Eva M. Müller-Oehring

Stability of Visual Field Enlargements Following Computer-Based Restitution Training - Results of a Follow-up

In a previous randomized placebo-controlled clinical trial, we observed significant visual field enlargements induced by computer-based restitution training in patients with cerebral lesions (Kasten et al., Nature med., 4, 1998, 108387). Now we asked the question whether this effect is stable after training was discontinued Here we report data of a follow-up study after a training-free interval (mean 23.52.3 months after end of therapy). 16 patients of the original restitution group and 6 patients of the placebo group were re-examined. On average, in high resolution computer campimetry (stimulus detection: PeriMa, form recognition: PeriForm, color perception: PeriColor) as well as in conventional automatic perimetry (TAP-2000) both groups showed no significant decline in the number of correctly detected stimuli after training was discontinued. However, cluster analysis revealed three different types of patients, who showed either increase (Type-I), decrease (Type-II) or stability (Type-III) in performance. We propose that many patients learn to use the regained visual capacities not only in the setting of a computer training but also in every day life, while other patients do not use the areas of restored vision and show a decrease of visual functions after the end of training. The Type-I group does not need continuous training, while the Type-II group may benefit from phases of refreshment exercises.

Local–global interference is modulated by age, sex and anterior corpus callosum size

To identify attentional and neural mechanisms affecting global and local feature extraction, we devised a global-local hierarchical letter paradigm to test the hypothesis that aging reduces functional cerebral lateralization through corpus callosum (CC) degradation. Participants (37 men and women, 26-79 years) performed a task requiring global, local, or global+local attention and underwent structural MRI for CC measurement. Although reaction time (RT) slowed with age, all participants had faster RTs to local than global targets. This local precedence effect together with greater interference from incongruent local information and greater response conflict from local targets each correlated with older age and smaller callosal genu (anterior) areas. These findings support the hypothesis that the CC mediates lateralized local-global processes by inhibition of task-irrelevant information under selective attention conditions. Further, with advancing age smaller genu size leads to less robust inhibition, thereby reducing cerebral lateralization and permitting interference to influence processing. Sex was an additional modifier of interference, in that callosum-interference relationships were evident in women but not in men. Regardless of age, smaller splenium (posterior) areas correlated with less response facilitation from repetition priming of global targets in men, but with greater response facilitation from repetition priming of local targets in women. Our data indicate the following dissociation: anterior callosal structure was associated with inhibitory processes (i.e., interference from incongruency and response conflict), which are vulnerable to the effects of age and sex, whereas posterior callosal structure was associated with facilitation processes from repetition priming dependent on sex and independent of age.

The Resting Brain of Alcoholics

Chronic alcohol consumption affects multiple cognitive processes supported by far-reaching cerebral networks. To identify neurofunctional mechanisms underlying selective deficits, 27 sober alcoholics and 26 age-matched controls underwent resting-state functional magnetic resonance imaging and neuropsychological testing. Functional connectivity analysis assessed the default mode network (DMN); integrative executive control (EC), salience (SA), and attention (AT) networks; primary somatosensory, auditory, and visual (VI) input networks; and subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive overlap of intrinsic connectivity in all brain networks examined, suggesting overall integrity of large-scale functional networks. Despite these similar patterns, connectivity analyses identified network-specific differences of weaker within-network connectivity and expanded connectivity to regions outside the main networks in alcoholics compared with controls. For AT and VI networks, better task performance was related to expanded connectivity in alcoholism, supporting the concept of network expansion as a neural mechanism for functional compensation. For default mode, SA, RW, and EC networks, both weaker within-network and expanded outside-network connectivity correlated with poorer performance and mood. Current smoking contributed to some of these abnormalities in connectivity. The observed pattern of resting-state connectivity might reflect neural vulnerability of intrinsic networking in alcoholics and suggests a mechanism to explain signature impairments in EM, RW evaluation, and EC ability.

Remapping the Brain to Compensate for Impairment in Recovering Alcoholics

Abnormal brain activity may reflect compensation when observed in patients who perform normally on tests requiring functions usually observed as impaired. Operational criteria defining compensation have been described and aid in distinguishing compensatory from chance events. Here, we tested whether previously published functional magnetic resonance imaging data acquired in 15 recovering alcoholics and 15 controls at rest and while performing a spatial working memory task would fulfill criteria defining functional compensation. Multivariate analysis tested how well abnormal activation in the affected group predicted normal performance, despite low or no activation in brain regions invoked by controls to accomplish the same task. By identifying networks that uniquely and positively correlated with good performance, we provide evidence for compensatory recruitment of cerebellar-based functional networks by alcoholics. Whereas controls recruited prefrontal-cerebellar regions VI/Crus I known to subserve working memory, alcoholics recruited 2 other parallel frontocerebellar loops: dorsolateral prefrontal cortex (DLPFC)-cerebellar VIII system during rest and DLPFC-cerebellar VI system while task engaged. Greater synchronous activity between cerebellar lobule VIII and DLPFC at rest and greater activation within cerebellar lobule VI and DLPFC during task predicted better working memory performance. Thus, higher intrinsic cerebellar activity in alcoholics was an adequate condition for triggering task-relevant activity in the frontal cortex required for normal working memory performance.

A selective insular perfusion deficit contributes to compromised salience network connectivity in recovering alcoholic men.

BACKGROUND Alcoholism can disrupt neural synchrony between nodes of intrinsic functional networks that are maximally active when resting relative to engaging in a task, the default mode network (DMN) pattern. Untested, however, are whether the DMN in alcoholics can rebound normally from the relatively depressed task state to the active resting state and whether local perfusion deficits could disrupt network synchrony when switching from conditions of rest to task to rest, thereby indicating a physiological mechanism of neural network adaptation capability. METHODS Whole-brain, three-dimensional pulsed-continuous arterial spin labeling provided measurements of regional cerebral blood flow (CBF) in 12 alcoholics and 12 control subjects under three conditions: pretask rest, spatial working-memory task, and posttask rest. RESULTS With practice, alcoholics and control subjects achieved similar task accuracy and reaction times. Both groups exhibited a high-low-high pattern of perfusion levels in DMN regions during the rest-task-rest runs and the opposite pattern in posterior and cerebellar regions known to be associated with spatial working memory. Alcoholics showed selective differences from control subjects in the rest-task-rest CBF pattern in the anterior precuneus and CBF level in the insula, a hub of the salience network. Connectivity analysis identified activation synchrony from an insula seed to salience nodes (parietal, medial frontal, anterior cingulate cortices) in control subjects only. CONCLUSIONS We propose that attenuated insular CBF is a mechanism underlying compromised connectivity among salience network nodes. This local perfusion deficit in alcoholics has the potential to impair ability to switch from cognitive states of interoceptive cravings to cognitive control for curbing internal urges.

Improving residual vision by attentional cueing in patients with brain lesions.

Visual attention is crucial for almost all processes of visual perception, particularly when perception is difficult. We were interested in the effects of cueing spatial attention in patients with cerebral lesions who face difficulties in visual perception in areas of residual vision at the border of visual field defects. In 23 patients with visual field loss due to post-geniculate brain lesions, stimulus detection performance and reaction times were mapped with high-resolution computer-based perimetry. A cueing procedure using Gestalt completion to attract attention to areas of residual vision was implemented in this test and performance compared in attended and unattended conditions. Stimulus detection and reaction times in areas of residual vision improved significantly under attended conditions. The extent of this effect depended on the size of areas of residual vision within the cued field. Unexpectedly, facilitation was also observed, though to a lesser extent, in invalid cueing conditions, suggesting an unspecific increase of alertness in unattended areas. Our findings show that top-down influences are relevant for visual field testing. Visuo-spatial attention may change patterns of neural activation and induce short-term plasticity not only in the intact visual system but also in the presence of visual field loss after brain lesions. Attentional cueing induces a co-activation of the lesioned visual system and (intact) attentional networks in the brain inducing immediate facilitation of visual perception. This effect may be relevant for designing new strategies to permanently improve vision during neuropsychological rehabilitation.

Automobile driving performance of brain-injured patients with visual field defects.

The purpose of this study was to examine whether patients with visual field defects resulting from cerebral injury are handicapped in their driving ability, because visual field loss as assessed in standard perimetry is often the basis for withdrawal of a persons driving license. Driving performance was tested on a driving simulator to obtain standardized results and for safety reasons. The visual field was assessed both with standard automated perimetry and computer-based, high-resolution, qualitative perimetry. We investigated nine patients with purely cerebral field defects (mostly homonymous binocular defects) who had no further neuropsychological or ophthalmological deficits. Their performance (driving speed, reaction time, and driving error rate) was compared with that of a control group of ten subjects. We found no differences in any of the tested parameters between the visually impaired subjects and the normal participants. This suggests that individuals with visual field defects, including those who suffer from homonymous hemianopia, may perform as adequately as normal individuals in realistic driving scenarios. The perimetrically assessed visual field may, thus, be of limited value for the prediction of driving safety, and we conclude that patients who have field defects should not summarily be denied a driving license.

Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men

BACKGROUND Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity. METHODS We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict. RESULTS Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity. CONCLUSIONS Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment.

Callosal degradation in HIV-1 infection predicts hierarchical perception: A DTI study

HIV-1 infection affects white matter circuits linking frontal, parietal, and subcortical regions that subserve visuospatial attention processes. Normal perception requires the integration of details, preferentially processed in the left hemisphere, and the global composition of an object or scene, preferentially processed in the right hemisphere. We tested whether HIV-related callosal white matter degradation contributes to disruption of selective lateralized visuospatial and attention processes. A hierarchical letter target detection paradigm was devised, where large (global) letters were composed of small (local) letters. Participants were required to identify target letters among distractors presented at global, local, both or neither level. Attention was directed to one (global or local) or both levels. Participants were 21 HIV-1 infected and 19 healthy control men and women who also underwent Diffusion Tensor Imaging (DTI). HIV-1 participants showed impaired hierarchical perception owing to abnormally enhanced global facilitation effects but no impairment in attentional control on local-global feature selection. DTI metrics revealed poorer fiber integrity of the corpus callosum in HIV-1 than controls that was more pronounced in posterior than anterior regions. Analysis revealed a double dissociation of anterior and posterior callosal compromise in HIV-1 infection: compromise in anterior but not posterior callosal fiber integrity predicted response conflict elicited by global targets, whereas compromise in posterior but not anterior callosal fiber integrity predicted response facilitation elicited by global targets. We conclude that component processes of visuospatial perception are compromised in HIV-1 infection attributable, at least in part, to degraded callosal microstructural integrity relevant for local-global feature integration.

Global-local interference is related to callosal compromise in alcoholism: a behavior-DTI association study.

BACKGROUND Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in alcoholism, however, has not been clearly determined. We used a global-local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism-related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes. METHODS A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age-matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure. RESULTS Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits. CONCLUSION Global-local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference-callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.