The rises and falls of disconnection syndromes. Brain

Centre for Neuroimaging Sciences, Institute of Psychiatry, De Crespigny Park, London, UK.
Brain (Impact Factor: 9.2). 11/2005; 128(Pt 10):2224-39. DOI: 10.1093/brain/awh622
Source: PubMed


In a brain composed of localized but connected specialized areas, disconnection leads to dysfunction. This simple formulation underlay a range of 19th century neurological disorders, referred to collectively as disconnection syndromes. Although disconnectionism fell out of favour with the move against localized brain theories in the early 20th century, in 1965, an American neurologist brought disconnection to the fore once more in a paper entitled, 'Disconnexion syndromes in animals and man'. In what was to become the manifesto of behavioural neurology, Norman Geschwind outlined a pure disconnectionist framework which revolutionized both clinical neurology and the neurosciences in general. For him, disconnection syndromes were higher function deficits that resulted from white matter lesions or lesions of the association cortices, the latter acting as relay stations between primary motor, sensory and limbic areas. From a clinical perspective, the work reawakened interest in single case studies by providing a useful framework for correlating lesion locations with clinical deficits. In the neurosciences, it helped develop contemporary distributed network and connectionist theories of brain function. Geschwind's general disconnectionist paradigm ruled clinical neurology for 20 years but in the late 1980s, with the re-emergence of specialized functional roles for association cortex, the orbit of its remit began to diminish and it became incorporated into more general models of higher dysfunction. By the 1990s, textbooks of neurology were devoting only a few pages to classical disconnection theory. Today, new techniques to study connections in the living human brain allow us, for the first time, to test the classical formulation directly and broaden it beyond disconnections to include disorders of hyperconnectivity. In this review, on the 40th anniversary of Geschwind's publication, we describe the changing fortunes of disconnection theory and adapt the general framework that evolved from it to encompass the entire spectrum of higher function disorders in neurology and psychiatry.

  • Source
    • "This work along with contemporary connectionist theories (Catani & ffytche, 2005) underscores the distributed network effects of focal brain injury (diaschisis). A hodotopic model of visual hallucinations emphasizes dysfunction localized within specific brain regions (topological) and aberrant connectivity between regions (hodological) (Catani & ffytche, 2005; ffytche, 2008). Advances in human brain imaging , in particular resting-state functional connectivity MRI (rsfcMRI ), allow for the direct testing of atypical functional connection in the living human brain. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Brainstem lesions causing peduncular hallucinosis (PH) produce vivid visual hallucinations occasionally accompanied by sleep disorders. Overlapping brainstem regions modulate visual pathways and REM sleep functions via gating of thalamocortical networks. A 66-year-old man with paroxysmal atrial fibrillation developed abrupt-onset complex visual hallucinations with preserved insight and violent dream enactment behavior. Brain MRI showed restricted diffusion in the left rostrodorsal pons suggestive of an acute ischemic stroke. REM sleep behavior disorder (RBD) was diagnosed on polysomnography. We investigated the integrity of ponto-geniculate-occipital circuits with seed-based resting-state functional connectivity MRI (rs-fcMRI) in this patient compared to 46 controls. Rs-fcMRI revealed significantly reduced functional connectivity between the lesion and lateral geniculate nuclei (LGN), and between LGN and visual association cortex compared to controls. Conversely, functional connectivity between brainstem and visual association cortex, and between visual association cortex and prefrontal cortex (PFC) was significantly increased in the patient. Focal damage to the rostrodorsal pons is sufficient to cause RBD and PH in humans, suggesting an overlapping mechanism in both syndromes. This lesion produced a pattern of altered functional connectivity consistent with disrupted visual cortex connectivity via de-afferentation of thalamocortical pathways.
    Full-text · Article · Nov 2015 · Cortex
    • "One of the most important contributions of Norman Geschwind's seminal papers on disconnection syndrome (1965) was the idea that higher brain functions arise from distributed brain networks that, when lesioned, produce behavioral disturbance (Catani, 2005). Traumatic brain injury (TBI) provides a prime example of such network dysfunction (Bigler, 2001). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. TBI has a negative impact on distributed brain networks that lead to behavioral disturbance.
    No preview · Article · Nov 2015 · Journal of the International Neuropsychological Society
  • Source
    • "Unlike other methods, DWI allows the study of brain connectivity by non-invasively tracing connections in the living tissue. Using DWI, we can better understand the disconnecting lesions in relation to their clinical symptoms (Catani and ffytche 2005). The disconnection paradigm – advanced by Geschwind in 1965 (Geschwind 1965a, b), has been proposed to partially explain AD symptomatology (Morrison et al. 1986; Morris 1996; Delbeuck et al. 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer's disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics - fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter - the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.
    Full-text · Article · Oct 2015 · Brain Imaging and Behavior
Show more