Early anatomically based models of language consisted of an arcuate tract connecting Broca's speech and Wernicke's comprehension centers; a lesion of the tract resulted in conduction aphasia. However, the heterogeneous clinical presentations of conduction aphasia suggest a greater complexity of perisylvian anatomical connections than allowed for in the classical anatomical model. This article re-explores perisylvian language connectivity using in vivo diffusion tensor magnetic resonance imaging tractography. Diffusion tensor magnetic resonance imaging data from 11 right-handed healthy male subjects were averaged, and the arcuate fasciculus of the left hemisphere reconstructed from this data using an interactive dissection technique. Beyond the classical arcuate pathway connecting Broca's and Wernicke's areas directly, we show a previously undescribed, indirect pathway passing through inferior parietal cortex. The indirect pathway runs parallel and lateral to the classical arcuate fasciculus and is composed of an anterior segment connecting Broca's territory with the inferior parietal lobe and a posterior segment connecting the inferior parietal lobe to Wernicke's territory. This model of two parallel pathways helps explain the diverse clinical presentations of conduction aphasia. The anatomical findings are also relevant to the evolution of language, provide a framework for Lichtheim's symptom-based neurological model of aphasia, and constrain, anatomically, contemporary connectionist accounts of language.

Diffusion tensor MRI (DT-MRI) provides information about the structural organization and orientation of white matter fibres and, through the technique of 'tractography', reveals the trajectories of cerebral white matter tracts. We used tractography in the living human brain to address the disputed issue of the nature of occipital and temporal connections. Classical anatomical studies described direct fibre connections between occipital and anterior temporal cortex in a bundle labelled the inferior longitudinal fasciculus (ILF). However, their presence has been challenged by more recent evidence suggesting that connections between the two regions are entirely indirect, conveyed by the occipito-temporal projection system--a chain of U-shaped association fibres. DT-MRI data were collected from 11 right-handed healthy subjects (mean age 33.3 +/- 4.7 years). Each data set was co-registered with a standard MRI brain template, and a group-averaged DT-MRI data set was created. 'Virtual' in vivo dissection of occipito-temporal connections was performed in the group-averaged data. Further detailed virtual dissection was performed on the single brain data sets. Our results suggest that in addition to the indirect connections of the occipito-temporal projection system: (i) a major associative connection between the occipital and anterior temporal lobe is provided by a fibre bundle whose origin, course and termination are consistent with classical descriptions of the ILF in man and with monkey visual anatomy; (ii) the tractography-defined ILF is structurally distinct from fibres of the optic radiation and from U-shaped fibres connecting adjacent gyri; (iii) it arises in extrastriate visual 'association' areas; and (iv) it projects to lateral and medial anterior temporal regions. While the function of the direct ILF pathway is unclear, it appears to mediate the fast transfer of visual signals to anterior temporal regions and neuromodulatory back-projections from the amygdala to early visual areas. Future tractography studies of patients with occipito-temporal disconnection syndromes may help define the functional roles of the direct and indirect occipito-temporal pathways.

Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

No abstract

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.

We have studied a patient, G.Y., who was rendered hemianopic following a lesion affecting the primary visual cortex (area VI), sustained 31 years ago, with the hope of characterizing his ability to discriminate visual stimuli presented in his blind field, both psychophysically and in terms of the brain activity revealed by imaging methods. Our results show that (i) there is a correlation between G.Y.'s capacity to discriminate stimuli presented in his blind field and his conscious awareness of the same stimuli and (ii) that G.Y.'s performance on some tasks is characterized by a marked variability, both in terms of his awareness for a given level of discrimination and in his discrimination for a given level of awareness. The observations on G.Y., and a comparison of his capacities with those of normal subjects, leads us to propose a simple model of the relationship between visual discrimination and awareness. This supposes that the two independent capacities are very tightly coupled in normal subjects (gnosopsia) and that the effect of a VI lesion is to uncouple them, but only slightly. This uncoupling leads to two symmetrical departures, on the one hand to gnosanopsia (awareness without discrimination) and on the other to agnosopsia (discrimination without awareness). Our functional MRI studies show that V5 is always active when moving stimuli, whether slow or fast, are presented to his blind field and that the activity in V5 co-varies with less intense activity in other cortical areas. The difference in cerebral activity between gnosopsia and agnosopsia is that, in the latter, the activity in V5 is less intense and lower statistical thresholds are required to demonstrate it. Direct comparison of the brain activity during individual 'aware' and 'unaware' trials, corrected for the confounding effects of motion, has also allowed us, for the first time, to titrate conscious awareness against brain activity and show that there is a straightforward relationship between awareness and activity, both in individual cortical areas, in this case area V5, and in the reticular activating system. The imaging evidence, together with the variability in his levels of awareness and discrimination, manifested in his capacity to discriminate consciously on some occasions and unconsciously on others, leads us to conclude that agnosopsia, gnosopsia and gnosanopsia are all manifestations of a single condition which we call the Riddoch syndrome, in deference to the British neurologist who, in 1917, first characterized the major aspect of this disability. We discuss the significance of these results in relation to historical views about the organization of the visual brain.

The ability to maintain adequate nutrient intake is critical for survival. Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour, from food-seeking to meal termination. The hypothalamus and brainstem are thought to be the principal homeostatic brain areas responsible for regulating body weight. However, in the current 'obesogenic' human environment food intake is largely determined by non-homeostatic factors including cognition, emotion and reward, which are primarily processed in corticolimbic and higher cortical brain regions. Although the pleasure of eating is modulated by satiety and food deprivation increases the reward value of food, there is currently no adequate neurobiological account of this interaction between homeostatic and higher centres in the regulation of food intake in humans. Here we show, using functional magnetic resonance imaging, that peptide YY3-36 (PYY), a physiological gut-derived satiety signal, modulates neural activity within both corticolimbic and higher-cortical areas as well as homeostatic brain regions. Under conditions of high plasma PYY concentrations, mimicking the fed state, changes in neural activity within the caudolateral orbital frontal cortex predict feeding behaviour independently of meal-related sensory experiences. In contrast, in conditions of low levels of PYY, hypothalamic activation predicts food intake. Thus, the presence of a postprandial satiety factor switches food intake regulation from a homeostatic to a hedonic, corticolimbic area. Our studies give insights into the neural networks in humans that respond to a specific satiety signal to regulate food intake. An increased understanding of how such homeostatic and higher brain functions are integrated may pave the way for the development of new treatment strategies for obesity.

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications.