The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.

Emotional dysregulation in alcoholism (ALC) may result from disturbed inhibitory mechanisms. We therefore tested emotion and alcohol cue reactivity and inhibitory processes using negative priming. To test the neural correlates of cue reactivity and negative priming, 26 ALC and 26 age-matched controls underwent functional MRI performing a Stroop color match-to-sample task. In cue reactivity trials, task-irrelevant emotion and alcohol-related pictures were interspersed between color samples and color words. In negative priming trials, pictures primed the semantic content of an alcohol or emotion Stroop word. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to primed trials. For cue reactivity to emotion and alcohol pictures, ALC showed midbrain-limbic activation. By contrast, controls activated frontoparietal executive control regions. Greater midbrain-hippocampal activation in ALC correlated with higher amounts of lifetime alcohol consumption and higher anxiety. With negative priming, ALC exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal activation to alcohol-priming correlated with less craving and to emotion-priming with fewer depressive symptoms. The findings suggest that neurofunctional systems in ALC can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.

Brain responses to emotional salience and reward in alcohol use disorder.

Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executive control ability and relapse propensity during abstinence.

Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention--A Comparison with Parkinson's Disease.

Recent advances in highly active anti-retroviral therapy (HAART) in their various combinations have dramatically increased the life expectancies of HIV-infected persons. People diagnosed with HIV are living beyond the age of 50 but are experiencing the cumulative effects of HIV infection and aging on brain function. In HIV-infected aging individuals, the potential synergy between immunosenescence and HIV viral loads increases susceptibility to HIV-related brain injury and functional brain network degradation similar to that seen in Parkinson's disease (PD), the second most common neurodegenerative disorder in the aging population. Although there are clear diagnostic differences in the primary pathology of both diseases, i.e., death of dopamine-generating cells in the substantia nigra in PD and neuroinflammation in HIV, neurotoxicity to dopaminergic terminals in the basal ganglia (BG) has been implied in the pathogenesis of HIV and neuroinflammation in the pathogenesis of PD. Similar to PD, HIV infection affects structures of the BG, which are part of interconnected circuits including mesocorticolimbic pathways linking brainstem nuclei to BG and cortices subserving attention, cognitive control, and motor functions. The present review discusses the combined effects of aging and neuroinflammation in HIV individuals on cognition and motor function in comparison with age-related neurodegenerative processes in PD. Despite the many challenges, some HIV patients manage to age successfully, most likely by redistribution of neural network resources to enhance function, as occurs in healthy elderly; such compensation could be curtailed by emerging PD.

Midbrain-driven emotion and reward processing in alcoholism.

Alcohol dependence is associated with impaired control over emotionally motivated actions, possibly associated with abnormalities in the frontoparietal executive control network and midbrain nodes of the reward network associated with automatic attention. To identify differences in the neural response to alcohol-related word stimuli, 26 chronic alcoholics (ALC) and 26 healthy controls (CTL) performed an alcohol-emotion Stroop Match-to-Sample task during functional MR imaging. Stroop contrasts were modeled for color-word incongruency (eg, word RED printed in green) and for alcohol (eg, BEER), positive (eg, HAPPY) and negative (eg, MAD) emotional word content relative to congruent word conditions (eg, word RED printed in red). During color-Stroop processing, ALC and CTL showed similar left dorsolateral prefrontal activation, and CTL, but not ALC, deactivated posterior cingulate cortex/cuneus. An interaction revealed a dissociation between alcohol-word and color-word Stroop processing: ALC activated midbrain and parahippocampal regions more than CTL when processing alcohol-word relative to color-word conditions. In ALC, the midbrain region was also invoked by negative emotional Stroop words thereby showing significant overlap of this midbrain activation for alcohol-related and negative emotional processing. Enhanced midbrain activation to alcohol-related words suggests neuroadaptation of dopaminergic midbrain systems. We speculate that such tuning is normally associated with behavioral conditioning to optimize responses but here contributed to automatic bias to alcohol-related stimuli.

White matter fiber compromise contributes differentially to attention and emotion processing impairment in alcoholism, HIV-infection, and their comorbidity.

Alcoholism (ALC) and HIV-1 infection (HIV) each affects emotional and attentional processes and integrity of brain white matter fibers likely contributing to functional compromise. The highly prevalent ALC+HIV comorbidity may exacerbate compromise. We used diffusion tensor imaging (DTI) and an emotional Stroop Match-to-Sample task in 19 ALC, 16 HIV, 15 ALC+HIV, and 15 control participants to investigate whether disruption of fiber system integrity accounts for compromised attentional and emotional processing. The task required matching a cue color to that of an emotional word with faces appearing between the color cue and the Stroop word in half of the trials. Nonmatched cue-word color pairs assessed selective attention, and face-word pairs assessed emotion. Relative to controls, DTI-based fiber tracking revealed lower inferior longitudinal fasciculus (ilf) integrity in HIV and ALC+HIV and lower uncinate fasciculus (uf) integrity in all three patient groups. Controls exhibited Stroop effects to positive face-word emotion, and greater interference was related to greater callosal, cingulum and ilf integrity. By contrast, HIV showed greater interference from negative Stroop words during color-nonmatch trials, correlating with greater uf compromise. For face trials, ALC and ALC+HIV showed greater Stroop-word interference, correlating with lower cingulate and callosal integrity. Thus, in HIV, conflict resolution was diminished when challenging conditions usurped resources needed to manage interference from negative emotion and to disengage attention from wrongly cued colors (nonmatch). In ALC and ALC+HIV, poorer callosal integrity was related to enhanced emotional interference suggesting curtailed interhemispheric exchange needed between preferentially right-hemispheric emotion and left-hemispheric Stroop-word functions.

Visual hallucinations during spontaneous and training-induced visual field recovery.

Visual hallucinations after post-geniculate visual system lesions were shown to be associated with spontaneous recovery of visual functions. We investigated the occurrence of hallucinations during spontaneous recovery and additionally tested whether hallucinations were re-instated in a phase of vision restoration therapy (VRT). Nineteen patients with post-geniculate lesions and homonymous visual loss participated in a prospective study, and 121 patients with various lesions were included in a retrospective study using a questionnaire including verbal descriptions as well as drawings of hallucinations experienced by the patients. In both samples, visual-field size was determined before and after 6 months of VRT. Many patients in both groups experienced post-lesion hallucinations (mostly colors, objects, motion) which subsided after spontaneous recovery of visual functions (increase of visual field size, recovery of more complex visual function) was ended. Hallucinations re-emerged during training. However, the majority of patients reported simple, unformed visual hallucinations (uncolored phosphenes, spots, flashes), especially when visual field recovery was most intense. Hallucinations were mainly found in patients with large shifts of the visual field border. They occurred in blind areas, particularly in areas of residual vision where recovery was predominantly observed. Hallucinations may reflect functional recovery in partially lesioned brain areas. While the colored/formed hallucinations during spontaneous recovery may represent non-specific activation of higher visual areas, the simple, unformed training-related hallucinations may indicate recovery in the primary visual cortex during treatment. Hallucinations should not generally be discarded as pathological or unimportant symptoms, but they may be functional indicators of visual system plasticity.

Callosal involvement in a lateralized stroop task in alcoholic and healthy subjects.

To investigate the role of interhemispheric attentional processes, 25 alcoholic and 28 control subjects were tested with a Stroop match-to-sample task and callosal areas were measured with magnetic resonance imaging. Stroop color-word stimuli were presented to the left or right visual field (VF) and were preceded by a color cue that did or did not match the word's color. For matching colors, both groups showed a right VF advantage; for nonmatching colors, controls showed a left VF advantage, whereas alcoholic subjects showed no VF advantage. For nonmatch trials, VF advantage correlated with callosal splenium area in controls but not alcoholic subjects, supporting the position that information presented to the nonpreferred hemisphere is transmitted via the splenium to the hemisphere specialized for efficient processing. The authors speculate that alcoholism-associated callosal thinning disrupts this processing route.

fMRI evidence for individual differences in premotor modulation of extrastriatal visual-perceptual processing of redundant targets.

To perceive the vast array of stimuli in the world around us, the visual system employs parallel processing mechanisms that ensure efficiency in perceiving multiple objects in a scene. A way to test this efficiency is to measure reaction time (RT) to pairs of identical stimuli, presented singly or as doublets; typically, the resulting phenomenon is the redundant targets effect (RTE), which manifests as faster RTs to paired than singly presented stimuli. It is controversial, however, whether the neural locus of the parallel processing mechanisms invoked to produce the RTE is perceptual or motor and why some studies observe a substantial RTE and others do not. To resolve these two issues, we measured the RTE in young adults while undergoing functional MRI. Regarding the question of a perceptual or motor basis for the RTE, we observed that bilateral activation of extrastriate cortex was prominent in paired vs. the sum of the two single stimulus conditions, indicating that the RTE invoked perceptual mechanisms; by contrast, the motor cortex was not disproportionately activated in this comparison. Regarding the magnitude of the RTE, we compared activation patterns in individuals with small vs. large RTEs and observed that frontal and premotor areas were activated with small RTEs. These data indicate that the primary processing level of response facilitation, observed as the RTE, is perceptual, but the modulation of the RTE magnitude is premotor and associated with basic aspects of response selection and preparation.

Corpus callosal microstructural integrity influences interhemispheric processing: a diffusion tensor imaging study.

Normal aging and chronic alcoholism result in disruption of brain white matter microstructure that does not typically cause complete lesions but may underlie degradation of functions requiring interhemispheric information transfer. We examined whether the microstructural integrity of the corpus callosum assessed with diffusion tensor imaging (DTI) would relate to interhemispheric processing speed. DTI yields estimates of fractional anisotropy (FA), a measure of orientation and intravoxel coherence of water diffusion usually in white matter fibers, and diffusivity (), a measure of the amount of intracellular and extracellular fluid diffusion. We tested the hypothesis that FA and would be correlated with (i) the crossed-uncrossed difference (CUD), testing visuomotor interhemispheric transfer; and (ii) the redundant targets effect (RTE), testing parallel processing of visual information presented to each cerebral hemisphere. FA was lower and higher in alcoholics than in controls. In controls but not alcoholics, large CUDs correlated with low FA and high in total corpus callosum and regionally in the genu and splenium. In alcoholics but not controls, small RTEs, elicited with equiluminant stimuli, correlated with low FA in genu and splenium and high in the callosal body. The results provide in vivo evidence for disruption of corpus callosum microstructure in normal aging and alcoholism that has functional ramifications for efficiency in interhemispheric processing.

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, 1083-87). 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 23.5 +/- 2.3 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.

Acute effects of alcohol on divided and covert attention in men.

RATIONALE: While several studies identified divided attention to be sensitive to alcohol effects, the impact of alcohol on covert visual attention is still not clear, despite the latter's important role in perception. OBJECTIVES: The study tests the effect of acute moderate doses of alcohol on divided and covert attention in right-handed, male volunteers. METHODS: The design of the study involved a double-blind trial with an alcohol and a placebo condition; measurements were taken before and after an oral dose of 0.6 g/kg alcohol versus placebo. In the divided-attention task, simultaneous visuo-spatial and auditory stimulation was applied. In a test of covert attention, subjects had to shift their attentional focus according to a central cue, from one location in the visual field to another. RESULTS: Under the divided-attention condition, reaction times were significantly prolonged after alcohol ingestion compared to placebo. Covert attention pre-post change was also significantly different between the alcohol and placebo groups. There is a reduction of false-cueing disturbance for left-appearing stimuli under moderate alcohol but an increase of disturbance for rightward stimuli, i.e. we found a lateralised pattern of reaction for spatial orienting. In the placebo group, no significant differences in right-left performance were obtained. CONCLUSION: The results suggest that sensory-attentional mechanisms play a key role in altered visual perceptual performance after alcohol ingestion. Furthermore, differences between the right and left visual field in the cued target-detection task indicate that alcohol exerts an influence on right-hemispheric attentional priming.

Unusual spontaneous and training induced visual field recovery in a patient with a gunshot lesion.

Over a period of more than 3 years, changes in visual and neuropsychological functions were examined in a patient with a visual field defect caused by a cerebral gunshot lesion. Initially, the patient had been completely blind, but after 6 months of spontaneous recovery, he showed a homonymous bilateral lower quadrantanopia and impairment of higher visual functions. Unexpectedly, recovery still continued after the first 6 months. This process was documented in detail by visual field examinations using high resolution perimetry. When visual field size had stabilised almost 16 months after the lesion, further improvement could be achieved by visual restitution training. The duration and extent of spontaneous recovery were unusual. In spontaneous as well as in training induced recovery, progress was mainly seen in partially defective areas (areas of residual vision) along the visual field border. Thus, it is speculated that modulation of perceptual thresholds in transition zones of visual field defects contributes to spontaneous and training induced recovery.

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 person's 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.

Restoration of vision II: residual functions and training-induced visual field enlargement in brain-damaged patients.

PURPOSE: Brain damage is often accompanied by visual field defects which have been considered to be non-treatable. In recent years, however, new diagnostic methods have revealed hitherto unknown residual vision, which was found, for instance, in transition zones near the blind visual field sectors and in spared islands of vision within the blind regions ("blindsight"). Furthermore, animal studies revealed a high degree of plasticity in the visual system suggesting the possibility that recovery of vision may be induced by systematic visual training. METHODS: Here we summarize a series of studies with patients suffering from visual field defects after brain lesion using some most recently developed computer-based programs for the diagnosis and treatment of visual field defects. Specifically, high-resolution perimetry (HRP) was applied to first diagnose residual function in or near the "blind" sector of the visual field. Thereafter, visual restitution training (VRT, see Kasten et al., Nature med. 4, 1998, p. 1083) was used daily for 6 months to provide systematic stimulation of these areas of residual vision. RESULTS: In a number of studies, we have observed not only residual visual functions within or near the field defect, but we were also able to follow the course of spontaneous recovery of visual functions within weeks or months after visual system damage. Furthermore, even long after spontaneous recovery is complete, computer-based visual restitution training (VRT) in or near the areas of residual vision results in a significant enlargement of intact areas, both after optic nerve damage and postchiasmatic lesions. Using VRT, we found a border shift of about 5 degrees of visual angle which cannot be explained by eye movements or eccentric fixation. We observed a transfer of this training effects to other tasks such as form and color detection, as well as to tests of visual exploration which were not specifically trained. Moreover, 72 % of the patients reported subjective improvements of vision. Training-induced visual field enlargement persisted for at least one year, even in the absence of training beyond 6 months of treatment. CONCLUSIONS: The visual system possesses a remarkable plasticity which becomes apparent in visual field enlargement during spontaneous recovery and specific visual training. Animal studies indicate that a minimum number of residual neurons surviving the lesion, in the order of 10%, provides a sufficient substrate for recovery of vision. Though the precise mechanisms of training-induced visual field enlargement need to be further explored, VRT can be introduced for routine clinical treatment of patients with visual field defects.

[Chronic visual hallucinations and illusions following brain lesions. A single case study]. / Chronische visuelle Halluzinationen und Illusionen nach Hirnschädigung. Eine Einzelfallstudie.

Lesions of the visual system do not necessarily lead to deficits in visual function. In some cases, there may even occur Positive Spontaneous Visual Phenomena (PSVP) following cerebral damage. We present data from a male patient with continuous, long-term visual illusions after having experienced cerebral infarction at the age of 56. Basing on conventional Magnetic Resonance Imaging, lesions could be located in areas supported by the lateral and medial occipital artery. Initially, homonymous hemianopsia of the right visual field was found in perimetric examinations, but in the course of six months, visual function recovered completely. Ever since the incident, the patient has been suffering from permanent photopsia, intense colourful visual hallucinations and perseverations located in the former defective area which continued unabated even after the remission of his visual field defects. While many authors have published data on PSVP lasting for several seconds, usually vanishing completely within days or weeks after cerebral lesion, in our patient the symptoms continued over a period of so far nine months. Surprisingly, he was even able to make drawings of his illusions so that we were able to include some of his pictures.