Biology subjects

Riva-Posse, P.

Publications and source records attributed to Riva-Posse, P..

6 recordsLinked to original sources

bioRxiv2025

Longitudinal Changes in Cortical Response Dynamics with Deep Brain Stimulation to the Subcallosal Cingulate for Treatment-Resistant Depression

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is a promising intervention for treatment-resistant depression, yet objective biomarkers that track recovery remain limited. This study examined longitudinal changes in stimulation-evoked potentials (SEPs) to characterize how SCC-driven cortical communication evolves during treatment. Ten patients across three SCC-DBS trials underwent high-density EEG recordings at 4 and 24 weeks. SEP features were extracted from source-localized SCC signals and related to clinical outcomes and fractional anisotropy (FA) of midcingulate cingulum. Cortical responses showed a consistent reduction in latency and an increase in magnitude over time, indicating faster and stronger electrocortical signaling with chronic stimulation. Higher baseline midcingulate FA predicted greater latency acceleration, linking SEP timing to white-matter integrity. These findings identify temporal SEP dynamics as candidate mechanistic biomarkers that reflect circuit engagement during SCC-DBS and offer a pathway toward physiology-guided optimization of neuromodulation for depression. HighlightsO_LIReduced latency of stimulation evoked potential after 6 months of DBS C_LIO_LILarger cortical evoked response to single pulse perturbation after 6 months of DBS C_LIO_LIBaseline myelin integrity in MCC predicts magnitude of change in EP latency C_LI

neuroscience↗

bioRxiv2023

Neural Interoceptive Processing is Modulated by Deep Brain Stimulation for Treatment Resistant Depression

BackgroundA critical advance in depression research is to clarify the hypothesized role of interoceptive processing in neural mechanisms of treatment efficacy. This study tests whether cortical interoceptive processing, as indexed by the heartbeat-evoked potential (HEP), is modulated by deep brain stimulation (DBS) to the subcallosal cingulate (SCC) for treatment resistant depression (TRD). MethodsEight patients with TRD were enrolled in a study of SCC DBS safety and efficacy. Electroencephalography (EEG) and symptom severity measures were sampled in a laboratory setting over the course of a six-month treatment protocol. The primary outcome measure was an EEG-derived HEP, which reflects cortical processing of heartbeat sensation. Cluster-based permutation analyses were used to test the effect of stimulation and time in treatment on the HEP. The change in signal magnitude after treatment was correlated with change in depression severity as measured by the 17-item Hamilton Depression Rating Scale. ResultsHEP amplitude was greater after 24 weeks of treatment (t(7)=-4.40, p=.003, g=-1.38, 95% Cl [-2.3, -0.42]), and this change was inversely correlated with latency of treatment response (rho = -0.75, 95% Cl [-0.95, -0.11], p=.03). An acute effect of DBS was also observed, but as a decrease in HEP amplitude (t(6) =6.66, p<.001, g=2.19, 95% Cl [0.81, 3.54]). HEP differences were most pronounced over left posterior sensors from 405-425 ms post-stimulus. ConclusionBrain-based evidence substantiates a theorized link between interoception and depression, and suggests an interoceptive contribution to the mechanism of treatment efficacy with deep brain stimulation for severe depression.

neuroscience↗

bioRxiv2022

Decoding Depression During Subcallosal Cingulate Deep Brain Stimulation

AO_SCPLOWBSTRACTC_SCPLOWDeep brain stimulation of subcallosal cingulate white matter (SCCwm-DBS) alleviates symptoms of treatment resistant depression (TRD) over months of therapy. Readouts of depression symptom severity derived from neural recordings are needed for more systematic study and improvement of the therapy. In this study, we measured local field potentials (LFP) multiple times a day alongside seven months of therapy using the Activa PC+S in six patients treated with SCCwm-DBS. We found significant changes in oscillatory power between early and late therapy after accounting for stimulation-related distortions, particularly within the {beta} band. We then used a decoder strategy to identify oscillatory activity that tracked with depression measurements over seven months, with asymmetric{delta} and {beta} oscillations contributing to a statistically significant prediction of 10% of the measured depression signal. Simulating its use in clinical decision-making, we demonstrated that the DR-SCC yield clinically meaningful information that can augment other measures of depression state. Ultimately, this DR-SCC provides a data-driven first-step towards objectively tracking chronic recovery after antidepressant DBS implantation and developing adaptive DBS strategies in the presence of active stimulation.

neuroscience↗

bioRxiv2021

Dynamic functional connectivity links with treatment response of electroconvulsive therapy in major depressive disorder

BackgroundElectroconvulsive Therapy (ECT) is one of the most effective treatments for major depressive disorder (DEP). There is recently increasing attention to evaluate ECTs effect on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of DEP patients with healthy participants, investigate whether dynamic functional network connectivity network (dFNC) estimated from rs-fMRI predicts the ECT outcome, and explore the effect of ECT on brain network states. MethodResting-state fMRI data were collected from 119 patients with depression or DEP (76 females), and 61 Healthy (HC) participants (34 females) with an age mean of 52.25 (N=180) years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale (HDRS) were 25.59{+/-}6.14 and 11.48{+/-}9.07, respectively. Twenty-four independent components from default mode (DMN) and cognitive control network (CCN) were extracted using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each participant. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each individual spends in each state, called occupancy rate or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, number of treatment, and site. Finally, we evaluated the effectiveness of ECT by comparing pre-and post-ECT OCR of DEP and HC participants. ResultsThe main findings include: 1) DEP patients had significantly lower OCR values than the HC group in a state, where connectivity between CCN and DMN was relatively higher than other states (corrected p= 0.015), 2) Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, predicted the HDRS changes (R=0.23 corrected p=0.03). This means that those DEP patients who spend less time in this state showed more HDRS change, and 3) The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spend in state 2 (corrected p=0.03). Finally, we found ECT increases the total traveled distance in DEP. ConclusionOur finding suggests that dFNC features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identified a possible underlying mechanism associated with the ECT effect in DEP patients.

neuroscience↗

bioRxiv2020

Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium- and long-chain acylcarnitines, suggesting an SSRI effect on {beta}-oxidation and mitochondrial function. Amines - including arginine, proline, and methionine-sulfoxide - were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17[≤]7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine and serotonin; and b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2 and PC aa C36:4. These findings suggest that mitochondrial energetics - including acylcarnitine metabolism, transport and its link to {beta}-oxidation - and lipid membrane remodeling may play roles in SSRI treatment response.

neuroscience↗

bioRxiv2019

Acylcarnitine Metabolomic Profiles Inform Clinically-Defined Major Depressive Phenotypes

BackgroundAcylcarnitines have important functions in mitochondrial energetics and {beta}-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD)--(core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+))--following treatment with a selective serotonin reuptake inhibitor (SSRI).\n\nMethodsDepressed outpatients (n=240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and eight weeks post-treatment were profiled for multiple-, short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ(R)p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminate the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differ between groups.\n\nResultsAt baseline, significantly lower concentrations of short- and long-chain acylcarnitines were found in CD+ and NVSM+ compared to ANX+, and the short-chain acylcarnitines remained lower after eight weeks. At eight weeks, the medium- and long-chain acylcarnitines were significantly lower in NVSM+ compared to ANX+. Regarding changes baseline to week eight, short-chain acylcarnitine levels significantly increased in CD+ and ANX+, and medium- and long-chain acylcarnitines significantly decreased in NVSM+ and CD+.\n\nConclusionsIn depressed patients treated with SSRIs, {beta}-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.

biochemistry↗