Sandra E. Leh

Fronto-striatal connections in the human brain: A probabilistic diffusion tractography study

Anatomical studies in animals have described multiple striatal circuits and suggested that sub-components of the striatum, although functionally related, project to distinct cortical areas. To date, anatomical investigations in humans have been limited by methodological constraints such that most of our knowledge of fronto-striatal networks relies on nonhuman primate studies. To better identify the fronto-striatal pathways in the human brain, we used Diffusion Tensor Imaging (DTI) tractography to reconstruct neural connections between the frontal cortex and the caudate nucleus and putamen in vivo. We demonstrate that the human caudate nucleus is interconnected with the prefrontal cortex, inferior and middle temporal gyrus, frontal eye fields, cerebellum and thalamus; the putamen is interconnected with the prefrontal cortex, primary motor area, primary somatosensory cortex, supplementary motor area, premotor area, cerebellum and thalamus. A connectivity-based seed classification analysis identified connections between the dorsolateral prefrontal areas (DLPFC) and the dorsal-posterior caudate nucleus and between the ventrolateral prefrontal areas (VLPFC) and the ventral-anterior caudate nucleus. For the putamen, connections exist between the supplementary motor area (SMA) and dorsal-posterior putamen while the premotor area projects to medial putamen, and the primary motor area to the lateral putamen. Identifying the anatomical organization of the fronto-striatal network has important implications for understanding basal ganglia function and associated disease processes.

The neural circuitry of executive functions in healthy subjects and Parkinson's disease.

In our constantly changing environment, we are frequently faced with altered circumstances requiring generation and monitoring of appropriate strategies, when novel plans of action must be formulated and conducted. The abilities that we call upon to respond accurately to novel situations are referred to as ‘executive functions’, and are frequently engaged to deal with conditions in which routine activation of behavior would not be sufficient for optimal performance. Here, we summarize important findings that may help us understand executive functions and their underlying neuronal correlates. We focus particularly on observations from imaging technology, such as functional magnetic resonance imaging, position emission tomography, diffusion tensor imaging, and transcranial magnetic stimulation, which in the past few years have provided the bulk of information on the neurobiological underpinnings of the executive functions. Further, emphasis will be placed on recent insights from Parkinsons disease (PD), in which the underlying dopaminergic abnormalities have provided new exciting information into basic molecular mechanisms of executive dysfunction, and which may help to disentangle the cortical/subcortical networks involved in executive processes.

The connectivity of the human pulvinar: a diffusion tensor imaging tractography study.

Previous studies in nonhuman primates and cats have shown that the pulvinar receives input from various cortical and subcortical areas involved in vision. Although the contribution of the pulvinar to human vision remains to be established, anatomical tracer and electrophysiological animal studies on cortico-pulvinar circuits suggest an important role of this structure in visual spatial attention, visual integration, and higher-order visual processing. Because methodological constraints limit investigations of the human pulvinars function, its role could, up to now, only be inferred from animal studies. In the present study, we used an innovative imaging technique, Diffusion Tensor Imaging (DTI) tractography, to determine cortical and subcortical connections of the human pulvinar. We were able to reconstruct pulvinar fiber tracts and compare variability across subjects in vivo. Here we demonstrate that the human pulvinar is interconnected with subcortical structures (superior colliculus, thalamus, and caudate nucleus) as well as with cortical regions (primary visual areas (area 17), secondary visual areas (area 18, 19), visual inferotemporal areas (area 20), posterior parietal association areas (area 7), frontal eye fields and prefrontal areas). These results are consistent with the connectivity reported in animal anatomical studies.

Blindsight mediated by an s-cone-independent collicular pathway: An fmri study in hemispherectomized subjects

The purpose of our study was to investigate the ability to process achromatic and short-wavelength-sensitive cone (S-cone)-isolating (blue–yellow) stimuli in the blind visual field of hemispherectomized subjects and to demonstrate that blindsight is mediated by a collicular pathway that is independent of S-cone inputs. Blindsight has been described as the ability to respond to visual stimuli in the blind visual field without conscious awareness [Weiskrantz, L., Warrington, E. K., Sanders, M. D., & Marshall, J. Visual capacity in the hemianopic field following a restricted occipital ablation. Brain, 97, 709–728, 1974]. The roles of the subcortical neural structures in blindsight, such as the pulvinar and the superior colliculus, have been debated and an underlying neural correlate has yet to be confirmed. Using fMRI, we tested the ability to process visual stimuli that isolated the achromatic and short-wavelength-sensitive (S-)-cone pathways in three subjects: one control subject, one hemispherectomized subject with blindsight, and one hemispherectomized subject without blindsight. We demonstrated that (1) achromatic and S-cone-isolating stimuli presented to the normal visual hemifield of hemispherectomized subjects and to both visual hemifields of the control subject activated contralateral visual areas (V1/V2), as expected; (2) achromatic stimulus presentation but not S-cone-isolating stimulus presentation to the blind hemifield of the subject with blindsight activated visual areas FEF/V5; (3) whereas the cortical activation of the control subject was enhanced by an additional stimulus (achromatic and S-cone isolating) presented in the contralateral visual field, activation pattern of the subject with blindsight was enhanced by achromatic stimuli only. We conclude that the human superior colliculus is blind to the S-cone-isolating stimuli, and blindsight is mediated by an S-cone-independent collicular pathway.

Neural Substrates of Blindsight After Hemispherectomy

Blindsight is a visual phenomenon whereby hemianopic patients are able to process visual information in their blind visual field without awareness. Previous research demonstrating the existence of blindsight in hemianopic patients has been criticized for the nature of the paradigms used, for the presence of methodological artifacts, and for the possibility that spared islands of visual cortex may have sustained the phenomenon because the patients generally had small circumscribed lesions. To respond to these criticisms, the authors have been investigating for several years now residual visual abilities in the blind field of hemispherectomized patients in whom a whole cerebral hemisphere has been removed or disconnected from the rest of the brain. These patients have offered a unique opportunity to establish the existence of blindsight and to investigate its underlying neuronal mechanisms because in these cases, spared islands of visual cortex cannot be evoked to explain the presence of visual abilities in the blind field. In addition, the authors have been using precise behavioral paradigms, strict control for potential methodological artifacts such as light scatter, fixation, criterion effects, and macular sparing, and they have utilized new neuroimaging techniques such as diffusion tensor imaging tractography to enhance their understanding of the phenomenon. The following article is a review of their research on the involvement of the superior colliculi in blindsight in hemispherectomized patients. NEUROSCIENTIST 13(5):506—518, 2007.

Absence of S-cone input in human blindsight following hemispherectomy.

Destruction of the occipital cortex presumably leads to permanent blindness in the contralateral visual field. Residual abilities to respond to visual stimuli in the blind field without consciously experiencing them have, however, been described in cortically blind patients and are termed ‘blindsight’. Although the neuronal basis of blindsight remains unknown, possible neuronal correlates have been proposed based on the nature of the residual vision observed. The most prominent but still controversial hypothesis postulates the involvement of the superior colliculi in blindsight. Here we demonstrate, using a computer‐based reaction time test in a group of hemispherectomized subjects, that human ‘attention‐blindsight’ can be measured for achromatic stimuli but disappears for stimuli that solely activate S‐cones. Given that primate data have shown that the superior colliculi lacks input from S‐cones, our results lend strong support to the hypothesis that ‘attention‐blindsight’ is mediated through a collicular pathway. The contribution of a direct geniculo‐extrastriate‐koniocellular projection was ruled out by testing hemispherectomized subjects in whom a whole hemisphere has been removed or disconnected for the treatment of epilepsy. A direct retino‐pulvinar‐cortical connection is also unlikely as the pulvinar nucleus is known to receive input from S‐cones as well as from L/M‐cone‐driven colour‐opponent ganglion cells.

The involvement of the superior colliculi in hemispherectomized subjects with blindsight

Purpose: The ability in cortically blind patients to respond to visual stimuli without consciously experiencing has been termed ‘blindsight’. The goal of this study is to investigate the involvement of the superior colliculi (SC) in mediating blindsight in hemispherectomized (HS) subjects. Methods: We used the achromatic properties of collicular cells, which receive no input from S-cones, to design a reaction time test of a spatial summation effect (SSE), in which reaction times to two bilaterally presented stimuli are significantly faster compared to a single one. Achromatic (SC-visible) and blue/yellow (SC-invisible) gabor patches (1cpd, spatial σ=1cycle, temporal σ=250ms) were displayed on a CRT monitor and isolated either the achromatic or the S-cone opponent (blue/yellow) pathway. Stimuli were presented 10° in the right, left, or in both visual fields. Stimulus onset-time was randomized at 0/500/1000ms with an ITI of 2000ms. Fixation was monitored with an eye tracker. Three HS subjects with and two without blindsight were tested. Results: Subjects with blindsight showed a SSE to achromatic stimuli confirming the presence of blindsight. Presentation of blue/yellow stimuli, however, failed to alter reaction times demonstrating that their blindsight is colour-blind for blue/yellow stimuli. HS subjects without blindsight showed no SSE to either achromatic or blue/yellow stimuli. Conclusions: Blindsight, at least in HS subjects, is color blind, and hence we conclude that it is mediated by the SC. Furthermore, by testing HS subjects we could reject the possibility that spared islands of visual cortex subtend blindsight.

Right impairment of temporal order judgements in dyslexic children.

This study investigates the spatial bias of visual attention measured by a temporal order judgement (TOJ) task and the influence of a high attentional load condition in a group of dyslexic children compared to a control group with normal reading skills (each group N=10). The TOJ task (T2) was placed after a shape discrimination task (T1). In a low attentional load block participants worked only on T2, whereas in the high attentional load block they were required to process both T1 and T2. Several t-tests were executed to compare performance between conditions and groups. In the low attentional load conditions, results in dyslexic children were significantly impaired for the right visual field compared to a control group. The high attentional load conditions did not enhance these effects and seems to provoke the same leftward bias in the control group.