Menstrual cycle effects on selective attention and its underlying cortical networks.

It was the aim of the present study to investigate menstrual cycle effects on selective attention and its underlying functional cerebral networks. Twenty-one healthy, right-handed, normally cycling women were investigated by means of functional magnetic resonance imaging using a go/no-go paradigm during the menstrual, follicular and luteal phase. On the behavioral level there was a significant interaction between visual half field and cycle phase with reaction times to right-sided compared to left-sided stimuli being faster in the menstrual compared to the follicular phase. These results might argue for a more pronounced functional cerebral asymmetry toward the left hemisphere in selective attention during the menstrual phase with low estradiol and progesterone levels. Functional imaging, however, did not reveal clear-cut menstrual phase-related changes in activation pattern in parallel to these behavioral findings. A functional connectivity analysis identified differences between the menstrual and the luteal phase: During the menstrual phase, left inferior parietal cortex showed a stronger negative correlation with the right middle frontal gyrus while the left medial frontal cortex showed a stronger negative correlation with the left middle frontal gyrus. These results can serve as further evidence of a modulatory effect of steroid hormones on networks of lateralized cognitive functions not only by interhemispheric inhibition but also by affecting intrahemispheric functional connectivity.

Combined space and alertness related therapy of visual hemineglect: effect of therapy frequency.

The combined efficacy of space- and alertness related training in chronic hemineglect was tested behaviorally and in a longitudinal fMRI study. Earlier results had shown that both space as well as alertness related training as single intervention methods lead to short term improvement which, however, is not stable for longer time periods. The neurobiological data obtained in these studies revealed differential cortical reorganization patterns for the two training approaches thereby leading to the hypothesis that a combination of both trainings might result in stronger and longer lasting effects. The results of our current study, however, - at least at first glance - do not clearly corroborate this hypothesis, because neither alertness training alone nor the combination with OKS on the group level led to significant behavioral improvement, although four of the six patients after alertness and even more after combined training showed a higher percentage of behavioral improvement than during baseline. Despite the lack of clearcut behavioral training induced improvement we found right parietal or fronto-parietal increase of activation in the imaging data immediately after combined training and at follow-up 3 weeks later. The study design had called for splitting up training time between the two training approaches in order to match total training time with our earlier single training studies. The results of our current study are discussed as a possible consequence of reduced training time and intensity of both training measures under the combined training situation.

Effects of a CACNA1C genotype on attention networks in healthy individuals.

BACKGROUND: Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be over-represented in patients with psychosis, including schizophrenia, bipolar disorder and major depressive disorder. In these disorders, attention deficits are among the main cognitive symptoms and have been related to altered neural activity in cerebral attention networks. The particular effect of CACNA1C on neural function, such as attention networks, remains to be elucidated. METHOD: The current event-related functional magnetic resonance imaging (fMRI) study investigated the effect of the CACNA1C gene on brain activity in 80 subjects while performing a scanner-adapted version of the Attention Network Test (ANT). Three domains of attention were probed simultaneously: alerting, orienting and executive control of attention. RESULTS: Risk allele carriers showed impaired performance in alerting and orienting in addition to reduced neural activity in the right inferior parietal lobule [Brodmann area (BA) 40] during orienting and in the medial frontal gyrus (BA 8) during executive control of attention. These areas belong to networks that have been related to impaired orienting and executive control mechanisms in neuropsychiatric disorders. CONCLUSIONS: Our results suggest that CACNA1C plays a role in the development of specific attention deficits in psychiatric disorders by modulation of neural attention networks.

The effect of nicotine on visuospatial attention in chronic spatial neglect depends upon lesion location.

The deficit to reorient attention from ipsilesional to contralesional space is one key feature of the spatial neglect syndrome. As previous studies suggest that reorienting of visuospatial attention is modulated by cholinergic neurotransmission, we investigated whether cholinergic stimulation with nicotine (Nicorette 2 mg, Pharmacia/Pfizer, Helsingborg, Sweden) facilitates attentional reorienting in spatial neglect patients. Nine nonsmoking patients with stable neglect symptoms were investigated in a within-subject cross-over design. We used a location-cueing paradigm and analysed reaction time (RT) differences between validly and invalidly cued, as well as between neutrally cued and uncued targets as a function of hemifield and drug. Moreover, since the nicotine effect is mediated by parietal brain areas in healthy subjects, we tested whether lesion location influences the pharmacological effect. Nicotine speeded RTs in valid and invalid trials nonspecifically, without modulating the validity effect in the location-cueing task in the whole group of patients. Lesion-symptom mapping revealed a relationship between lesion site and the pharmacological effect on reorienting to contralesional space in right parietal and temporal brain regions. We conclude that in patients with chronic spatial neglect the performance in the location-cueing paradigm can be modulated by a cholinergic stimulant provided that the lesion spares right parietal and temporal cortex.

Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation.

Transcranial direct current stimulation is a painless, non-invasive brain stimulation technique that allows one to induce polarity-specific excitability changes in the human brain. Here, we investigated, for the first time in a 'proof of principle' study, the behavioural effect of transcranial direct current stimulation on visuospatial attention in both healthy controls and stroke patients suffering from left visuospatial neglect. We applied anodal, cathoP:dal or sham transcranial direct current stimulation (57 microA/cm(2), 10 min) to the left or right posterior parietal cortex. Using a visual detection task in a group of right-handed healthy individuals (n = 20), we observed that transcranial direct current stimulation enhanced or impaired performance depending on stimulation parameters (i.e. current polarity) and stimulated hemisphere. These results are in good accordance with classic models of reciprocal interhemispheric competition ('rivalry'). In a second experiment, we investigated the potential of transcranial direct current stimulation to ameliorate left visuospatial neglect (n = 10). Interestingly, both the inhibitory effect of cathodal transcranial direct current stimulation applied over the unlesioned posterior parietal cortex and the facilitatory effect of anodal transcranial direct current stimulation applied over the lesioned posterior parietal cortex reduced symptoms of visuospatial neglect. Taken together, our findings suggest that transcranial direct current stimulation applied over the posterior parietal cortex can be used to modulate visuospatial processing and that this effect is exerted by influencing interhemispheric reciprocal networks. These novel findings also suggest that a transcranial direct current stimulation-induced modulation of interhemispheric parietal balance may be used clinically to ameliorate visuospatial attention deficits in neglect patients.

Neural correlates of recovery from acute hemispatial neglect.

PURPOSE: To investigate the neural correlates associated with recovery from acute spatial neglect resulting from right hemispheric stroke. METHODS: Four neglect patients were investigated both behaviourally and by fMRI at an acute (18 +/- 5 days) and at a chronic stage (123 +/- 18 days) post stroke. RESULTS: At the second assessment all patients showed substantial behavioural improvements. These were associated with an increase of neural activity in the right middle frontal gyrus, right inferior parietal cortex, right inferior temporal gyrus/fusiform gyrus, left superior temporal gyrus/angular gyrus and left anterior cingulate gyrus. Decreased neural activity at the second assessment was found in the right parahippocampal gyrus and left fusiform gyrus. CONCLUSIONS: The pattern of neural reorganisation comprises areas of a right hemisphere fronto-parietal attentional network and corresponding left hemisphere areas suggesting a compensatory recruitment of analogous contralesional areas. Interestingly, a more complex pattern of neural changes was observed in the fusiform gyri which have previously been implicated in lateralised directed spatial attention. There was an increase in the right hemisphere and a decrease in the left hemisphere. This pattern of recovery is reminiscent of a "push-pull" pattern previously described for the dorsal parietal cortex by Corbetta et al. (2005) in the recovery from spatial neglect.

Alertness-training in neglect: behavioral and imaging results.

PURPOSE: It has been proposed that the right hemisphere alerting network co-activates, either directly or via the brainstem, the spatial attention system in the parietal cortex. The observation that measures of impaired alertness and sustained attention can be used to predict the outcome of neglect might suggest such a relationship, too. The aim of the present study was to investigate the effects of alertness training on hemispatial neglect. METHOD: A three-week computerised alertness training was applied to patients with chronic (> 3 months) stable visuospatial hemineglect. Training effects were investigated both in a single case and in a group of 7 patients by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). RESULTS: After the training, the patients showed a significant improvement in a neglect test battery above any natural fluctuation during a three-week baseline phase. Improvements in the neglect tasks were accompanied by an increase of both right and left hemisphere frontal, anterior cingulate and superior parietal activation, areas known to be associated with both alertness and spatial attention. Four weeks after the end of the training, the patients' neglect test performance had mostly returned to baseline. Despite decreases of activation in some of the initially reactivated areas, increases in neural activity bilaterally in frontal areas, in the right anterior cingulate cortex, the right angular gyrus and in the left temporoparietal cortex remained. An Optokinetic Stimulation Training (OKS) in a control group of another 7 neglect patients led to comparable behavioral results. After the training, however, there was a reactivation mainly in posterior parts of both hemispheres suggesting training specific functional reorganization. CONCLUSION: The limited stability of the behavioral and reactivation results over time demonstrates that a three-week alertness or OKS training alone does not result in long lasting behavioral improvements and stable reactivation patterns in every patient. We rather suggest that combining alertness and spatial attention oriented training procedures might lead to a more stable amelioration of neglect symptoms.

Impact of alertness training on spatial neglect: a behavioural and fMRI study.

The effects of a 3-week computerised alertness training on chronic (>3 months) visuospatial hemineglect were investigated prospectively in seven patients by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). Following the alertness training, the group showed improved alertness and a significant improvement in the performance of a neglect test battery over and above any improvement during a 3-week baseline phase. Improvements in the neglect tasks were accompanied by an increase of right hemisphere neural activity in frontal cortex, anterior cingulate cortex, precuneus, cuneus and angular gyrus. These areas have previously been associated with alertness and spatial attention. A similar pattern of increased neural activity was found for the left hemisphere. Four weeks after the end of the training, the patients' neglect test performance had mostly returned to baseline, while the increases in neural activity bilaterally in frontal areas, in the right anterior cingulate cortex, the right angular gyrus and the left temporoparietal cortex remained. The data show that a 3-week computerised alertness training can improve performance both in alertness and neglect tests and that these behavioural improvements are associated with reactivation in areas associated with alerting and visuospatial attention. The limited stability of these effects over time suggests that a 3-week alertness training alone does not result in long lasting improvements in every patient, but refining the treatment protocol may lead to a more stable amelioration of neglect symptoms.

Dopaminergic modulation of semantic network activation.

In order to examine the effect of dopamine on semantic processing, we performed a double-blind, placebo-controlled study. Healthy volunteers (n = 31) were tested in a lexical decision paradigm after ingestion of either L-dopa 100 mg with benserazide 25 mg or placebo. While direct semantic priming was influenced only marginally by L-dopa, the indirect priming effects was reduced significantly. These data support the hypothesis that dopamine increases the signal-to-noise ratio in semantic networks by reducing the spread of semantic processing, thereby leading to a focussing of activation.