Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a ...stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control.
Voluntary action control requires selection of appropriate responses and stopping of inappropriate responses. Selection and stopping are often investigated separately, but they appear to recruit ...similar brain regions, including the pre-supplementary motor area (preSMA) and inferior frontal gyrus. We therefore examined the evidence for overlap of selection and stopping using two approaches: a meta-analysis of existing studies of selection and stopping, and a novel within-subject fMRI study in which action selection and a stop signal task were combined factorially. The novel fMRI study also permitted us to investigate hypotheses regarding a common mechanism for selection and stopping. The preSMA was identified by both methods as common to selection and stopping. However, stopping a selected action did not recruit preSMA more than stopping a specified action, nor did stop signal reaction times differ significantly across the two conditions. These findings suggest that the preSMA supports both action selection and stopping, but the two processes may not require access to a common inhibition mechanism. Instead, the preSMA might represent information about potential actions that is used in both action selection and stopping in order to resolve conflict between competing available responses.
•GingerALE meta-analysis shows overlap of action selection and stopping in preSMA.•Within-subjects fMRI study confirms overlap using same stimuli and subjects.•Although selection and stopping overlap, there is no behavioural interaction.•The preSMA may support the representation of competing action options.
•The brain circuits underlying perseverative cognition (PC) are still unidentified.•ALE meta-analysis was used to clarify its neurobiological basis across diagnoses.•PC was coupled with engagement of ...brain areas involved in self-referential activity.•Present results support the transdiagnostic nature of PC.
Perseverative cognition (i.e. rumination and worry) describes intrusive, uncontrollable, repetitive thoughts. These negative affective experiences are accompanied by physiological arousal, as if the individual were facing an external stressor. Perseverative cognition is a transdiagnostic symptom, yet studies of neural mechanisms are largely restricted to specific clinical populations (e.g. patients with major depression). The present study applied activation likelihood estimation (ALE) meta-analyses to 43 functional neuroimaging studies of perseverative cognition to elucidate the neurobiological substrates across individuals with and without psychopathological conditions. Task-related and resting state functional connectivity studies were examined in separate meta-analyses. Across task-based studies, perseverative cognition engaged medial frontal gyrus, cingulate gyrus, insula, and posterior cingulate cortex. Resting state functional connectivity studies similarly implicated posterior cingulate cortex together with thalamus and anterior cingulate cortex (ACC), yet the involvement of ACC distinguished between perseverative cognition in healthy controls (HC) and clinical groups. Perseverative cognition is accompanied by the engagement of prefrontal, insula and cingulate regions, whose interaction may support the characteristic conjunction of self-referential and affective processing with (aberrant) cognitive control and embodied (autonomic) arousal. Within this context, ACC engagement appears critical for the pathological expression of rumination and worry.
The current neuroimaging literature is unrepresentative of the world's population due to bias towards particular types of people living in a subset of geographical locations. This is true of both the ...people running the research and those participating in it. These biases mean we may be missing insights into how the brain works. As neuroimaging research expands out to more of the world, the reality of global economic disparities becomes salient. With economic conditions having an effect on many background conditions for research, we can ask whether they also influence the neuroimaging research being done. To investigate this, the number of neuroimaging publications originating from a country was used as a proxy for the type of research being done there in terms of imaging modalities employed. This was then related to local economic conditions, as represented by national gross domestic product and research and development spending. National financial metrics were positively associated with neuroimaging output. The imaging modalities used were also found to be associated with local economic conditions, with magnetic resonance imaging (MRI) research positively and electroencephalography (EEG) negatively associated with national research spending. These results suggest that economic conditions may be relevant when planning how neuroimaging research can be expanded globally.
Tourette syndrome is a hyperkinetic movement disorder. Characteristic features include tics, recurrent movements that are experienced as compulsive and "unwilled"; uncomfortable premonitory ...sensations that resolve through tic release; and often, the ability to suppress tics temporarily. We demonstrate how these symptoms and features can be understood in terms of aberrant predictive (Bayesian) processing in hierarchical neural systems, explaining specifically: why tics arise, their "unvoluntary" nature, how premonitory sensations emerge, and why tic suppression works-sometimes. In our model, premonitory sensations and tics are generated through over-precise priors for sensation and action within somatomotor regions of the striatum. Abnormally high precision of priors arises through the dysfunctional synaptic integration of cortical inputs. These priors for sensation and action are projected into primary sensory and motor areas, triggering premonitory sensations and tics, which in turn elicit prediction errors for unexpected feelings and movements. We propose experimental paradigms to validate this Bayesian account of tics. Our model integrates behavioural, neuroimaging, and computational approaches to provide mechanistic insight into the pathophysiological basis of Tourette syndrome.
Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we ...proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson's disease.
Influential theories concerning personality argue that many impulsive individuals show physiological underarousal at rest. This interoceptive state is proposed to be egodystonic, motivating impulsive ...maladaptive actions to enhance arousal. However, there is little empirical research on this matter. The current study tested the relationship between physiological markers of arousal, measures of interoceptive (in)sensitivity, and trait impulsivity in a nonclinical sample of young adults. Experiment 1 investigated whether individuals (N = 31) with high trait impulsivity show decreased resting measures of arousal (indexed from heart rate, heart rate variability, and sympathetic electrodermal activity). Experiment 2 assessed whether trait impulsivity is linked to interoceptive abilities (N = 60). Overall, our results do not provide any compelling support for the underarousal theory of impulsivity. However, impaired interoceptive (cardiac discrimination) accuracy predicted the degree of Barratt nonplanning impulsivity, such that individuals with a better ability to distinguish between internal (bodily) and external signals manifest lower levels of nonplanning trait impulsivity. These findings open an avenue for potential novel interventions aimed at improving planning abilities via better interoceptive discrimination.
The current study explored the relationship between physiological markers of resting arousal, measures of interoceptive (in)sensitivity, and trait impulsivity. Overall, our results do not provide any compelling support for the underarousal theory of impulsivity, stating that impulsive individuals show physiological underarousal at rest. Instead, impaired interoceptive (cardiac discrimination) accuracy predicted the degree of Barratt nonplanning impulsivity, suggesting that lower levels of nonplanning trait impulsivity might be in part due to impaired discrimination between internal (heartbeats) and external (auditory tones) signals. These findings open an avenue for potential novel interventions aimed at improving planning abilities via better interoceptive discrimination.
Diffusion magnetic resonance imaging is increasingly used as a non-invasive method to investigate white matter structure in neurological and neuropsychiatric disease. However, many options are ...available for the acquisition sequence and analysis method. Here we used Parkinson's disease as a model neurodegenerative disorder to compare imaging protocols and analysis options. We investigated fractional anisotropy and mean diffusivity of white matter in patients and age-matched controls, comparing two datasets acquired with different imaging protocols. One protocol prioritised the number of b value acquisitions, whilst the other prioritised the number of gradient directions. The dataset with more gradient directions was more sensitive to reductions in fractional anisotropy in Parkinson's disease, whilst the dataset with more b values was more sensitive to increases in mean diffusivity. Moreover, the areas of reduced fractional anisotropy were highly similar to areas of increased mean diffusivity in PD patients. Next, we compared two widely used analysis methods: tract-based spatial statistics identified reduced fractional anisotropy and increased mean diffusivity in Parkinson's disease in many of the major white matter tracts in the frontal and parietal lobes. Voxel-based analyses were less sensitive, with similar patterns of white matter pathology observed only at liberal statistical thresholds. We also used tract-based spatial statistics to identify correlations between a test of executive function (phonemic fluency), fractional anisotropy and mean diffusivity in prefrontal white matter in both Parkinson's disease patients and controls. These findings suggest that in Parkinson's disease there is widespread pathology of cerebral white matter, and furthermore, pathological white matter in the frontal lobe may be associated with executive dysfunction. Diffusion imaging protocols that prioritised the number of directions versus the number of b values were differentially sensitive to alternative markers of white matter pathology, such as fractional anisotropy and mean diffusivity.
► DTI shows abnormal frontal white matter in Parkinson's disease. ► FA and MD in the frontal lobe correlate with executive function in PD. ► The number of directions and b values affects sensitivity to FA/MD changes in PD. ► TBSS is more sensitive than VBM to white matter change in Parkinson's disease.
Tourette Syndrome (TS) is a neurodevelopmental condition characterized by chronic multiple tics, which are experienced as compulsive and 'unwilled'. Patients with TS can differ markedly in the ...frequency, severity, and bodily distribution of tics. Moreover, there are high comorbidity rates with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), anxiety disorders, and depression. This complex clinical profile may account for apparent variability of findings across neuroimaging studies that connect neural function to cognitive and motor behavior in TS. Here we crystalized information from neuroimaging regarding the functional circuitry of TS, and furthermore, tested specifically for neural determinants of tic severity, by applying activation likelihood estimation (ALE) meta-analyses to neuroimaging (activation) studies of TS. Fourteen task-based studies (13 fMRI and one H2O-PET) met rigorous inclusion criteria. These studies, encompassing 25 experiments and 651 participants, tested for differences between TS participants and healthy controls across cognitive, motor, perceptual and somatosensory domains. Relative to controls, TS participants showed distributed differences in the activation of prefrontal (inferior, middle, and superior frontal gyri), anterior cingulate, and motor preparation cortices (lateral premotor cortex and supplementary motor area; SMA). Differences also extended into sensory (somatosensory cortex and the lingual gyrus; V4); and temporo-parietal association cortices (posterior superior temporal sulcus, supramarginal gyrus, and retrosplenial cortex). Within TS participants, tic severity (reported using the Yale Global Tic Severity Scale; YGTSS) selectively correlated with engagement of SMA, precentral gyrus, and middle frontal gyrus across tasks. The dispersed involvement of multiple cortical regions with differences in functional reactivity may account for heterogeneity in the symptomatic expression of TS and its comorbidities. More specifically for tics and tic severity, the findings reinforce previously proposed contributions of premotor and lateral prefrontal cortices to tic expression.
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