Person:

Janes, Amy

Craving is a key aspect of drug dependence that is thought to motivate continued drug use. Numerous brain regions have been associated with craving, suggesting that craving is mediated by a distributed brain network. Whether an increase in subjective craving is associated with enhanced interactions among brain regions was evaluated using resting state functional magnetic imaging (fMRI) in nicotine dependent participants. We focused on craving-related changes in the orbital and medial prefrontal cortex (OMPFC) network, which also included the subgenual anterior cingulate cortex (sgACC) extending into the ventral striatum. Brain regions in the OMPFC network are not only implicated in addiction and reward, but, due to their rich anatomic interconnections, may serve as the site of integration across craving-related brain regions. Subjective craving and resting state fMRI were evaluated twice with an ∼1 hour delay between the scans. Cigarette craving was significantly increased at the end, relative to the beginning of the scan session. Enhanced craving was associated with heightened coupling between the OMPFC network and other cortical, limbic, striatal, and visceromotor brain regions that are both anatomically interconnected with the OMPFC, and have been implicated in addiction and craving. This is the first demonstration confirming that an increase in craving is associated with enhanced brain region interactions, which may play a role in the experience of craving.

Parkinson's disease (PD) is largely attributed to disruptions in the nigrostriatal dopamine system. These neurodegenerative changes may also have a more global effect on intrinsic brain organization at the cortical level. Functional brain connectivity between neurocognitive systems related to cognitive processing is critical for effective neural communication, and is disrupted across neurological disorders. Three core neurocognitive networks have been established as playing a critical role in the pathophysiology of many neurological disorders: the default-mode network (DMN), the salience network (SN), and the central executive network (CEN). In healthy adults, DMN–CEN interactions are anti-correlated while SN–CEN interactions are strongly positively correlated even at rest, when individuals are not engaging in any task. These intrinsic between-network interactions at rest are necessary for efficient suppression of the DMN and activation of the CEN during a range of cognitive tasks. To identify whether these network interactions are disrupted in individuals with PD, we used resting state functional magnetic resonance imaging (rsfMRI) to compare between-network connectivity between 24 PD participants and 20 age-matched controls (MC). In comparison to the MC, individuals with PD showed significantly less SN–CEN coupling and greater DMN–CEN coupling during rest. Disease severity, an index of striatal dysfunction, was related to reduced functional coupling between the striatum and SN. These results demonstrate that individuals with PD have a dysfunctional pattern of interaction between core neurocognitive networks compared to what is found in healthy individuals, and that interaction between the SN and the striatum is even more profoundly disrupted in those with greater disease severity.

It is widely accepted that the fluctuations in resting state blood oxygenation level dependent (BOLD) functional MRI (fMRI) reflect baseline neuronal activation through neurovascular coupling; this data is used to infer functional connectivity in the human brain during rest. Consistent activation patterns, i.e., resting state networks (RSN) are seen across groups, conditions, and even species. In this study, we show that some of these patterns can also be generated from the dynamic, systemic, non-neuronal physiological low frequency oscillations (sLFOs) in the BOLD signal alone. We have previously used multimodal imaging to demonstrate the wide presence of the same sLFOs in the brain (BOLD) and periphery with different time delays. This study shows that these sLFOs from BOLD signals alone can give rise to stable spatial patterns, which can be detected during resting state analyses. We generated synthetic resting state data for 11 subjects based only on subject-specific, dynamic sLFO information obtained from resting state data using concurrent peripheral optical imaging or a novel recursive procedure. We compared the results obtained by performing a group independent component analysis (ICA) on this synthetic data (i.e., the result from simulation) to the results obtained from analysis of the real data. ICA detected most of the eight well-known RSNs, including visual, motor, and default mode networks (DMNs), in both the real and the synthetic data sets. These findings suggest that RSNs may reflect, to some extent, vascular anatomy associated with systemic fluctuations, rather than neuronal connectivity.

Focusing on sex differences is necessary to fully understand basic neurobiological processes such as the engagement of large-scale brain networks involved in attention. Prior work suggests that women show enhanced attention during tasks of reward/punishment relative to men. Yet, sex differences in the engagement of neural networks sub serving internal and external focus has been unexplored in regard to reward and punishment. Using data from a large sample (n = 190) of healthy participants from the Human Connectome Project, we investigated sex differences in default mode network (DMN), dorsal attention network (DAN), and frontal parietal network (FPN) activation during exposure to reward and punishment. To determine if sex differences are specific to valenced stimuli, we analyzed network activation during working memory. Results indicate that, relative to men, women have increased suppression of the DMN and greater activation of the DAN during exposure to reward and punishment. Given the relative roles of these networks in internal (DMN) and external (DAN) attention, this pattern of activation suggests that women have enhanced external attention to reward and punishment. In contrast, there were no sex differences in network activation during working memory, indicating that this sex difference is specific to the processing of reward and punishment. These findings suggest a neurobiological explanation for prior work showing women have greater sensitivity to reward/punishment and are more prone to psychiatric disorders characterized by enhanced attention to such stimuli. Furthermore, given the large sample from the Human Connectome Project, the current findings provide general implications for the study of sex as a biological variable in investigation of reward processes.