Biology subjects

Tendolkar, I.

Publications and source records attributed to Tendolkar, I..

5 recordsLinked to original sources

bioRxiv2023

Unpacking the functional heterogeneity of the Emotional Face Matching Task: a normative modelling approach

Functional neuroimaging has contributed substantially to understanding brain function but is dominated by group analyses that index only a fraction of the variation in these data. It is increasingly clear that parsing the underlying heterogeneity is crucial to understand individual differences and the impact of different task manipulations. We estimate large-scale (N=7728) normative models of task-evoked activation during the Emotional Face Matching Task, which enables us to bind heterogeneous datasets to a common reference and dissect heterogeneity underlying group-level analyses. We apply this model to a heterogenous patient cohort, to map individual differences between patients with one or more mental health diagnoses relative to the reference cohort and determine multivariate associations with transdiagnostic symptom domains. For the face>shapes contrast, patients have a higher frequency of extreme deviations which are spatially heterogeneous. In contrast, normative models for faces>baseline have greater predictive value for individuals transdiagnostic functioning.

neuroscience↗

bioRxiv2022

Association of Striatal Connectivity Gradients to Functional Domains Across Psychiatric Disorders

ObjectiveTo uncover transdiagnostic domains of functioning across stress- and neurodevelopmental disorders, and to map these on to the topographic functional organization of cortico-striatal circuitry. MethodsIn a clinical sample (n=186) of subjects with high rates of comorbidity of major depressive disorder, anxiety disorder, attention-deficit/hyperactivity disorder and/or autism spectrum disorder, we use exploratory factor analysis on a wide range of clinical questionnaires to identify consistent functional domains of symptomatology across disorders, then replicate these functional domains in an independent dataset (n=188). Then, we use canonical correlation analysis link these functional domains to the topographic organization of the striatum as represented by connectopic maps. ResultsWe reveal four functional domains that transcend current diagnostic categories relating to negative valence, cognition, social functioning and inhibition/arousal. These functional domains are replicated in an independent sample and are associated with the fine-grained topographical organization of functional connectivity in the striatum (out of sample r=0.20, p=0.026), a central hub in motor, cognitive, affective and reward-related brain circuits. Conclusions and relevanceFunctional domains across stress- and neurodevelopmental disorders are associated with the functional organization of the striatum. We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.

neuroscience↗

bioRxiv2021

Neural excitation/inhibition imbalance and the treatment of severe depression

An influential hypothesis holds that depression is related to a neural excitation/inhibition imbalance, but its role in the treatment of depression remains unclear. Here, we show that unmedicated patients with severe depression demonstrated reduced inhibition of brain-wide resting-state networks relative to healthy controls. Patients using antidepressants showed inhibition that was higher than unmedicated patients and comparable to controls, but they still suffered from severe depression. Subsequent treatment with electroconvulsive therapy (ECT) reduced depressive symptoms, but its effectiveness did not depend on changes in network inhibition. Concomitant pharmacotherapy increased the effectiveness of ECT, but only when the strength of neural inhibition before ECT was within the normal range and not when inhibition was excessive. These findings suggest that reversing the excitation/inhibition imbalance may not be sufficient nor necessary for the effective treatment of severe depression, and that brain-state informed pharmacotherapy management may enhance the effectiveness of ECT.

neuroscience↗

bioRxiv2021

Non-REM sleep in major depressive disorder

Disturbed sleep is a key symptom in major depressive disorder (MDD). REM sleep alterations are well described in the current fliterature, but little is known about non-REM sleep alterations. Additionally, sleep disturbances relate to a variety of cognitive symptoms in MDD, but which features of non-REM sleep EEG contribute to this, remains unknown. We comprehensively analyzed non-REM sleep EEG features in three independently collected datasets (N=284). These included MDD patients with a broad age range, varying duration and severity of depression, unmedicated or medicated, age- and gender-matched to healthy controls. We explored changes in sleep architecture including sleep stages and cycles, spectral power, sleep spindles, slow waves (SW), and SW-spindle coupling. Next, we analyzed the association of these sleep features with acute measures of depression severity and overnight consolidation of procedural memory. Overall, no major systematic alterations in non-REM sleep architecture were found in patients compared to controls. For the microstructure of non-REM sleep, we observed a higher spindle amplitude in unmedicated patients compared to controls, and after the start of antidepressant medication longer SWs with lower amplitude and a more dispersed SW-spindle coupling. In addition, long-term, but not short-term medication seemed to lower spindle density. Overnight procedural memory consolidation was impaired in medicated patients and associated with lower sleep spindle density. Our results suggest that alterations in non-REM sleep EEG might be more subtle than previously reported. We discuss these findings in the context of antidepressant medication intake and age. Statement of SignificanceDepression affects large and diverse populations worldwide, including their sleep. Most sleep is non-REM sleep, which is vital to cognitive function, including memory. How non-REM is affected during a depression or medical treatment remains poorly investigated. We classified non-REM sleep of depressive patients against healthy controls in unprecedented analysis detail and confidence using the largest dataset published so far while also test sleep alterations associations with impaired memory. Surprisingly, severe depression alone did not alter sleep. We observed severe non-REM sleep alterations only worsening under patient medication, which ultimately coincided with 24-hour memory impairments. Though causal influences of medication on sleep in depressive patients remains to be investigated, this cautions common clinical practice in long-term treatment with antidepressants.

neuroscience↗

bioRxiv2019

The influence of transcranial magnetic stimulation of the medial prefrontal cortex on emotional memory schemas

Memory bias for negative information is a critical characteristic of major depression, but the underlying neural mechanisms are largely unknown. The recently revived concept of memory schemas may shed new light on memory bias in depression: negative schemas might enhance the encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to transiently perturb processing in the medial prefrontal cortex (mPFC), a core region involved in schema memory, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data was recorded continuously during the night before and after encoding. Secondary measures included sleep and mood questionnaires. We observed a significantly lower number of false recognition of negative critical lures following mPFC perturbation compared to the control group, whereas no differences in veridical memory performance were observed. These findings were supported by reaction time data. No relation between REM sleep and (false) emotional memory performance was observed. These findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.

neuroscience↗