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Neuroimage. 2014 Aug 15;97:321-32. doi: 10.1016/j.neuroimage.2014.04.019. Epub 2014 Apr 13.

Resting state functional connectivity of the basal nucleus of Meynert in humans: in comparison to the ventral striatum and the effects of age.

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Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Department of Neurobiology, Yale University, New Haven, CT 06520, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA. Electronic address:
Department of Psychiatry, Yale University, New Haven, CT 06519, USA; Department of Science and Technology, Federal University of Sao Paulo, Sao Jose dos Campos, SP 12231, Brazil.
Department of Psychiatry, Yale University, New Haven, CT 06519, USA.
Department of Internal Medicine, Yale University New Haven, CT 06519, USA; Medical Service, VA Connecticut Health Care System, West Haven, CT 06516, USA.
Center for Molecular and Behavioral Neuroscience, Rutgers, NJ 07102, USA.


The basal nucleus of Meynert (BNM) provides the primary cholinergic inputs to the cerebral cortex. Loss of neurons in the BNM is linked to cognitive deficits in Alzheimer's disease and other degenerative conditions. Numerous animal studies described cholinergic and non-cholinergic neuronal responses in the BNM; however, work in humans has been hampered by the difficulty of defining the BNM anatomically. Here, on the basis of a previous study that delineated the BNM of post-mortem human brains in a standard stereotaxic space, we sought to examine functional connectivity of the BNM, as compared to the nucleus accumbens (or ventral striatum, VS), in a large resting state functional magnetic resonance imaging data set. The BNM and VS shared but also showed a distinct pattern of cortical and subcortical connectivity. Compared to the VS, the BNM showed stronger positive connectivity with the putamen, pallidum, thalamus, amygdala and midbrain, as well as the anterior cingulate cortex, supplementary motor area and pre-supplementary motor area, a network of brain regions that respond to salient stimuli and orchestrate motor behavior. In contrast, compared to the BNM, the VS showed stronger positive connectivity with the ventral caudate and medial orbitofrontal cortex, areas implicated in reward processing and motivated behavior. Furthermore, the BNM and VS each showed extensive negative connectivity with visual and lateral prefrontal cortices. Together, the distinct cerebral functional connectivities support the role of the BNM in arousal, saliency responses and cognitive motor control and the VS in reward related behavior. Considering the importance of BNM in age-related cognitive decline, we explored the effects of age on BNM and VS connectivities. BNM connectivity to the visual and somatomotor cortices decreases while connectivity to subcortical structures including the midbrain, thalamus, and pallidum increases with age. These findings of age-related changes of cerebral functional connectivity of the BNM may facilitate research of the neural bases of cognitive decline in health and illness.


Basal forebrain; Functional connectivity; Nucleus of Meynert; Resting state; Ventral striatum; fMRI

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