PAUL NEWHOUSE

Professor
Psychiatry

M.D., Loyola University, 1978
Postdoctoral training: Walter Reed Army Medical Center and Institute of Research, National Institute of Mental Health

Paul.Newhouse@uvm.edu

Cognition, broadly defined, includes attention, learning, memory, and emotion. Cognitive processes involve a variety of brain systems including discrete structures in the brain such as the hippocampus and amygdala as well as specific neurotransmitters such as acetylcholine and hormones such as estrogen. Cognitive abilities change with aging and our laboratory (Clinical Neuroscience Research Unit) investigates how alterations in learning, memory, and emotion may be caused by specific neurobiological changes in the aging brain.

We are particularly interested in how sex hormones such as estrogen and progesterone interact with neurotransmitter systems that are specifically involved in attention and memory including acetylcholine. Interestingly, estrogen appears to have the ability to stimulate or modulate brain cholinergic systems. We utilize both short-and long-term hormone and drug administration studies along with cognitive testing and functional brain imaging to examine complex hormone-neurotransmitter interactions in women after menopause.

Brain activity map (BOLD) during the performance of a working memory task (N-back task).

We are also interested in how sex hormones affect emotion and emotion-regulating structures of the brain such as the amygdala and frontal cortex in older women.  We are also studying how chemotherapy after breast cancer affects cognition, brain function, and brain anatomy (so-called "chemobrain").

Other studies in our laboratory focus on the effects of nicotinic cholinergic system activation on cognition in older memory-impaired individuals with Mild Cognitive Impairment (MCI) and the effects of nicotinic stimulation on behavioral impulsivity on individuals with Attention Deficit-Hyperactivity Disorder (ADHD).

We utilize computerized cognitive assessment including virtual reality as well as functional and structural human brain imaging utilizing the University of Vermont Research Imaging Center which includes a Phillips 3 Tesla (3T) research human magnetic resonance imaging system, and a state-of-the-art stimulus and image capture system. Most of our support for these projects comes from the National Institute on Aging, the National Institute for Mental Health, and the Breast Cancer Research Foundation.

For more information, visit http://www.uvm.edu/~cnru/.

White matter fiber tracts in the brain mapped using diffusion tensor imaging (DTI). (courtesy, C. Filippi)

• Effects of Estrogen on Sensitivity to Cholinergic Blockade, Cognitive Symptomatology, and Brain Morphology in Younger Postmenopausal Women.
  This project seeks to examine the relationship between memory complaints that may occur in the postmenopausal period of a woman's life, brain morphology and and function utilizing structural magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), and the effect of estrogen on cholinergic-related cognition. The goal is to establish whether there are factors that may help to predict which women will respond positively to estrogen after menopause.  Supported by the National Institute on Aging.

• The Effects of Estrogen with or without Progesterone on Cholinergic-Related cognitive functioning after Menopause.
  This project studies the effect of estradiol and micronized progesterone on cholinergic-related cognitive functioning (including attention and memory) in younger and older postmenopausal women.  As estrogen alone appears to have positive effects on both attention and memory that is controlled by brain cholinergic systems, it is necessary to study whether progesterone supports or antagonizes these effects. Supported by the National Institute on Aging.

• The Effects of Acute versus Chronic Estrogen on Cholinergic-Related cognitive functioning after Menopause.
  This study examines the neurobiological underpinnings of estrogen's beneficial effects on cholinergic-related attention and memory functioning in older women by studying the effects of a single dose versus chronic dosing of estradiol on cholinergic-related cognitive performance. Supported by the National Institute on Aging.

• Nicotine Treatment of Mild Cognitive Impairment.
  This multicenter trial is studying whether transdermal nicotine patch can improve the symptoms and cognitive performance of patients with mild cognitive impairment (MCI), a precursor condition to Alzheimer's disease. Patients are studied for one year (six months double-blind and six months open label). The study is funded by the National Institute on Aging.
  

• The Effects of Estradiol Administration on Emotional Responses and Brain Activation to Emotional Stimuli in Older Women.
  This study examines the effect of estradiol on the brain activity responses utilizing fMRI to negative emotional stimuli in postmenopausal women. The goal is to establish how exogenously administered estradiol modulates the activity of emotion-related structures in the brain.  Supported by UVM COM NRI.

• The Effects of Adjuvant Chemotherapy for Early Breast Cancer on Brain Imaging and Cognitive Function.
  This project examines the effect of chemotherapy on brain function and anatomy in patients with newly diagnosed breast cancer. The goal of this study is to correlate changes in cognitive functioning (so-called "chemobrain") with alterations in brain activity utilizing functional magnetic resonance imaging (fMRI) and brain anatomy, particularly white matter integrity using diffusion tensor imaging (DTI).  Supported by the Breast Cancer Research Foundation.

Newhouse P.A., Dumas J.A., Hancur-Bucci C., Naylor M., Sites C., Benkelfat C., Young S. Estrogen administration negatively alters mood following monoaminergic depletion and psychosocial stress in postmenopausal women. Neuropsychopharmacology 33: 1514-1527, 2008

Dumas, JA, Saykin, AJ, McAllister, TW, McDonald, BC, Hynes, ML, Newhouse, P.A. Nicotinic versus Muscarinic Blockade Alters Verbal Working Memory-Related Brain Activity in Older Women. American Journal of Geriatric Psychiatry 16: 272-282, 2008

Coderre, E, Filippi, C, Newhouse, PA, Dumas, J. A Brain fMRI Study of the Stroop Effect in Native Japanese Speakers. Brain and Language doi:10.1016/j.bandl.2008.01.011

Dumas, JA, Hancur-Bucci, C, Naylor, M, Sites, C, Newhouse, PA. Estradiol Interacts with the Cholinergic System to Affect Verbal Memory in Post-Menopausal Women: Evidence for the Critical Period Hypothesis. Hormones and Behavior 53: 159-169, 2008

Potter, A, Newhouse, PA. Acute Nicotine Improves Cognitive Deficits in Young Adults with Attention-Deficit/Hyperactivity Disorder. Pharmacology, Biochemistry, and Behavior 88: 407-417, 2008

Newhouse, P.A., Newhouse, C.D., Astur, R. Gender Differences in Visual-Spatial Learning Using a Virtual Water Maze in Pre-Pubertal Children. Behavioural Brain Research 183: 1-7, 2007

Dumas, J.A., Naylor, M., Sites, C., Hancur, C., Newhouse, P.A. Estrogen Effects on anticholinergic-induced cognitive dysfunction in postmenopausal women. Neuropsychopharmacology 31: 2065-2078, 2006