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      Motor, cognitive, and affective areas of the cerebral cortex influence the adrenal medulla

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      Proceedings of the National Academy of Sciences
      Proceedings of the National Academy of Sciences

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          Abstract

          Modern medicine has generally viewed the concept of "psychosomatic" disease with suspicion. This view arose partly because no neural networks were known for the mind, conceptually associated with the cerebral cortex, to influence autonomic and endocrine systems that control internal organs. Here, we used transneuronal transport of rabies virus to identify the areas of the primate cerebral cortex that communicate through multisynaptic connections with a major sympathetic effector, the adrenal medulla. We demonstrate that two broad networks in the cerebral cortex have access to the adrenal medulla. The larger network includes all of the cortical motor areas in the frontal lobe and portions of somatosensory cortex. A major component of this network originates from the supplementary motor area and the cingulate motor areas on the medial wall of the hemisphere. These cortical areas are involved in all aspects of skeletomotor control from response selection to motor preparation and movement execution. The second, smaller network originates in regions of medial prefrontal cortex, including a major contribution from pregenual and subgenual regions of anterior cingulate cortex. These cortical areas are involved in higher-order aspects of cognition and affect. These results indicate that specific multisynaptic circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness.

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          Most cited references51

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          Human cingulate cortex and autonomic control: converging neuroimaging and clinical evidence.

          Human anterior cingulate function has been explained primarily within a cognitive framework. We used functional MRI experiments with simultaneous electrocardiography to examine regional brain activity associated with autonomic cardiovascular control during performance of cognitive and motor tasks. Using indices of heart rate variability, and high- and low-frequency power in the cardiac rhythm, we observed activity in the dorsal anterior cingulate cortex (ACC) related to sympathetic modulation of heart rate that was dissociable from cognitive and motor-related activity. The findings predict that during effortful cognitive and motor behaviour the dorsal ACC supports the generation of associated autonomic states of cardiovascular arousal. We subsequently tested this prediction by studying three patients with focal damage involving the ACC while they performed effortful cognitive and motor tests. Each showed abnormalities in autonomic cardiovascular responses with blunted autonomic arousal to mental stress when compared with 147 normal subjects tested in identical fashion. Thus, converging neuroimaging and clinical findings suggest that ACC function mediates context-driven modulation of bodily arousal states.
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            Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans.

            1. States of peripheral autonomic arousal accompany emotional behaviour, physical exercise and cognitive effort, and their central representation may influence decision making and the regulation of social and emotional behaviours. However, the cerebral functional neuroanatomy representing and mediating peripheral autonomic responses in humans is poorly understood. 2. Six healthy volunteer subjects underwent H215O positron emission tomography (PET) scanning while performing isometric exercise and mental arithmetic stressor tasks, and during corresponding control tasks. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored during scanning. 3. Data were analysed using statistical parametric mapping (SPM99). Conjunction analyses were used to determine significant changes in regional cerebral blood flow (rCBF) during states of cardiovascular arousal common to both exercise and mental stressor tasks. 4. Exercise and mental stressor tasks, relative to their control tasks, were associated with significantly (P < 0.001) increased MAP and HR. Significant common activations (increased rCBF) were observed in cerebellar vermis, brainstem and right anterior cingulate. In both exercise and mental stress tasks, increased rCBF in cerebellar vermis, right anterior cingulate and right insula covaried with MAP; rCBF in pons, cerebellum and right insula covaried with HR. Cardiovascular arousal in both categorical and covariance analyses was associated with decreased rCBF in prefrontal and medial temporal regions. 5. Neural responses in discrete brain regions accompany peripheral cardiovascular arousal. We provide evidence for the involvement of areas previously implicated in cognitive and emotional behaviours in the representation of peripheral autonomic states, consistent with a functional organization that produces integrated cardiovascular response patterns in the service of volitional and emotional behaviours.
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              Frontal lobe inputs to the digit representations of the motor areas on the lateral surface of the hemisphere.

              We examined the frontal lobe connections of the digit representations in the primary motor cortex (M1), the dorsal premotor area (PMd), and the ventral premotor area (PMv) of cebus monkeys. All of these digit representations lie on the lateral surface of the hemisphere. We used intracortical stimulation to identify the digit representations physiologically, and then we injected different tracers into two of the three cortical areas. This approach enabled us to compare the inputs to two digit representations in the same animal. We found that the densest inputs from the premotor areas to the digit representation in M1 originate from the PMd and the PMv. Both of these premotor areas contain a distinct digit representation, and the two digit representations are densely interconnected. Surprisingly, the projections from the digit representation in the supplementary motor area (SMA) to the PMd and PMv are stronger than the SMA projections to M1. The projections from other premotor areas to M1, the PMd, and the PMv are more modest. Of the three digit areas on the lateral surface, only the PMv receives dense input from the prefrontal cortex. Based on these results, we believe that M1, the PMd, and the PMv form a densely interconnected network of cortical areas that is concerned with the generation and control of hand movements. Overall, the laminar origins of neurons that interconnect the three cortical areas are typical of "lateral" interactions. Thus, from an anatomical perspective, this cortical network lacks a clear hierarchical organization.
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                Proc Natl Acad Sci USA
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                August 30 2016
                August 30 2016
                August 30 2016
                August 15 2016
                : 113
                : 35
                : 9922-9927
                Article
                10.1073/pnas.1605044113
                5024624
                27528671
                3d118d0e-3cc9-4d62-b2cd-b2aaddbb97a8
                © 2016

                Free to read

                http://www.pnas.org/site/misc/userlicense.xhtml

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