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Arjun Sethi

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

4 papers

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YNICL Journal 2023 Journal Article

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors

Julia E. Werhahn
Lukasz Smigielski
Seda Sacu
Susanna Mohl
David Willinger
Jilly Naaijen
Leandra M. Mulder
Jeffrey C. Glennon

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

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YNICL Journal 2021 Journal Article

Disruption of brainstem monoaminergic fibre tracts in multiple sclerosis as a putative mechanism for cognitive fatigue: a fixel-based analysis

Tiziana Carandini
Matteo Mancini
Iulia Bogdan
Charlotte L. Rae
Andrew W. Barritt
Arjun Sethi
Neil Harrison
Waqar Rashid

In multiple sclerosis (MS), monoaminergic systems are altered as a result of both inflammation-dependent reduced synthesis and direct structural damage. Aberrant monoaminergic neurotransmission is increasingly considered a major contributor to fatigue pathophysiology. In this study, we aimed to compare the integrity of the monoaminergic white matter fibre tracts projecting from brainstem nuclei in a group of patients with MS (n = 68) and healthy controls (n = 34), and to investigate its association with fatigue. Fibre tracts integrity was assessed with the novel fixel-based analysis that simultaneously estimates axonal density, by means of 'fibre density', and white matter atrophy, by means of fibre 'cross section'. We focused on ventral tegmental area, locus coeruleus, and raphe nuclei as the main source of dopaminergic, noradrenergic, and serotoninergic fibres within the brainstem, respectively. Fourteen tracts of interest projecting from these brainstem nuclei were reconstructed using diffusion tractography, and compared by means of the product of fibre-density and cross-section (FDC). Finally, correlations of monoaminergic axonal damage with the modified fatigue impact scale scores were evaluated in MS. Fixel-based analysis revealed significant axonal damage - as measured by FDC reduction - within selective monoaminergic fibre-tracts projecting from brainstem nuclei in MS patients, in comparison to healthy controls; particularly within the dopaminergic-mesolimbic pathway, the noradrenergic-projections to prefrontal cortex, and serotoninergic-projections to cerebellum. Moreover, we observed significant correlations between severity of cognitive fatigue and axonal damage within the mesocorticolimbic tracts projecting from ventral tegmental area, as well as within the locus coeruleus projections to prefrontal cortex, suggesting a potential contribution of dopaminergic and noradrenergic pathways to central fatigue in MS. Our findings support the hypothesis that axonal damage along monoaminergic pathways contributes to the reduction/dysfunction of monoamines in MS and add new information on the mechanisms by which monoaminergic systems contribute to MS pathogenesis and fatigue. This supports the need for further research into monoamines as therapeutic targets aiming to combat and alleviate fatigue in MS.

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YNICL Journal 2018 Journal Article

An fMRI investigation of empathic processing in boys with conduct problems and varying levels of callous-unemotional traits

Arjun Sethi
Elizabeth O'Nions
Eamon McCrory
Geoffrey Bird
Essi Viding

The ability to empathise relies in part on using one's own affective experience to simulate the affective experience of others. This process is supported by a number of brain areas including the anterior insula (AI), anterior cingulate cortex (ACC), medial prefrontal cortex (mPFC), and the amygdala. Children with conduct problems (CP), and in particular those with high levels of callous-unemotional traits (CP/HCU) present with less empathy than their peers. They also show reduced neural response in areas supporting empathic processing when viewing other people in distress. The current study focused on identifying brain areas co-activated during affective introspection of: i) One's own emotions (‘Own emotion’); ii) Others' emotions (‘Other emotion’); and iii) One's feelings about others' emotions (‘Feel for other’) during fearful vs neutral scenarios in typically developing boys (TD; n = 31), boys with CP/HCU (n = 31), and boys with CP and low levels of CU (CP/LCU; n = 33). The conjunction analysis across conditions within the TD group revealed significant clusters of activation in the AI, ACC/mPFC, and occipital cortex. Conjunction analyses across conditions in the CP/HCU and CP/LCU groups did not identify these areas as significantly activated. However, follow-up analyses were not able to confirm statistically significant differences between groups across the whole network, and Bayes-factor analyses did not provide substantial support for either the null or alternate hypotheses. Post-hoc comparisons indicated that the lack of conjunction effects in the CP/HCU group may reflect reduced affective introspection in the ‘Other emotion’ and ‘Feel for other’ conditions, and by reduced affective introspection in the ‘Own emotion’ condition in the CP/LCU group. These findings provide limited and ultimately equivocal evidence for altered affective introspection regarding others in CP/HCU, and altered affective introspection for own emotions in CP/LCU, and highlight the need for further research to systematically investigate the precise nature of empathy deficits in children with CP.

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YNICL Journal 2017 Journal Article

Magnetization transfer imaging identifies basal ganglia abnormalities in adult ADHD that are invisible to conventional T1 weighted voxel-based morphometry

Arjun Sethi
Edwin Evelyn-Rahr
Nicholas Dowell
Sanjay Jain
Valerie Voon
Hugo D. Critchley
Neil A. Harrison
Mara Cercignani

In childhood, Attention Deficit Hyperactivity Disorder (ADHD) is reliably associated with reduced volume of the striatum. In contrast, striatal abnormalities are infrequently detected in voxel-based morphometry (VBM) neuroimaging studies of adults with ADHD. This discrepancy has been suggested to reflect normalisation of striatal morphology with age and prolonged treatment of symptoms. If so, this would indicate that while striatal abnormalities are linked to symptom expression in childhood, they cannot explain the persistence of these symptoms in adulthood. However, this may not be case. Instead, we hypothesized that the lack of evidence for striatal abnormalities in adult ADHD may reflect poor sensitivity of typical (T1-weighted) neuroimaging to detect subcortical differences. To address this, we acquired both magnetisation transfer (MT) saturation maps optimised for subcortical contrast, and conventional T1-weighted images in 30 adults with ADHD and 30 age, IQ, gender and handedness-matched controls. Using VBM of both datasets, we demonstrate volumetric reductions within the left ventral striatum on MT that are not observed on identically pre-processed T1-weighted images from the same participants. Nevertheless, both techniques reported similar sensitivity to cortical abnormalities in the right inferior parietal lobe. Additionally, we show that differences in striatal iron may potentially explain this reduced sensitivity of T1-weighted images in adults. Together, these findings indicate that prior VBM studies reporting no abnormalities in striatal volume in adult ADHD might have been compromised by the methodological insensitivity of T1-weighted VBM to subcortical differences, and that structural abnormalities of the striatum in ADHD do indeed persist into adulthood.

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