Neural Correlates for Apathy: Frontal-Prefrontal and Parietal Cortical- Subcortical Circuits

Abstract

Apathy is an uncertain nosographical entity, which includes reduced motivation, abulia, decreased empathy, and lack of emotional involvement; it is an important and heavy-burden clinical condition which strongly impacts in everyday life events, affects the common daily living abilities, reduced the inner goal directed behavior, and gives the heaviest burden on caregivers. Is a quite common comorbidity of many neurological disease, However, there is no definite consensus on the role of apathy in clinical practice, no definite data on anatomical circuits involved in its development, and no definite instrument to detect it at bedside. As a general observation, the occurrence of apathy is connected to damage of prefrontal cortex (PFC) and basal ganglia; “emotional affective” apathy may be related to the orbitomedial PFC and ventral striatum; “cognitive apathy” may be associated with dysfunction of lateral PFC and dorsal caudate nuclei; deficit of “autoactivation” may be due to bilateral lesions of the internal portion of globus pallidus, bilateral paramedian thalamic lesions, or the dorsomedial portion of PFC. On the other hand, apathy severity has been connected to neurofibrillary tangles density in the anterior cingulate gyrus and to gray matter atrophy in the anterior cingulate (ACC) and in the left medial frontal cortex, confirmed by functional imaging studies. These neural networks are linked to projects, judjing and planning, execution and selection common actions, and through the basolateral amygdala and nucleus accumbens projects to the frontostriatal and to the dorsolateral prefrontal cortex. Therefore, an alteration of these circuitry caused a lack of insight, a reduction of decision-making strategies, and a reduced speedness in action decision, major responsible for apathy. Emergent role concerns also the parietal cortex, with its direct action motivation control. We will discuss the importance of these circuits in different pathologies, degenerative or vascular, acute or chronic.

Rivastigmine as a Symptomatic Treatment for Apathy in Parkinson’s Dementia Complex: New Aspects for This Riddle

“…Functional connectivity within the striatum and between striatal and ventrolateral prefrontal regions has been demonstrated in support of those studies, in patients with PD with high apathy compared to low [31], but results are not univocal, as they have been rejected by other studies [32, 33]. In general, many others are the brain networks related to apathy in PD, extending from the nigrostriatal up to frontal, cingulate, and limbic areas, precuneus, parietal inferior lobule, and so on (see data and literature in [22, 34]). If functional localization of networks underlying apathy is uncertain, even more complex is the neurochemical and pharmacological face.…”

“…However, among all the NPS, one of the most intriguing (for the complicate pathophysiological mechanism underlying it) [22] and one of the most disturbing (for caregivers and for patients) is apathy. The presence of apathy has been associated with greater cognitive impairment [[23–27]; see data in [22]], and its prevalence in PDD varies between 16.5% and 51%, depending upon the instrument for assessment and on the samples examined [28–30].…”

“…The presence of apathy has been associated with greater cognitive impairment [[23–27]; see data in [22]], and its prevalence in PDD varies between 16.5% and 51%, depending upon the instrument for assessment and on the samples examined [28–30]. It has been hypothesized that dysfunction of the nigrostriatal pathway might be involved in the pathophysiology of apathy in PD, [29], confirmed by functional connectivity study which documented a conspicuous impairment of striatal and ventrolateral prefrontal regions connections [31].…”

“…To be precise, the extension of brain networks involved in apathy in PDD is enormous, and many other neuroimaging and functional studies indicate different brain areas involvement, not only nigrostriatal pathways [data and literature in [22]] documented it. Reijnders et al [25] found an association between higher apathy and lower gray matter density in the bilateral inferior frontal gyrus and precentral gyrus, in the bilateral inferior parietal gyrus, and right precuneus, confirmed by Skidmore et al [35], who showed that the severity of apathy was best predicted by a greater sufferance of the right middle orbitofrontal cortex and bilateral subgenual cingulate cortex, of the left supplementary motor cortex, and of the left inferior parietal lobule and left fusiform gyrus [35].…”

Apathy in corticobasal degeneration: possible parietal involvement

“…Apathy is an intriguing symptom in PD, too, and one of the most studied in recent years (Moretti and Signori, 2016); it has been considered one of its most disturbing psychiatric symptoms (Starkstein and Leentjens, 2008). Some studies have related PD apathy to dysfunction of the nigro-striatal pathway (Starkstein et al, 1992;Cutberth and Insel, 2013;Stuss et al, 2000), a suggestion supported by functional connectivity studies (Rejinders et al, 2010;Robert et al, 2012) and evidence of a marked impairment of connectivity in striatal and ventrolateral prefrontal regions (Baggio et al, 2015), although data remain controversial (Huang et al, 2013;Skidmore et al, 2013;Kos et al, 2016;Moretti and Signori, 2016). In the present paper, we examine our findings and discuss the emerging role of parietal-frontal loops as one of the most recently discovered neural correlates underlying apathy in motor-dominant pathologies.…”