The neuroanatomical and neurochemical basis of apathy and impulsivity in frontotemporal lobar degeneration

Passamonti, Luca; Lansdall, Claire; Rowe, James B.

doi:10.1016/j.cobeha.2017.12.015

Cited by 63 publications

(88 citation statements)

References 51 publications

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“…Finally, taking this multidimensional approach could inform a transdiagnostic selection process for treatment, therapy or clinical trials; in order to select a group of patients with relatively homogeneous behavioural symptoms, one could select patients who occupy a shared region of the multidimensional space (thereby sharing symptomatology across the core language systems captured by the dimensions), irrespective of their clinical diagnosis. Indeed, the importance of a transdiagnostic approach has been highlighted for frontotemporal lobar degeneration (FTLD) with regards to shared apathy and impulsivity symptomatology ( Lansdall et al , 2017 , 2019 ; Passamonti et al , 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia

Ingram

Halai

Pobric

et al. 2020

Brain

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Language impairments caused by stroke (post-stroke aphasia, PSA) and neurodegeneration (primary progressive aphasia, PPA) have overlapping symptomatology, nomenclature and are classically divided into categorical subtypes. Surprisingly, PPA and PSA have rarely been directly compared in detail. Rather, previous studies have compared certain subtypes (e.g. semantic variants) or have focused on a specific cognitive/linguistic task (e.g. reading). This study assessed a large range of linguistic and cognitive tasks across the full spectra of PSA and PPA. We applied varimax-rotated principal component analysis to explore the underlying structure of the variance in the assessment scores. Similar phonological, semantic and fluency-related components were found for PSA and PPA. A combined principal component analysis across the two aetiologies revealed graded intra- and intergroup variations on all four extracted components. Classification analysis was used to test, formally, whether there were any categorical boundaries for any subtypes of PPA or PSA. Semantic dementia formed a true diagnostic category (i.e. within group homogeneity and distinct between-group differences), whereas there was considerable overlap and graded variations within and between other subtypes of PPA and PSA. These results suggest that (i) a multidimensional rather than categorical classification system may be a better conceptualization of aphasia from both causes; and (ii) despite the very different types of pathology, these broad classes of aphasia have considerable features in common.

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Section: Discussionmentioning

confidence: 99%

Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia

Ingram

Halai

Pobric

et al. 2020

Brain

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“…The association between the locus coeruleus integrity and disease severity raises the possibility of noradrenergic treatment strategies [41]. One study reported that alpha 2 noradrenergic receptor antagonism did not alleviate motor symptoms in PSP [43].…”

Section: Discussionmentioning

confidence: 99%

Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity

Kaalund

Passamonti

Allinson

et al. 2020

acta neuropathol commun

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The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson's syndrome. We test the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP. We used immunohistochemistry in post mortem tissues from 31 patients with a clinical diagnosis of PSP (22 with Richardson's syndrome) and 6 control cases. We quantified the presence of hyperphosphorylated tau, the number of pigmented cells indicative of noradrenergic neurons, and the percentage of pigmented neurons with tau-positive inclusions. Ante mortem assessment of clinical severity using the PSP rating scale was available within 1.8 (±0.9) years for 23 patients. We found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions. Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.

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“…Clinical apathy is associated with disruptions to frontal-subcortical circuits that are involved in self-initiated, goal-directed behaviour (Levy & Dubois, 2005). Lesions of the prefrontal cortices have long been known to impair goal-directed behaviour (Luria, 1995), and apathy is an important feature of neurodegenerative diseases affecting prefrontal regions (Passamonti, Lansdall, & Rowe, 2018). Lesion and neuroimaging studies have also implicated the anterior cingulate cortex and basal ganglia in apathy (Le Heron, Apps, & Husain, 2017;Levy & Dubois, 2005).…”

Section: Discussionmentioning

confidence: 99%

Apathy is Associated with Reduced Precision of Prior Beliefs about Action Outcomes

Hezemans

Wolpe

Rowe

2019

Preprint

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Apathy is a debilitating syndrome that is associated with reduced goal-directed behaviour. Although apathy is common and detrimental to prognosis in many neuropsychiatric diseases, its underlying mechanisms remain controversial. We propose a new model of apathy, in the context of Bayesian theories of brain function, whereby actions require predictions of their outcomes to be held with sufficient precision for 'explaining away' differences in sensory inputs. In this active inference model, apathy would result from reduced precision of prior beliefs about action outcomes. Healthy adults (N=47) performed a visuomotor task that independently manipulated physical effort and reward, and served to estimate the precision of priors. Participants' perception of their performance was biased towards the target, which was accounted for by precise prior beliefs about action outcomes. Crucially, prior precision was negatively associated with apathy. The results support a Bayesian account of apathy, that could inform future studies of clinical populations.

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The neuroanatomical and neurochemical basis of apathy and impulsivity in frontotemporal lobar degeneration

Cited by 63 publications

References 51 publications

Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia

Graded, multidimensional intra- and intergroup variations in primary progressive aphasia and post-stroke aphasia

Locus coeruleus pathology in progressive supranuclear palsy, and its relation to disease severity

Apathy is Associated with Reduced Precision of Prior Beliefs about Action Outcomes

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