Klemens Gutbrod

Does excessive memory load attenuate activation in the prefrontal cortex? Load-dependent processing in single and dual tasks: functional magnetic resonance imaging study

Functional magnetic resonance imaging was used to investigate the relationship between cortical activation and memory load in dual tasks. An n-back task at four levels of difficulty was used with auditory-verbal and visual-nonverbal material, performed separately as single tasks and simultaneously as dual tasks. With reference to single tasks, activation in the prefrontal cortex (PFC) commonly increases with incremental memory load, whereas for dual tasks it has been hypothesized previously that activity in the PFC decreases in the face of excessive processing demands, i.e., if the capacity of the working memorys central executive system is exceeded. However, our results show that during both single and dual tasks, prefrontal activation increases continuously as a function of memory load. An increase of prefrontal activation was observed in the dual tasks even though processing demands were excessive in the case of the most difficult condition, as indicated by behavioral accuracy measures. The hypothesis concerning the decrease in prefrontal activation could not be supported and was discussed in terms of motivation factors. Similar changes in load-dependent activation were observed in two other regions outside the PFC, namely in the precentral gyrus and the superior parietal lobule. The results suggest that excessive processing demands in dual tasks are not necessarily accompanied by a diminution in cortical activity.

Theta burst stimulation reduces disability during the activities of daily living in spatial neglect

Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham stimulation or in the control group without stimulation. These results provide Class I evidence that continuous theta burst stimulation is a viable add-on therapy in neglect rehabilitation that facilitates recovery of normal everyday behaviour.

Memory without context: amnesia with confabulations after infarction of the right capsular genu.

OBJECTIVE--To explore the mechanism of an amnesia marked by confabulations and lack of insight in a patient with an infarct of the right inferior capsular genu. The confabulations could mostly be traced back to earlier events, indicating that the memory disorder ensued from an inability to store the temporal and spatial context of information acquisition rather than a failure to store new information. METHODS--To test the patients ability to store the context of information acquisition, two experiments were composed in which she was asked to decide when or where she had learned the words from two word lists presented at different points in time or in different rooms. To test her ability to store new information, two continuous recognition tests with novel non-words and nonsense designs were used. Recognition of these stimuli was assumed to be independent of the context of acquisition because the patient could not have an a priori sense of familiarity with them. RESULTS--The patient performed at chance in the experiments probing knowledge of the context of information acquisition, although she recognised the presented words almost as well as the controls. By contrast, her performance was normal in the recognition tests with non-words and nonsense designs. CONCLUSION--These findings indicate that the patients amnesia was based on an inability to store the context of information acquisition rather than the information itself. Based on an analysis of her lesion, which disconnected the thalamus from the orbitofrontal cortex and the amygdala, and considering the similarities between her disorder, Wernicke-Korsakoff syndrome, and the amnesia after orbitofrontal lesions, it is proposed that contextual amnesia results from interruption of the loop connecting the amygdala, the dorsomedial nucleus, and the orbitofrontal cortex.

Decision-making in amnesia: do advantageous decisions require conscious knowledge of previous behavioural choices?

Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be taken before the advantageous strategy is known [Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275, 1293-1295]. In order to test whether explicit memory is essential for the acquisition of a behavioural preference for advantageous choices, we measured behavioural performance and skin conductance responses (SCRs) in five patients with dense amnesia following damage to the basal forebrain and orbitofrontal cortex, six amnesic patients with damage to the medial temporal lobe or the diencephalon, and eight control subjects performing the IGT. Across 100 trials healthy participants acquired a preference for advantageous choices and generated large SCRs to high levels of punishment. In addition, their anticipatory SCRs to disadvantageous choices were larger than to advantageous choices. However, this dissociation occurred much later than the behavioural preference for advantageous alternatives. In contrast, though exhibiting discriminatory autonomic SCRs to different levels of punishment, 9 of 11 amnesic patients performed at chance and did not show differential anticipatory SCRs to advantageous and disadvantageous choices. Further, the magnitude of anticipatory SCRs did not correlate with behavioural performance. These results suggest that the acquisition of a behavioural preference--be it for advantageous or disadvantageous choices--depends on the memory of previous reinforcements encountered in the task, a capacity requiring intact explicit memory.

About the role of visual field defects in pure alexia.

Pure alexia is an acquired reading disorder characterized by a disproportionate prolongation of reading time as a function of word length. Although the vast majority of cases reported in the literature show a right-sided visual defect, little is known about the contribution of this low-level visual impairment to their reading difficulties. The present study was aimed at investigating this issue by comparing eye movement patterns during text reading in six patients with pure alexia with those of six patients with hemianopic dyslexia showing similar right-sided visual field defects. We found that the role of the field defect in the reading difficulties of pure alexics was highly deficit-specific. While the amplitude of rightward saccades during text reading seems largely determined by the restricted visual field, other visuo-motor impairments-particularly the pronounced increases in fixation frequency and viewing time as a function of word length-may have little to do with their visual field defect. In addition, subtracting the lesions of the hemianopic dyslexics from those found in pure alexics revealed the largest group differences in posterior parts of the left fusiform gyrus, occipito-temporal sulcus and inferior temporal gyrus. These regions included the coordinate assigned to the centre of the visual word form area in healthy adults, which provides further evidence for a relation between pure alexia and a damaged visual word form area. Finally, we propose a list of three criteria that may improve the differential diagnosis of pure alexia and allow appropriate therapy recommendations.

Determination of language dominance: Wada test confirms functional transcranial Doppler sonography

Objective: To determine the efficacy of the invasive Wada test in determining language dominance, and to validate the functional transcranial Doppler sonography (fTCD) examination in patients. Background: Previous work shows that simultaneous bilateral fTDC may identify cognitive hemispheric dominance in healthy individuals. Method:— fTDC and the Wada test were performed prospectively in 14 patients with various diseases (tumors, cerebrovascular events, head injury, intractable epilepsy). fTDC hemispheric dominance was determined based on the hemispheric blood flow velocity shift for language and visuospatial tasks. Results: fTDC was performed easily in patients. One patient could not be examined by fTDC because of absent temporal bone window for ultrasonic transmission. Two Wada tests were inconclusive due to patient somnolence. One of these patients suffered from right frontal tumor and had aphasia remitted under steroids when examined. fTDC indicated a bilateral language dominance. In the remaining 11 patients the correlation between fTDC and Wada language lateralization indices was 0.75 (p = 0.008). If a post hoc cutoff score was taken for the fTDC language lateralization index, in eight patients, both fTDC and Wada testing determined the left hemisphere to be dominant for language; in the other three patients, language function was bilateral in both examinations. Conclusion: Although the current results are preliminary and require replication in a larger sample, fTDC seems to be able to assess hemispheric language dominance not only in healthy individuals, but also in patients. It might become an alternative noninvasive or complementary tool to the Wada test, particularly in patients in whom the Wada test is impractical or gives inconclusive results.

Very severe amnesia with acute onset after isolated hippocampal damage due to systemic lupus erythematosus.

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Spinal cerebrospinal fluid leak as the cause of chronic subdural hematomas in nongeriatric patients

OBJECT The etiology of chronic subdural hematoma (CSDH) in nongeriatric patients (≤ 60 years old) often remains unclear. The primary objective of this study was to identify spinal CSF leaks in young patients, after formulating the hypothesis that spinal CSF leaks are causally related to CSDH. METHODS All consecutive patients 60 years of age or younger who underwent operations for CSDH between September 2009 and April 2011 at Bern University Hospital were included in this prospective cohort study. The patient workup included an extended search for a spinal CSF leak using a systematic algorithm: MRI of the spinal axis with or without intrathecal contrast application, myelography/fluoroscopy, and postmyelography CT. Spinal pathologies were classified according to direct proof of CSF outflow from the intrathecal to the extrathecal space, presence of extrathecal fluid accumulation, presence of spinal meningeal cysts, or no pathological findings. The primary outcome was proof of a CSF leak. RESULTS Twenty-seven patients, with a mean age of 49.6 ± 9.2 years, underwent operations for CSDH. Hematomas were unilateral in 20 patients and bilateral in 7 patients. In 7 (25.9%) of 27 patients, spinal CSF leakage was proven, in 9 patients (33.3%) spinal meningeal cysts in the cervicothoracic region were found, and 3 patients (11.1%) had spinal cysts in the sacral region. The remaining 8 patients (29.6%) showed no pathological findings. CONCLUSIONS The direct proof of spinal CSF leakage in 25.9% of patients suggests that spinal CSF leaks may be a frequent cause of nongeriatric CSDH.

Theta Burst Stimulation Over the Right Broca's Homologue Induces Improvement of Naming in Aphasic Patients

Background and Purpose— Improvements of language production in aphasic patients have been reported following repeated 1-Hz transcranial magnetic stimulation over the nondamaged right hemisphere. Most studies examined aphasic patients in the chronic phase. The effect of transcranial magnetic stimulation application in acute or subacute patients has not been systematically studied. We aimed to evaluate whether continuous theta burst stimulation, an inhibitory protocol with a shorter application time than the common 1-Hz protocol, is able to improve naming performance in aphasic patients in different poststroke phases. Methods— Eighteen right-handed aphasic patients performed a picture naming task and a language independent alertness test before and after the application of theta burst stimulation over the intact right Brocas homologue localized by the 10–20 electroencephalogram system in a randomized, sham-controlled, crossover trial. Results— We found that naming performance was significantly better, and naming latency was significantly shorter, after theta burst stimulation than after the sham intervention. Patients who responded best were in the subacute phase after stroke. Conclusions— This setting with the short theta burst stimulation application time and the simple stimulation localization procedure is suitable for clinical purposes.

Personal neglect—A disorder of body representation?

The cognitive mechanisms underlying personal neglect are not well known. One theory postulates that personal neglect is due to a disorder of contralesional body representation. In the present study, we have investigated whether personal neglect is best explained by impairments in the representation of the contralesional side of the body, in particular, or a dysfunction of the mental representation of the contralesional space in general. For this, 22 patients with right hemisphere cerebral lesions (7 with personal neglect, 15 without personal neglect) and 13 healthy controls have been studied using two experimental tasks measuring representation of the body and extrapersonal space. In the tasks, photographs of left and right hands as well as left and right rear-view mirrors presented from the front and the back had to be judged as left or right. Our results show that patients with personal neglect made more errors when asked to judge stimuli of left hands and left rear-view mirrors than either patients without personal neglect or healthy controls. Furthermore, regression analyses indicated that errors in interpreting left hands were the best predictor of personal neglect, while other variables such as extrapersonal neglect, somatosensory or motor impairments, or deficits in left extrapersonal space representation had no predictive value of personal neglect. These findings suggest that deficient body representation is the major mechanism underlying personal neglect.