Most recent paper

eNeuro. 2025 Mar 3:ENEURO.0408-24.2025. doi: 10.1523/ENEURO.0408-24.2025. Online ahead of print.

ABSTRACT

Impulsivity is often considered a risk factor for drug addiction; however, not all evidence supports this view. In the present study, we used a food reward delay-discounting task (DDT) to categorize rats as low-, middle-, and high-impulsive but failed to find any difference among these groups in the acquisition and maintenance of cocaine self-administration, regardless of electrical foot-shock punishment. Additionally, there were no group differences in locomotor responses to acute cocaine in rats with or without a history of cocaine self-administration. Unexpectedly, chronic cocaine self-administration selectively increased impulsive choice in low-impulsive rats. Resting-state fMRI analysis revealed a positive correlation between impulsivity and cerebral blood volume in the midbrain, thalamus, and auditory cortex. Using these three regions as seeds, we observed a negative correlation between impulsivity and functional connectivity between the midbrain and frontal cortex, as well as between the thalamus and frontal cortex (including the orbitofrontal, primary, and parietal cortices) in low-impulsive rats. These correlations were attenuated following chronic cocaine self-administration. RNAscope in situ hybridization assays revealed a significant reduction in DA D1, D2, and D3 receptor mRNA expression in the corticostriatal regions of low-impulsive rats after cocaine self-administration. Our findings challenge the widely held view that impulsivity is a vulnerability factor for cocaine addiction. Instead, chronic cocaine use appears to selectively increase impulsive choice decision-making in low-impulsive rats, associated with reduced functional connectivity and DA receptor expression in the mesocorticolimbic DA network.Significance statement Impulsivity has long been considered a risk factor for substance use disorders (SUD). However, findings across different impulsivity measures have been inconsistent or controversial. In this study, we did not find evidence supporting the notion that preexisting choice impulsivity is a predictive factor for compulsive cocaine self-administration. Instead, we found that chronic cocaine self-administration led to a significant increase in impulsive choice decision-making in normally low-impulsive rats. This increase was associated with reduced functional connectivity and reduced dopamine receptor expression in the dopamine-related network. Our findings suggest that choice impulsivity does not predict SUD; rather, chronic cocaine use is a risk factor for developing impulsive behavior in healthy individuals.

PMID:40032530 | DOI:10.1523/ENEURO.0408-24.2025

IEEE Trans Neural Syst Rehabil Eng. 2024 Nov 13;PP. doi: 10.1109/TNSRE.2024.3497893. Online ahead of print.

ABSTRACT

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising neurostimulation approach for emotion regulation. This research aimed to clarify the underlying neural basis responsible for taVNS's impact on emotional regulation related brain regions. Thirty-two healthy volunteers were allocated into a taVNS group, which received electrical stimulation at the concha area of the ear, and a sham group, which received earlobe stimulation. Resting-state functional magnetic resonance imaging data were collected from both the taVNS and sham groups pre- and post-stimulation. To evaluate the alterations in neural activity and connectivity resulting from auricular electrical stimulation, degree centrality and functional connectivity analyses were used. The results indicated that taVNS modulated the neural activity of several brain regions, including the bilateral precuneus, temporal gyrus, precentral gyrus, and postcentral gyrus, whereas earlobe stimulation did not produce such effects. taVNS may improve emotion regulation by modulating neural activation and functional connectivity in key brain regions, then facilitating the integration of emotional responses, memories, and experiences. Thus, these brain regions may serve as potential therapeutic targets for taVNS in treating disorders associated with emotional dysregulation. These findings provide insight into the neural basis through which taVNS influences emotion regulation and hold potential for the development of neuromodulation-based therapeutic strategies for emotional disorders.

PMID:40030198 | DOI:10.1109/TNSRE.2024.3497893

Res Dir Depress. 2024 Oct 1;1:e21. doi: 10.1017/dep.2024.6. eCollection 2024.

ABSTRACT

BACKGROUND: Neural predictors underlying variability in depression outcomes are poorly understood. Functional MRI measures of subgenual cortex connectivity, self-blaming and negative perceptual biases have shown prognostic potential in treatment-naïve, medication-free and fully remitting forms of major depressive disorder (MDD). However, their role in more chronic, difficult-to-treat forms of MDD is unknown.

METHODS: Forty-five participants (n = 38 meeting minimum data quality thresholds) fulfilled criteria for difficult-to-treat MDD. Clinical outcome was determined by computing percentage change at follow-up from baseline (four months) on the self-reported Quick Inventory of Depressive Symptomatology (16-item). Baseline measures included self-blame-selective connectivity of the right superior anterior temporal lobe with an a priori Brodmann Area 25 region-of-interest, blood-oxygen-level-dependent a priori bilateral amygdala activation for subliminal sad vs happy faces, and resting-state connectivity of the subgenual cortex with an a priori defined ventrolateral prefrontal cortex/insula region-of-interest.

FINDINGS: A linear regression model showed that baseline severity of depressive symptoms explained 3% of the variance in outcomes at follow-up (F[3,34] = .33, p = .81). In contrast, our three pre-registered neural measures combined, explained 32% of the variance in clinical outcomes (F[4,33] = 3.86, p = .01).

CONCLUSION: These findings corroborate the pathophysiological relevance of neural signatures of emotional biases and their potential as predictors of outcomes in difficult-to-treat depression.

PMID:40028885 | PMC:PMC11869767 | DOI:10.1017/dep.2024.6

Front Psychiatry. 2025 Feb 14;16:1458602. doi: 10.3389/fpsyt.2025.1458602. eCollection 2025.

ABSTRACT

BACKGROUND: Apathy is a prevalent psychiatric condition after stroke, affecting approximately 30% of stroke survivors. It is associated with slower recovery and an increased risk of depression. Understanding the pathophysiological mechanisms of post stroke apathy (PSA) is crucial for developing targeted rehabilitation strategies.

METHODS: In this study, we recruited a total of 18 PSA patients, 18 post-stroke non-apathy (NPSA) patients, and 18 healthy controls (HCs). Apathy was measured using the Apathy Evaluation Scale (AES). Resting-state functional magnetic resonance imaging (rs-fMRI) was utilized to investigate spontaneous brain activity. We estimated the amplitude of low-frequency fluctuation (ALFF) across three different frequency bands (typical band: 0.01-0.08 Hz; slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz) and the fractional amplitude of low-frequency fluctuation (fALFF).

RESULTS: Band-specific ALFF differences among the three groups were analyzed. Significant differences were found in the typical band within the left lingual gyrus, right fusiform gyrus, right superior temporal gyrus (STG), and left insula. In the slow-4 band, significant differences were observed in the left middle frontal gyrus (MFG) and right STG. In the slow-5 band, significant differences were identified in the left calcarine cortex and right insula. For fALFF values, significant differences were found in the left lingual gyrus and right thalamus. Moreover, positive correlations were observed between AES scores and the ALFF values in the right STG (r = 0.490, p = 0.002) in the typical band, left MFG (r = 0.478, p = 0.003) and right STG (r = 0.451, p = 0.006) in the slow-4 band, and fALFF values of the right thalamus (r = 0.614, p < 0.001).

CONCLUSION: This study is the first to investigate the neural correlates of PSA using voxel-level analysis and different ALFF banding methods. Our findings indicate that PSA involves cortical and subcortical areas, including the left MFG, right STG, and right thalamus. These results may help elucidate the neural mechanisms underlying PSA and could serve as potential neuroimaging indicators for early diagnosis and intervention.

PMID:40027597 | PMC:PMC11868042 | DOI:10.3389/fpsyt.2025.1458602