Katja Cattapan-Ludewig

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia.

Current treatments for Alzheimers disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

Help-seeking pathways in early psychosis

IntroductionUnderstanding the help-seeking pathways of patients with a putative risk of developing psychosis helps improving development of specialised care services. This study aimed at obtaining information about: type of health professionals contacted by patients at putative risk for psychosis on their help-seeking pathways; number of contacts; type of symptoms leading to contacts with health professionals; interval between initial contact and referral to a specialised outpatient service.MethodThe help-seeking pathways were assessed as part of a prospective study in 104 patients with suspected at-risk states for psychosis.ResultsThe mean number of contacts prior to referral was 2.38. Patients with psychotic symptoms more often contacted mental health professionals, whereas patients with insidious and more unspecific features more frequently contacted general practitioners (GPs).ConclusionsGPs have been found to under-identify the insidious features of emerging psychosis (Simon et al. (2005) Br J Psychiatry 187:274–281). The fact that they were most often contacted by patients with exactly these features calls for focussed and specialised help for primary care physicians. Thus, delays along the help-seeking pathways may be shortened. This may be of particular relevance for patients with the deficit syndrome of schizophrenia.

Cognitive functioning in at-risk mental states for psychosis and 2-year clinical outcome

BACKGROUND Cognitive impairment is prevalent in at-risk mental states (ARMS) for psychosis. METHOD We studied cognitive functioning at baseline in ARMS individuals and investigated its power to predict ARMS persistence and remission at 2-year follow-up. RESULTS 196 patients were recruited. At baseline the ARMS population included 26 subjects meeting basic symptom (BS) criteria and 73 subjects fulfilling ultra-high risk (UHR) criteria. Two control groups were defined: 48 patients in a first episode of psychosis (FE), and 49 help-seeking patient controls (PCO). In 144 patients follow-up data were obtained. The 2-year risk of conversion to psychosis was 20%. Remission from an initial UHR state occurred in two thirds of the follow-up sample. UHR patients that converted to psychosis or did not remit during the follow-up (UHR(n-rem)) showed similar impairment in global cognitive functioning at baseline as the FE group, whereas global cognitive functioning in UHR patients with subsequent remission (UHR(rem)) approximated performances of the BS and PCO groups. UHR(n-rem) and UHR(rem) patients differed significantly on immediate verbal memory, but showed similarly impaired executive functions. Normal immediate verbal memory uniquely predicted remission from an at-risk state with a positive predictive value of 82%. CONCLUSIONS Cognitive deficits are a characteristic feature of true ARMS patients. Verbal memory function appears critical in determining outcome.

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: The impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

Subclinical hallucinations in adolescent outpatients: An outcome study

OBJECTIVE We assessed the continued prevalence at one year and association with clinical variables of subclinical hallucinations ascertained at baseline in a cohort of adolescent outpatients referred to a specialized early psychosis service. We further assessed the prevalence of psychiatric disorders in adolescents presenting subclinical hallucinations. METHOD 84 adolescent patients were sampled from a longitudinal, prospective study that assesses the course of clinical and neuropsychological measures in patients identified as at high clinical risk for psychosis. Subclinical hallucinations were measured using the Scale of Prodromal Symptoms (SOPS) with its companion interview manual (Structured Interview for Prodromal Symptoms, SIPS) [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatr. Q. 70, 273-287; McGlashan, T.H., Miller, T.J., Woods, S.W., Rosen, J.L., Hoffman, R.E., Davidson, L., 2001. Structured Interview for Prodromal Syndromes (Version 3.0, unpublished manuscript). PRIME Research Clinic, Yale School of Medicine New Haven, Connecticut. ], and the Schizophrenia Proneness Instrument -Adult Version (SPI-A) [Schultze-Lutter, F., Addington, J., Ruhrmann, S., Klosterkötter, J., 2007. Schizophrenia Proneness Instrument (SPI-A). Giovanni Fioriti, Rome, Italy]. At one-year follow-up, only patients reporting subclinical hallucinations at initial assessment were studied. RESULTS Full remission of subclinical hallucinations occurred in over half and at least partial remission in two thirds of these patients at one-year follow-up. Mood disorders were present in 62.5% of adolescents with subclinical hallucinations at initial assessment. SOPS measures for depression, deficient attention and for unusual/delusional thought were significantly associated with subclinical hallucinations at baseline. However, sustained experience of subclinical hallucinations at one-year follow-up was only predicted by the global level of functioning at baseline, while cannabis abuse, psychiatric and psychopharmacological treatment were not predictors. CONCLUSIONS Subclinical hallucinations occur across a wide range of mental states in adolescents and show high rates of remission. Our results warrant that the clinical meaning of such phenomena needs to be carefully weighed against the specific developmental phenomena in this particular age range.

Jazz Drummers Recruit Language-Specific Areas for the Processing of Rhythmic Structure

Rhythm is a central characteristic of music and speech, the most important domains of human communication using acoustic signals. Here, we investigated how rhythmical patterns in music are processed in the human brain, and, in addition, evaluated the impact of musical training on rhythm processing. Using fMRI, we found that deviations from a rule-based regular rhythmic structure activated the left planum temporale together with Brocas area and its right-hemispheric homolog across subjects, that is, a network also crucially involved in the processing of harmonic structure in music and the syntactic analysis of language. Comparing the BOLD responses to rhythmic variations between professional jazz drummers and musical laypersons, we found that only highly trained rhythmic experts show additional activity in left-hemispheric supramarginal gyrus, a higher-order region involved in processing of linguistic syntax. This suggests an additional functional recruitment of brain areas usually dedicated to complex linguistic syntax processing for the analysis of rhythmical patterns only in professional jazz drummers, who are especially trained to use rhythmical cues for communication.

Sustained attention and planning deficits but intact attentional set-shifting in neuroleptic-naïve first-episode schizophrenia patients

Introduction: The nature of deficits in tests of sustained attention, planning and attentional set-shifting has not been investigated in neuroleptic-naïve first-episode (FE) schizophrenia patients. Based on previous literature of chronic and medicated FE schizophrenia patients, we predicted that the neuroleptic-naïve patients would show deficits in these cognitive processes. Methods: Twenty-nine neuroleptic-naïve FE schizophrenia patients and 33 healthy controls – matched by age, gender, and nicotine consumption – performed 3 tests from the Cambridge Automated Neuropsychological Test Battery (CANTAB) thought to measure these cognitive processes: the Rapid Visual Information Processing task (RVIP, sustained attention), the Stockings of Cambridge task (SOC, planning), and the Intradimensional/Extradimensional set-shifting task (IDED, attention shifting). Results: The patients were significantly impaired in the sensitivity index (A′) of the RVIP, and in the number of problems solved with minimum moves on the SOC. Nevertheless, the groups did not differ regarding the number of participants who failed at the crucial extradimensional shift stage of the IDED. Conclusion: Sustained attention and planning abilities are already impaired in neuroleptic-naïve FE schizophrenia patients, whereas set-shifting abilities as measured with the IDED task seem to be intact at illness onset. Since chronic schizophrenia patients have been shown to have impaired IDED performance, we tentatively propose that IDED performance deteriorates over time with illness chronicity and/or medication.

Neural correlates of pre‐attentive processing of pattern deviance in professional musicians

Pre‐attentive registration of aberrations in predictable sound patterns is attributed to the temporal cortex. However, electrophysiology suggests that frontal areas become more important when deviance complexity increases. To play an instrument in an ensemble, professional musicians have to rely on the ability to detect even slight deviances from expected musical patterns and therefore have highly trained aural skills. Here, we aimed to identify the neural correlates of experience‐driven plasticity related to the processing of complex sound features. We used functional magnetic resonance imaging in combination with an event‐related oddball paradigm and compared brain activity in professional musicians and non‐musicians during pre‐attentive processing of melodic contour variations. The melodic pattern consisted of a sequence of five tones each lasting 50 ms interrupted by silent interstimulus intervals of 50 ms. Compared to non‐musicians, the professional musicians showed enhanced activity in the left middle and superior temporal gyri, the left inferior frontal gyrus and in the right ventromedial prefrontal cortex in response to pattern deviation. This differential brain activity pattern was correlated with behaviorally tested musical aptitude. Our results thus support an experience‐related role of the left temporal cortex in fast melodic contour processing and suggest involvement of the prefrontal cortex. Hum Brain Mapp, 2009.

Rapid Visual Information Processing in Schizophrenic Patients: The Impact of Cognitive Load and Duration of Stimulus Presentation

The inability to sustain attention has been proposed as a core deficit in schizophrenia. The Continuous Performance Task (AX-CPT) and the Rapid Visual Information Processing Task (RVP) are widely used neuropsychological tasks to measure sustained attention. The RVP displays numbers as stimuli, whereas the AX-CPT uses letters. Ten patients with chronic schizophrenia and 18 healthy control subjects were studied using four different versions of the RVP. The versions differed with regard to stimulus presentation time (600 vs. 1,200 ms) and the number of target sequences to be memorized: either one sequence (low cognitive load) or two sequences (high cognitive load). Schizophrenic patients showed a reduced number of hits only on the task version with 600 ms stimulus duration coupled with high cognitive load. The combination of high cognitive load and short stimulus duration created a critical performance breaking point for schizophrenic patients. This finding supports the hypothesis that patients have an impaired ability to coactivate different cognitive performances; thus the results favor the theory of impaired functional connectivity in schizophrenia.

Interference during the implicit learning of two different motor sequences

It has been demonstrated that learning a second motor task after having learned a first task may interfere with the long-term consolidation of the first task. However, little is known about immediate changes in the representation of the motor memory in the early acquisition phase within the first minutes of the learning process. Therefore, we investigated such early interference effects with an implicit serial reaction time task in 55 healthy subjects. Each subject performed either a sequence learning task involving two different sequences, or a random control task. The results showed that learning the first sequence led to only a slight, short-lived interference effect in the early acquisition phase of the second sequence. Overall, learning of neither sequence was impaired. Furthermore, the two processes, sequence-unrelated task learning (i.e. general motor training) and the sequence learning itself did not appear to interfere with each other. In conclusion, although the long-term consolidation of a motor memory has been shown to be sensitive to other interfering memories, the present study suggests that the brain is initially able to acquire more than one new motor sequence within a short space of time without significant interference.