Ilona Henseler

Rhythm in disguise: Why singing may not hold the key to recovery from aphasia

The question of whether singing may be helpful for stroke patients with non-fluent aphasia has been debated for many years. However, the role of rhythm in speech recovery appears to have been neglected. In the current lesion study, we aimed to assess the relative importance of melody and rhythm for speech production in 17 non-fluent aphasics. Furthermore, we systematically alternated the lyrics to test for the influence of long-term memory and preserved motor automaticity in formulaic expressions. We controlled for vocal frequency variability, pitch accuracy, rhythmicity, syllable duration, phonetic complexity and other relevant factors, such as learning effects or the acoustic setting. Contrary to some opinion, our data suggest that singing may not be decisive for speech production in non-fluent aphasics. Instead, our results indicate that rhythm may be crucial, particularly for patients with lesions including the basal ganglia. Among the patients we studied, basal ganglia lesions accounted for more than 50% of the variance related to rhythmicity. Our findings therefore suggest that benefits typically attributed to melodic intoning in the past could actually have their roots in rhythm. Moreover, our data indicate that lyric production in non-fluent aphasics may be strongly mediated by long-term memory and motor automaticity, irrespective of whether lyrics are sung or spoken.

Disturbed functional connectivity within brain networks subserving domain-specific subcomponents of working memory in schizophrenia: Relation to performance and clinical symptoms

INTRODUCTION Disturbed interregional functional connectivity has been hypothesized to be a promising marker of schizophrenia. The relationship between working memory (WM) impairment, disturbed functional connectivity, and the characteristic symptoms of schizophrenia, however, remains elusive. METHODS We used functional MRI (fMRI) to investigate in patients with schizophrenia and matched controls the patterns of functional connectivity during the performance of different tasks selectively engaging subcomponent processes of working memory. RESULTS Compared with controls, patients showed reduced connectivity of the prefrontal cortex with the intraparietal cortex and the hippocampus and abnormal negative interactions between the ventrolateral and dorsolateral prefrontal cortex during the non-articulatory maintenance of phonological information. During the maintenance of visuospatial information, patients presented reduced connectivity between regions in the superior parietal and occipital cortex, as well as enhanced positive connectivity of the frontal eye field with visual processing areas. DISCUSSION Our findings suggest complex dysregulations within the networks supporting working memory functions in schizophrenia, which manifest as decreased positive and abnormal negative interactions. Correlations between the connection strength and WM performance suggest that these dysregulations may be neurofunctional correlates of the WM deficits seen in schizophrenia. Altered prefronto-hippocampal and parieto-occipital connectivity was further found to be associated with higher positive symptoms, providing a possible explanation for the development of delusions and disorganization symptoms. CONCLUSION The present findings can help to better understand the relationship between altered patterns of synchronized brain activity and the cognitive and clinical symptoms of schizophrenia.

A systematic fMRI investigation of the brain systems subserving different working memory components in schizophrenia.

Working memory impairment is one of the cardinal cognitive disturbances in schizophrenia and considerable evidence suggests that it can be traced to functional alterations in the brain. The exact allocation of specific deficits to regional specific dysfunctions, however, remains elusive. The aim of this study was to examine the functional integrity of three distinguishable brain systems underlying maintenance‐related subprocesses of working memory (articulatory rehearsal, non‐articulatory maintenance of phonological information, maintenance of visuospatial information) in patients with schizophrenia. Using an experimental paradigm, which had been designed to selectively activate these different brain systems, we assessed the brain activation of patients and controls with functional magnetic resonance imaging. Compared with controls, patients showed reduced activation of the fronto‐opercular, intraparietal and anterior cingulate cortex during the non‐articulatory maintenance of phonological information, as well as attenuated deactivation of the hippocampus. Additionally, we found prefrontal activation to depend critically on the patients’ current symptom status. During visuospatial maintenance, patients showed impaired activation of the superior parietal, temporal and occipital cortex, combined with enhanced activation of the frontal eye field and the inferior parietal cortex. No abnormal activations were observed during the articulatory rehearsal task. All activation differences were independent of group differences in task performance. Our fine‐grained analysis of dysfunctions in particular aspects of working memory circuitry provides evidence for a differential impairment of the brain systems supporting working memory subcomponents in schizophrenia and extends knowledge of the relationship between cognitive deficits, brain activation abnormalities and symptoms in schizophrenia.

Pathological amygdala activation during working memory performance: Evidence for a pathophysiological trait marker in bipolar affective disorder

Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit‐specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory‐related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit‐specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication. Hum Brain Mapp, 2010.

How to engage the right brain hemisphere in aphasics without even singing: Evidence for two paths of speech recovery

There is an ongoing debate as to whether singing helps left-hemispheric stroke patients recover from non-fluent aphasia through stimulation of the right hemisphere. According to recent work, it may not be singing itself that aids speech production in non-fluent aphasic patients, but rhythm and lyric type. However, the long-term effects of melody and rhythm on speech recovery are largely unknown. In the current experiment, we tested 15 patients with chronic non-fluent aphasia who underwent either singing therapy, rhythmic therapy, or standard speech therapy. The experiment controlled for phonatory quality, vocal frequency variability, pitch accuracy, syllable duration, phonetic complexity and other influences, such as the acoustic setting and learning effects induced by the testing itself. The results provide the first evidence that singing and rhythmic speech may be similarly effective in the treatment of non-fluent aphasia. This finding may challenge the view that singing causes a transfer of language function from the left to the right hemisphere. Instead, both singing and rhythmic therapy patients made good progress in the production of common, formulaic phrases—known to be supported by right corticostriatal brain areas. This progress occurred at an early stage of both therapies and was stable over time. Conversely, patients receiving standard therapy made less progress in the production of formulaic phrases. They did, however, improve their production of non-formulaic speech, in contrast to singing and rhythmic therapy patients, who did not. In light of these results, it may be worth considering the combined use of standard therapy and the training of formulaic phrases, whether sung or rhythmically spoken. Standard therapy may engage, in particular, left perilesional brain regions, while training of formulaic phrases may open new ways of tapping into right-hemisphere language resources—even without singing.

Modulating brain mechanisms resolving lexico-semantic interference during word production: A transcranial direct current stimulation study

The aim of the current study was to shed further light on control processes that shape semantic access and selection during speech production. These processes have been linked to differential cortical activation in the left inferior frontal gyrus (IFG) and the left middle temporal gyrus (MTG); however, the particular function of these regions is not yet completely elucidated. We applied transcranial direct current stimulation to the left IFG and the left MTG (or sham stimulation) while participants named pictures in the presence of associatively related, categorically related, or unrelated distractor words. This direct modulation of target regions can help to better delineate the functional role of these regions in lexico-semantic selection. Independent of stimulation, the data show interference (i.e., longer naming latencies) with categorically related distractors and facilitation (i.e., shorter naming latencies) with associatively related distractors. Importantly, stimulation location interacted with the associative effect. Whereas the semantic interference effect did not differ between IFG, MTG, and sham stimulations, the associative facilitation effect was diminished under MTG stimulation. Analyses of latency distributions suggest this pattern to result from a response reversal. Associative facilitation occurred for faster responses, whereas associative interference resulted in slower responses under MTG stimulation. This reduction of the associative facilitation effect under transcranial direct current stimulation may be caused by an unspecific overactivation in the lexicon or by promoting competition among associatively related representations. Taken together, the results suggest that the MTG is especially involved in the processes underlying associative facilitation and that semantic interference and associative facilitation are linked to differential activation in the brain.

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks

Background: Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. Methods: We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. Results: We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Brocas area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. Conclusion: These findings provide evidence for a slightly lower capacity in both WM modalities in females.

Disturbed cortico-amygdalar functional connectivity as pathophysiological correlate of working memory deficits in bipolar affective disorder.

Abstract Patients suffering from bipolar affective disorder show deficits in working memory functions. In a previous functional magnetic resonance imaging study, we observed an abnormal hyperactivity of the amygdala in bipolar patients during articulatory rehearsal in verbal working memory. In the present study, we investigated the dynamic neurofunctional interactions between the right amygdala and the brain systems that underlie verbal working memory in both bipolar patients and healthy controls. In total, 18 euthymic bipolar patients and 18 healthy controls performed a modified version of the Sternberg item-recognition (working memory) task. We used the psychophysiological interaction approach in order to assess functional connectivity between the right amygdala and the brain regions involved in verbal working memory. In healthy subjects, we found significant negative functional interactions between the right amygdala and multiple cortical brain areas involved in verbal working memory. In comparison with the healthy control subjects, bipolar patients exhibited significantly reduced functional interactions of the right amygdala particularly with the right-hemispheric, i.e., ipsilateral, cortical regions supporting verbal working memory. Together with our previous finding of amygdala hyperactivity in bipolar patients during verbal rehearsal, the present results suggest that a disturbed right-hemispheric “cognitive–emotional” interaction between the amygdala and cortical brain regions underlying working memory may be responsible for amygdala hyperactivation and affects verbal working memory (deficits) in bipolar patients.

Integration demands modulate effective connectivity in a fronto-temporal network for contextual sentence integration

ABSTRACT Previous neuroimaging studies demonstrated that a network of left‐hemispheric frontal and temporal brain regions contributes to the integration of contextual information into a sentence. However, it remains unclear how these cortical areas influence and drive each other during contextual integration. The present study used dynamic causal modeling (DCM) to investigate task‐related changes in the effective connectivity within this network. We found increased neural activity in left anterior inferior frontal gyrus (aIFG), posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and anterior superior temporal sulcus/MTG (aSTS/MTG) that probably reflected increased integration demands and restructuring attempts during the processing of unexpected or semantically anomalous relative to expected endings. DCM analyses of this network revealed that unexpected endings increased the inhibitory influence of left aSTS/MTG on pSTS/MTG during contextual integration. In contrast, during the processing of semantically anomalous endings, left aIFG increased its inhibitory drive on pSTS/MTG. Probabilistic fiber tracking showed that effective connectivity between these areas is mediated by distinct ventral and dorsal white matter association tracts. Together, these results suggest that increasing integration demands require an inhibition of the left pSTS/MTG, which presumably reflects the inhibition of the dominant expected sentence ending. These results are important for a better understanding of the neural implementation of sentence comprehension on a large‐scale network level and might influence future studies of language in post‐stroke aphasia after focal lesions.

Arbeitsgedächtnisstörungen bei psychiatrischen Erkrankungen

ZusammenfassungArbeitsgedächtnisstörungen treten bei verschiedenen psychiatrischen Erkrankungen auf und spielen eine wichtige Rolle für die kognitive Leistungsfähigkeit im Alltag und damit auch für die soziale Integration von Patienten. Für die Schizophrenie und die bipolaren Störungen besteht gute Evidenz für eine Assoziation von Arbeitsgedächtnisdefiziten mit der Erkrankung und für eine Verbindung zu dem genetisch vermittelten Krankheitsrisiko. Neuere Studien legen zudem nahe, dass die Heterogenität der traditionellen diagnostischen Kategorien durch eine exakte Charakterisierung von Patienten anhand entsprechender neurokognitiver Funktionsparameter reduziert und die Differenzialdiagnose zwischen Störungsbildern verbessert werden kann. Das Wissen über selektive Störungen von Subkomponenten des Arbeitsgedächtnisses könnte somit in der klinischen Praxis als zusätzliche Informationsquelle für diagnostische und therapeutische Entscheidungen dienen.SummaryWorking memory disturbances occur in various psychiatric disorders and play a major role for general cognitive ability in everyday life and thus social integration of the patients. In schizophrenia and bipolar disorder, working memory deficits have been found to be associated with certain genotypes and clinical symptoms. This makes them promising endophenotypes, i.e., mediators between genotype and phenotype. Furthermore recent studies indicate that the identification of selective deficits in working memory may be useful in order to define patient subgroups that are more homogenous with respect to the functional integrity or dysfunction of neural systems underlying working memory subcomponents. This scientific approach may ultimately lead to better understanding of the pathophysiologic mechanisms underlying working memory dysfunctions in psychiatric disorders and may provide clinicians with additional information for diagnostic and therapeutic decisions.Working memory disturbances occur in various psychiatric disorders and play a major role for general cognitive ability in everyday life and thus social integration of the patients. In schizophrenia and bipolar disorder, working memory deficits have been found to be associated with certain genotypes and clinical symptoms. This makes them promising endophenotypes, i.e., mediators between genotype and phenotype. Furthermore recent studies indicate that the identification of selective deficits in working memory may be useful in order to define patient subgroups that are more homogenous with respect to the functional integrity or dysfunction of neural systems underlying working memory subcomponents. This scientific approach may ultimately lead to better understanding of the pathophysiologic mechanisms underlying working memory dysfunctions in psychiatric disorders and may provide clinicians with additional information for diagnostic and therapeutic decisions.