Pradeep J. Nathan

YNIMG Journal 2014 Journal Article

Structural neuroimaging correlates of allelic variation of the BDNF val66met polymorphism

• Natalie J. Forde
• Lisa Ronan
• John Suckling
• Cathy Scanlon
• Simon Neary
• Laurena Holleran
• Alexander Leemans
• Roger Tait

Background The brain-derived neurotrophic factor (BDNF) val66met polymorphism is associated with altered activity dependent secretion of BDNF and a variable influence on brain morphology and cognition. Although a met-dose effect is generally assumed, to date the paucity of met-homozygotes have limited our understanding of the role of the met-allele on brain structure. Methods To investigate this phenomenon, we recruited sixty normal healthy subjects, twenty in each genotypic group (val/val, val/met and met/met). Global and local morphology were assessed using voxel based morphometry and surface reconstruction methods. White matter organisation was also investigated using tract-based spatial statistics and constrained spherical deconvolution tractography. Results Morphological analysis revealed an “inverted-U” shaped profile of cortical changes, with val/met heterozygotes most different relative to the two homozygous groups. These results were evident at a global and local level as well as in tractography analysis of white matter fibre bundles. Conclusion In contrast to our expectations, we found no evidence of a linear met-dose effect on brain structure, rather our results support the view that the heterozygotic BDNF val66met genotype is associated with cortical morphology that is more distinct from the BDNF val66met homozygotes. These results may prove significant in furthering our understanding of the role of the BDNF met-allele in disorders such as Alzheimer's disease and depression.

YNIMG Journal 2010 Journal Article

Differentiation of the Mu-opioid ligand GSK1521498 from naltrexone using [11C]carfentanil PET and fMRI

• John D. Beaver
• Edward T. Bullmore
• Graham E. Searle
• Christopher J. Long
• Samuel P. Hill
• Jonathan Howard
• Pradeep J. Nathan
• Paul M. Matthews

YNIMG Journal 2009 Journal Article

Reproducibility of graph metrics of human brain functional networks

• Lorena Deuker
• Edward T. Bullmore
• Marie Smith
• Soren Christensen
• Pradeep J. Nathan
• Brigitte Rockstroh
• Danielle S. Bassett

Graph theory provides many metrics of complex network organization that can be applied to analysis of brain networks derived from neuroimaging data. Here we investigated the test–retest reliability of graph metrics of functional networks derived from magnetoencephalography (MEG) data recorded in two sessions from 16 healthy volunteers who were studied at rest and during performance of the n-back working memory task in each session. For each subject's data at each session, we used a wavelet filter to estimate the mutual information (MI) between each pair of MEG sensors in each of the classical frequency intervals from γ to low δ in the overall range 1–60 Hz. Undirected binary graphs were generated by thresholding the MI matrix and 8 global network metrics were estimated: the clustering coefficient, path length, small-worldness, efficiency, cost-efficiency, assortativity, hierarchy, and synchronizability. Reliability of each graph metric was assessed using the intraclass correlation (ICC). Good reliability was demonstrated for most metrics applied to the n-back data (mean ICC=0. 62). Reliability was greater for metrics in lower frequency networks. Higher frequency γ- and β-band networks were less reliable at a global level but demonstrated high reliability of nodal metrics in frontal and parietal regions. Performance of the n-back task was associated with greater reliability than measurements on resting state data. Task practice was also associated with greater reliability. Collectively these results suggest that graph metrics are sufficiently reliable to be considered for future longitudinal studies of functional brain network changes.

YNIMG Journal 2006 Journal Article

Beyond threat: Amygdala reactivity across multiple expressions of facial affect

• Daniel A. Fitzgerald
• Mike Angstadt
• Laura M. Jelsone
• Pradeep J. Nathan
• K. Luan Phan

The amygdala has been consistently isolated as a key neural substrate for processing facial displays of affect. Recent evidence from human lesion and functional neuroimaging studies have begun to challenge the notion that the amygdala is reserved for signals of threat (fear/anger). We performed a 4 T fMRI study in which 20 subjects viewed a contemporary set of photographs displaying 6 different facial expressions (fearful, disgusted, angry, sad, neutral, happy) while performing a task with minimal cognitive demand. Across subjects, the left amygdala was activated by each face condition separately, and its response was not selective for any particular emotion category. These results challenge the notion that the amygdala has a specialized role in processing certain emotions and suggest that the amygdala may have a more general-purpose function in processing salient information from faces.

YNIMG Journal 2006 Journal Article

Exploring the temporal dynamics of the spatial working memory n-back task using steady state visual evoked potentials (SSVEP)

• Kathryn A. Ellis
• Richard B. Silberstein
• Pradeep J. Nathan

The neural networks associated with spatial working memory (SWM) are well established. However, the temporal dynamics of SWM-related brain activity are less clear. This study examined changes in temporal neurophysiology during the spatial n-back task using steady state probe topography (SSPT) to record cortical steady state visual evoked potentials (SSVEPs) at 64 scalp locations. Twenty healthy male volunteers participated in the study. The findings identified three different time periods of significance during the spatial n-back task — an early perceptual/encoding period (approximately 0–500 ms), an early delay period just following the stimulus disappearing from view (approximately 850–1400 ms), and a late period lasting the final second of the delay and anticipation of the new stimulus (approximately 2500–3500 ms). The delay period was associated with increases in frontal and occipital region amplitude, consistent with previous findings in more basic working memory tasks. The two different SSVEP components during the delay appear reflective of the additional “executive” demands associated with the n-back and may suggest variable roles for the PFC during different stages of the delay. All three n-back levels demonstrated a relative consistent electrophysiological profile, indicating that this pattern is specific to the spatial n-back task. Nevertheless, these findings supported the hypothesis that memory load modulates activity within the networks identified, consistent with previous neuroimaging studies. The current findings may offer a framework in which to further investigate the temporal aspects of SWM.

YNIMG Journal 2005 Journal Article

Functional connectivity during Stroop task performance

• Ben J. Harrison
• Marnie Shaw
• Murat Yücel
• Rosemary Purcell
• Warrick J. Brewer
• Stephen C. Strother
• Gary F. Egan
• James S. Olver

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2 15O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two “parallel” networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

YNIMG Journal 2001 Journal Article

Cholinergic modulation of brain electrical activity during delayed matching-to-sample performance

• James C. Thompson
• Pradeep J. Nathan
• Con Stough
• David Ames
• John Tiller
• Richard Silberstein