eating behaviour are one of the diagnostic features of behavioural variant frontotemporal dementia (bvFTD). It is hypothesised that underlying brain network disturbances and atrophy to key structures may affect macronutrient preference in bvFTD. We aimed to establish whether a preference for dietary fat exists in bvFTD, its...

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, a...

Primary progressive aphasia (PPA) is characterised by predominant language and communication impairment. However, behavioural changes, such as apathy, are increasingly recognised. Apathy is defined as a reduction in motivation and goal-directed behaviour. Recent theoretical models have suggested that apathy can be delineated into multiple dimension...

Objective To comprehensively examine the clinical presentation of patients diagnosed with frontotemporal dementia–motor neuron disease (FTD–MND) compared to FTD subtypes. To clarify the heterogeneity of behavioural and language deficits in FTD–MND using a data-driven approach.Methods Patients with FTD–MND (n = 31), behavioural variant FTD (n = 119)...

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 strik...

Deficits in episodic memory are commonplace in dementia, yet mounting evidence indicates pervasive impairments in future-oriented thinking in these syndromes. How such impairments manifest in the daily lives of people with dementia remain unclear, as do their neural bases. This study aimed to determine the neurocognitive mechanisms of past-and futu...

Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its cont...

Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its cont...

Introduction Primary progressive aphasia (PPA) comprises three main variants: logopenic (lv-PPA), non-fluent (nfv-PPA) and semantic variant (sv-PPA). Differentiating the language profiles of the PPA variants remains challenging, especially for lv-PPA and nfv-PPA. As such, diagnostic tools that do not rely on speech and language may offer some utili...

Logopenic progressive aphasia (LPA) is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal atrophy. Clinical descriptions of LPA largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits even on t...

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 pro...

Co-operative 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 stri...

Traditional analyses of autobiographical construction have tended to focus on the ‘internal’ or episodic details of the narrative. Contemporary studies employing fine-grained scoring measures, however, reveal the ‘external’ component of autobiographical narratives to contain important information relevant to the individual’s life story. Here, we us...

Logopenic Progressive Aphasia is a rare language disorder characterised by repetition and naming difficulties, reflecting the progressive degeneration of left-lateralized peri-sylvian temporal and inferior parietal regions. Mounting evidence suggests that cognitive impairments in this syndrome extend beyond the language domain to include episodic e...

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....

Objective While patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and...

Scene construction refers to the capacity to imagine richly detailed scenes in one's mind's eye and has been demonstrated to be compromised across a range of clinical disorders in which episodic memory processes are also affected. It remains unclear however, how task demands modulate the content of the to-be-simulated scenes. Here, we sought to inv...

Apathy is one of the most prevalent and disabling non-cognitive symptoms of dementia. This loss of motivation and pervasive decline in goal-directed behaviour represents a core diagnostic feature of behavioural-variant frontotemporal dementia (bvFTD) and is also common in Alzheimer's disease (AD). However, despite growing recognition of a multidime...

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative brain disorders, primarily affecting the frontal and/or temporal lobes. Three main subtypes are recognised, each with distinct clinical and cognitive profiles: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). Subtype-specifi...

Visual hallucinations are an underappreciated symptom affecting the majority of patients during the natural history of Parkinson's disease. Little is known about other forms of abstract and internally generated cognition - such as mind-wandering - in this population, but emerging evidence suggests that an interplay between the brain's primary visua...

Logopenic progressive aphasia (LPA) is a neurodegenerative disorder characterised by profound naming and sentence repetition disturbances, attributable to disproportionately left-sided temporo-parietal atrophy. Accumulating evidence suggests, in addition to language impairments, the presence of stark verbal and nonverbal episodic memory impairments...

Frontotemporal dementia (FTD) is a neurodegenerative brain disorder primarily affecting the frontal and/or temporal lobes. Three main subtypes have been recognized: behavioural-variant FTD (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA), each of which has a distinct clinical and cognitive profile. Although the role of the...

The capacity to generate naturalistic three-dimensional and spatially coherent representations of the world, i.e., scene construction, is posited to lie at the heart of a wide range of complex cognitive endeavours. Clinical populations with selective damage to key nodes of a putative scene construction network of the brain have provided important i...

Logopenic Progressive Aphasia is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal brain atrophy. Mapping of the clinical phenomenology of this syndrome has largely concentrated on its language deficits. Accumulating evidence, however, points to the presence of co...

An fMRI experiment reveals distinct brain regions that respond in a graded manner as humans process distance information across increasing spatial scales.

Autobiographical memory is widely posited to serve self, social and directive functions. Recent evidence suggests marked autobiographical memory impairments in Huntington's disease (HD), however, no study to date has determined how the perceived functions of autobiographical reminiscence may be altered in HD. The current study aimed to assess the s...

Introduction Frontotemporal dementia-motor neuron disease (FTD-MND) is diagnosed when patients meet criteria for the diagnosis of both FTD and MND, but the mode presentation of this disorder is currently unknown. This study aimed to compare the mode of presentation, and profiles of behavioural and language disturbances, of FTD-MND with that of othe...

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 wi...

An intriguing aspect of human cognition is the unique capacity to mentally retreat from our immediate surroundings to consider perspectives distinct from the here and now. Despite increasing interest in this phenomenon, relatively little is known regarding age-related changes in off-task, self-generated thought (often referred to as “mind-wandering...

Memory and the self have long been considered intertwined, leading to the assumption that without memory, there can be no self. This line of reasoning has led to the misconception that a loss of memory in dementia necessarily results in a diminished sense of self. Here, we challenge this assumption by considering discrete facets of self-referential...

This study systematically investigated the neuropsychological profile of language disturbance in frontotemporal dementia–motor neuron disease (FTD–MND) using a data-driven approach. Neuroanatomical correlates of language profiles were also examined. Patients with FTD–MND (N = 26), pure motor neuron disease (N = 34), progressive non-fluent aphasia (...

OBJECTIVES: Approximately 30% of Alzheimer’s disease (AD) patients are misdiagnosed due to overlapping and evolving clinical features. In particular, the distinction of AD from behavioural variant frontotemporal dementia (bvFTD) can be challenging. Measures of visuospatial ability, which rely on parietal lobe function, show promise as markers of AD...

Much of human interaction is predicated upon our innate capacity to infer the thoughts, beliefs, emotions, and perspectives of others, in short, to possess a “theory of mind” (ToM). While the term has evolved considerably since its inception, ToM encompasses our unique ability to apprehend the mental states of others, enabling us to anticipate and...

Significance Humans spend much of their waking life engaged in mind wandering. Underlying brain systems supporting this complex ability have been established in healthy individuals, yet it remains unclear how mind wandering is altered in neuropsychiatric populations. We reveal changes in the thought profiles elicited during periods of low cognitive...

Memory and the self have long been considered intertwined, leading to the common assumption that without memory, there can be no self. This line of reasoning has led to the common misconception that a loss of memory in dementia necessarily results in a diminished sense of self. Here, we challenge this assumption by considering discrete facets of th...

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 c...

Background: Frontotemporal dementia (FTD) is characterised by changes in behaviour including alterations in sexual function. While hypersexual behaviour is commonly thought to predominate, emerging evidence suggests that hyposexual behaviour is in fact most prevalent. The underlying mechanisms driving these behavioural changes remain unclear; howe...

Much of human life revolves around anticipating and planning for the future. It has become increasingly clear that this capacity for prospective cognition is a core adaptive function of the mind. Here, we review the role of prospection in two key functional domains: goal-directed behavior and flexible decision-making. We then survey and categorize...

Mind wandering represents the human capacity for internally focussed thought, and relies upon the brain’s default network and its interactions with attentional networks. Studies have characterised mind wandering in healthy people, yet there is limited understanding of how this capacity is affected in clinical populations. This study used a validate...

Objectives: The Addenbrooke's Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff scores for the detection of dementia, and explored its relationship with functional ability. Methods: Stud...

Posterior Cortical Atrophy (PCA) is a rare neurodegenerative syndrome characterised by profound visuoperceptual processing disturbances, attributable to focal parieto-occipital cortical atrophy. Despite relative sparing of the medial temporal lobes, converging evidence reveals significant autobiographical memory impairments in this syndrome, unders...