David Luck

Fronto-temporal disconnectivity and clinical short-term outcome in first episode psychosis: A DTI-tractography study

Determining reliable markers of clinical outcome for psychosis is essential to adjust intervention efforts. White matter alterations exist prior to psychosis onset but its association with clinical outcome in the very early phase of psychosis is currently unknown. In the present study, white matter was assessed by diffusion tensor imaging (DTI) in patients with first episode psychosis (FEP) and healthy controls. Forty-four FEP patients and 30 matched healthy controls completed a DTI scan. The patient group was split in poor (n = 24) and good (n = 20) outcome subgroups based on 6-month clinical data. DTI tractography was used to estimate fractional anisotropy (FA) in the three main tracts connecting frontal and temporal regions (i.e. the cingulum, the superior longitudinal fasciculus and the uncinate fasciculus). The analyses showed selective FA reductions in both the uncinate and the superior longitudinal fasciculi, but not in the cingulum, when comparing FEP patients to healthy controls. FEP subgroup analyses revealed greater white matter changes in these tracts in patients with poor outcome as compared to patients with good outcome. These findings confirm that abnormal fronto-temporal connectivity contributes to the physiopathology of FEP and constitutes an early marker of clinical short-term outcome.

The right parahippocampal gyrus contributes to the formation and maintenance of bound information in working memory.

Working memory is devoted to the temporary storage and on-line manipulation of information. Recently, an integrative system termed the episodic buffer has been proposed to integrate and hold information being entered or retrieved from episodic memory. Although the brain system supporting such an integrative buffer is still in debate, the medial temporal lobe appears to be a promising candidate for the maintenance of bound information. In the current work, binding was assessed by comparing two conditions in which participants had to retain three letters and three spatial locations presented either bound or separate. At the behavioral level, lower performance was found for bound information than for separate information. When contrasting the two conditions, activation in the right parahippocampal gyrus was greater for the encoding and maintenance of bound information. No activation was observed in the medial temporal lobe during the retrieval of bound information. Together, our results suggest that the parahippocampal gyrus may underlie the integrative and maintenance functions of the episodic buffer.

Abnormal Medial Temporal Activity for Bound Information During Working Memory Maintenance in Patients With Schizophrenia

Alterations of binding in long‐term memory in schizophrenia are well established and occur as a result of aberrant activity in the medial temporal lobe (MTL). In working memory (WM), such a deficit is less clear and the pathophysiological bases remain unstudied. Seventeen patients with schizophrenia and 17 matched healthy controls performed a WM binding task while undergoing functional magnetic resonance imaging. Binding was assessed by contrasting two conditions comprising an equal amount of verbal and spatial information (i.e., three letters and three spatial locations), but differing in the absence or presence of a link between them. In healthy controls, MTL activation was observed for encoding and maintenance of bound information but not for its retrieval. Between‐group comparisons revealed that patients with schizophrenia showed MTL hypoactivation during the maintenance phase only. In addition, BOLD signals correlated with behavioral performance in controls but not in patients with schizophrenia. Our results confirm the major role that the MTL plays in the pathophysiology of schizophrenia. Short‐term and long‐term relational memory deficits in schizophrenia may share common cognitive and functional pathological bases. Our results provide additional information about the episodic buffer that represents an integrative interface between WM and long‐term memory.

The Incidence and Nature of Cerebellar Findings in Schizophrenia: A Quantitative Review of fMRI Literature

Clinical evidence and structural neuroimaging studies linked cerebellar deficits to cognitive-related symptoms in schizophrenia. Yet, in functional neuroimaging literature to date, the role of the cerebellum in schizophrenia was not explored in a systematic fashion. Here, we reviewed 234 functional magnetic resonance imaging studies indexed by PubMed and published in 1997-2010 that had at least one group of schizophrenia patients, used blood oxygenation level dependent contrast and the general linear model to assess neuronal activity. We quantified presence/absence of cerebellar findings and the frequency of hypo- and hyperactivations (ie, less or more activity in patients relative to healthy controls). We used peaks of activations reported in these studies to build a topographical representation of group differences on a cerebellar map. Cerebellar activity was reported in patients in 41.02% of the articles, with more than 80% of these dedicated to cognitive, emotional, and executive processes in schizophrenia. Almost two-thirds of group comparisons resulted in cerebellar hypoactivation, with a frequency that presented an inverted U shape across different age categories. The majority of the hypoactivation foci were located in the medial portion of the anterior lobe and the lateral hemispheres (lobules IV-V) of the cerebellum. Even though most experimental manipulations did not target explicitly the cerebellums functions in schizophrenia, the cerebellar findings are frequent and cerebellar hypoactivations predominant. Therefore, although the cerebellum seems to play an important functional role in schizophrenia, the lack of reporting and interpretation of these data may hamper the full understanding of the disorder.

Disrupted integrity of the fornix in first-episode schizophrenia.

Alterations of the fornix in chronic patients with psychosis are well established, but its integrity in the early stage of schizophrenia remains unknown. Thirty-two patients experiencing first-episode schizophrenia (FES) and 25 matched controls completed a DTI scan. DTI-tractography was used to estimate fractional anisotropy (FA) in bilateral fornices. The analysis showed significant overall FA reductions in the fornix in FES patients relative to controls. No significant correlations were found between FA values and clinical and sociodemographic data in FES patients. These findings revealed slight alterations along the fornix in early stage of schizophrenia.

Subjective and Objective Cognitive Dysfunction in Schizophrenia – is there a Link?

Cognitive dysfunction is a well recognized symptom of schizophrenia, as well as patients having poor insight into their illness. The subjective scale to investigate cognition in schizophrenia (SSTICS) is one of several scales that have been developed to study subjective cognitive dysfunction and has been compared to patients’ objective cognitive level. A literature search was performed using PubMed, psychINFO, Web of Science, and cross-referencing to find 26 articles which used 14 different subjective cognitive dysfunction scales to investigate the relationship between subjective and objective measures of cognition in schizophrenia. Although the majority of studies using the SSTICS found significant correlations between subjective and objective measures of cognition, the findings from the other scales were less clear. From this review, the issue of whether or not schizophrenic patients have good cognitive insight remains unsure. However, due to the heterogeneous nature of the study designs and their outcome measures, continued work in this area with consistency on these points is necessary; on the path to better provide management options for a very debilitating component of this illness.

Assessment of single and bound features in a working memory task in schizophrenia

If disturbance of binding in long term memory is well established in schizophrenia, data concerning working memory maintenance are less clear. Feature binding in working memory was investigated in 19 patients with schizophrenia and 19 healthy controls. Binding was assessed by comparing two conditions in which participants had to retain four letters and four spatial locations. These features were presented either bound or separate. Results showed that both groups had better performances for bound than separate features, despite the fact that patients performed significantly worse than controls. When maintenance for isolated features was assessed, patients were severely disturbed for spatial locations but not for letters. Such a result suggests that reduced working memory performance in patients with schizophrenia for bound features is probably a consequence of a spatial deficit rather than a specific deficit of the binding process. Thus, not all form of binding are disturbed in schizophrenia.

Diffusion tensor imaging tractography of the fornix and belief confidence in first-episode psychosis

Previous studies have demonstrated that patients with psychosis are more confident in beliefs and judgments compared to healthy participants and psychiatric controls with major depression. A recent study conducted by our research group has provided evidence for hippocampal pathology in association with overconfidence in a first-episode psychosis sample. The fornix is the primary efferent neural pathway of the hippocampus and may also play a role in self-certainty pathophysiology. The current investigation applied diffusion tensor imaging tractography to a first-episode psychosis sample to explore whether integrity of the fornix is associated with self-certainty. High resolution structural magnetic resonance and diffusion tensor images were obtained in 44 people with a first-episode psychosis. Diffusion tensor imaging tractography was used to estimate fractional anisotrophy (FA), a measure of white matter integrity, in the fornix. Confidence in beliefs and judgments was measured with the self-certainty subscale of the Beck Cognitive Insight Scale (BCIS). The analysis showed that self-certainty significantly correlated to FA values in the right fornix but was nonsignificant for the left fornix. The findings indicate anatomical dysconnectivity of the right fornix in correlation with BCIS-rated self-certainty in our first-episode psychosis sample. When considered with our previously published self-certainty-hippocampus result in a first-episode psychosis sample, overlapping with that of this study, the results indicate a concurrence of volumetric reductions in hippocampus and fornix pathology in correlation with self-certainty.

Selective pair recognition memory impairment with no response bias in schizophrenia

Memory is one of the cognitive functions most affected in schizophrenia, but the severity of deficits varies from one task to another. In particular, greater impairments have been reported for pair recognition than item recognition. However, decision biases and how they could affect memory dysfunction in schizophrenia have received scant attention. In this study, 26 people with schizophrenia and 28 healthy controls were administrated an association item recognition task. During encoding, participants studied pairs of visual objects, and they had to memorise objects and their pairing. In a subsequent retrieval task, participants performed an item recognition test (old/new items) and a pair recognition test (intact/rearranged pairs). Results showed that both groups were better at recognizing items than pairs, with lower performance for pair recognition, but not for item recognition, in people with schizophrenia. Analyses of response biases revealed that patients had a conservative response bias for items but not for pairs. The study also provides evidence that associative impairment may not result from decisional bias but rather from impairments in mnesic processes.

The puzzling question of inhibitory control in Tourette syndrome: A meta-analysis

HIGHLIGHTSImpulse control disorders are somewhat frequent in Tourette syndrome (TS) patients.Inhibitory control is impaired in TS patients, even when they do not have any comorbid disorder.Comorbid ADHD has a potentiating effect on the inhibitory deficits of TS patients.TS patients have impairments in verbal inhibition and Stroop interference, but show intact Go/No‐Go performance. ABSTRACT Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic tics. Inhibitory control is a key issue in TS, and many disruptive or impulsive behaviors might arise from inhibitory deficits. However, conflicting findings regarding TS patients’ inhibitory performance in neuropsychological tasks have been reported throughout the literature. Therefore, this meta‐analysis aimed to evaluate inhibitory control through neuropsychological tasks, and to analyze the factors modulating inhibitory deficits. To this end, a literature search was performed through MEDLINE and PsycINFO, to retrieve studies including neuropsychological tasks that assessed inhibitory control in TS patients. Of the 4020 studies identified, 61 were included in the meta‐analysis, for a total of 1717 TS patients. Our analyses revealed a small to medium effect in favor of inhibitory deficits in TS patients. This effect was larger in TS + ADHD patients, but pure TS patients also showed some inhibitory deficits. Therefore, deficits in inhibitory control seem to be an inherent component of TS, and are exacerbated when ADHD is concomitant.