Domenico Errico

Apathy in Parkinson's disease: diagnosis, neuropsychological correlates, pathophysiology and treatment.

Apathy has been defined as lack of motivation. It has been traditionally considered as a symptom of psychiatric disorders, such as major depression and schizophrenia, but more recently it has been recognized as a specific neuropsychiatric syndrome associated with neurodegenerative such as Parkinson’s disease (PD). As a consequence the reported prevalence of apathy in PD ranges from 13.9% to 70%; the mean prevalence is 35%. Prevalence of “pure apathy” (i.e., of apathy without comorbid depression and dementia) seems to be substantially lower, from 3 to 47.9%. High levels of apathy in PD are associated with decreased daily function, specific cognitive deficits and increased stress for families. Although neuroimaging studies do not provide a unique anatomic pattern, several data suggest that the ventromedial prefrontal cortex and the basal ganglia connected through frontal-subcortical circuits, are particularly involved in the genesis of apathy. At present, there are no approved medications for the treatment of apathy in and no proof of efficacy exists for any drug in current use. Further studies and innovative pharmacologic approaches are thus needed to ameliorate our understanding and treatment of apathy in PD.

Transcranial Electrical Stimulation over Dorsolateral Prefrontal Cortex Modulates Processing of Social Cognitive and Affective Information.

Recent neurofunctional studies suggested that lateral prefrontal cortex is a domain-general cognitive control area modulating computation of social information. Neuropsychological evidence reported dissociations between cognitive and affective components of social cognition. Here, we tested whether performance on social cognitive and affective tasks can be modulated by transcranial direct current stimulation (tDCS) over dorsolateral prefrontal cortex (DLPFC). To this aim, we compared the effects of tDCS on explicit recognition of emotional facial expressions (affective task), and on one cognitive task assessing the ability to adopt another person’s visual perspective. In a randomized, cross-over design, male and female healthy participants performed the two experimental tasks after bi-hemispheric tDCS (sham, left anodal/right cathodal, and right anodal/left cathodal) applied over DLPFC. Results showed that only in male participants explicit recognition of fearful facial expressions was significantly faster after anodal right/cathodal left stimulation with respect to anodal left/cathodal right and sham stimulations. In the visual perspective taking task, instead, anodal right/cathodal left stimulation negatively affected both male and female participants’ tendency to adopt another’s point of view. These findings demonstrated that concurrent facilitation of right and inhibition of left lateral prefrontal cortex can speed-up males’ responses to threatening faces whereas it interferes with the ability to adopt another’s viewpoint independently from gender. Thus, stimulation of cognitive control areas can lead to different effects on social cognitive skills depending on the affective vs. cognitive nature of the task, and on the gender-related differences in neural organization of emotion processing.

Observing functional actions affects semantic processing of tools: evidence of a motor-to-semantic priming.

Recent evidence shows that activation of motor information can favor identification of related tools, thus suggesting a strict link between motor and conceptual knowledge in cognitive representation of tools. However, the involvement of motor information in further semantic processing has not been elucidated. In three experiments, we aimed to ascertain whether motor information provided by observation of actions could affect processing of conceptual knowledge about tools. In Experiment 1, healthy participants judged whether pairs of tools evoking different functional handgrips had the same function. In Experiment 2 participants judged whether tools were paired with appropriate recipients. Finally, in Experiment 3 we again required functional judgments as in Experiment 1, but also included in the set of stimuli pairs of objects having different function and similar functional handgrips. In all experiments, pictures displaying either functional grasping (aimed to use tools) or structural grasping (just aimed to move tools independently from their use) were presented before each stimulus pair. The results demonstrated that, in comparison with structural grasping, observing functional grasping facilitates judgments about tools’ function when objects did not imply the same functional manipulation (Experiment 1), whereas worsened such judgments when objects shared functional grasp (Experiment 3). Instead, action observation did not affect judgments concerning tool–recipient associations (Experiment 2). Our findings support a task-dependent influence of motor information on high-order conceptual tasks and provide further insights into how motor and conceptual processing about tools can interact.

Subthreshold depression and subjective cognitive complaints in Parkinson's disease

Subthreshold depression (SubD) is characterized by clinically relevant depressive symptoms not meeting criteria for major depression. The possible association of SubD with subjective cognitive complaints and/or objective cognitive impairments was investigated in a sample of consecutive, non‐demented Parkinsons disease (PD) outpatients.

Cognitive and affective theory of mind in patients with essential tremor

The theory of mind (ToM) is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one’s own. The aim of the present study was to explore the neuropsychological correlates of cognitive and affective ToM in patients affected by essential tremor (ET). Thirty consecutive ET outpatients and 30 healthy age-, sex- and education-matched control subjects underwent tasks assessing short-term memory, verbal learning and executive functions, as well as tasks assessing “cognitive” and “affective” ToM; questionnaires evaluating behavioral disorders and quality of life were also administered. Although the two groups did not differ on demographic variables, ET patients scored worse on memory tasks, and showed more apathy and worse quality of life than controls. After covarying for mnestic, behavioral and quality of life scores, ET patients achieved significantly lower scores than controls on task assessing cognitive ToM, whereas no difference was found between the two groups on task assessing affective ToM. In ET, “Cognitive” ToM was significantly associated with frontal tasks, whereas “Affective” ToM was not correlated with cognitive, behavioral or quality of life scales. Our results indicate that cognitive aspects of ToM may be selectively impaired in ET. Possible underlying neural mechanisms of the deficits are discussed.

Body Constraints on Motor Simulation in Autism Spectrum Disorders

Developmental data suggested that mental simulation skills become progressively dissociated from overt motor activity across development. Thus, efficient simulation is rather independent from current sensorimotor information. Here, we tested the impact of bodily (sensorimotor) information on simulation skills of adolescents with Autism Spectrum Disorders (ASD). Typically-developing (TD) and ASD participants judged laterality of hand images while keeping one arm flexed on chest or while holding both arms extended. Both groups were able to mentally simulate actions, but this ability was constrained by body posture more in ASD than in TD adolescents. The strong impact of actual body information on motor simulation implies that simulative skills are not fully effective in ASD individuals.

Impact of body posture on laterality judgement and explicit recognition tasks performed on self and others’ hands

Judgments on laterality of hand stimuli are faster and more accurate when dealing with one’s own than others’ hand, i.e. the self-advantage. This advantage seems to be related to activation of a sensorimotor mechanism while implicitly processing one’s own hands, but not during explicit one’s own hand recognition. Here, we specifically tested the influence of proprioceptive information on the self-hand advantage by manipulating participants’ body posture during self and others’ hand processing. In Experiment 1, right-handed healthy participants judged laterality of either self or others’ hands, whereas in Experiment 2, an explicit recognition of one’s own hands was required. In both experiments, the participants performed the task while holding their left or right arm flexed with their hand in direct contact with their chest (“flexed self-touch posture”) or with their hand placed on a wooden smooth surface in correspondence with their chest (“flexed proprioceptive-only posture”). In an “extended control posture”, both arms were extended and in contact with thighs. In Experiment 1 (hand laterality judgment), we confirmed the self-advantage and demonstrated that it was enhanced when the subjects judged left-hand stimuli at 270° orientation while keeping their left arm in the flexed proprioceptive-only posture. In Experiment 2 (explicit self-hand recognition), instead, we found an advantage for others’ hand (“self-disadvantage”) independently from posture manipulation. Thus, position-related proprioceptive information from left non-dominant arm can enhance sensorimotor one’s own body representation selectively favouring implicit self-hands processing.

Compulsive Drumming Induced by Dopamine Agonists in Parkinson’s Disease: Another Aspect of Punding

We report the case of a man affected by Parkinson’s disease who developed an unusual, severe, repetitive behavior characterized by an irrepressible need to drum and beat percussion instruments following to the introduction of pramipexole. This compulsive behavior was not associated to a pattern of chronic inappropriate overuse of dopaminergic medication or other psychiatric symptoms. Sharing many features with other repetitive behaviors, compulsive drumming might be considered a distinct manifestation of punding in Parkinson’s disease.

Whose hand is this? Differential responses of right and left extrastriate body areas to visual images of self and others’ hands

The extrastriate body area (EBA) is involved in perception of human bodies and nonfacial body parts, but its role in representing body identity is not clear. Here, we used on-line high-frequency repetitive transcranial magnetic stimulation (rTMS) to test the role of EBA in self–other distinction. In Experiments 1 and 2 we compared rTMS of right EBA with stimulation of left ventral premotor cortex (vPM), whereas in Experiment 3 we compared stimulation of right and left EBA. RTMS was applied during a hand laterality task in which self or others’ hand images were presented in first- versus third-person view (Experiments 1 and 3), or while participants had to explicitly recognize their own hands (Experiment 2) presented in first- versus third-person view. Experiment 1 showed that right EBA stimulation selectively speeded judgments on others’ hands, whereas no effect of left vPM stimulation was found. Experiment 2 did not reveal any effect of rTMS. Experiment 3 confirmed faster responses on others’ hands while stimulating right EBA and also showed an advantage when judging self with respect to others’ hands during stimulation of left EBA. These results would demonstrate that EBA responds to morphological features of human body contributing to identity processing.

Affective theory of mind in patients with Parkinson's disease: comment.

WE HAVE READ with interest the study in which Poletti et al. investigated the affective component of theory of mind (ToM) in patients at early or moderate/advanced stages of Parkinson’s disease (PD), and in a group of healthy subjects (HC). Poletti et al. found impaired affective ToM in PD patients in comparison to HC, while no significant difference between early and moderate patients was found after covarying for all variables significantly different in the PD groups (age, motor disability, general cognitive abilities). Previous studies have produced contrasting findings on impairment of the affective ToM in early PD. Two studies did not report significant differences between PD and HC, whereas Tsuruya et al. found impaired affective ToM. In line with the latter findings, we recently reported dysfunction of both the affective and the cognitive ToM in early PD patients; moreover, altered affective ToM was significantly associated with apathy, a behavioral disturbance associated with dysfunction of non-motor fronto-subcortical circuits in PD. These observations would suggest that a dysfunction of orbitofrontal–limbic circuits may contribute to an impairment of the affective ToM in early PD. There are several methodological differences between the Poletti et al. study and ours: Poletti et al. assessed affective ToM using a non-verbal task mainly based on visual emotion recognition (Reading the Mind in the Eyes Task), whereas we used two verbal tasks (the Emotion Attribution Task, and the Advanced Test of ToM) more specifically tapping the ability to attribute emotions or intentions to others. Moreover, we closely matched early PD patients and HC for demographic and cognitive variables, so that we could directly compare these two groups without relying on the same problematic statistical procedure that Poletti et al. had to adopt. In conclusion, the Poletti et al. results confirmed the impairment of affective ToM in PD, but it is important to note that sensitive tasks may identify such a defect in the early stage of the disease.