Mesial temporal dopamine: From biology to behaviour.

While colloquially recognized for its role in pleasure, reward, and affect, dopamine is also necessary for proficient action control. Many motor studies focus on dopaminergic transmission along the nigrostriatal pathway, using Parkinson's disease as a model of a dorsal striatal lesion. Less attention to the mesolimbic pathway and its role in motor control has led to an important question related to the limbic-motor network. Indeed, secondary targets of the mesolimbic pathway include the hippocampus and amygdala, and these are linked to the motor cortex through the substantia nigra and thalamus. The modulatory impact of dopamine in the hippocampus and amygdala in humans is a focus of current investigations. This review explores dopaminergic activity in the mesial temporal lobe by summarizing dopaminergic networks and transmission in these regions and examining their role in behaviour and disease.

The Role of a Dopamine-Dependent Limbic-Motor Network in Sensory Motor Processing in Parkinson Disease.

Limbic and motor integration is enabled by a mesial temporal to motor cortex network. Parkinson disease (PD) is characterized by a loss of dorsal striatal dopamine but relative preservation of mesolimbic dopamine early in disease, along with changes to motor action control. Here, we studied 47 patients with PD using the Simon conflict task and [18F]fallypride PET imaging. Additionally, a cohort of 16 patients participated in a single-blinded dextroamphetamine (dAMPH) study. Task performance was evaluated using the diffusion model for conflict tasks, which allows for an assessment of interpretable action control processes. First, a voxel-wise examination disclosed a negative relationship, such that longer non-decision time is associated with reduced D2-like binding potential (BPND) in the bilateral putamen, left globus pallidus, and right insula. Second, an ROI analysis revealed a positive relationship, such that shorter non-decision time is associated with reduced D2-like BPND in the amygdala and ventromedial OFC. The difference in non-decision time between off-dAMPH and on-dAMPH trials was positively associated with D2-like BPND in the globus pallidus. These findings support the idea that dysfunction of the traditional striatal-motor loop underlies action control deficits but also suggest that a compensatory parallel limbic-motor loop regulates motor output.

Racial Differences in the Presentation and Progression of Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that predominantly impacts a Caucasian population, but few efforts have explored racial differences in presentation and progression. OBJECTIVE: The aim was to assess the presentation and progression of HD across race groups using the Enroll-HD longitudinal observational study. METHODS: We applied propensity score matching for cytosine-adenine-guanine age product score, and age, to identify White, Hispanic, Asian, and Black participants from the Enroll-HD database. We compared clinical presentations at baseline, and progression over time, using White participants as a control cohort. RESULTS: Black participants were more severe at baseline across all clinical measures. No significant differences in progression were observed between race groups. CONCLUSIONS: We consider the factors driving clinical differences at baseline for Black participants. Our data emphasize the necessary improvement in underrepresented minority recruitment for studies of rare diseases. © 2023 International Parkinson and Movement Disorder Society.

D2-Like Receptor Expression in the Hippocampus and Amygdala Informs Performance on the Stop-Signal Task in Parkinson's Disease.

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D2 receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-blinded d-amphetamine (dAMPH) study. Participants completed [18F]fallypride positron emission topography (PET) imaging in both placebo and dAMPH conditions. A voxel-wise analysis of the relationship between binding potential (BPND) and stop-signal reaction time (SSRT) revealed that faster SSRT is associated with greater D2-like BPND in the amygdala and hippocampus (right cluster qFDR-corr = 0.026, left cluster qFDR-corr = 0.002). A region of interest (ROI) examination confirmed this association in both the amygdala (coefficient = -48.26, p = 0.005) and hippocampus (coefficient = -104.94, p = 0.007). As healthy dopaminergic systems in the dorsal striatum appear to regulate response inhibition, we interpret our findings in PD to indicate either nigrostriatal damage unmasking a mesolimbic contribution to response inhibition, or a compensatory adaptation from the limbic and mesial temporal dopamine systems. These novel results expand the conceptualization of action-control networks, whereby limbic and motor loops may be functionally connected.SIGNIFICANCE STATEMENT While Parkinson's disease (PD) is characteristically recognized for its motor symptoms, some patients develop impulsive and compulsive behaviors (ICBs), manifested as repetitive and excessive participation in reward-driven activities, including sex, gambling, shopping, eating, and hobbyism. Such cognitive alterations compel a consideration of response inhibition in PD. To investigate inhibitory control and assess the brain regions that may participate, we assessed PD patients using a single-blinded d-amphetamine (dAMPH) study, with [18F]fallypride positron emission topography (PET) imaging, and stop-signal task performance. We find a negative relationship between D2-like binding in the mesial temporal region and top-signal reaction time (SSRT), with greater BPND associated with a faster SSRT. These discoveries indicate a novel role for mesolimbic dopamine in response inhibition, and advocate for limbic regulation of action control in this clinical population.

Emotion matters: The influence of valence on episodic future thinking in young and older adults.

In young adults, valence not only alters the degree to which future events are imagined in rich episodic detail, but also how memorable these events are later on. For older adults, how valence influences episodic detail generation while imagining future events, or recalling these details at another time, remains unclear. We investigated the effect of valence on the specificity and memorability of episodic future thinking (EFT) in young and older adults. Among young and older adults, negative EFT was accompanied by less episodic detail generation relative to positive and neutral EFT. A similar reduction in episodic specificity for negative EFT was found two days later when participants recalled their previously imagined events. Notably, while older adults generated less episodically specific future thoughts relative to young adults, age did not influence the effect of valence on episodic detail generation at imagination or recollection.