Every waking minute we have thoughts, we observe new things, we make decisions, we solve problems. How do these mental phenomena arise from the physical activity of neurons in the brain? This is the question our laboratory addresses.
The focus of our work in recent years has been the neural basis of working memory, the “sketchpad” of the mind, which allows us to represent information temporarily, in our train of thought. The techniques we use include neurophysiological recordings from multiple neurons in non-human primates, MRI and PET imaging, electrical stimulation, and computational analysis and modeling.
Questions we are actively pursuing include the roles of different cortical areas in working memory, the changes neural activity undergoes during adolescent development and in aging, and how working memory can be improved with training and deep brain stimulation.
|Christos Constantinidis, PhD
Xuelian Qi, PhD
Saravanan Subramaniam, PhD
Lab Tech II
Our laboratory has been investigating the changes in cognitive ability and concomitant anatomical and neurophysiological changes that occur between the time of puberty and adulthood. We are focusing on two cognitive domains, working memory and response inhibition. We are assessing improvements in behavioral performance, structural brain changes and functional network changes observable with MRI, and changes in neural activity.
There is strong evidence that cognitive functions are distributed across multiple brain areas. What are the roles of each area? In recent years we have focused on two critical nodes of the network that mediates spatial working memory, the dorsolateral prefrontal and posterior parietal cortex. Simultaneous recordings in both brain regions during performance of working memory tasks allow us to investigate the unique and complementary roles of each, as a model for understanding the distributed nature of cognition.
Working memory is notoriously limited to a handful of items (about 7 digits or numbers, even less for other types of stimuli that cannot be easily grouped into chunks). However, working memory capacity can be improved with computerized training, and improvements often generalize (“transfer”) to other cognitive domains that were not explicitly trained. What are the changes in neural activity that underlie the phenomenon? Recordings with arrays of microelectrodes investigate this question in subjects, as they are being trained in working memory tasks.
We have shown that intermittent electrical stimulation of the basal forebrain targeting the Nucleus Basalis of Meynert can improve behavioral performance of working memory and attention tasks. We try to understand the neural basis of the phenomenon and to optimize the intervention. Such Deep Brain Stimulation improving cognitive function holds promise for conditions such as Alzheimer’s disease, and age-related dementia. Human clinical trials are planned next.
Differential Processing of Isolated Object and Multi-item Pop-Out Displays in LIP and PFC.. Meyers EM, Liang A, Katsuki F, Constantinidis C. Cereb. Cortex. 2018 Nov; 28(11):3816-3828.
Persistent Spiking Activity Underlies Working Memory.. Constantinidis C, Funahashi S, Lee D, Murray JD, Qi XL, Wang M, Arnsten AFT. J. Neurosci. 2018 Aug; 38(32):7020-7028.
Representation of Spatial and Feature Information in the Monkey Dorsal and Ventral Prefrontal Cortex.. Constantinidis C, Qi XL. Front Integr Neurosci. 2018; 12:31.
Intermittent stimulation in the nucleus basalis of meynert improves sustained attention in rhesus monkeys.. Liu R, Crawford J, Callahan PM, Terry AV, Constantinidis C, Blake DT. Neuropharmacology. 2018 07; 137:202-210.
Potential for intermittent stimulation of nucleus basalis of Meynert to impact treatment of alzheimer's disease.. Blake DT, Terry AV, Plagenhoef M, Constantinidis C, Liu R. Commun Integr Biol. 2017; 10(5-6):e1389359.