The D'Esposito Lab is a cognitive neuroscience research laboratory within the
Helen Wills Neuroscience Institute
and the Department of Psychology.

Recent Publications

Tambini, A, Nee DE, D'Esposito M.  2018.  Hippocampal-targeted Theta-burst Stimulation Enhances Associative Memory Formation., 2018 Jun 19. Journal of cognitive neuroscience. :1-21. Abstract

The hippocampus plays a critical role in episodic memory, among other cognitive functions. However, few tools exist to causally manipulate hippocampal function in healthy human participants. Recent work has targeted hippocampal-cortical networks by performing TMS to a region interconnected with the hippocampus, posterior inferior parietal cortex (pIPC). Such hippocampal-targeted TMS enhances associative memory and influences hippocampal functional connectivity. However, it is currently unknown which stages of mnemonic processing (encoding or retrieval) are affected by hippocampal-targeted TMS. Here, we examined whether hippocampal-targeted TMS influences the initial encoding of associations (vs. items) into memory. To selectively influence encoding and not retrieval, we performed continuous theta-burst TMS before participants encoded object-location associations and assessed memory after the direct effect of stimulation dissipated. Relative to control TMS and baseline memory, pIPC TMS enhanced associative memory success and confidence. Item memory was unaffected, demonstrating a selective influence on associative versus item memory. The strength of hippocampal-pIPC functional connectivity predicted TMS-related memory benefits, which was mediated by parahippocampal and retrosplenial cortices. Our findings indicate that hippocampal-targeted TMS can specifically modulate the encoding of new associations into memory without directly influencing retrieval processes and suggest that the ability to influence associative memory may be related to the fidelity of hippocampal TMS targeting. Our results support the notion that pIPC TMS may serve as a potential tool for manipulating hippocampal function in healthy participants. Nonetheless, future work combining hippocampal-targeted continuous theta-burst TMS with neuroimaging is needed to better understand the neural basis of TMS-induced memory changes.

Kornblith, E, Abrams G, Chen AJ-W, Burciaga J, D'Esposito M, Novakovic-Agopian T.  2018.  Impact of baseline neurocognitive functioning on outcomes following rehabilitation of executive function training for veterans with history of traumatic brain injury., 2018 Oct 08. Applied neuropsychology. Adult. :1-13. Abstract

Traumatic brain injury (TBI) is common among Veterans, and sequelae frequently include deficits in attention and executive function and problems with emotional regulation. Although rehabilitation has been shown to be effective, it is not clear how patient characteristics such as baseline cognitive status may impact response to rehabilitation in this sample. Explore the relationship between baseline neuropsychological status and postintervention functional outcomes in Veterans with chronic TBI. Thirty-three Veterans with chronic mild-severe TBI completed a neuropsychological evaluation, a functional assessment of executive function (EF), and measures of emotional and everyday functioning pre- and post-EF training or control training. Performance on baseline neuropsychological measures was used to cluster participants. Participants' performance at baseline and postintervention assessments was compared by cluster using multivariate analyses of variance (MANOVAs). Cognitive Difficulty (CD; n = 19) and Cognitively Normal (CN; n = 14) clusters were identified. CD was characterized by z ≤ -.75 on neuropsychological measures of overall attention/EF, working memory, and memory. CD participants performed worse on functional EF assessment and endorsed more PTSD symptoms and community integration problems, at baseline. CD participants improved post-EF training, but not control training, on neuropsychological and functional measures. CN participants did not show statistically significant improvement. For Veterans with chronic TBI, cognitive assessment can aid in identifying functional impairment and assist treatment planning. Cognitive rehabilitation training appears to be a beneficial treatment option for TBI patients with cognitive, emotional, and daily living difficulties.

Sadaghiani, S, Dombert PL, Løvstad M, Funderud I, Meling TR, Endestad T, Knight RT, Solbakk A-K, D'Esposito M.  2018.  Lesions to the Fronto-Parietal Network Impact Alpha-Band Phase Synchrony and Cognitive Control., 2018 Dec 07. Cerebral cortex (New York, N.Y. : 1991). Abstract

Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10-12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility.

Bertolero, MA, Yeo TBT, Bassett DS, D'Esposito M.  2018.  A mechanistic model of connector hubs, modularity and cognition., 2018 Oct. Nature human behaviour. 2(10):765-777. Abstract

The human brain network is modular-comprised of communities of tightly interconnected nodes. This network contains local hubs, which have many connections within their own communities, and connector hubs, which have connections diversely distributed across communities. A mechanistic understanding of these hubs and how they support cognition has not been demonstrated. Here, we leveraged individual differences in hub connectivity and cognition. We show that a model of hub connectivity accurately predicts the cognitive performance of 476 individuals in four distinct tasks. Moreover, there is a general optimal network structure for cognitive performance-individuals with diversely connected hubs and consequent modular brain networks exhibit increased cognitive performance, regardless of the task. Critically, we find evidence consistent with a mechanistic model in which connector hubs tune the connectivity of their neighbors to be more modular while allowing for task appropriate information integration across communities, which increases global modularity and cognitive performance.

Cameron, IGM, Wallace DL, Al-Zughoul A, Kayser AS, D'Esposito M.  2018.  Effects of tolcapone and bromocriptine on cognitive stability and flexibility., 2018 Feb 09. Psychopharmacology. Abstract

The prefrontal cortex (PFC) and basal ganglia (BG) have been associated with cognitive stability and cognitive flexibility, respectively. We hypothesized that increasing PFC dopamine tone by administering tolcapone (a catechol-O-methyltransferase (COMT) inhibitor) to human subjects should promote stability; conversely, increasing BG dopamine tone by administering bromocriptine (a D2 receptor agonist) should promote flexibility.