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G R Fink

Publications and source records attributed to G R Fink.

At least 37 records · Page 2Linked to original sources

Task instructions influence the cognitive strategies involved in line bisection judgements: evidence from modulated neural mechanisms revealed by fMRI.

Manual line bisection and a perceptual variant thereof (the Landmark test) are widely used to assess visuospatial neglect in neurological patients, but little is known about the cognitive strategies involved. In the Landmark test, one could explicitly compare the lengths of the left and right line segments; alternatively, one could compute the centre of mass of the display. We here investigate with functional MRI if these cognitive strategies modulate the neural mechanisms underlying judgements whether pre-transected horizontal lines are correctly bisected (the Landmark test) in normal volunteers. Functional neuroimaging (fMRI) was carried out in 12 healthy volunteers who judged: (a) whether the line segments on either side of the transection mark were of equal length, and (b) whether the transection mark was in the centre of the line. Line centre judgements were made significantly faster than line length comparisons. Increased neural activity common to both strategies was observed in inferior parietal lobes bilaterally and right temporooccipital cortex. Further activations, most likely reflecting general task demands like response selection and motor control, were found in the precentral gyrus bilaterally, supplementary motor area bilaterally, right anterior cingulate, right dorsolateral prefrontal cortex, cerebellar vermis, and right thalamus and right putamen. Explicit length comparisons (relative to line centre judgements) differentially activated left superior posterior parietal cortex, with a tendency toward activation of the equivalent area on the right, while the reverse comparison revealed differential activation in the lingual gyrus bilaterally and anterior cingulate cortex. The activations observed in inferior parietal cortex during task performance using either strategy are consistent with the results of lesion studies. The differential activation of superior posterior parietal cortex following length instructions suggests that explicit comparisons of spatial extent were implicated. The differential activation of bilateral occipital cortex following centre judgements suggests that the centre of a line is extracted at an early stage of visual processing.

Adult↗

The importance of seeing it coming: a functional magnetic resonance imaging study of motion-in-depth towards the human observer.

Despite their crucial biological relevance, the neural structures differentially activated by the detection of optic flow towards the observer remain to be elucidated. Here, we deploy functional magnetic resonance imaging with normal volunteers to locate the areas differentially activated when motion towards the observer is detected. Motion towards the observer, compared with motion away, showed significant activations (P<0.05, corrected for multiple comparisons), as assessed using statistical parametric mapping, in the lateral inferior occipital cortex bilaterally and in right lateral superior occipital cortex. The areas implicated do not extend into area V5 or subdivisions thereof.Our data suggest that the representations of motion towards the observer implicate perceptual and attentional mechanisms acting at early stages of visual processing in extrastriate cortex. From the standpoint of efficient biological engineering, it makes sense that such crucially important functions as object motion towards the observer would be computed in early visual processing areas. Further studies will be required to determine the extent to which the effects we observed in lateral occipital cortex reflect differential attention to different types of motion, as contrasted with the derivation of explicit representations of motion towards the observer.

Adult↗

Neural activity in human primary motor cortex areas 4a and 4p is modulated differentially by attention to action.

The mechanisms underlying attention to action are poorly understood. Although distracted by something else, we often maintain the accuracy of a movement, which suggests that differential neural mechanisms for the control of attended and nonattended action exist. Using functional magnetic resonance imaging (fMRI) in normal volunteers and probabilistic cytoarchitectonic maps, we observed that neural activity in subarea 4p (posterior) within the primary motor cortex was modulated by attention to action, while neural activity in subarea 4a (anterior) was not. The data provide the direct evidence for differential neural mechanisms during attended and unattended action in human primary motor cortex.

Adult↗

The influence of explicit instructions and stimulus material on lateral frontal responses to an encoding task.

In this functional magnetic resonance imaging study, we explored the effects of both stimulus material and encoding task demands on activation in lateral prefrontal cortex (PFC). Two factors were manipulated: material type and task instructions. Subjects encoded words or abstract figures (factor 1: stimulus type) and were required to make either a meaning-based or a form-based (letter or shape) decision about each stimulus (factor 2: task instructions). Abstract figures engendered significantly higher levels of right PFC activity than did words. This effect was seen for meaning-based and form-based processing tasks and was significantly greater for the former. We did not observe a differential response of left lateral PFC to verbal and pictorial material. A double dissociation, however, was found within left PFC. A ventrolateral region (within left inferior frontal gyrus) showed the highest levels of activity when words were processed according to their meaning whereas activity in a more dorsolateral region (within left middle frontal gyrus) was greatest when words were processed according to their form (constituent letters). We have therefore observed a main effect of material type in producing lateralized activation of frontal lobes, although the strength of this effect is sensitive to the nature of the task that subjects are asked to perform. Left-side lateral PFC activity is also sensitive to task instructions but this effect was specific to verbal material. The complex patterns of frontal effect counsel against any simple dichotomy of frontal function at the level of either material or task type.

Adult↗

Polyploids require Bik1 for kinetochore-microtubule attachment.

The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore-MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics.

Binding Sites↗

Drought- and salt-tolerant plants result from overexpression of the AVP1 H+-pump.

Transgenic plants overexpressing the vacuolar H(+)-pyrophosphatase are much more resistant to high concentrations of NaCl and to water deprivation than the isogenic wild-type strains. These transgenic plants accumulate more Na(+) and K(+) in their leaf tissue than the wild type. Moreover, direct measurements on isolated vacuolar membrane vesicles derived from the AVP1 transgenic plants and from wild type demonstrate that the vesicles from the transgenic plants have enhanced cation uptake. The phenotypes of the AVP1 transgenic plants suggest that increasing the vacuolar proton gradient results in increased solute accumulation and water retention. Presumably, sequestration of cations in the vacuole reduces their toxic effects. Genetically engineered drought- and salt-tolerant plants could provide an avenue to the reclamation of farmlands lost to agriculture because of salinity and a lack of rainfall.

Abscisic Acid↗

Plant growth homeostasis is controlled by the Arabidopsis BON1 and BAP1 genes.

Wild-type Arabidopsis plants maintain a relatively constant size over a wide range of temperatures. Here we show that this homeostasis requires the BONZAI1 (BON1) gene because bon1 null mutants make miniature fertile plants at 22 degrees C but have wild-type appearance at 28 degrees C. The expression of BON1 and a BON1-associated protein (BAP1) is modulated by temperature. Thus BON1 and BAP1 may have a direct role in regulating cell expansion and cell division at lower temperatures. BON1 contains a Ca(2+)-dependent phospholipid-binding domain and is associated with the plasma membrane. It belongs to the copine gene family, which is conserved from protozoa to humans. Our data suggest that this gene family may function in the pathway of membrane trafficking in response to external conditions.

Animals↗

The glyoxylate cycle is required for fungal virulence.

Candida albicans, a normal component of the mammalian gastrointestinal flora, is responsible for most fungal infections in immunosuppressed patients. Candida is normally phagocytosed by macrophages and neutrophils, which secrete cytokines and induce hyphal development in this fungus. Neutropenic patients, deficient in these immune cells, are particularly susceptible to systemic candidiasis. Here we use genome-wide expression profiles of the related yeast Saccharomyces cerevisiae to obtain a signature of the events that take place in the fungus on ingestion by a mammalian macrophage. Live S. cerevisiae cells isolated from the phagolysosome are induced for genes of the glyoxylate cycle, a metabolic pathway that permits the use of two-carbon compounds as carbon sources. In C. albicans, phagocytosis also upregulates the principal enzymes of the glyoxylate cycle, isocitrate lyase (ICL1) and malate synthase (MLS1). Candida albicans mutants lacking ICL1 are markedly less virulent in mice than the wild type. These findings in fungi, in conjunction with reports that isocitrate lyase is both upregulated and required for the virulence of Mycobacterium tuberculosis, demonstrate the wide-ranging significance of the glyoxylate cycle in microbial pathogenesis.

Animals↗

Bakers' yeast, a model for fungal biofilm formation.

Biofilms are formed by the aggregation of microorganisms into multicellular structures that adhere to surfaces. Here we show that bakers' yeast Saccharomyces cerevisiae can initiate biofilm formation. When grown in low-glucose medium, the yeast cells adhered avidly to a number of plastic surfaces. On semi-solid (0.3% agar) medium they formed "mats": complex multicellular structures composed of yeast-form cells. Both attachment to plastic and mat formation require Flo11p, a member of a large family of fungal cell surface glycoproteins involved in adherence. The ability to study biofilm formation in a tractable genetic system may facilitate the identification of new targets for antifungal therapy.

Agar↗

Deriving numerosity and shape from identical visual displays.

We presented identical displays of three to five dots in a functional magnetic resonance imaging (fMRI) experiment with normal volunteers. Two distinct directed attention tasks were performed on these displays: In one condition, subjects assessed the numerosity of the display; in the other condition, they assessed the shape of the display. Decisions based on numerosity activated differentially striate and extrastriate visual processing areas as well as left inferior frontal cortex. Decisions based on shape derived from arrangement activated differentially temporoparietal cortex bilaterally, medial posterior cingulate cortex, and left dorsolateral prefrontal cortex. These divergent neural activations in response to identical stimuli suggest that attentional mechanisms are deployed in very different ways in rapid enumeration of visual objects and in linking spatially discrete elements to one form.

Adult↗

Mind reading: neural mechanisms of theory of mind and self-perspective.

Human self-consciousness as the metarepresentation of ones own mental states and the so-called theory of mind (TOM) capacity, which requires the ability to model the mental states of others, are closely related higher cognitive functions. We address here the issue of whether taking the self-perspective (SELF) or modeling the mind of someone else (TOM) employ the same or differential neural mechanisms. A TOM paradigm was used and extended to include stimulus material that involved TOM and SELF capacities in a two-way factorial design. A behavioral study in 42 healthy volunteers showed that TOM and SELF induced differential states of mind: subjects assigned correctly first or third person pronouns when providing responses to the stimuli. Following the behavioral study, we used functional magnetic resonance imaging (fMRI) in eight healthy, right-handed males to study the common and differential neural mechanisms underlying TOM and SELF. The main factor TOM led to increased neural activity in the anterior cingulate cortex and left temporopolar cortex. The main factor SELF led to increased neural activity in the right temporoparietal junction and in the anterior cingulate cortex. A significant interaction of both factors TOM and SELF was observed in the right prefrontal cortex. These divergent neural activations in response to TOM and SELF suggest that these important differential mental capacities of human self-consciousness are implemented at least in part in distinct brain regions. Press

Adult↗

Space coding in primate posterior parietal cortex.

Neuropsychological studies of patients with lesions of right frontal (premotor) or posterior parietal cortex often show severe impairments of attentive sensorimotor behavior. Such patients frequently manifest symptoms like hemispatial neglect or extinction. Interestingly, these behavioral deficits occur across different sensory modalities and are often organized in head- or body-centered coordinates. These neuropsychological data provide evidence for the existence of a network of polymodal areas in (primate) premotor and inferior parietal cortex representing visual spatial information in a nonretinocentric frame of reference. In the monkey, a highly modular structural and functional specialization has been demonstrated especially within posterior parietal cortex. One such functionally specialized area is the ventral intraparietal area (VIP). This area is located in the fundus of the intraparietal sulcus and contains many neurons that show polymodal directionally selective discharges, i.e., these neurons respond to moving visual, tactile, vestibular, or auditory stimuli. Many of these neurons also encode sensory information from different modalities in a common, probably head-centered, frame of reference. Functional imaging data on humans reveal a network of cortical areas that respond to polymodal stimuli conveying motion information. One of these regions of activation is located in the depth of human intraparietal sulcus. Accordingly, it is suggested that this area constitutes the human equivalent of monkey area VIP. The functional role of area VIP for polymodal spatial perception in normals as well as the functional implications of lesions of area VIP in parietal patients needs to be established in further experiments.

Animals↗

The neural basis of vertical and horizontal line bisection judgments: an fMRI study of normal volunteers.

Bisection of horizontal lines is used as a clinical test of spatial cognition in patients with left visuospatial neglect after right hemisphere lesions. Bisection of vertical lines has also been employed, albeit less frequently. Interestingly, normal subjects often bisect horizontal lines too far left and vertical lines too high. We used fMRI to investigate whether vertical/horizontal stimulus orientation interacts with the neural mechanisms associated with line bisection judgments (the Landmark task). For control of orientation per se, subjects performed a visual detection task with the same stimuli. Statistical analysis of evoked BOLD responses employed SPM99. The Landmark task increased neural activity (P < 0.05, corrected) in the superior and inferior parietal lobes bilaterally, though predominantly on the right; early visual processing areas bilaterally; and cerebellar vermis, left cerebellar hemisphere, anterior cingulate, and prefrontal cortex bilaterally. Vertical lines (relative to horizontal lines and vice versa) increased neural activity in early visual processing areas, consistent with differential retinotopic stimulation. In addition, vertical lines activated right parietooccipital and superior posterior parietal cortex bilaterally. No significant interactions between the neural mechanisms associated with task and stimuli were observed. Increased neural activation in parietal and parietooccipital cortex associated with vertical lines may reflect increased attentional demands associated with this stimulus orientation. The right hemispheric dominance observed in posterior parietal during the Landmark task irrespective of stimulus orientation is consistent with lesion studies. Our results suggest that the behavioral patterns observed in normal subjects and neurological patients result from different stimulus effects rather than differential task demands.

Adult↗

Spatial cognition: where we were and where we are.

Some highlights of the ongoing study of visuospatial cognition from Descartes to the advent of functional neuroimaging are reviewed. We emphasize that parietal cortex contains multiple representations of space, appropriate to the demands of perception and action in near and far space. Converging evidence from the behavioral effects of relatively focal brain lesions on different aspects of spatial cognition and from the locus of maximal physiological activation when normal volunteers perform spatial tasks is described. Clinical pathologies of spatial attention, including visual extinction, simultanagnosia, and unilateral neglect, are examined for the light they cast on the basic functions of brain circuits involving the parietal lobes.

Agnosia↗

Polymodal motion processing in posterior parietal and premotor cortex: a human fMRI study strongly implies equivalencies between humans and monkeys.

In monkeys, posterior parietal and premotor cortex play an important integrative role in polymodal motion processing. In contrast, our understanding of the convergence of senses in humans is only at its beginning. To test for equivalencies between macaque and human polymodal motion processing, we used functional MRI in normals while presenting moving visual, tactile, or auditory stimuli. Increased neural activity evoked by all three stimulus modalities was found in the depth of the intraparietal sulcus (IPS), ventral premotor, and lateral inferior postcentral cortex. The observed activations strongly suggest that polymodal motion processing in humans and monkeys is supported by equivalent areas. The activations in the depth of IPS imply that this area constitutes the human equivalent of macaque area VIP.

Acoustic Stimulation↗