Poor reward sensitivity and apathy after stroke: implication of basal ganglia.

OBJECTIVE: To examine the relationship between reward sensitivity and self-reported apathy in stroke patients and to investigate the neuroanatomical correlates of both reward sensitivity and apathy. METHODS: In this prospective study, 55 chronic stroke patients were administered a questionnaire to assess apathy and a laboratory task to examine reward sensitivity by measuring motivationally driven behavior ("reinforcement-related speeding"). Fifteen participants without brain damage served as controls for the laboratory task. Negative mood, working memory, and global cognitive functioning were also measured to determine whether reward insensitivity and apathy were secondary to cognitive impairments or negative mood. Voxel-based lesion-symptom mapping was used to explore the neuroanatomical substrates of reward sensitivity and apathy. RESULTS: Participants showed reinforcement-related speeding in the highly reinforced condition of the laboratory task. However, this effect was significant for the controls only. For patients, poorer reward sensitivity was associated with greater self-reported apathy (p < 0.05) beyond negative mood and after lesion size was controlled for. Neither apathy nor reward sensitivity was related to working memory or global cognitive functioning. Voxel-based lesion-symptom mapping showed that damage to the ventral putamen and globus pallidus, dorsal thalamus, and left insula and prefrontal cortex was associated with poorer reward sensitivity. The putamen and thalamus were also involved in self-reported apathy. CONCLUSIONS: Poor reward sensitivity in stroke patients with damage to the ventral basal ganglia, dorsal thalamus, insula, or prefrontal cortex constitutes a core feature of apathy. These results provide valuable insight into the neural mechanisms and brain substrate underlying apathy.

Dopamine reverses reward insensitivity in apathy following globus pallidus lesions.

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.

L'apathie, un symptôme transnosographique: diagnostic différentiel et prise en charge [Apathy, a transnosographic symptom: diagnosis and treatment]

Apathy defined as a loss of motivation and interest for novelty is a frequent symptom encountered in a number of psychiatric and somatic disorders. The purpose of this article is to provide an overview of the many different medical contexts where apathy may occur and help clinicians to differentiate it from a depressive syndrome. The treatment of apathy requires a diagnostic clarification in order to treat the underlying condition. Then, pharmacological or non-pharmacological interventions may help to specifically improve apathy.

Positive Emotions Program for Schizophrenia (PEPS): a pilot intervention to reduce anhedonia and apathy.

BACKGROUND: Recent literature has distinguished the negative symptoms associated with a diminished capacity to experience (apathy, anhedonia) from symptoms associated with a limited capacity for expression (emotional blunting, alogia). The apathy-anhedonia syndrome tends to be associated with a poorer prognosis than the symptoms related to diminished expression. The efficacy of drug-based treatments and psychological interventions for these symptoms in schizophrenia remains limited. There is a clear clinical need for new treatments. METHODS: This pilot study tested the feasibility of a program to reduce anhedonia and apathy in schizophrenia and assessed its impact on 37 participants meeting the ICD-10 criteria for schizophrenia or schizoaffective disorders. Participants were pre- and post-tested using the Scale for the Assessment of Negative Symptoms (SANS) and the Calgary Depression Scale for Schizophrenia (CDSS). They took part in eight sessions of the Positive Emotions Program for Schizophrenia (PEPS)--an intervention that teaches participants skills to help overcome defeatist thinking and to increase the anticipation and maintenance of positive emotions. RESULTS: Thirty-one participants completed the program; those who dropped out did not differ from completers. Participation in the program was accompanied by statistically significant reductions in the total scores for Avolition-Apathy and Anhedonia-Asociality on the SANS, with moderate effect sizes. Furthermore, there was a statistically significant reduction of depression on the CDSS, with a large effect size. Emotional blunting and alogia remain stable during the intervention. DISCUSSION: Findings indicate that PEPS is both a feasible intervention and is associated with an apparently specific reduction of anhedonia and apathy. However, these findings are limited by the absence of control group and the fact that the rater was not blind to the treatment objectives. CONCLUSIONS: PEPS is a promising intervention to improve anhedonia and apathy which need to be tested further in a controlled study. TRIAL REGISTRATION NUMBER: ISRCTN registry ISRCTN74048461, registered 18 may 2015.

Assessment of depression, anxiety and apathy in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess Depression, Anxiety and Apathy in prHD and early HD individuals.

Validation of the brazilian version of the apathy inventory

Background Apathy is a frequent neuropsychiatric condition in neurodegenerative disorders, depression, and often in mild cognitive impairment. The Apathy Inventory (AI) is a reliable instrument for improving the accuracy of the apathy diagnosis. The aim was to establish the validity of the Apathy Inventory for the Brazilian community. Methods We established the concurrent validity, internal consistency, inter-rater reliability, and the sensitivity and specificity of AI for the Brazilian community in a cohort of 175 individuals with Alzheimer's disease, Parkinson's disease, depression, mild cognitive impairment, and healthy controls. The three dimensions of the AI (emotional blunting, lack of initiative, and lack of interest) were compared with the Apathy domain of the Neuropsychiatric Inventory-Clinician rating scale (NPI-C) in an independent scheme. Results The analyses demonstrated high correlation coefficients in AI's individual dimensions and in AI-total score (F = 0.965). Concerning the NPI-C/Apathy domain, intra-class correlation coefficients were also high (F = 0.977). Concurrent validity was high according to both raters on AI dimensions × NPI-C/Apathy domain and regarding total score (rater 1: rho = 0.956 vs. rater 2: rho = 0.970). The internal consistency of the AI was also high concerning the AI's individual dimensions and total score (rater 1: 0.945 vs. rater 2: 0.958). Conclusion We observed high internal consistency, high concurrent validity, and inter-rater reliability of the Apathy Inventory. In addition, we found that its sensitivity and specificity were high. We suggest that the Brazilian version of the Apathy Inventory would be an appropriate instrument to identify the apathy syndrome in Brazilian patients. © 2012 John Wiley & Sons, Ltd.

Neurobiological Correlates of Apathy in Alzheimer's Disease and Mild Cognitive Impairment: A Critical Review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Validation of a Spanish Version of the Lille Apathy Rating Scale for Parkinson’s Disease

Introduction. To date, no rating scales for detecting apathy in Parkinson’s disease (PD) patients have been validated in Spanish. For this reason, the aim of this study was to validate a Spanish version of Lille apathy rating scale (LARS) in a cohort of PD patients from Spain. Participants and Methods. 130 PD patients and 70 healthy controls were recruited to participate in the study. Apathy was measured using the Spanish version of LARS and the neuropsychiatric inventory (NPI). Reliability (internal consistency, test-retest, and interrater reliability) and validity (construct, content, and criterion validity) were measured. Results. Interrater reliability was 0.93. Cronbach’s α for LARS was 0.81. The test-retest correlation coefficient was 0.97. The correlation between LARS and NPI scores was 0.61. The optimal cutoff point under the ROC curve was , whereas the value derived from healthy controls was . The prevalence of apathy in our population tested by LARS was 42%. Conclusions. The Spanish version of LARS is a reliable and useful tool for diagnosing apathy in PD patients. Total LARS score is influenced by the presence of depression and cognitive impairment. However, both disorders are independent identities with respect to apathy. The satisfactory reliability and validity of the scale make it an appropriate instrument for screening and diagnosing apathy in clinical practice or for research purposes.

Between Apathy and Anger: Challenges to the Union from the 2014 Elections to the European Parliament. EPIN [Working] Paper No. 39, 20 May 2014

This EPIN study brings together contributions from a ​broad selection of member states ​and ​provid​es ​insightful analysis ​into the 2014 elections to the European Parliament on the ground. The report reveals the different factors that impede the development of genuine European elections and the consequences of the ballot in the member states covered by the study​, namely Bulgaria, Finland, France, Germany, Greece, Italy, the Netherlands, Poland, Romania, Spain and the UK​,​ and at EU level. The report finds that: • The EP Resolution to encourage European parties to nominate candidates for the next Commission President has not really increased public interest in the EU and voter turnout will probably remain low. • Visibility of the European top candidates in most member states has been quite limited. • National manifestos do not coincide – and sometimes event conflict with – the European parties’ manifestos. • Election debates focus on national issues; EU issues are only brought to public debate when they are relevant for domestic politics. • Again, we will see a protest vote against governments and large parties. The EP elections are still perceived as a test ahead of local and national elections, or as a vote of confidence in national governments. • This year the protest vote also concerns the EU. The report predicts a more eurosceptic ballot that might complicate decision-making in the EU, exacerbate the conflict between the national and European levels and increase tensions among member states.

From apathy to nationalist mobilisation: politics makes a comeback in Armenia. OSW COMMENTARY NUMBER 215 | 08.06.2016

In the military dimension, the Four-Day War in Nagorno-Karabakh (2–5 April 2016) changed little in the conflict zone. It has, however, had a significant impact on the situation in Armenia. The country was shocked out of the political malaise that had been the dominant mood in the last few years, and the Karabakh question, which used to animate political life in the late 1980s and early 1990s, once again became a driving force behind developments. In the internal dimension, the renewed fighting galvanised the political scene, triggered a rise in nationalist sentiments, mobilised the public and consolidated it around the Karabakh question, overshadowing the frustrations caused by the country’s difficult economic situation. In the external dimension, the war, which was viewed as Moscow-endorsed Azerbaijani aggression, undermined people’s trust in Russia and the Armenian-Russian alliance. It also made it clear for Armenians how uncertain the Russian security guarantees were and exacerbated their feelings of vulnerability and isolation on the international stage.

Isolation of Mycobacterium tuberculosis from Captive Ateles paniscus

An adult female red-faced black spider monkey (Ateles paniscus), housed for 2 years in the Parque Estoril Zoo in Sao Paulo, Brazil, showed apathy. Clinical examination revealed discrete emaciation, swelling and induration of lymph nodes, and presence of a mass in the abdominal cavity. Therapies with enrofloxacin, azithromycin, and ceftiofur were ineffective. The animal died after 6 months. Necropsy and histopathology confirmed granulommas in lymph nodes, parietal and visceral pleura, lungs, liver, spleen, and kidneys. Acid-fast bacilli were isolated and identified as Mycobacterium tuberculosis by polymerase chain reaction restriction analysis and Spoligotyping techniques. The zoo personnel and other animals that had had contact with the infected primate were negative to tuberculosis diagnostic procedures, such as sputum exam (baciloscopy) and thorax radiography. It was impossible to determine whether the infection occurred before or after the arrival of the animal to the Parque Estoril Zoo. This is the first report of M. tuberculosis infection in Ateles paniscus, a neotropical primate.

'We're not going to take it!' - Academics on the rampage

What are the social factors that can change apathy to action? Two survey-based field studies were conducted with National Tertiary Education Union members, to investigate the interplay between individual and group-based psychological processes in union support. The first study was conducted in an industrially calm context and the second, following a national strike in the Australian university sector. Drawing on social identity theory, the studies investigated both individual and group-related factors including: (a) instrumental and ideological attitudes; (b) employee identity; (c) perceptions of employment-related threat, and of relations with management; and (d) normative support for the union amongst fellow employees. Consistent with predictions, groupbased factors (i.e., perceived context and normative support) moderated the role of instrumental and ideological beliefs in the behavioural expression of union support. A subset of participants, who responded at both times, provided additional evidence for the importance of contextually activated group-processes to changes in union behaviour.

Ehrlichia canis in dogs attended in a veterinary hospital from Botucatu, Sao Paulo State, Brazil

This study investigated the etiology of canine ehrlichiosis and possible clinical and epidemiological data associated with the infection in 70 dogs suspect of ehrlichiosis attended at the Veterinary Hospital of the Sao Paulo State University in Botucatu city during 2001 and 2002. Dogs were evaluated by clinical-epidemiological and hematological data and molecular analysis by partial amplification and DNA sequencing of the ehrlichial dsb gene. E. canes DNA was amplified and sequenced in 28 (40.0%) dogs. Dogs younger than 12 months old showed significantly higher infection rates (65.0%; P < 0.05). Diarrhea, apathy, and anorexia were the major clinical signs observed in 55.2% (P = 0.05), 47.0% (P > 0.05), and 42.4% (P > 0.05) of the PCR-positive dogs, respectively. Twenty-five anemic (<5.5 x 10(6) RBC.mu L(-1)), and 8 leukopenic (<5.5 x 10(3) WBC.mu L(-1)) dogs were PCR-positive (P > 0.05). All 28 PCR-positive dogs showed thrombocytopenia (<175 x 10(3) platelets.mu L(-1)) and revealed statistical significance (P < 0.05). E. canis was the only Ehrlichia species found in dogs in the studied region, with higher infection rates in younger dogs, and statistically associated with thrombocytopenia.

Hepatogenous photosensitization associated with liver copper accumulation in buffalos

Four 1.5-year-old, male, Murrah buffalos were maintained during eight months without direct solar exposure during a study of copper toxicosis. Four days after solar exposure, all buffalos presented clinical manifestations consistent with acute photosensitization, including anorexia, apathy, loss of body weight, and generalized cutaneous lesions. Gross lesions were characterized by severe erythema, localized edema, fissures, tissue necrosis, gangrene and crust formation with h serous exudation. Liver copper concentration was evaluated, and cutaneous biopsies were taken when clinical signs were evident. The liver copper concentration before solar exposure was increased in all animals. Histopathologic examination of the skin revealed hepatogenous photosensitization characterized by parakeratotic hyperkeratosis, acantholysis, degeneration of squamous epithelial cells, epidermal necrosis with atrophy of sweat glands, and multifocal superficial and deep dermal edema. These findings suggest that asymptomatic accumulation of copper within the liver might have induced hepatic insufficiency thereby resulting in secondary photosensitization when these buffalos were exposed to sunlight. (C) 2009 Elsevier Ltd. All rights reserved.

Accumulative copper poisoning in buffaloes

The main objective of this study was to evaluate the clinical and hematological alterations, and the hepatic concentration of Cu in buffaloes with chronic copper poisoning (CCP). Ten buffalo yearling steers were randomly distributed into two groups: one copper supplemented (BUFCu; n = 6) and another control group (BUF; n = 4). The group BUFCu received, by ruminal fistula, 2 mg Cu/kgBW (as CuSO4.5H2O) daily during one week; after which 2 mg Cu/kgBW was added during each additional week, until the end or the experiment (105(th) day). Three liver biopsies were realized during the experiment (day zero, 45(th), and 105(th) day) to determine the degree of copper accumulation. Alterations in body weight, clinical examination, and hematological values were monitored every 15 days. Two buffaloes supplemented with copper demonstrated clinical manifestations consistent with CCP, and died. Two distinct clinical manifestations were observed, one classical (n = 1) and another atypical (n = 1), characterized by remarkable high levels of liver copper, progressive hyporexia followed by anorexia, dehydration, severe apathy, decreased rumen movements, oliguria, and death. Some animals were resistant to CCP although high copper intake. In buffalos with clinical picture similar to the one described as atypical, CCP should be considered as a possible diagnostic even without presence of macroscopic hemoglobinuria.