Subbulakshmi Sankarasubramanian

All Publications

• Dissociable structural and molecular pathways of age-related change in sustained attention. bioRxiv : the preprint server for biology Subbulakshmi, S., Park, J., Rathmann-Bloch, J., Ward, T., Cheng, G. L., Miller, D. S., Schwartz, S. T., Sheng, J., Tran, T. T., Sha, S. J., Deutsch, G., Trelle, A. N., Mormino, E. C., Wagner, A. D. 2026

  Abstract

  Sustained attention, the capacity to maintain goal-directed attention over extended periods, declines with age but with substantial individual variability across cognitively unimpaired (CU) older adults. The neurobiological mechanisms driving both the decline and its variability across CU remain poorly understood. Two candidate processes may contribute: microstructural deterioration of the superior longitudinal fasciculus (SLF), the principal white-matter tract coupling prefrontal and parietal nodes of the dorsal attention network, and subclinical accumulation of Alzheimer's disease (AD)-related pathology, which may erode attentional function through disruption of neuromodulatory systems and progressive involvement of frontoparietal cortical substrates. We combined (a) diffusion MRI tractography, quantifying SLF fractional anisotropy (FA) and mean diffusivity (MD) alongside two control tracts, the corticospinal tract (CST) and cingulum (CGC), with (b) a plasma panel indexing AD-related pathology (pTau-181, pTau-217), neuroaxonal injury (NfL), and astrocytic reactivity (GFAP) in 162 CU older adults drawn from two Stanford cohorts (plasma subsample N = 146). Sustained attention was assessed using the gradual-onset Continuous Performance Task (gradCPT) and indexed by a composite score (Att-Z) derived from discriminability (d') and response-time variability (RTV). Parallel mediation and commonality analyses were used to test whether structural and molecular pathways contribute independently to age-related attentional decline. Older age was associated with lower Att-Z (β = -0.315, p < 0.001). In simultaneous three-tract regression models, only SLF microstructure uniquely predicted Att-Z (FA: β = +0.275, p < 0.001; MD: β = -0.320, p < 0.001). SLF microstructure mediated the age-attention relationship. At the molecular level, plasma pTau-181 (β = -0.212, pFDR < 0.03) and pTau-217 (β = -0.163, pFDR < 0.05) predicted Att-Z and each mediated age-related attentional decline. Yet, neither pTau isoform predicted SLF microstructure, indicating that the molecular pathway operates independently of white-matter integrity. NfL also reached FDR-corrected significance for Att-Z (β = -0.156, pFDR < 0.05) but attenuated to non-significance when modelled jointly with pTau-181 or pTau-217, suggesting that the attentionally relevant component of molecular ageing is specific to AD-related pathology rather than NfL-related neuroaxonal damage. GFAP showed no association with sustained attention in any model. In parallel mediation models, SLF microstructure and plasma pTau carried significant independent indirect effects with negligible shared variance, and both pathways retained significance when modelled jointly. These findings reveal a multi-pathway architecture of attentional ageing in which structural disconnection of the dorsal attention network and accumulation of AD-related pathology operate as dissociable and additive mediators of individual differences in attention and of age-related attentional decline, detectable before clinical impairment. Their mechanistic independence identifies two separable biological targets for preserving attentional capacity in CU older adults, including those in the preclinical phase of AD.

  View details for DOI 10.64898/2026.06.29.735429

  View details for PubMedID 42427721

  View details for PubMedCentralID PMC13344983

• EXPRESS: Amnesia in healthy people via hippocampal inhibition: A new forgetting mechanism. Quarterly journal of experimental psychology (2006) Anderson, M., Subbulakshmi, S. 2023: 17470218231202728

  Abstract

  Structural damage to the hippocampus gives rise to a severe memory deficit for personal experiences known as organic amnesia. Remarkably, such structural damage may not be the only way of creating amnesia; windows of amnesia can also arise when people deliberately disengage from memory via a process known as retrieval suppression. In this review, we discuss how retrieval suppression induces systemic inhibition of the hippocampus, creating 'amnesic shadow' intervals in people's memory for their personal experiences. When new memories are encoded or older memories are reactivated during this amnesic shadow, these memories are disrupted, and such disruption even arises when older memories are subliminally cued. Evidence suggests that the systemic inhibition of the hippocampus during retrieval suppression that gives rise to the amnesic shadow may be mediated by engagement of hippocampal GABAergic inhibitory interneurons. Similar amnesic shadow effects are observed during working memory tasks like the n-back, which also induce notable hippocampal downregulation. We discuss our recent proposal that cognitive operations that require the disengagement of memory retrieval, such as retrieval suppression, are capable of mnemonic process inhibition (the inhibition of mnemonic processes such as encoding, consolidation, and retrieval and not simply individual memories). We suggest that people engage mnemonic process inhibition whenever they shift attention from internal processes to demanding perceptual-motor tasks that may otherwise be disrupted by distraction from our inner world. This hitherto unstudied model of inhibition is a missing step in understanding what happens when attentional shifts occur between internally and externally oriented processes to facilitate goal-directed behavior. This process constitutes an important novel mechanism underlying the forgetting of life events.

  View details for DOI 10.1177/17470218231202728

  View details for PubMedID 37691157