Steffen Landgraf

Effective Connectivity of the Multiplication Network: A Functional MRI and Multivariate Granger Causality Mapping Study

Developmental neuropsychology and functional neuroimaging evidence indicates that simple and complex mental calculation is subserved by a fronto‐parietal network. However, the effective connectivity (connection direction and strength) among regions within the fronto‐parietal network is still unexplored. Combining event‐related fMRI and multivariate Granger Causality Mapping (GCM), we administered a multiplication verification task to healthy participants asking them to solve single and double‐digit multiplications. The goals of our study were first, to identify the effective connectivity of the multiplication network, and second, to compare the effective connectivity patterns between a low and a high arithmetical competence (AC) group. The manipulation of multiplication difficulty revealed a fronto‐parietal network encompassing bilateral intraparietal sulcus (IPS), left pre‐supplementary motor area (PreSMA), left precentral gyrus (PreCG), and right dorsolateral prefrontal cortex (DLPFC). The network was driven by an intraparietal IPS‐IPS circuit hosting a representation of numerical quantity intertwined with a fronto‐parietal DLPFC‐IPS circuit engaged in temporary storage and updating of arithmetic operations. Both circuits received additional inputs from the PreCG and PreSMA playing more of a supportive role in mental calculation. The high AC group compared to the low AC group displayed a greater activation in the right IPS and based its calculation more on a feedback driven intraparietal IPS‐IPS circuit, whereas the low competence group more on a feedback driven fronto‐parietal DLPFC‐IPS circuit. This study provides first evidence that multivariate GCM is a sensitive approach to investigate effective connectivity of mental processes involved in mental calculation and to compare group level performances for different populations. Hum Brain Mapp, 2010.

“To see or not to see: that is the question.” The “Protection-Against-Schizophrenia” (PaSZ) model: evidence from congenital blindness and visuo-cognitive aberrations

The causes of schizophrenia are still unknown. For the last 100 years, though, both “absent” and “perfect” vision have been associated with a lower risk for schizophrenia. Hence, vision itself and aberrations in visual functioning may be fundamental to the development and etiological explanations of the disorder. In this paper, we present the “Protection-Against-Schizophrenia” (PaSZ) model, which grades the risk for developing schizophrenia as a function of an individuals visual capacity. We review two vision perspectives: (1) “Absent” vision or how congenital blindness contributes to PaSZ and (2) “perfect” vision or how aberrations in visual functioning are associated with psychosis. First, we illustrate that, although congenitally blind and sighted individuals acquire similar world representations, blind individuals compensate for behavioral shortcomings through neurofunctional and multisensory reorganization. These reorganizations may indicate etiological explanations for their PaSZ. Second, we demonstrate that visuo-cognitive impairments are fundamental for the development of schizophrenia. Deteriorated visual information acquisition and processing contribute to higher-order cognitive dysfunctions and subsequently to schizophrenic symptoms. Finally, we provide different specific therapeutic recommendations for individuals who suffer from visual impairments (who never developed “normal” vision) and individuals who suffer from visual deterioration (who previously had “normal” visual skills). Rather than categorizing individuals as “normal” and “mentally disordered,” the PaSZ model uses a continuous scale to represent psychiatrically relevant human behavior. This not only provides a scientific basis for more fine-grained diagnostic assessments, earlier detection, and more appropriate therapeutic assignments, but it also outlines a trajectory for unraveling the causes of abnormal psychotic human self- and world-perception.

Impact of phonological processing skills on written language acquisition in illiterate adults

Illiteracy remains a world-wide problem not only for children but also for adults. Phonological processing has been defined as a crucial factor for the acquisition of written language, which usually occurs in childhood. However, it is unclear to what extent phonological processing is necessary in order for adults to acquire written language skills. We tested 47 illiterate adults before and after a one-year alphabetization course in several cognitive domains relevant to phonological processing and compared their results to 41 matched controls who did not take part in the alphabetization course. Phonological awareness in the narrower sense (e.g., phoneme association) was a stronger predictor of alphabetization outcome than demographic variables such as years of education. In addition, despite improvement of illiterate individuals in phonological awareness, short-term memory, and visual attention from before to after the alphabetization course, they did not reach the phonological processing level of literate controls. Our results confirm that the alphabetization of adults requires and enhances phonological processes similar to those of children. Nevertheless, specific aspects, such as improvements in short-term memory or visual attention, need to be considered in order to improve and optimize alphabetization programs for adults.

Temporal Information Processing in Short- and Long-Term Memory of Patients with Schizophrenia

Cognitive deficits of patients with schizophrenia have been largely recognized as core symptoms of the disorder. One neglected factor that contributes to these deficits is the comprehension of time. In the present study, we assessed temporal information processing and manipulation from short- and long-term memory in 34 patients with chronic schizophrenia and 34 matched healthy controls. On the short-term memory temporal-order reconstruction task, an incidental or intentional learning strategy was deployed. Patients showed worse overall performance than healthy controls. The intentional learning strategy led to dissociable performance improvement in both groups. Whereas healthy controls improved on a performance measure (serial organization), patients improved on an error measure (inappropriate semantic clustering) when using the intentional instead of the incidental learning strategy. On the long-term memory script-generation task, routine and non-routine events of everyday activities (e.g., buying groceries) had to be generated in either chronological or inverted temporal order. Patients were slower than controls at generating events in the chronological routine condition only. They also committed more sequencing and boundary errors in the inverted conditions. The number of irrelevant events was higher in patients in the chronological, non-routine condition. These results suggest that patients with schizophrenia imprecisely access temporal information from short- and long-term memory. In short-term memory, processing of temporal information led to a reduction in errors rather than, as was the case in healthy controls, to an improvement in temporal-order recall. When accessing temporal information from long-term memory, patients were slower and committed more sequencing, boundary, and intrusion errors. Together, these results suggest that time information can be accessed and processed only imprecisely by patients who provide evidence for impaired time comprehension. This could contribute to symptomatic cognitive deficits and strategic inefficiency in schizophrenia.

Correlates between neurological soft signs and saccadic parameters in schizophrenia

OBJECTIVE Neurological Soft Signs (NSS) and impairments in oculomotor saccadic paradigms are both frequent in patients with schizophrenia but their correlation has never been explored. METHODS 78 patients with DSM-IV schizophrenia (including 43 non-treated) and 41 matched healthy controls were tested for NSS, and on three saccadic tasks: prosaccades, predictive saccades and memory-guided saccades) using infrared oculometry. We analyzed correlations between NSS scores and latencies in all three tasks, rate of errors in memory-guided saccades, and rate of anticipated predictive saccades. RESULTS No correlations were found in healthy controls. In the patient group, the NSS total and motor coordination scores were positively correlated with three saccadic variables: the latency of prosaccades (r=0.36, p<0.01 and r=0.36, p<0.01 respectively), of memory-guided saccades (r=0.35, p<0.01 and r=0.32, p<0.05 respectively) and, negative correlations were found, with the rate of anticipated predictive saccades (r=-0.33, p<0.01; r=-0.35, p<0.01 respectively). NSS total, motor coordination and sensory integration scores were correlated to the latency of non-anticipated predictive saccades (r=0.34, p<0.01; r=0.24, p<0.05 and r=0.40, p<0.001 respectively). The NSS total, motor integration and sensory integration scores were correlated with the rate of errors in memory-guided saccades (r=0.38, p<0.01; r=0.37, p<0.01 and r=0.34, p<0.01 respectively). CONCLUSIONS These results support a common pathological mechanism with partial overlapping neural substrates between NSS and saccades in schizophrenia.

Inflexible information acquisition strategies mediate visuo-spatial reasoning in stabilized schizophrenia patients

Abstract Objectives. Cognitive deficits are of fundamental importance to the clinical picture of schizophrenia and are on the verge to be included as diagnostic criteria in the DSM-V. While focusing on information processing deficits, no emphasis has been put on whether patients’ deficits can be accounted for by maladaptive information acquisition strategy deployment. Methods. We tested 24 stabilized patients with schizophrenia and 25 matched controls in a visuo-spatial analogy task with graded difficulty. Eye movement recordings served to identify information acquisition strategies. Results. Patients compared to healthy controls showed slower reaction times in the easiest condition and higher error rates in the more difficult conditions. Eye movement recordings illustrated that overall mean fixation duration increased with increasing task difficulty in healthy controls only. Further, patients deployed a more efficient strategy (“constructive matching”) less often than healthy controls in the easier conditions. Conclusions. These results suggest that information acquisition strategies mediate visuo-spatial cognitive performance in schizophrenia. Patients adopt a less efficient strategy independently of task difficulty indicated by a characteristic behavioural pattern. Our results point to a powerful tool of improving patients’ performance in cognitively demanding tasks by training them in more flexible cognitive (e.g., information acquisition) strategy deployment.

Discerning Temporal Expectancy Effects in Script Processing: Evidence from Pupillary and Eye Movement Recordings

Accessing the temporal position of events (early or late in the event sequence) can influence the generation of predictions about upcoming events. However, it is unclear how the temporal position is processed strategically. To investigate this, we presented event pairs to 23 healthy volunteers manipulating temporal order (chronological, inverse) and temporal position (early, late). Pupil dilation, eye movements, and behavioral data, showed that chronological and early event pairs are processed with more ease than inverse and late event pairs. Indexed by the pupillary response late events and inversely presented event pairs elicited greater cognitive processing demands than early events and chronologically presented event pairs. Regarding eye movements, fixation duration was less sensitive to temporal position than to temporal order. Looking at each item of the event sequence only once was behaviorally more effective than looking multiple times at each event regardless of whether temporal position or temporal order was processed. These results emphasize that accessing temporal position and temporal order information results in dissociable behavioral patterns. While more cognitive resources are necessary for processing late and inverse items, change of information acquisition strategies turns out to be most effective when temporal order processing is required.

Dissociating improvement of attention and intelligence during written language acquisition in adults

About one tenth of the world’s population cannot read and write sufficiently. Cognitive abilities, such as selective attention and crystallized as well as fluid intelligence, have been defined as crucial factors for the acquisition of written language skills. However, it is unclear whether these abilities are necessary also for the alphabetization of adults. Before and after a one-year alphabetization course, we compared the attention and intelligence of 47 illiterate individuals to 41 matched literate controls who did not take part in the alphabetization course. Illiterate individuals improved in selective attention and crystallized intelligence from before to after the alphabetization course; however, they did not reach the same level of functioning as literate controls. In addition, the fluid intelligence of illiterates did not improve. More importantly, when controlling for attention improvement, we found that improvement in crystallized intelligence was associated with alphabetization above and beyond the influence of attention. Our results suggest that alphabetization is closely related to improvements in attention and crystallized intelligence. Specifically, socio-cultural, knowledge- specific learning processes improve during the acquisition of written language skills and may not depend on only the enhancement of the ability to attend to relevant stimuli. Alphabetization programs may, therefore, benefit from distinct considerations of attentional, intellectual, and literacy related skill acquisitions.

A clinical and demographic comparison between a forensic and a general sample of female patients with schizophrenia

Diagnoses of psychiatric diseases do not include criminal behavior. In schizophrenia, a non-negligible subgroup is incarcerated for capital and other crimes. Most studies that compared offender and non-offender patients with schizophrenia have only focused on male patients. With this study, we compared demographic and disease-related characteristics between 35 female incarcerated forensic patients (fSZ) and 35 female inpatients with schizophrenia (SZ). Basic clinical documentation and basic forensic clinical documentation revealed significant clinical and demographic differences between the two groups. Compared to SZ, fSZ were more severely clinically impaired, showing higher rates of comorbid alcohol and substance disorder, more suicide attempts, had more previous hospitalizations, and were younger at disease onset. Regarding demographic variables, fSZ showed a higher rate of unemployment and homelessness and had to rely more often on housing and legal guardianships compared to SZ. These results suggest that female forensic patients with schizophrenia are more severely affected by clinical and non-clinical variables requiring an adapted intervention program. These results may also indicate two developmental trajectories for criminal and non-criminal schizophrenia in females.

Shielding voices: The modulation of binding processes between voice features and response features by task representations

Vocal events offer not only semantic-linguistic content but also information about the identity and the emotional-motivational state of the speaker. Furthermore, most vocal events have implications for our actions and therefore include action-related features. But the relevance and irrelevance of vocal features varies from task to task. The present study investigates binding processes for perceptual and action-related features of spoken words and their modulation by the task representation of the listener. Participants reacted with two response keys to eight different words spoken by a male or a female voice (Experiment 1) or spoken by an angry or neutral male voice (Experiment 2). There were two instruction conditions: half of participants learned eight stimulus-response mappings by rote (SR), and half of participants applied a binary task rule (TR). In both experiments, SR instructed participants showed clear evidence for binding processes between voice and response features indicated by an interaction between the irrelevant voice feature and the response. By contrast, as indicated by a three-way interaction with instruction, no such binding was found in the TR instructed group. These results are suggestive of binding and shielding as two adaptive mechanisms that ensure successful communication and action in a dynamic social environment.