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.

Altered neural function during episodic memory encoding and retrieval in major depression.

Memory impairments are common in major depression. Neural processing during non-emotional episodic memory in depressed patients has only sparsely been investigated, since the majority of studies have focused on emotional stimuli. The aim of this study was to explore neural correlates of episodic memory in depressive patients and to assess brain regions related to subsequent memory performance. Forty-six participants (23 depressed patients) performed a non-emotional episodic memory encoding and retrieval task while brain activation was measured with functional magnetic resonance imaging. Patients with depression showed decreased activation in the right prefrontal cortex and right cingulate cortex during memory encoding, but increased activation in the right inferior frontal gyrus (IFG) during recognition memory. While a strong association between hippocampal and parahippocampal activation during memory encoding with subsequent memory performance became evident in healthy controls, this relationship was absent in patients with depression. Taken together, these findings demonstrate that memory related brain regions are affected in their appropriate functioning during memory encoding in depressed patients. Therefore, patients with depression may rely to a greater degree on other brain regions such as the IFG during episodic memory retrieval.

Increased neural activity during overt and continuous semantic verbal fluency in major depression: mainly a failure to deactivate.

Major depression is associated with impairments in semantic verbal fluency (VF). However, the neural correlates underlying dysfunctional cognitive processing in depressed subjects during the production of semantic category members still remain unclear. In the current study, an overt and continuous semantic VF paradigm was used to examine these mechanisms in a representative sample of 33 patients diagnosed with a current episode of unipolar depression and 33 statistically matched healthy controls. Subjects articulated words in response to semantic category cues while brain activity was measured with functional magnetic resonance imaging (fMRI). Compared to controls, patients showed poorer task performance. On the neural level, a group by condition interaction analysis, corrected for task performance, revealed a reduced task-related deactivation in patients in the right parahippocampal gyrus, the right fusiform gyrus, and the right supplementary motor area. An additional and an increased task-related activation in patients were observed in the right precentral gyrus and the left cerebellum, respectively. These results indicate that a failure to suppress potentially interfering activity from inferior temporal regions involved in default-mode network functions and visual imagery, accompanied by an enhanced recruitment of areas implicated in speech initiation and higher-order language processes, may underlie dysfunctional cognitive processing during semantic VF in depression. The finding that patients with depression demonstrated both decreased performance and aberrant brain activation during the current semantic VF task demonstrates that this paradigm is a sensitive tool for assessing brain dysfunctions in clinical populations.

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.

Neural correlates of continuous causal word generation.

Causality provides a natural structure for organizing our experience and language. Causal reasoning during speech production is a distinct aspect of verbal communication, whose related brain processes are yet unknown. The aim of the current study was to investigate the neural mechanisms underlying the continuous generation of cause-and-effect coherences during overt word production. During fMRI data acquisition participants performed three verbal fluency tasks on identical cue words: A novel causal verbal fluency task (CVF), requiring the production of multiple reasons to a given cue word (e.g. reasons for heat are fire, sun etc.), a semantic (free association, FA, e.g. associations with heat are sweat, shower etc.) and a phonological control task (phonological verbal fluency, PVF, e.g. rhymes with heat are meat, wheat etc.). We found that, in contrast to PVF, both CVF and FA activated a left lateralized network encompassing inferior frontal, inferior parietal and angular regions, with further bilateral activation in middle and inferior as well as superior temporal gyri and the cerebellum. For CVF contrasted against FA, we found greater bold responses only in the left middle frontal cortex. Large overlaps in the neural activations during free association and causal verbal fluency indicate that the access to causal relationships between verbal concepts is at least partly based on the semantic neural network. The selective activation in the left middle frontal cortex for causal verbal fluency suggests that distinct neural processes related to cause-and-effect-relations are associated with the recruitment of middle frontal brain areas.

Neural basis of altered physical and social causality judgements in schizophrenia.

Patients with schizophrenia (SZ) often make aberrant cause and effect inferences in non-social and social situations. Likewise, patients may perceive cause-and-effect relationships abnormally as a result of an alteration in the physiology of perception. The neural basis for dysfunctions in causality judgements in the context of both physical motion and social motion is unknown. The current study used functional magnetic resonance imaging (fMRI) to investigate a group of patients with SZ and a group of control subjects performing judgements of causality on animated collision sequences (launch-events, Michotte, 1963) and comparable "social" motion stimuli. In both types of animations, similar motion trajectories of the affected object were configured, using parametrical variations of space (angle deviation) and time (delay). At the behavioural level, SZ patients made more physical and less social causal judgements than control subjects, and their judgements were less influenced by motion attributes (angle/time delay). In the patients group, fMRI revealed greater BOLD-responses, during both physical and social causality judgements (group×task interaction), in the left inferior frontal gyrus (L.IFG). Across conditions (main effect), L.IFG-interconnectivity with bilateral occipital cortex was reduced in the patient group. This study provides the first insight into the neural correlates of altered causal judgements in SZ. Patients with SZ tended to over-estimate physical and under-estimate social causality. In both physical and social contexts, patients are influenced less by motion parameters (space and time) than control subjects. Imaging findings of L.IFG-disconnectivity and task-related hyper-activation in the patient group could indicate common dysfunctions in the neural activations needed to integrate external cue-information (space/time) with explicit (top-down) cause-effect judgements of object motions in physical and social settings.

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.

Insular and hippocampal gray matter volume reductions in patients with major depressive disorder.

BACKGROUND: Major depressive disorder is a serious psychiatric illness with a highly variable and heterogeneous clinical course. Due to the lack of consistent data from previous studies, the study of morphometric changes in major depressive disorder is still a major point of research requiring additional studies. The aim of the study presented here was to characterize and quantify regional gray matter abnormalities in a large sample of clinically well-characterized patients with major depressive disorder. METHODS: For this study one-hundred thirty two patients with major depressive disorder and 132 age- and gender-matched healthy control participants were included, 35 with their first episode and 97 with recurrent depression. To analyse gray matter abnormalities, voxel-based morphometry (VBM8) was employed on T1 weighted MRI data. We performed whole-brain analyses as well as a region-of-interest approach on the hippocampal formation, anterior cingulate cortex and amygdala, correlating the number of depressive episodes. RESULTS: Compared to healthy control persons, patients showed a strong gray-matter reduction in the right anterior insula. In addition, region-of-interest analyses revealed significant gray-matter reductions in the hippocampal formation. The observed alterations were more severe in patients with recurrent depressive episodes than in patients with a first episode. The number of depressive episodes was negatively correlated with gray-matter volume in the right hippocampus and right amygdala. CONCLUSIONS: The anterior insula gray matter structure appears to be strongly affected in major depressive disorder and might play an important role in the neurobiology of depression. The hippocampal and amygdala volume loss cumulating with the number of episodes might be explained either by repeated neurotoxic stress or alternatively by higher relapse rates in patients showing hippocampal atrophy.

Differences and commonalities in the judgment of causality in physical and social contexts: an fMRI study.

Understanding cause and effect is a fundamental aspect of human cognition. When shown videos of simple two-dimensional shapes colliding, humans experience one object causing the other to move, e.g., one billiard-like ball seeming to hit and move the other. The impression of causality can also occur when people attribute social interactions to moving objects. Whether the judgment of social and physical causality engages distinct or shared neural networks is not known. In a functional magnetic imaging (fMRI) study, participants were presented with two types of dynamic videos: a blue ball colliding with a red ball (P; physical condition) and a blue ball ("Mr. Blue") passing a red ball ("Mrs. Red") without making contact (S; social condition). Participants judged causal relationships (C) or movement direction (D; control task) in both video types, resulting in four conditions (PC; SC; PD; SD). We found common neural activations for physical and social causality judgments (SC > SD)∩(PC > PD) in the right middle/inferior frontal gyrus, right inferior parietal lobule, the right supplementary motor area, and bilateral insulae. For social causal judgments (SC > PC), we found distinct neural activity in the right temporo-parietal junction (rTPJ). These results provide evidence for a common neural network underlying judgments of causality that apply to both physical and social situations. The results also indicate that social causality judgments recruit additional neural resources in an area critical for determining animacy and intentionality.