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Background: Apathy is a common and early symptom in Alzheimer's disease (AD) and is linked to poorer prognosis. Theoretical interpretations of apathy implicate alterations of connections amongst fronto-striatal and limbic regions., Objective: To test the association between presence of apathy and patterns of brain functional connectivity in patients with clinically-established AD., Methods: Seventy AD patients were included. Thirty-five patients experienced apathy as defined by the screening question of the Neuropsychiatric Inventory, and thirty-five did not. All patients agreed to undergo an MRI protocol inclusive of resting-state acquisitions. The hemodynamic-dependent signal was extracted bilaterally from five regions of interest: ventromedial prefrontal cortices, anterior cingulate cortices, dorsolateral prefrontal cortices, insulae and amygdalae. t tests were run to compare connectivity maps of apathetic and non-apathetic patients. Age, education, Mini Mental State Examination score, gray matter volumes and gray matter fractions served as covariates., Results: At a p FWE < .05 threshold, apathetic patients had reduced connectivity between the left insula and right superior parietal cortex. Apathetic patients had also increased connectivity between the right dorsolateral prefrontal seed and the right superior parietal cortex. Patients with apathy were significantly more likely to experience other psychiatric symptoms., Conclusion: Our findings support a role of frontal and insular connections in coordinating value-based decisions in AD. Both down-regulation and maladaptive up-regulation mechanisms appear to be at play in these regions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Apathy is the most prevalent and disabling non-cognitive symptom of dementia and affects 90% of patients across the disease course. Despite its pervasiveness, how apathy manifests across dementia syndromes and the neurobiological mechanisms driving these symptoms are poorly understood. Here, we applied the multidimensional ABC model of apathy, which recognizes Affective, Behavioural and Cognitive apathy, in Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD)., Methods: One hundred and twenty-two patients (53 AD; 69 bvFTD) were included. Informants completed the Neuropsychiatric Inventory (NPI), Cambridge Behavioral Inventory and Disability and Dementia scale to quantify Affective, Behavioural and Cognitive apathy. All patients underwent structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) was employed to identify brain regions correlated with increased Affective, Behavioural and Cognitive apathy., Results: On the NPI, 60% of AD and 84% of bvFTD patients had some degree of apathy, but bvFTD had more severe and more frequent symptoms than AD. Importantly, bvFTD patients had higher affective and cognitive apathy whereas AD had higher cognitive apathy only. Neuroimaging analyses revealed that affective apathy was associated with the ventral prefrontal cortex; behavioural apathy with the basal ganglia; and cognitive apathy with the dorsomedial prefrontal cortex. Finally, affective and behavioural apathy significantly predicted carer burden., Conclusions: Our results support the notion that apathy is multidimensional and manifests differently across dementia syndromes. Thus, novel interventions which target these divergent mechanisms will be necessary to improve motivation and goal-directed behaviour in people with dementia., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Apathy and cognitive dysfunction are prominent symptoms of Amyotrophic lateral sclerosis (ALS). More specifically ALS patients show increased Initiation apathy-a lack of motivation for self-generation of thoughts as assessed by the Dimensional Apathy Scale. This study aimed to investigate the cognitive underpinnings of apathy subtypes in ALS. We hypothesized that increased Initiation apathy would be associated deficits on tests of intrinsic response generation, such as verbal fluency. We also explored the relationship of other apathy subtypes to cognitive processes, in particular emotional apathy with emotional and social cognition deficits and executive apathy with planning and goal management deficits. ALS patients, and their carers (N = 30), and healthy matched controls, and their informants (N = 29) were recruited. All participants completed self- and informant/carer-rated Dimensional Apathy Scale, to quantify apathy subtypes (Executive, Emotional and Initiation), along with standard apathy and depression measures. Patients and controls completed the Edinburgh Cognitive and behavioural ALS Screen, and a comprehensive neuropsychological battery including emotional recognition, social cognition, intrinsic response generation tasks (verbal fluency and random number generation) and a new ecologically valid, computerised measure of planning and goal management. The results demonstrated that increased Initiation apathy was the only significantly elevated subtype in ALS (self-rated p < .05, informant/carer-rated p < .01). Initiation apathy was found to be significantly associated with verbal fluency deficit, while Emotional apathy was significantly associated with emotional recognition deficits. No associations were found between apathy subtypes and depression or in controls. This is the first study to show specific associations between apathy subtypes (Emotional and Initiation) and executive and emotional cognitive dysfunction, indicating possible distinct underlying mechanisms to these demotivational symptoms., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Anosognosia is present in a large proportion of patients with mild Alzheimer's disease (AD), and its frequency increases with the progression of the illness. Several instruments have been validated to assess anosognosia in AD, but there is no consensus regarding the best diagnostic strategy. Anosognosia in AD is a significant predictor of apathy and is significantly related to lower depression and anxiety scores, more severe caregiver burden and dangerous behaviours. Studies using different imaging modalities have demonstrated an association between anosognosia and dysfunction in frontal, temporomedial and temporoparietal regions. The mechanism of anosognosia remains unknown, but it has been explained as a consequence of deficits of encoding and updating biographical memory, and dysfunction of comparator, executive and metacognitive systems., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Schizophrenia is a chronic and severe mental illness that affects over 1% of the population, characterized by multiple symptom dimensions. One of this class of symptoms, "negative symptoms", have received more attention over the last few years. Negative symptoms, including among others blunted affect, withdrawal or apathy, are particularly important for recovery and are associated with negative functional outcomes, such as inability to get an employment and conduct normal daily living activities. While positive symptoms are usually treated by antipsychotic drugs, negative symptoms are usually persistent, which indicates the need for better treatment. The aim of this article is to highlight recent scientific progress on apathy and to explore current multidimensional approaches of this concept in schizophrenia. Apathy is a symptom frequently encountered in schizophrenia and in many neurological disorders. Therefore, it can be regarded as a transnosographic symptom., Literature Findings: A long time considered as a loss of motivation (psychological concept hard to define), recent descriptive and etiological models have proposed to consider apathy as a multidimensional phenomenon. Marin et al., have proposed a model of apathy in reference to the motivation concept. Marin et al.'s apathy model is composed of three dimensions: firstly, cognitive dimension, secondly, sensory-motor dimension and thirdly, affective dimension. These authors propose to differentiate "apathy syndrome" from "apathy symptom". "Apathy syndrome" resulting from a lack of motivation whereas "apathy symptom" results from cognitive and/or emotional/affective disorders. In addition, Marin et al. propose that apathy syndrome corresponds to the "lack of motivation" not attributable to diminished level of consciousness, cognitive impairment or emotional distress. Following this proposal, Levy and Dubois propose to define apathy as a quantitative reduction of self-generated, voluntary and purposeful behaviors. It is therefore observable and can be quantified. Levy and Dubois have proposed an apathy model considering: firstly, apathy as a syndrome related to reduction in goal-directed behaviors; secondly, anatomically, apathy can be secondary to dysfunctions or lesions of the prefrontal cortex. Since the prefrontal cortex is functionally and anatomically heterogeneous, subtypes of apathy occur in diseases affecting the basal ganglia, because these diseases disrupt associative and limbic pathways from/to the prefrontal cortex; thirdly, from a pathophysiological point of view, apathy may be explained by the impact of lesions or dysfunctions of the basal ganglia, because these lesions or dysfunctions lead to a loss of temporal and spatial focalization, both of which result in a diminished extraction of the relevant signal within the frontal cortex, thereby inhibiting the capacity of the frontal cortex to select, initiate, maintain and shift programs of action., (Copyright © 2012 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Apathy is a complex, behavioural disorder associated with reduced spontaneous initiation of actions. Although present in mild forms in some healthy people, it is a pathological state in conditions such as Alzheimer's and Parkinson's disease where it can have profoundly devastating effects. Understanding the mechanisms underlying apathy is therefore of urgent concern but this has proven difficult because widespread brain changes in neurodegenerative diseases make interpretation difficult and there is no good animal model. Here we present a very rare case with profound apathy following bilateral, focal lesions of the basal ganglia, with globus pallidus regions that connect with orbitofrontal (OFC) and ventromedial prefrontal cortex (VMPFC) particularly affected. Using two measures of oculomotor decision-making we show that apathy in this individual was associated with reward insensitivity. However, reward sensitivity could be established partially with levodopa and more effectively with a dopamine receptor agonist. Concomitantly, there was an improvement in the patient's clinical state, with reduced apathy, greater motivation and increased social interactions. These findings provide a model system to study a key neuropsychiatric disorder. They demonstrate that reward insensitivity associated with basal ganglia dysfunction might be an important component of apathy that can be reversed by dopaminergic modulation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We propose to defined apathy as a quantitative reduction of goal-directed behaviour. As such, the neural bases of apathy rely on lesions or dysfunctions of the brain structures that generate and control goal-directed behaviour: the frontal lobes, the basal ganglia and the frontal-basal ganglia circuits. Lesions or dysfunctions of the limbic territories of the frontal lobes (the orbital-mesial prefrontal cortex) and the basal ganglia (e.g., the ventral striatum) lead to apathy through difficulties to provide the affective value of a given behavioural context. We also suggest that lesions or dysfunctions of the associative ("cognitive") territories of the frontal lobes (the dorsal prefrontal cortex) and the basal ganglia (e.g., the dorsal caudate) contribute to apathy via a "cognitive inertia" - an inability to generate or activate strategies required to successfully complete a given program of actions. The most severe forms of apathy ("auto-activation deficit" syndrome), due to bilateral lesions in the prefrontal-basal ganglia circuits can be explained either by the addition of lesions in the cognitive and limbic territories or by a more general and elementary impairment that mirrored the presumed normal functions of the prefrontal-basal ganglia circuits, that is to selectively amplified the behaviour that one considers as the most adapted to one's personal needs or environmental demands. These lesions may limit the selective amplification of the signal that represents relevant thoughts and actions, leading to difficulties to disambiguate decision-making at the level of the prefrontal cortex., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Apathy was defined by Marin as diminished motivation not attributable to diminished level of consciousness, cognitive impairment, or emotional distress. Up to 42% of Parkinson's disease patients could be concerned. It has a pejorative impact on quality of life and could be predictive of cognitive decline. It has been shown that deep brain stimulation in Parkinson's disease may induce apathy. It seems directly related to the stimulation target, i.e. the subthalamic nucleus, since such an effect has not been observed so far in thalamic and pallidal stimulation. It should certainly not make us question the remarkable effectiveness of subthalamic stimulation in Parkinson's disease patients, but encourages us to be very careful about operability criteria. We must, in this sense, improve identification of at risk patients, seeking a thoroughly diminished motivation, loss of interest or blunting affects., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Apathy is widely recognized as a lack of motivation, which expresses through the cognitive, behavioral and emotional dimensions of living. It is described within several neuropsychiatric syndromes such as degenerative disorder and is associated with poorer outcomes. In order to better understand the underpinnings of apathy and to develop specific treatment strategies, much research has been conducted to define its neural bases. In the present review, perfusion, metabolic, pathologic and functional results of apathy neural bases in Alzheimer's and Parkinson's diseases are displayed. Methods and strategies to control for confounding factors such as depression, cognitive impairments and other behavioral disorders are described. Results are not strictly identical between disorders and even within disorders. Variation of methods employed on assessment tools and control for confounding factors such as cognitive disorders, depression, other behavioral disorders and medical treatment is thought to be the main reason for this discrepancy. However, it seems that the inferior prefrontal cortex, especially the orbitofrontal cortex, the lateral prefrontal cortex and the anterior cingulate are of particular interest. The second part of the review discusses the literature in these three areas in conditional learning essentially via the reward characteristic encoding, auto-initiated and perseverance behaviors and emotional experience and its regulation., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Apathy is a loss of motivation compared to the previous level of functioning of the subject. It affects the subject's behavior, cognition and emotional state. It is one of the main behavioral manifestations of Parkinson's disease. Although it may be a symptom of depression, it often exists as an isolated syndrome in Parkinson's disease patients. Apathy is usually not related to the severity of the motor symptoms, but frequently associated with the severity of cognitive impairment. Apathy is also a possible complication of treatment by stimulation of the subthalamic nucleus. Screening and assessment of apathy require the use of specific tools, some of which are validated in Parkinson's disease. From a pathophysiological point of view, apathy results from a dysfunction of the limbic circuit connecting the ventral striatum to orbitofrontal and anterior cingulate cortex. The dopaminergic denervation in these regions seems to play a key role, but other mechanisms are probably involved. Further studies are warranted to progress in the therapeutic management of this invalidating syndrome., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)