‘ An investigation of the nervous control of defecation ’ by Denny-Brown and Robertson: a classic paper revisited

In 1935 two young neurologists, Derek Denny-Brown and E. Graeme Robertson, published an article explaining the mechanisms underlying human defaecation based on a manometric study in patients with sacral root and spinal cord lesions, and normal subjects. This article is still routinely cited in studies of rectal and sphincter ani function. Unfortunately, however, the article itself is not written well, being composed of long convoluted sentences and containing 79 often indecipherable figures. Difficult-to-understand articles were common to the publications of Denny-Brown, who became one of the most prominent neurologists of the twentieth century. In accord with our prior work explaining Denny-Brown and Robertson's earlier paper on micturition, we provide here what we hope is a clear explanation of the methods and results in their study on defaecation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73905/1/j.1463-1318.2004.00636.x.pd

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Altered Cerebellar-Cerebral Functional Connectivity in Geriatric Depression

Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (n = 11) and healthy controls (n = 18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus II–vmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermis–posterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellum–vmPFC coupling may be related to cognitive function whereas cerebellum–PCC coupling may be related to emotion processing in geriatric depression

Postural Hypo-Reactivity in Autism is Contingent on Development and Visual Environment: A Fully Immersive Virtual Reality Study

Although atypical motor behaviors have been associated with autism, investigations regarding their possible origins are scarce. This study assessed the visual and vestibular components involved in atypical postural reactivity in autism. Postural reactivity and stability were measured for younger (12–15 years) and older (16–33 years) autistic participants in response to a virtual tunnel oscillating at different frequencies. At the highest oscillation frequency, younger autistic participants showed significantly less instability compared to younger typically-developing participants; no such group differences were evidenced for older participants. Additionally, no significant differences in postural behavior were found between all 4 groups when presented with static or without visual information. Results confirm that postural hypo-reactivity to visual information is present in autism, but is contingent on both visual environment and development

Cortical Representation of Lateralized Grasping in Chimpanzees (Pan troglodytes): A Combined MRI and PET Study

Functional imaging studies in humans have localized the motor-hand region to a neuroanatomical landmark call the KNOB within the precentral gyrus. It has also been reported that the KNOB is larger in the hemisphere contralateral to an individual's preferred hand, and therefore may represent the neural substrate for handedness. The KNOB has also been neuronatomically described in chimpanzees and other great apes and is similarly associated with handedness. However, whether the chimpanzee KNOB represents the hand region is unclear from the extant literature. Here, we used PET to quantify neural metabolic activity in chimpanzees when engaged in unilateral reach-and-grasping responses and found significantly lateralized activation of the KNOB region in the hemisphere contralateral to the hand used by the chimpanzees. We subsequently constructed a probabilistic map of the KNOB region in chimpanzees in order to assess the overlap in consistency in the anatomical landmarks of the KNOB with the functional maps generated from the PET analysis. We found significant overlap in the anatomical and functional voxels comprising the KNOB region, suggesting that the KNOB does correspond to the hand region in chimpanzees. Lastly, from the probabilistic maps, we compared right- and left-handed chimpanzees on lateralization in grey and white matter within the KNOB region and found that asymmetries in white matter of the KNOB region were larger in the hemisphere contralateral to the preferred hand. These results suggest that neuroanatomical asymmetries in the KNOB likely reflect changes in connectivity in primary motor cortex that are experience dependent in chimpanzees and possibly humans

The pathophysiology of restricted repetitive behavior

Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism