Helmut Hildebrandt

Response Shifting and Inhibition, but Not Working Memory, Are Impaired After Long-Term Heavy Alcohol Consumption

Chronic alcohol abuse leads to cognitive deficits. The authors investigated whether a systematic increase of interference in a 2-back working memory paradigm would lead to cognitive deficits in alcoholic participants and compared their performance in such a task with that in an alternate-response task. Twenty-four nonamnesic and nondemented alcohol abuse (AA) patients and 12 patients with Korsakoffs syndrome (KS) were compared with a control group. AA patients were impaired in the alternate-response task but not in working memory interference resolution. KS patients performed worse than the AA patients and the controls in both tasks. The neurotoxic side effects of alcohol therefore lead to a specific deficit in alternating between response rules but not in working memory, independently of whether the working memory task involves interference resolution or not.

New brain lesions after carotid revascularization are not associated with cognitive performance

PURPOSE Carotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA) for patients with significant carotid stenosis. However, diffusion-weighted imaging (DWI) has indicated that CAS is associated with a significantly higher burden of microemboli. This study evaluated the potential effect on intellectual functions of new DWI lesions after CEA or CAS. METHODS This prospective study analyzed the neuropsychologic outcomes after revascularization in 24 CAS and 31 CEA patients with severe carotid stenosis compared with a control group of 27 healthy individuals. All patients underwent clinical examinations, magnetic resonance imaging scans, and a neuropsychologic test battery that assessed six major cognitive domains performed immediately before CEA or CAS, ≤ 72 hours after, and at 3 months. RESULTS New DWI lesions were detected among 15 of 21 (71%) of the CAS patients immediately after treatment but in only 1 of the 28 CEA patients (4%; P < .01). As a group, patients with new DWI lesions showed a decline in their performance in the cognitive domains, attention, and visuoconstructive functions within 72 hours of carotid revascularization. Individually, however, in none of the cognitive domains did the decreases reach a clinically relevant threshold of z < -1.5. Moreover, the cognitive performance was not significantly different between patients with and without new DWI lesions 3 months after treatment. The cognitive performance was similar between CEA and CAS patients at all points. CONCLUSIONS The findings support the assumption that new brain lesions, as detected with DWI after CAS or CEA, do not affect cognitive performance in a manner that is long-lasting or clinically relevant. Despite the higher embolic load detected by DWI, CAS is not associated with a greater cognitive decline than CEA.

Prism adaptation improves visual search in hemispatial neglect

Visuomotor prism adaptation has been found to induce a lateral bias of spatial attention in chronic hemispatial neglect patients. Here, two experiments were conducted to explore the effects of 10 degrees prism adaptation on visual search tasks and standard visual inattention tests. Baselines and intervention effects were measured on separate days for all patients. The first experiment explored whether prism adaptation affects performance on a time restricted visual search task (maximum 3500ms presentation followed by visual and auditory feedback). No positive effects of prism adaptation were found on accuracy in visual search nor on traditional neglect tests. These results accord well with previous studies showing that increased cognitive load can lead to prism de-adaptation or unchanged performance following prism adaptation. Response times in visual search became faster following intervention but this was not the case for the standard neglect tests. In the second experiment, the same single-featured search task was used, but the participants had unlimited search time and received no feedback on their response. This time, the patients showed accuracy improvements in visual search and all four on regular neglect tests. Therapeutic effects lasted for at least 90-120min. Response times on all tasks became faster after prism adaptation. The results are consistent with studies showing effects of prism adaptation on neuropsychological neglect tests and other attentional tasks that are not speeded or time restricted, where feedback is not provided, or are performed following non-feedback-based tasks. The current findings show that prism adaptation improves visual search in neglect and that these beneficial effects can disappear with feedback.

Dissociation of egocentric and allocentric coding of space in visual search after right middle cerebral artery stroke

Spatial representations rely on different frames of reference. Patients with unilateral neglect may behave as suffering from either egocentric or allocentric deficiency. The neural substrates representing these reference frames are still under discussion. Here we used a visual search paradigm to distinguish between egocentric and allocentric deficits in patients with right hemisphere cortical lesions. An attention demanding search task served to divide patients according to egocentric versus allocentric deficits. The results indicate that egocentric impairment was associated with damage in premotor cortex involving the frontal eye fields. Allocentric impairment on the other hand was linked to lesions in more ventral regions near the parahippocampal gyrus (PHG).

The association between California Verbal Learning Test performance and fibre impairment in multiple sclerosis: evidence from diffusion tensor imaging

The California Verbal Learning Test (CVLT) is recognized as a standard clinical tool for assessing episodic memory difficulties in multiple sclerosis (MS), but its neural correlates have not yet been examined in detail in this patient population. We combined neuropsychological examination and diffusion tensor imaging (DTI) analysis in a group of MS patients (N = 50) and demographically matched healthy participants (N = 20). We investigated the degree of impairment of the uncinate fascicle (UF), the superior longitudinal fascicle (SLF), the fornix (FX) and the cingulum (CG). The patients were impaired on all CVLT parameters and the DTI parameters correlated moderately with disease-related variables. Regression analyses in the complete study sample showed that CVLT learning scores correlated with impairment of the right UF. This association reached marginal significance in the patient sample. In contrast to other studies claiming retrieval deficits, our results suggest that encoding and consolidation deficits may play a major role in verbal memory impairments in MS. The findings also provide evidence for an association between degree of myelination of prefrontal fibre pathways and encoding efficiency. Finally, DTI-derived measurements appear to reflect disease progression in MS. The results are discussed in light of functional MRI studies investigating compensatory brain activity during cognitive processing in MS.

Memory performance in multiple sclerosis patients correlates with central brain atrophy

Objective To assess whole brain and central brain atrophy as well as their differential relation to memory, cognitive performance, fatigue, depression and quality of life in patients with relapsingremitting multiple sclerosis (RRMS). Methods A 3D flow compensated gradient recalled T1-weighted MRI was acquired in 45 RRMS patients. An automated analysis tool was used to calculate brain parenchymal fraction (BPF) and ventricular brain fraction (VF). All patients were assessed with neuropsychological tests focusing on memory and self-rating scales for depression, fatigue and quality of life. Age corrected partial correlations between brain atrophy, motor performance, psychological scales and test scores were calculated. Results BPF correlated moderately (0.35≤r<0.5) with duration of symptoms and disease, the Expanded Disability Status Scale (EDSS), the upper extremity motor performance, and with mental aspects of quality of life. VF correlated moderately with EDSS, upper and lower extremity motor performance and memory functions. Neither BPF nor VF correlated with fatigue and depression. Results of several cognitive tests correlated moderately with depression and fatigue, the Paced Auditory Serial Addition Test (PASAT) showing the largest correlation. Conclusions Memory performance shows a correlation with relative ventricular size in RRMS patients, indicating the strategic location of the ventricle system along the structures of the limbic system and its vulnerability in MS. The PASAT and several other cognitive tests show moderate correlations with depression and fatigue, arguing for an inter relation between the cognitive functioning and the emotional state of patients. However, this relation is independent of measurable brain atrophy.

Recovery from auditory and visual neglect after optokinetic stimulation with pursuit eye movements – Transient modulation and enduring treatment effects

Optokinetic stimulation (OKS) modulates many facets of the neglect syndrome. This sensory stimulation technique is known to activate multiple brain regions (temporo-parietal cortex, basal ganglia, brain stem, cerebellum) some of which are involved in auditory and visual space coding. Here, we evaluated whether OKS modulates auditory neglect transiently and induces a sustained effect (Study 1), and whether repetitive OKS permanently recovers auditory neglect (Study 2). In Study 1, 20 patients with visuospatial neglect and auditory neglect in an auditory midline task following rightsided stroke were randomly allocated to an experimental and a control group matched for neglect severity and socio-demographic factors. Both groups showed a stable, pathological shift of their auditory subjective median plane (ASMP) in front space to the right side. During leftward OKS the experimental group showed a complete normalization of the shift of the ASMP, which endured until 30 min poststimulation, and returned almost to baseline values 24h after OKS. In contrast, the control group who viewed the identical but static dot pattern, showed neither change in their ASMP during this condition, nor any significant change at 30 min or 24h poststimulation. In Study 2, we show in two samples of neglect patients (N = 3 each) that repetitive leftward OKS with smooth pursuit eye movements as a therapy induces lasting improvements in auditory (the ASMP) and visual neglect while visual scanning therapy yielded no measurable effects on auditory and significantly smaller effects on visual neglect. In conclusion, the experiments show that a single session of OKS induces rapid though transient recovery from auditory neglect including a sustained effect after termination of stimulation, while repetitive OKS therapy yields enduring and multimodal recovery from auditory and visual neglect. OKS therapy with pursuit eye movements therefore represents a multimodally effective and easily applicable technique for the treatment of auditory and visual neglect.

A long-lasting improvement of tactile extinction after galvanic vestibular stimulation: Two Sham-stimulation controlled case studies

Sensory extinction is frequent and often persistent after brain damage. Previous studies have shown the transient influence of sensory stimulation on tactile extinction. In the present two case studies we investigated whether subliminal galvanic vestibular stimulation (GVS) modulates tactile extinction. GVS induces polarity-specific changes in cerebral excitability in the vestibular cortices and adjacent cortical areas in the temporo-parietal cortex via polarization of the vestibular nerves. Two patients (DL, CJ) with left-sided tactile extinction due to chronic (5 vs. 6 (1/2) years lesion age) right-hemisphere lesions (right fronto-parietal in DL, right frontal and discrete parietal in CJ) were examined. Both showed normal tactile sensitivity to light touch and yielded 90-100% correct identifications in unilateral tactile stimulations for both hands. In Baseline investigations without GVS and Sham-GVS both showed stable left-sided tactile extinction rates of 40-55% (DL) and 49-72% (CJ). In contrast, one session of right-cathodal GVS (intensity: 0.6 mA, duration: 20 min) permanently improved tactile identification of identical stimuli, while a second session with left-cathodal GVS significantly reduced left-sided extinction rates for different stimuli in DL. Patient CJs left-sided tactile extinction was significantly improved by left-cathodal GVS (0.5 mA, 20 min) for different stimuli, while right-cathodal GVS induced a significant reduction for identical materials. In contrast, Sham-stimulation was ineffective. Improvements remained stable for at least 1 year (DL) resp. 3 weeks (CJ). Control experiments ruled out improvements in tactile extinction merely by retesting. In conclusion, chronic tactile extinction may be permanently improved by GVS in a polarity-specific way.

Decreased hippocampal volume, indirectly measured, is associated with depressive symptoms and consolidation deficits in multiple sclerosis:

Background: The human hippocampus plays a role in episodic memory and depression. Recently, it has been shown, using manual tracings, that the hippocampus is smaller in volume in MS patients compared with healthy controls, and that, at least for depression, hippocampal atrophy correlates with symptom severity. Methods: Because manual tracing of the hippocampus is time consuming, we used a semi-automatic procedure for temporal horn volumetry in 72 multiple sclerosis (MS) patients and 16 control subjects as an indirect measure of hippocampal volume. We analysed memory performance with the California Verbal Learning Test (using separate indices for encoding, consolidation and retrieval) and depressive mood with the Beck’s Depression Inventory (distinguishing between psychic and somatic aspects). Results: MS patients had significantly larger temporal horn volumes and volume correlated with psychic symptoms of depressive mood. Temporal horn volume was also associated with consolidation, in particular in the most impaired group. Conclusions: Temporal horn volume can be measured relatively easily and appears to correlate with two major clinical problems in MS patients: memory performance and depressive mood. The link between temporal horn volume, consolidation and depression may be hippocampal atrophy, as suggested by their adjacent neuroanatomical localization, and by the similarity in functional loss following impairment of these two structures.

Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial

We evaluated a rehabilitation programme for executive deficits in multiple sclerosis patients by comparing outcome scores of a cognitive intervention group (CIG; n = 11) with those of a placebo group (n = 14) and an untreated group (n = 15). Executive functioning and verbal learning improved significantly more in the CIG. The treatment effect on verbal learning was still present at 1-year follow-up. Baseline brain atrophy, quantified by the brain parenchymal fraction, was associated with treatment effects for one aspect of executive functioning. Consequently, cognitive intervention may be beneficial and baseline brain atrophy has some predictive value in determining treatment outcome for executive functioning.