Dissociation among preserved resistance to proactive interference and impaired behavioral inhibition in a patient with bilateral lesions in the inferior frontal gyrus: A single-case study.

Inhibition is not a unitary construct, as different inhibition-related functions have been disentangled. The present single-case study compares performance of a patient with bilateral lesions in the inferior frontal gyrus (IFG) and anterior insula to healthy age-matched controls in different inhibition-related tasks. Particular focus was on the resolution of proactive interference that is supposed to rely on bilateral IFG and anterior insula. Two working memory tasks previously proven sensitive to deficits in proactive interference (recent-probes, n-back) and two tasks measuring behavioral inhibition (verb generation task, Stroop task) were administered. Against expectations, the patient did not show any deficits in measures of proactive interference. However, compared to controls, she demonstrated considerably reduced performance in both measures of behavioral inhibition, thus resulting in a classical dissociation between proactive interference and behavioral inhibition. Although performance improved during the chronic phase post stroke, the overall pattern of a classical dissociation between proactive interference and behavioral inhibition remained stable across time. Taken together, the present data support the role of the IFG in inhibition-related functions, but a direct relationship between lesions in the IFG and difficulties in resolution of proactive interference could not be corroborated.

Distinct Neuropsychological Correlates in Positive and Negative Formal Thought Disorder Syndromes: The Thought and Language Disorder Scale in Endogenous Psychoses.

The correlation of formal thought disorder (FTD) symptoms and subsyndromes with neuropsychological dimensions is as yet unclear. Evidence for a dysexecutive syndrome and semantic access impairments has been discussed in positive FTD, albeit focusing mostly on patients with schizophrenia. We investigated the correlation of the full range of positive and negative as well as subjective and objective FTD with neuropsychological domains in different patient groups. Patients with ICD-10 schizophrenia (n = 51), depression (n = 51), and bipolar mania (n = 18), as well as healthy subjects (n = 60), were interviewed with the Rating Scale for the Assessment of Objective and Subjective Formal Thought and Language Disorder (TALD) and assessed using a multidimensional neuropsychological test battery (executive function, semantic and lexical verbal fluency, attention, working memory, and abstract thinking). Partial correlation analysis, controlling for age and word knowledge, revealed significant results for the objective positive FTD dimension and executive dysfunctions. Objective negative FTD was associated with deficits in lexico-semantic retrieval, as well as attention and working memory dysfunctions. The results suggest that different neuropsychological substrates correlate with the multidimensional and phenomenologically different FTD syndromes. FTD is a complex, multidimensional syndrome with a variety of neuropsychological impairments, which should be accounted for in future studies investigating the pathogenesis of FTD.

Predicting planning performance from structural connectivity between left and right mid-dorsolateral prefrontal cortex: moderating effects of age during postadolescence and midadulthood.

Complex cognitive abilities such as planning are known to critically rely on activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However, the functional relevance of the structural connectivity between left and right mid-dlPFC is yet unknown. Here, we applied global tractography to derive streamline counts as estimates of the structural connectivity between mid-dlPFC homologs and related it to planning performance in the Tower of London task across early to midadulthood, assuming a moderating effect of age. Multiple regression analyses with interaction effects revealed that streamline counts between left and right mid-dlPFC were negatively associated with planning performance specifically in early postadolescence. From the fourth life decade on, there was a trend for a reversed, positive association. These differential findings were corroborated by converging results from fractional anisotropy and white-matter density estimates in the genu of the corpus callosum where fibers connecting mid-dlPFC homologs traversed. Moreover, the results for streamline counts were regionally specific, marking the strength of mid-dlPFC connectivity as critical in predicting interindividual differences in planning performance across different stages of adulthood. Taken together, present findings provide first evidence for nonadditive effects of age on the relation between complex cognitive abilities and the structural connectivity of mid-dlPFC homologs.

A rating scale for the assessment of objective and subjective formal Thought and Language Disorder (TALD).

Formal thought disorder (FTD) is a core syndrome of schizophrenia. However, patients with other diagnoses, such as mania and depression amongst others, also present with FTD. We introduce a novel, comprehensive clinical rating scale, capturing the full variety of FTD phenomenology including subjective experiences. The 30-item Thought and Language Disorder (TALD) scale is based on a detailed review of the literature, encompassing all formal thought disorder symptoms reported from the early 20th century onwards. Objectively observable symptoms as well as subjective phenomena were included. Two hundred and ten participants (146 patients ICD-10 diagnoses: depression n=63, schizophrenia n=63, mania n=20; 64 healthy control subjects) were interviewed and symptoms rated with the TALD, TLC, HAMD, YMRS and SAPS/SANS. A principal component analyses was performed for the TALD to differentiate sub-syndromes. The principal component analysis revealed four FTD factors; objective and subjective as well as positive and negative factor dimensions. The correlation analyses with the TLC and the SAPS/SANS FTD sub-scores demonstrated the factor validity for the objective factors. The different diagnoses showed a distinct pattern of symptom severity in each of the factors, with mania patients exhibiting the highest value in the positive, objective dimension. The scale showed good psychometric results, which makes it a practicable, nosologically-open instrument for the detailed assessment of all FTD dimensions. The results strengthen the importance of subjective symptom assessment reported by the patient.

Differentiating cerebral ischemia from functional neurological symptom disorder: a psychosomatic perspective.

BACKGROUND: The differential diagnosis of pseudo-neurological symptoms often represents a clinical challenge. The Diagnostic and Statistical Manual of Mental Disorders, DSM-5, made an attempt to improve diagnostic criteria of conversion disorder (functional neurological symptom disorder). Incongruences of the neurological examination, i.e. positive neurological signs, indicate a new approach--whereas psychological factors are not necessary anymore. As the DSM-5 will influence the International Classification of Diseases, ICD-11, this is of importance. In the case presented, a history of psychological distress and adverse childhood experiences coexisted with a true neurological disorder. We discuss the relevance of an interdisciplinary assessment and of operationalized diagnostic criteria. CASE PRESENTATION: A 32-year-old man presented twice with neurological symptoms without obvious pathological organic findings. A conversion disorder was considered early on at the second admission by the neurology team. Sticking to ICD-10, this diagnosis was not supported by a specialist for psychosomatic medicine, due to missing hints of concurrent psychological distress in temporal association with neurological symptoms. Further investigations then revealed a deep vein thrombosis (though D-dimers had been negative), which had probably resulted in a crossed embolus. CONCLUSION: The absence of a clear proof of biological dysfunction underlying neurological symptoms should not lead automatically to the diagnosis of a conversion disorder. In contrast, at least in more complex patients, the work-up should include repeated psychological and neurological assessments in close collaboration. According to ICD-10 positive signs of concurrent psychological distress are required, while DSM-5 emphasizes an incongruity between neurological symptoms and neurophysiological patterns of dysfunction. In the case presented, an extensive medical work-up was initially negative, and neither positive psychological nor positive neurological criteria could be identified. We conclude, that, even in times of more sophisticated operationalization of diagnostic criteria, the interdisciplinary assessment has to be based on an individual evaluation of all neurological and psychosocial findings. Prospective studies of inter-rater reliability and validity of psychological factors and positive neurological signs are needed, as evidence for both is limited. With respect to ICD-11, we suggest that positive neurological as well as psychological signs for functional neurological symptom disorder should be considered to increase diagnostic certainty.

Working memory in schizophrenia: behavioral and neural evidence for reduced susceptibility to item-specific proactive interference.

BACKGROUND: Susceptibility to item-specific proactive interference (PI) contributes to interindividual differences in working memory (WM) capacity and complex cognition relying on WM. Although WM deficits are a well-recognized impairment in schizophrenia, the underlying pathophysiological effects on specific WM control functions, such as the ability to resist item-specific PI, remain unknown. Moreover, opposing hypotheses on increased versus reduced PI susceptibility in schizophrenia are both justifiable by the extant literature. METHODS: To provide first insights into the behavioral and neural correlates of PI-related WM control in schizophrenia, a functional magnetic resonance imaging experiment was conducted in a sample of 20 patients and 20 well-matched control subjects. Demands on item-specific PI were experimentally manipulated in a recent-probes task (three runs, 64 trials each) requiring subjects to encode and maintain a set of four target items per trial. RESULTS: Compared with healthy control subjects, schizophrenia patients showed a significantly reduced PI susceptibility in both accuracy and latency measures. Notably, reduced PI susceptibility in schizophrenia was not associated with overall WM impairments and thus constituted an independent phenomenon. In addition, PI-related activations in inferior frontal gyrus and anterior insula, typically assumed to support PI resistance, were reduced in schizophrenia, thus ruling out increased neural efforts as a potential cause of the patients' reduced PI susceptibility. CONCLUSIONS: The present study provides first evidence for a diminished vulnerability of schizophrenia patients to item-specific PI, which is presumably a consequence of the patients' more efficient clearing of previously relevant WM traces and the accordingly reduced likelihood for item-specific PI to occur.

Improving MRT image quality in patients with movement disorders.

OBJECTIVE: In order to improve image quality in a simultaneous fMRI-EEG study with patients suffering from the involuntary movements typical for Huntington's disease, the aim was to develop a technique for immobilizing the heads of our patients inside an MRI head coil. METHODS: We modified a mask technique previously used for reliable repositioning in temporally fractionated radiotherapy. The mask was tested in three patients with Huntington's disease, acquiring structural and functional MR images with simultaneous EEG with and without the mask. RESULTS: Image as well as EEG signal quality were significantly improved in patients wearing the mask. However, the image quality with mask was comparable to acquisitions from patients without movement disorders only in patients with light to moderate dyskinesia. Although image quality was also significantly improved in a patient suffering from severe dyskinesia with quasi-continuous involuntary movements, the quality of both the MR images as well as the EEG signal was lower than what would be expected in a healthy control person. CONCLUSION: We have succeeded in developing a mask that fits into the MRI head coil, does not disturb the MRI signal, and significantly improves both fMRI and EEG signal quality.

Revisiting the functional specialization of left inferior frontal gyrus in phonological and semantic fluency: the crucial role of task demands and individual ability.

Despite a large body of research, extant findings on the functional role of left inferior frontal gyrus (LIFG) in phonological and semantic fluency are still controversial. Based on cross-study comparisons, a recent meta-analysis of neuroimaging results suggests that posterior-dorsal (Brodmann area, BA, 44) and anterior-ventral parts (BA 45) of LIFG contribute differentially to processes of phonologically and semantically cued word retrieval, respectively. In contrast, a subsequent functional magnetic resonance imaging experiment failed to validate the proposed dissociation using a within-subjects design. In particular, no evidence for a specific role of BA 45 in semantic fluency was found. Here, we resolve this apparent controversy by showing that the conflicting findings can be accounted for when considering the influence of task demands and individual ability on resulting functional magnetic resonance imaging activation patterns. By comparing phonological versus semantic fluency, higher activation was robustly observed in BA 44. For the opposite comparison, higher activation was found in dorsal BA 45; however, this was more pronounced in posterior-dorsal parts of BA 45 for low-performing subjects and was only apparent in anterior-dorsal parts of BA 45 under high demands on controlled semantic retrieval. Our results thus disclose important determinants for detecting a functional segregation of LIFG in verbal fluency that also have implications for the controversial findings in previous lesion studies. Moreover, the present parcellation of dorsal BA 45 corresponds well with anatomical evidence suggesting a subdivision into an anterior (45A) and posterior part (45B) and may therefore represent evidence for its functional significance in humans.

The German translation and validation of the scale for the assessment of thought, language and communication: a factor analytic study.

The Scale for the Assessment of Thought, Language and Communication (TLC) represents an instrument for the assessment of formal thought disorder (FTD). The factorial dimensionality of the TLC has yielded ambiguous results for a distinction between positive (e.g. circumstantiality) and negative (e.g. poverty of speech) FTD. The purpose of the current study was to first translate and validate the TLC scale in German. Second, the internal structure was explored in order to identify different FTD dimensions. Two hundred and ten participants (146 patients with ICD-10 diagnoses: depression n = 63, schizophrenia n = 63, mania n = 20; 64 healthy subjects) were interviewed and FTD was rated with the TLC. The principal component analysis of the German TLC version revealed a 3-factor solution, reflecting a disorganized factor, an emptiness factor and a linguistic control factor. The current investigation yielded similar results to those originally reported for the TLC. Thus, a distinction between a positive disorganized, a negative and a semantic word level factor can be supported for the German translation.

Effects of substance P on memory and mood in healthy male subjects.

There is evidence from human and animal studies that substance P (SP) is involved in the etiopathology of depression and anxiety. Furthermore, animal studies have shown effects of SP on memory. In a double-blind, randomized cross-over study, 13 healthy young men received SP (1.5 pmol/kg/min) or placebo (NaCl) intravenously over 90 min at two different days. Before and during the infusion, symptoms of anxiety and depression were assessed by different self-rating questionnaires and cognitive functioning by the Auditory-Verbal Learning Test (AVLT) as well as by two subtests of the Test for Attentional Performance (TAP). Infusion of SP caused an increase of symptoms of inner tension and of anxiety as assessed by the Acute Panic Inventory (API) and a disturbance of short-term memory in the AVLT. The results may be interpreted as evidence for an anxiogenic and memory-disturbing effect of SP. Further studies will focus on the effects of SP in patients with depression, anxiety and cognitive disorders.