Activity in mouse pedunculopontine tegmental nucleus reflects action and outcome in a decision-making task

Recent studies across several mammalian species have revealed a distributed network of cortical and subcortical brain regions responsible for sensorimotor decision making. Many of these regions have been shown to be interconnected with the pedunculopontine tegmental nucleus (PPTg), a brain stem structure characterized by neuronal heterogeneity and thought to be involved in several cognitive and behavioral functions. However, whether this structure plays a general functional role in sensorimotor decision making is unclear. We hypothesized that, in the context of a sensorimotor task, activity in the PPTg would reflect task-related variables in a similar manner as do the cortical and subcortical regions with which it is anatomically associated. To examine this hypothesis, we recorded PPTg activity in mice performing an odor-cued spatial choice task requiring a stereotyped leftward or rightward orienting movement to obtain a reward. We studied single-neuron activity during epochs of the task related to movement preparation, execution, and outcome (i.e., whether or not the movement was rewarded). We found that a substantial proportion of neurons in the PPTg exhibited direction-selective activity during one or more of these epochs. In addition, an overlapping population of neurons reflected movement direction and reward outcome. These results suggest that the PPTg should be considered within the network of brain areas responsible for sensorimotor decision making and lay the foundation for future experiments to examine how the PPTg interacts with other regions to control sensory-guided motor output.

Download Full-text

Moral Reasoning in Children with Focal Brain Insults to Frontotemporal Regions

Brain Impairment ◽

10.1017/brimp.2016.33 ◽

2017 ◽

Vol 18 (1) ◽

pp. 102-116 ◽

Cited By ~ 2

Author(s):

V. Chiasson ◽

L. Elkaim ◽

A. G. Weil ◽

L. Crevier ◽

M. H. Beauchamp

Keyword(s):

Decision Making ◽

Moral Reasoning ◽

Brain Regions ◽

Adaptive Skills ◽

Childhood And Adolescence ◽

Distributed Network ◽

Moral Decision ◽

Moral Decision Making ◽

Neuropsychological Measures ◽

Brain Insults

Neuroscientific evidence indicates that human social functioning is supported by a distributed network of frontal and temporal brain regions that undergoes significant development during childhood and adolescence. Clinical studies of individuals with early brain insults (EBI) to frontotemporal regions suggest that such lesions may interfere with the maturation of sociocognitive skills and lead to increased sociobehavioural problems. However, little attention has focussed on the direct assessment of sociocognitive skills, such as moral reasoning, following focal EBI. In the present study, the performance of 15 patients with focal EBI (8–16 years) was compared to that of 15 demographically matched controls on basic neuropsychological measures (IQ and executive functions), sociocognitive tasks (moral reasoning, moral decision-making and empathy) and parent reports of sociobehavioural problems and social adaptive skills. Patients with focal EBI had significantly lower levels of moral reasoning maturity, moral decision-making, and empathy than their matched controls, but did not differ on more general measures of cognition. Their parents also reported increased sociobehavioural problems. These findings suggest that focal EBI to frontotemporal regions can result in reduced sociocognitive capacities, more specifically moral reasoning, and increased vulnerability to sociobehavioural problems.

Download Full-text

Midbrain contributions to sensorimotor decision making

Journal of Neurophysiology ◽

10.1152/jn.01181.2011 ◽

2012 ◽

Vol 108 (1) ◽

pp. 135-147 ◽

Cited By ~ 32

Author(s):

Gidon Felsen ◽

Zachary F. Mainen

Keyword(s):

Decision Making ◽

Brain Regions ◽

Delayed Response ◽

Subcortical Structures ◽

Spatial Choice ◽

Movement Initiation ◽

General Role ◽

Odor Cues ◽

Decision Variables ◽

Olfactory Stimuli

Making decisions about future actions is a fundamental function of the nervous system. Classical theories hold that separate sets of brain regions are responsible for selecting and implementing an action. Traditionally, action selection has been considered the domain of high-level regions, such as the prefrontal cortex, whereas action generation is thought to be carried out by dedicated cortical and subcortical motor regions. However, increasing evidence suggests that the activity of individual neurons in cortical motor structures reflects abstract properties of “decision variables” rather than conveying simple motor commands. Less is known, though, about the role of subcortical structures in decision making. In particular, the superior colliculus (SC) is critical for planning and initiating visually guided, gaze-displacing movements and selecting visual targets, but whether and how it contributes more generally to sensorimotor decisions are unclear. Here, we show that the SC is intimately involved in orienting decisions based on odor cues, even though the SC does not explicitly process olfactory stimuli. Neurons were recorded from the intermediate and deep SC layers in rats trained to perform a delayed-response, odor-cued spatial choice task. SC neurons commonly fired well in advance of movement initiation, predicting the chosen direction nearly 1 s before movement. Moreover, under conditions of sensory uncertainty, SC activity varied with task difficulty and reward outcome, reflecting the influence of decision variables on the intercollicular competition thought to underlie orienting movements. These results indicate that the SC plays a more general role in decisions than previously appreciated, extending beyond visuomotor functions.

Download Full-text

Distribution of terminals from pedunculopontine tegmental nucleus and synaptic organization in lateralis medialis-suprageniculate nucleus of cat's thalamus: Anterograde tracing, immunohistochemical studies, and quantitative analysis

Visual Neuroscience ◽

10.1017/s0952523800176084 ◽

2000 ◽

Vol 17 (6) ◽

pp. 893-904 ◽

Cited By ~ 5

Author(s):

KAEKO HOSHINO ◽

YOSHIMITSU Y. KATOH ◽

WANZHU BAI ◽

TADAYOSHI KAIYA ◽

MASAO NORITA

Keyword(s):

Brain Regions ◽

Pedunculopontine Tegmental Nucleus ◽

Association Cortex ◽

Projection Neurons ◽

Synaptic Organization ◽

Electron Microscopic ◽

Synaptic Contacts ◽

Tegmental Nucleus ◽

Visual Association Cortex ◽

Immunohistochemical Studies

The cat's lateralis medialis-suprageniculate nuclear complex (LM-Sg) in the thalamus receives input from various brain regions such as the superior colliculus, brain stem, and spinal cord, as well as from visual association cortex. In a previous study, we demonstrated that LM-Sg receives cholinergic fibers from the pedunculopontine tegmental nucleus (PPT) and that cholinergic terminals make synaptic contacts with the dendrites of glutamatergic projection neurons and of GABAergic interneurons (Hoshino et al., 1997). In this study, we investigate the distribution and the organization of PPT terminals by means of a combined anterograde tracer (biotinylated dextran amine, BDA) and immunohistochemical methods. When stained by acetylcholinesterase (AChE), the LM-Sg is not uniformly immunoreactive, but rather is patchily labeled and shows a streaming type of reactivity. The tissue content appears high in enzyme activity in AChE-positive zones and is much lighter in activity in AChE-negative zones. We compared the synaptic organization between AChE-positive and AChE-negative portions of the LM-Sg in separate groups of electron-microscopic material: four types of vesicle containing profiles (RS, RL, F1, and PSD) as well as synaptic glomeruli were observed in this nucleus. Among these, the PSD profiles were observed more frequently in AChE-positive portions than in AChE-negative zones. Furthermore, the number of glomeruli was significantly higher in AChE-positive than in AChE-negative zones. Following the injection of BDA into PPT, labeled terminals within LM-Sg were rather more concentrated in the AChE-positive portion. Although the majority of PPT terminals made synaptic contacts with dendrites in the neuropil, a few terminals were involved in the synaptic glomeruli. The present results show that the synaptic organization is distinctly different between the AChE-positive and AChE-negative portions of LM-Sg. These results suggest that the AChE-positive portions of LM-Sg are relatively more involved in integrating information arising from a diverse set of inputs and processing that information within glomeruli in a complex manner than occurs in the AChE-negative portion of LM-Sg.

Download Full-text

Altered cortico-subcortical network after adolescent alcohol exposure mediates behavioral deficits in flexible decision-making

10.1101/2021.03.12.435040 ◽

2021 ◽

Author(s):

Alexander Gómez-A ◽

Carol A. Dannenhoffer ◽

Amanda Elton ◽

SungHo Lee ◽

Woomi Ban ◽

...

Keyword(s):

Decision Making ◽

Functional Connectivity ◽

Behavioral Flexibility ◽

Alcohol Exposure ◽

Brain Structures ◽

Brain Regions ◽

Resting State Functional Connectivity ◽

Mediation Analyses ◽

Adolescent Alcohol ◽

Subcortical Regions

AbstractBehavioral flexibility, the ability to modify behavior according to changing conditions, is essential to optimize decision-making. Deficits in behavioral flexibility that persist into adulthood are one consequence of adolescent alcohol exposure, and another is decreased functional connectivity in brain structures involved in decision-making; however, a link between these two outcomes has not been established. We assessed effects of adolescent alcohol and sex on both Pavlovian and instrumental behaviors and functional connectivity in adult animals to determine associations between behavioral flexibility and resting-state functional connectivity. Alcohol exposure impaired attentional set reversals and decreased functional connectivity among cortical and subcortical regions-of-interest that underlie flexible behavior. Moreover, mediation analyses indicated that adolescent alcohol-induced reductions in functional connectivity within a subnetwork of affected brain regions mediated errors committed during reversal learning. These results provide a novel link between persistent reductions in brain functional connectivity and deficits in behavioral flexibility resulting from adolescent alcohol exposure.

Download Full-text

Hippocampal regenerative medicine: neurogenic implications for addiction and mental disorders

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00587-x ◽

2021 ◽

Author(s):

Lee Peyton ◽

Alfredo Oliveros ◽

Doo-Sup Choi ◽

Mi-Hyeon Jang

Keyword(s):

Decision Making ◽

Prefrontal Cortex ◽

Executive Function ◽

General Population ◽

Mental Disorders ◽

Psychiatric Illness ◽

Neural Circuitry ◽

Brain Regions ◽

Neuropsychiatric Disease ◽

Motivated Behavior

AbstractPsychiatric illness is a prevalent and highly debilitating disorder, and more than 50% of the general population in both middle- and high-income countries experience at least one psychiatric disorder at some point in their lives. As we continue to learn how pervasive psychiatric episodes are in society, we must acknowledge that psychiatric disorders are not solely relegated to a small group of predisposed individuals but rather occur in significant portions of all societal groups. Several distinct brain regions have been implicated in neuropsychiatric disease. These brain regions include corticolimbic structures, which regulate executive function and decision making (e.g., the prefrontal cortex), as well as striatal subregions known to control motivated behavior under normal and stressful conditions. Importantly, the corticolimbic neural circuitry includes the hippocampus, a critical brain structure that sends projections to both the cortex and striatum to coordinate learning, memory, and mood. In this review, we will discuss past and recent discoveries of how neurobiological processes in the hippocampus and corticolimbic structures work in concert to control executive function, memory, and mood in the context of mental disorders.

Download Full-text

HIV Infection Is Associated with Attenuated Frontostriatal Intrinsic Connectivity: A Preliminary Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617715000156 ◽

2015 ◽

Vol 21 (3) ◽

pp. 203-213 ◽

Cited By ~ 39

Author(s):

Jonathan C. Ipser ◽

Gregory G. Brown ◽

Amanda Bischoff-Grethe ◽

Colm G. Connolly ◽

Ronald J. Ellis ◽

...

Keyword(s):

Hiv Infection ◽

Brain Regions ◽

Group Differences ◽

Hiv Rna ◽

Functional Connections ◽

Intrinsic Connectivity ◽

Dorsolateral Prefrontal ◽

Independent Replication ◽

Subcortical Regions ◽

The Brain

AbstractHIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV – associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies. (JINS, 2015, 21, 1–11)

Download Full-text