Dorothea Weniger

Neural Correlates for the Acquisition of Natural Language Syntax

Some types of simple and logically possible syntactic rule never occur in human language grammars, leading to a distinction between grammatical and nongrammatical syntactic rules. Comparison of the neuroanatomical correlates underlying the acquisition of grammatical and nongrammatical rules can provide relevant evidence on the neural processes dedicated to language acquisition in a given developmental stage. Until present no direct evidence on the neural mechanisms subserving language acquisition at any developmental stage has been supplied. We used fMRI in investigating the acquisition of grammatical and nongrammatical rules in the specified sense in 14 healthy adults. Grammatical rules compared with nongrammatical rules specifically activated a left hemispheric network including Brocas area, as shown by direct comparisons between the two rule types. The selective role of Brocas area was further confirmed by time x condition interactions and by proficiency effects, in that higher proficiency in grammatical rule usage, but not in usage of nongrammatical rules, led to higher levels of activation in this area. These findings provide evidence for the neural mechanisms underlying language acquisition in adults.

Broca's Area: a Supramodal Hierarchical Processor?

Despite the presence of shared characteristics across the different domains modulating Brocas area activity (e.g., structural analogies, as between language and music, or representational homologies, as between action execution and action observation), the question of what exactly the common denominator of such diverse brain functions is, with respect to the function of Brocas area, remains largely a debated issue. Here, we suggest that an important computational role of Brocas area may be to process hierarchical structures in a wide range of functional domains.

Qualitative hemispheric differences in semantic category matching

A unilateral category matching task with words as stimuli was employed to investigate semantic processing in the right and left hemispheres (RH, LH). An overall right visual field (RVF)/LH dominance was observed and performances were better than chance, also in the left visual field (LVF)/RH. A qualitative analysis of reaction times with individual differences multidimensional scaling (INDSCAL) revealed that LVF/RH INDSCAL solutions were significantly more differentiated in structure than RVF/LH solutions in terms of number and size of dimensions. These findings support a depth of activation hypothesis of hemispheric processing, with the LH rapidly and focally and the RH slowly and diffusely activating the semantic network.

Patupilone (epothilone B) for recurrent glioblastoma: clinical outcome and translational analysis of a single-institution phase I/II trial.

Background: Patients with glioblastoma (GBM) inevitably develop recurrent or progressive disease after initial multimodal treatment and have a median survival of 6–9 months from time of progression. To date, there is no accepted standard treatment for GBM relapse or progression. Patupilone (EPO906) is a novel natural microtubule-stabilizing cytotoxic agent that crosses the blood-brain barrier and has been found to have preclinical activity in glioma models. Methods: This is a single-institution, early-phase I/II trial of GBM patients with tumor progression who qualified for second surgery with the goal of evaluating efficacy and safety of the single-agent patupilone (10 mg/m2, every 3 weeks). Patients received patupilone 1 week prior to second surgery and every 3 weeks thereafter until tumor progression or toxicity. Primary end points were progression-free survival (PFS) and overall survival (OS) at 6 months as well as patupilone concentration in tumor tissue. Secondary end points were toxicity, patupilone concentration in plasma and translational analyses for predictive biomarkers. Results: Nine patients with a mean age of 54.6 ± 8.6 years were recruited between June 2008 and April 2010. Median survival and 1-year OS after second surgery were 11 months (95% CI, 5–17 months) and 45% (95% CI, 14–76), respectively. Median PFS was 1.5 months (95% CI, 1.3–1.7 months) and PFS6 was 22% (95% CI, 0–46), with 2 patients remaining recurrence-free at 9.75 and 22 months. At the time of surgery, the concentration of patupilone in tumor tissue was 30 times higher than in the plasma. Tumor response was not predictable by the tested biomarkers. Treatment was generally well tolerated with no hematological, but cumulative, though reversible sensory neuropathy grade ≤3 was seen in 2 patients (22%) at 8 months and grade 4 diarrhea in the 2nd patient (11%). Non-patupilone-related peri-operative complications occurred in 2 patients resulting in discontinuation of patupilone therapy. There were no neurocognitive changes 3 months after surgery compared to baseline. Conclusions: In recurrent GBM, patupilone can be given safely pre- and postoperatively. The drug accumulates in the tumor tissue. The treatment results in long-term PFS in some patients. Patupilone represents a valuable novel compound which deserves further evaluation in combination with radiation therapy in patients with GBM.

Die globale Aphasie

SummaryGlobal aphasia is described as a unitary syndrome which is characterized by a severe impairment of all linguistic capabilities. Speech production is extremely limited and consists of stereotyped phrases, recurring utterances or a few isolated words which are usually neologistically distorted. The patients are unable to express their thoughts in a situationally adequate manner. Language comprehension is restricted to simple questions and commands. A clinical description of the syndrome is given and the neurolinguistic structure of the disorders is discussed.ZusammenfassungDie globale Aphasie wird als einheitliches Syndrom beschrieben, das durch eine schwere Beeinträchtigung aller sprachlichen Fähigkeiten charakterisiert ist. Die geringe Sprachproduktion besteht aus Floskeln, Automatismen (recurring utterances) oder aus wenigen, meist neologistisch entstellten Einzelwörtern. Die Patienten sind außerstande, ihre Gedanken der Situation angemessen jeweils neu zu formulieren. Das Sprachverständnis ist nur für die einfachsten Fragen und Aufforderungen erhalten. Zusammen mit der klinischen Beschreibung wird die neurolinguistische Struktur der Störungen im einzelnen erörtert.

Number representation deficit: a bilingual case of failure to access written verbal numeral representations.

This study reports the case of a Greek-German bilingual patient (S.V.) with specific deficit in Arabic number production from written German number words. S.V. was able to successfully complete the reverse task, i.e. to convert Arabic numerals into written or oral German number words. She also showed preserved ability to produce both German and Greek numbers and to accurately make oral magnitude judgments in both languages. However, when transcoding two-digit numbers from German written numerals to Arabic numbers she consistently reversed the digits. A series of in-house tasks were used to test her general abilities of number processing, i.e. number synesthesia and calculation. Moreover, a number magnitude comparison task was developed specifically for pairs of numbers with reverse digits and we found that out of pairs of numbers with reverse digits with magnitude less than 100, there exist 19 pair combinations for which distance and relative distance are not concordant. The results suggest that S.V.s performance was significantly worse as the absolute distance between the numbers in the number pairs increased. These investigations are discussed in analogy with a grammatical rule problem related to absolute and relative distance effects.

Communicating with pictographs: A graphic approach to the improvement of communicative interactions

Abstract Attempts have been made to improve the communicative abilities of severely impaired aphasics by teaching them a non-verbal communication system. The results from studies in which aphasics were trained to use alternative symbol systems have not been too encouraging. The possibility of teaching aphasic patients to communicate with the aid of pictographs has remained unexplored. A therapy programme aimed at training aphasic patients with little or no usable speech to convey messages pictorially is introduced. The programme proceeds from the receptive and expressive use of pictographs encountered in everyday life to the spontaneous production of line-drawings in response to questions.

Impaired verbal memory in Parkinson disease: relationship to prefrontal dysfunction and somatosensory discrimination

ObjectiveTo study the neurocognitive profile and its relationship to prefrontal dysfunction in non-demented Parkinsons disease (PD) with deficient haptic perception.MethodsTwelve right-handed patients with PD and 12 healthy control subjects underwent thorough neuropsychological testing including Rey complex figure, Rey auditory verbal and figural learning test, figural and verbal fluency, and Stroop test. Test scores reflecting significant differences between patients and healthy subjects were correlated with the individual expression coefficients of one principal component, obtained in a principal component analysis of an oxygen-15-labeled water PET study exploring somatosensory discrimination that differentiated between the two groups and involved prefrontal cortices.ResultsWe found significantly decreased total scores for the verbal learning trials and verbal delayed free recall in PD patients compared with normal volunteers. Further analysis of these parameters using Spearmans ranking correlation showed a significantly negative correlation of deficient verbal recall with expression coefficients of the principal component whose image showed a subcortical-cortical network, including right dorsolateral-prefrontal cortex, in PD patients.ConclusionPD patients with disrupted right dorsolateral prefrontal cortex function and associated diminished somatosensory discrimination are impaired also in verbal memory functions. A negative correlation between delayed verbal free recall and PET activation in a network including the prefrontal cortices suggests that verbal cues and accordingly declarative memory processes may be operative in PD during activities that demand sustained attention such as somatosensory discrimination. Verbal cues may be compensatory in nature and help to non-specifically enhance focused attention in the presence of a functionally disrupted prefrontal cortex.

Die Broca-Aphasie

SummaryBrocas aphasia is characterized by disorders on the phonemic, syntactic and lexical level of linguistic description. It is not only the patients speech which is impaired; abilities to comprehend, read and write are likewise impaired. Articulatory disorders (dysarthria) which are due to an impaired innervation of the phonatory and articulatory musculature may exist. However these disorders do not account for all the linguistic deficits found in cases of Brocas aphasia. The characteristic feature enabling a differential diagnosis of Brocas aphasia is agrammatism.ZusammenfassungDie Broca-Aphasie ist durch Störungen auf allen Ebenen der linguistischen Beschreibung (Phonologie, Syntax, Lexikon) charakterisiert. Diese Störungen zeigen sich nicht nur beim Sprechen, sondern auch beim Verstehen, Schreiben und Lesen. Daneben kommen Sprechstörungen (Dysarthrie) vor, die auf einer zentralen Innervationsstörung der Phonationsund Artikulationsmuskeln beruhen. Das für die Differentialdiagnose gegenüber anderen Aphasieformen entscheidende Merkmal ist der Agrammatismus.

Treating number transcoding difficulties in a chronic aphasic patient

Background : Number transcoding comprises the ability to read and write Arabic numerals and number words. Although number transcoding and counting are frequently impaired in aphasic patients, little attention has been given to the development of specific treatment methods and the evaluation of their efficiency. We report the treatment of the chronic aphasic patient PK who had severe difficulties in reading Arabic numerals. Number words could only be produced with an automatic counting strategy, always beginning with one. Aims : The therapy study was aimed at examining whether PKs numeral transcoding abilities could be improved by an intensive remediation programme that comprised tasks in which Arabic numerals had to be transcoded into number words. Methods & Procedures : Treatment consisted of specific training blocks of gradually increasing complexity. Therapy started with reading one-digit Arabic numerals, followed by teens, decades, and two- to five-digit numerals, which were divided into different subgroups according to complexity. Outcomes & Results : After an 8-week therapy period significant improvement in the processing of one- to five-digit numbers was observed. PK was able to read 49.4% of the Arabic numerals as compared to 2.2% before treatment. Performance was influenced significantly by number length and number word structure. Transcoding abilities improved remarkably for two- and three-digit numbers containing a zero or ending with two zeros. Stability of the treatment effects was assessed in a follow-up study 6 months after termination of the treatment programme. PK was still able to read 48.3% of the Arabic numerals successfully. Conclusions : In a single-case study of patient PK, suffering from chronic severe aphasia that was also characterised by severe transcoding and calculation impairments it could be demonstrated that these transcoding problems could be remedied to a substantial degree when employing a carefully graded intensive retraining programme for Arabic number naming.