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Functional Magnetic Resonance Imaging Reveals Subcortical Involvement in Failed Response Inhibition

Core Concepts
Functional neuroimaging data does not provide evidence for the involvement of the indirect or hyperdirect cortico-basal-ganglia pathways in successful response inhibition, but shows increased subcortical activity during failed inhibition trials.
This study investigates the functional network underlying response inhibition in the human brain, particularly the role of the basal ganglia in successful action cancellation. The authors merged five functional magnetic resonance imaging (fMRI) datasets using the stop-signal task (SST) to examine this network. Key highlights: The meta-analysis did not find evidence for the innervation of the hyperdirect or indirect cortico-basal-ganglia pathways in successful response inhibition. Instead, the authors found large subcortical activity profiles, including in the substantia nigra, subthalamic nucleus, thalamus, and ventral tegmental area, during failed stop trials. The authors discuss possible explanations for the mismatch between their fMRI findings and results from other research modalities that have implicated nodes of the basal ganglia in successful inhibition. They highlight the substantial effect that spatial smoothing can have on the conclusions drawn from task-specific general linear models. The study presents a proof of concept for meta-analytical methods that enable the merging of extensive, unprocessed or unreduced datasets, demonstrating the potential of open-access data sharing for the research community.
Median reaction times on go and stop trials were significantly different, consistent with the horse-race model of response inhibition. Mean stop-signal reaction times were within the normal range across datasets. Stopping accuracy was near 50% across datasets, indicating the staircase procedure operated as expected.
"Here, we reprocess and reanalyse five functional SST datasets to shed light on the discrepancies in subcortical BOLD responses." "Canonical methods of meta-analysis have the tendency to lose information when compiling multiple sources of data, due to reliance on summary statistics and a lack of raw data accessibility." "Taking advantage of the recent surge in open access data, we aimed to improve upon these methods by using the raw data now available instead of relying on simple summary measures (e.g., MNI coordinates)."

Deeper Inquiries

What other neuroimaging techniques, such as electrophysiology or neurochemical imaging, could be used to further investigate the role of the basal ganglia in response inhibition?

Electrophysiology techniques, such as local field potential recordings or single-unit recordings, could provide valuable insights into the neural activity of the basal ganglia during response inhibition. These techniques offer high temporal resolution, allowing researchers to observe the precise timing of neural activity in subcortical regions. By recording the electrical activity of neurons in the basal ganglia during the stop-signal task, researchers can directly measure the firing patterns and synchronization of neurons involved in response inhibition. This information can complement fMRI data by providing a more detailed understanding of the neural mechanisms underlying successful and failed inhibition. Neurochemical imaging techniques, such as positron emission tomography (PET) or magnetic resonance spectroscopy (MRS), can also be used to investigate the role of neurotransmitters in the basal ganglia during response inhibition. PET imaging can measure the distribution and binding of specific neurotransmitter receptors in the brain, providing information about the levels of neurotransmitters involved in inhibitory control. MRS, on the other hand, can quantify the concentrations of neurotransmitters, such as dopamine, glutamate, and GABA, in specific brain regions. By correlating neurotransmitter levels with behavioral performance on the stop-signal task, researchers can elucidate the role of specific neurotransmitter systems in response inhibition.

How might individual differences in brain structure and function influence the involvement of specific subcortical regions in successful versus failed response inhibition?

Individual differences in brain structure, such as variations in the size or connectivity of subcortical regions, can influence the recruitment of specific brain regions during response inhibition. For example, individuals with larger volumes of the STN or stronger connectivity between the prefrontal cortex and the basal ganglia may exhibit more efficient response inhibition. On the other hand, individuals with structural abnormalities in the basal ganglia or disrupted connectivity within the cortico-basal ganglia pathways may struggle with inhibitory control. In terms of brain function, variations in neurotransmitter levels or receptor densities in the basal ganglia can also impact response inhibition. For instance, individuals with lower dopamine levels in the basal ganglia may have difficulties in initiating the stopping process, leading to more failed inhibitions. Additionally, differences in the activation patterns of subcortical regions during response inhibition tasks may be influenced by individual differences in attention, motivation, or cognitive control abilities. Overall, individual differences in brain structure and function can modulate the engagement of specific subcortical regions during response inhibition, highlighting the importance of considering variability in neural mechanisms across individuals.

How do the findings from this study relate to the broader literature on the role of the basal ganglia in motor control and decision-making processes?

The findings from this study contribute to the broader literature on the role of the basal ganglia in motor control and decision-making processes by providing insights into the neural mechanisms underlying response inhibition. While previous research has implicated the basal ganglia, particularly the STN, SN, and GPe, in successful response inhibition, the results of this study suggest a different pattern of subcortical activation during the stop-signal task. By demonstrating a lack of evidence for the involvement of the canonical cortico-basal-ganglia pathways in successful inhibition, this study challenges existing models of response inhibition and highlights the complexity of subcortical contributions to cognitive control. The large subcortical activity profiles observed during failed stop trials suggest that inhibitory failures may be driven by a different neural mechanism than successful inhibitions. These findings underscore the need for further research to elucidate the specific roles of subcortical regions in response inhibition and their interactions with cortical areas. By refining our understanding of the basal ganglia's involvement in inhibitory control, we can enhance our knowledge of motor control and decision-making processes, ultimately advancing our understanding of cognitive function and dysfunction.