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Ventral Striatum

The ventral striatum (from Latin, 'striatus' meaning 'striped), is a subcortical brain region which regulates the limbic functions of reward expectation, motivation, and reward perception. By monitoring the subjective value of stimuli, it tracks the outcomes of both reward and adverse experience predictions and tracks errors made in those predictions. Whereas the dorsal striatum mediates flexible or automated motor actions, the ventral striatum mediates motivation, learning and mood. The ventral striatum is directly involved in emotional regulation, particularly when regulating responses to rewarding stimuli in addiction behaviours. It plays a vital role in reinforcement learning, which is to learn associations between stimulus choices that yield rewards. This role extends to making moral judgements about co-operative conspecifics.

Anatomy
The ventral striatum is a conglomeration of several brain areas. It consists of the main part of the olfactory tubercle, a multi-sensory processing centre, and the nucleus accumbens, which is innervated with dopamine when we experience reward and reinforcement. It also encompasses the continuity between the caudate nucleus and putamen, ventral to the rostral internal capsule. The internal capsule, a white matter tract, is overlaid with strands of grey matter between the caudate and putamen, creating a striped appearance; hence the brain region receiving the Latin name 'striatum', meaning 'striped'.

Connections
The ventral striatum receives afferent projections from various brain regions, including; Efferent projections from the ventral striatum project to the lateral hypothalamus, ventral pallidum, globus pallidus and the substantia nigra
 * Topographic cortico-striatal projections from the cerebral cortex, primarily from the orbital prefrontal cortex
 * The brain stem, particularly midbrain dopaminergic cells from the ventral tegmental area
 * The thalamus
 * The basolateral amygdala, which encodes emotional meaning of environmental stimuli and helps provide contextual information to inform motivational engagement
 * The hippocampal formation, which consults relevant prior memories of events and stimuli, which helps inform both decision-making and regulates responses to rewards

The Mesolimbic Pathway
The ventral striatum contains smaller and more densely packed dopaminergic neurons compared to its dorsal counterpart. Dopamine neurons play a key role in the reward circuit, also known as the mesolimbic pathway. The mesolimbic pathway is a dopaminergic projection from the ventral tegmental area to the nucleus accumbens of the ventral striatum. The release of dopamine to the nucleus accumbens regulates motivational cognition, incentive salience, and reinforcement learning.



Anticipation and evaluation of rewards
The nucleus accumbens has been found to respond to the anticipation of positive gains, which is additionally correlated to self-reported predictions of financial or object gains. Anticipation of loss has been found to be processed elsewhere, in the insula, suggesting that specifically the anticipation of positive gains is processed within the nucleus accumbens. This neural activity can also act as a predictor of an individual’s purchasing decisions; willingness to pay for a product has been found to correlate with activation in the nucleus accumbens.

Altruism
Functional magnetic resonance imaging evidence suggests observed differences in neural activity in the ventral striatum between participants can be used to predict an individual’s donation behaviours in charity-giving games. Participants with larger ventral striatum activation responses when giving money to charity were more likely to give larger amounts of money to charity, even at their own financial expense. Altruistic behaviour was directly correlated to high neural responses in the ventral striatum.

Co-operation and reciprocity
In the Prisoner’s Dilemma paradigm, individuals demonstrate increased neural activation in both the orbitofrontal cortex and the anteroventral striatum when reciprocating co-operative behaviour or experiencing mutual co-operation. Anteroventral striatum activity was specifically activated for conspecific interactions and did not occur in trials vs computer opponents. Neural activity was also compared to a control condition where participants received a free reward, and found the act of co-operation significantly enhanced these reward processing regions. The study suggests we feel more rewarded when obtaining rewards via mutually co-operative social interactions. More ventral striatum activity was correlated with an increased likelihood of continued co-operation, and deactivation of the anteroventral striatum occurred in both players when one of the players stopped co-operating.

The ability to determine who will reciprocate co-operation is vital in social interaction, and informs our decisions of whether to interact or avoid someone. A study investigating the neural activity of this evaluation process found that activity in the amygdala, extending anteriorly into the ventral striatum (the right putamen and nucleus accumbens), is significantly increased when participants view the faces of those who had previously co-operated in social dilemma games.

Addiction
Neural alterations to ventral striatal circuitry form the basis of addictive disorders. Over-expression of DeltaFosB (a splice variant of protein FosB) can be found in the D1-receptor neurons of the ventral striatum.

DeltaFosB is the most significant bio-molecular mechanism in addiction, as it causes alterations in gene expression in mesolimbic and mesocortical pathways. As a transcription factor, DeltaFosB transcribes genetic information in a cell from DNA into RNA, which ribosomes then translate into proteins. Over-expression of DeltaFosB in the nucleus accumbens causes over-production of GluR2 within the dopamine neuron. This temporarily stimulates the neuron and increases the sensitivity to the rewarding effects of addictive stimuli, particularly drug stimulants. GluR2 binds to AMPA receptors on the neuron, which are responsible for excitatory synaptic transmission. When AMPA receptors are blocked, it reduces calcium ion permeability and reduces the overall excitability in the D1-receptor neuron. This results in the dopamine neuron eliciting reduced neuronal firing in the absence of the addictive stimuli.

Over-expression of DeltaFosB in the nucleus accumbens is responsible for the behavioural effects seen in addictive behaviours (such as administering drugs or seeking addictive stimuli). DeltaFosB is increasingly expressed in the nucleus accumbens when individuals repeatedly overdose on addictive drugs, or over-expose themselves to addictive stimuli.

Studies investigating the pre-frontal striatal pathways in nicotine addiction have demonstrated that as nicotine cravings decrease, activity in the dorso-lateral prefrontal cortex increases (which reflects control over habits and behaviour, via the deployment of cognitive strategies to regulate cravings), which in turn exerts a decrease in activity on the ventral striatum.

Dysfunction
In rhesus macaques, lesions of the ventral striatum impaired learning of how to obtain rewards through selecting images. However, the ability to select rewarding actions remained intact, suggesting the ventral striatum is primarily involved specifically in reinforcement learning.

Individuals with focal lesions affecting the ventral striatum demonstrated significant impairment in recognising signals of anger and aggression in others, compared to individuals with more dorsal basal ganglia lesions. It is theorised that this failure to identify aggression reflects a deficiency in understanding behaviours that aim to procure, or protect, valued and/or contested resources.

Neuroimaging of individuals with obsessive-compulsive disorder found that increased connectivity of the ventral striatum, amygdala and ventromedial prefrontal cortex was correlated with aggressive symptoms, whilst increased connectivity in the ventral striatum and insula was indicative of intrusive sexual thoughts.