Early neglect is a key determinant of adult hair cortisol concentration and is associated with increased vulnerability to trauma in a transdiagnostic sample.

BACKGROUND: Childhood adversities and traumatic events have each been associated with hypothalamus-pituitary-adrenal (HPA) axis dysregulation and trauma-related symptoms in adulthood. Hair cortisol concentration (HCC) reflects cumulative cortisol levels over the course of months and is discussed as a potential marker between trauma-induced neuroendocrine dysfunction and trauma-related symptoms. The present study examines this hypothetical link by delineating the impact of exposure to categories of abuse and neglect during development and lifetime traumatic experiences on HCC and trauma-related symptoms. METHODS: The Maltreatment and Abuse Chronology Exposure (MACE) scale, Life Events Checklist, and predictive analytics were used to evaluate the importance of type and timing of maltreatment and trauma load on HCC in inpatients (n = 183) with different psychiatric diagnoses. Additionally, a comparison group of n = 75 controls were recruited from the community. The extent to which the relationship between trauma load and trauma-related symptoms was influenced by childhood adversities and HCC was determined by analysis of variance. RESULTS: Early neglect, in particular neglect at 3 years, emerged as the most important predictor of adult HCC. Post-hoc explanatory analysis showed that patients with high neglect at age 3 had lower HCC compared to patients with low neglect at age 3 and controls. Patients with high neglect at age 3 and low cortisol reported increased trauma-related symptoms upon trauma exposure. CONCLUSION: Results strengthen evidence that inadequate care and neglect during critical periods alter HPA axis biology towards enduring reduction in cortisol, the latter being associated with augmented trauma-related symptoms upon trauma exposure. If validated by longitudinal assessments these cross-sectional findings suggest biological mechanisms of childhood adversities into psychopathology in adulthood.

Motor imagery in stroke patients, or plegic patients with spinal cord or peripheral diseases.

OBJECTIVES: When motor imagery (MI) is impaired in stroke patients, it is not clear, whether this is caused by the central lesion with a disruption of networks or this may be due to inactivity/lack of practice following hemiparesis. To answer this question, we investigated MI in two groups of patients: stroke patients and patients with no central lesion, who suffered high-grade tetraparesis caused by myopathy or spinal muscular atrophy. MATERIALS AND METHODS: The first study measured MI in 31 sub-acute and chronic stroke patients with hand paresis. We used self-assessment questionnaires [Kinaesthetic and Visual Imagery Questionnaire (KVIQ), the Vividness of Motor Imagery Questionnaire (VMIQ)] as well as a new chronometric test (mental version and normal/physical version of Box and Block Test). The second study assessed MI in 10 patients without a central lesion, but with severe tetraparesis of peripheral origin. They were incapable of performing the requested task physically. RESULTS: MI in patients was better (i) for the third-person (VMIQ(3.P) ) compared to the first-person perspective (VMIQ(1.P) ), (ii) in patients without sensory impairment compared to those with impaired proprioception, (iii) in patients with light paresis compared to severe paresis and (iv) for the non-affected than the affected hand (KVIQ-10). Patients with severe tetraparesis were able to imagine another person's knee bends, but were not capable of imagining themselves performing knee bends. CONCLUSIONS: MI may be hampered on the affected side in severely paretic patients, particularly in the presence of impaired proprioception. Remarkably, the second study illustrates that motor experiences shape MI. This confirms the close relationship between MI and movement execution. The study advocates the careful use of test batteries for assessment of MI when investigating mental training in clinical trials. Not all patients might benefit to the same extent from MI training. This is possibly contingent on intact proprioception and preserved MI.

[Magnetoencephalography in psychiatry]. / Magnetoenzephalographie in der Psychiatrie.

Neuropsychiatric disorders usually come with only sublime structural changes. Functional imaging can point at specific disturbances in information processing in neural networks. Besides imaging of receptor and metabolic functions with PET and fMRI, electromagnetic methods such as electroencephalography (EEG) and magnetoencephalography (MEG) offer the possibility for imaging of dynamic dysfunctions. As compared to EEG, MEG has a shorter history and is less common despite offering considerable advantages in temporospatial resolution and sensitivity to detect impaired signal processing and network functioning which renders it particularly interesting for psychiatric applications. Disturbed processing in the auditory and visual domain emerging in schizophrenic, affective and anxiety disorders can be detected with high sensitivity. Moreover, the neuromagnetic baseline activity allows conclusions to be drawn regarding neural network functions. Due to its high sensitivity to single deficits in information processing and to pharmacological effects, MEG will achieve clinical significance in specific areas.

Electromagnetic brain activity in higher frequency bands during automatic word processing indicates recovery of function in aphasia.

AIM: Little is known about how treatment affects the neural substrate of language function in stroke sufferers. In the present study authors investigated neuronal correlates of treatment induced recovery of language functions in patients with chronic aphasia. METHODS: In 10 chronic aphasia patients and 10 age- and gender-matched control participants, evoked high-frequency activity (HFA, >20 Hz) was determined from the magnetoencephalogram in an automatic word recognition task, in which content, function, and pseudowords were visually presented at fast rate (350-ms). Recording was repeated after 2 weeks, in aphasics after intensive language training to evaluate training effects, in controls to establish HFA stability. RESULTS: In the first recording, bilateral HFA distribution in controls contrasted right-hemispheric predominance in the patients. After training, this right>left asymmetry in aphasics was reduced to a bilateral pattern similar to controls. While word class did not substantially affect HFA patterns in the two groups, enhanced right-hemispheric HFA in the patients varied with better language function (test performance) prior to training, while after training, left-temporal function- and pseudoword evoked HFA varied with performance in tests of written language. CONCLUSION: Results suggest that HFA might serve as a measure in the evaluation of rehabilitation efforts in chronic aphasia: enhanced right-hemispheric HFA might indicate compensatory activation of contralateral language areas, which tends towards patterns comparable to normal subjects after effective language training.

Recovery from aphasia as a function of language therapy in an early bilingual patient demonstrated by fMRI.

Knowledge about the recovery of language functions in bilingual aphasic patients who suffer from left-hemispheric stroke is scarce. Here, we present the case of an early bilingual patient (German/French) with chronic aphasia. Functional magnetic resonance imaging (fMRI) was used to investigate neural correlates of language performance during an overt picture naming task in German and French (a) 32 months after stroke to assess differential recovery of both languages as a function of the preceding language therapy that was provided exclusively in German and (b) after additional short-term intensive (German) language training. At the first investigation behavioral performance confirmed selective recovery of German naming ability which was associated with increased functional brain activation compared to the French naming condition. Changes in behavioral performance and brain activation pattern as disclosed by fMRI after an additional experimental treatment were confined to the trained (German) language and indicate bilateral neuroplastic reorganization. No generalization to the untrained (French) language was observed. The present case results demonstrate use and/or training-dependent differential recovery of expressive language functions and an enhanced pattern of brain activation as a function of the rehabilitation efforts that were focussed exclusively on the patient's German language abilities.

[New developments in stroke rehabilitation based on behavioral and neuroscientific principles: constraint-induced therapy]. / Die Fortentwicklung der Neurorehabilitation auf verhaltensneurowissenschaftlicher Grundlage. Beispiel Constraint-induced-Therapie.

Recent discoveries about the central nervous system's response to injury and how patients reacquire behavioral capabilities by training have yielded promising new therapies for neurorehabilitation. This family of interventions is termed constraint-induced (CI) therapy and is essentially behavioral in nature. Constraining movement of the arm which is less affected by the stroke and training (by shaping) the more affected arm for many hours a day for two consecutive weeks proved effective in the treatment of hemiplegia in many studies. Successful applications other than for stroke have been for traumatic brain injury, cerebral palsy, spinal cord injury, fractured hip, and focal hand dystonia. Extending the principles to other consequences of stroke such as aphasia is examined. Constraint-induced therapy is shown to produce large changes in the organization and function of the brain,which emphasizes the significance of cortical reorganization and learning for neurorehabilitation.

Grapheme monitoring in picture naming: an electrophysiological study of language production.

Electrocortical correlates of language production were examined in two picture naming tasks that involved grapheme monitoring. In both tasks subjects (N=12) had to detect target letters in picture names, the target letter being positioned either at the beginning or at the end of the picture name. Between tasks, the target letter was shown either before (target-picture, TP) or after (picture-target, PT) the presentation of the object pictures. In both tasks, subjects responded faster, whenever the target letter appeared at the beginning of the picture name than at its end. The EEG, recorded from 64 electrodes, was analyzed in the signal and in the source space (using the Minimum Norm estimate). Differences in the event-related potential (ERP) following the second stimulus became evident earlier in the PT (at 320 ms) than the TP (456 ms) task. This onset of diverging ERPs was called the "point of divergence" (POD). The ERP following the POD was characterized by a positive deflection in the "begin" condition in both tasks. In the "end" condition, the sources of brain activity were focused over the left hemisphere in the TP, while a bilateral distribution characterized the PT task. Performance and electrocortical indices support the hypothesis of serial "left-to-right" processing of a representation of the picture name. The left-hemispheric activity focus in the TP task is assumed to indicate the encoding of the picture name, while frontal symmetrical activity in the PT task might indicate the involvement of working memory processes.

Functional asymmetry in schizophrenic patients during auditory speech processing.

In two experiments, functional laterality and interhemispheric transfer was investigated in schizophrenic patients (n=14) and healthy controls (n=17). In Experiment 1, words and pseudowords were presented either to the left or right ear (monaural condition) or simultaneously to both ears (binaural condition). In Experiment 2, subjects had to discriminate two tones differing in frequency during monaural and binaural stimulation. Healthy controls showed a right ear advantage (REA) for word stimuli, indicating left-hemispheric superiority for word processing. The same lateralization pattern was found in schizophrenic patients, indicating unimpaired functional lateralization of auditory language processing. In both groups, no REA was found for pseudowords resulting in significant WordnessxEar interactions. When presented binaurally, auditory processing of words and pseudowords did not differ significantly from any of the two monaural conditions. Tone discrimination did not lead to any ear asymmetry. The results show normal patterns of functional asymmetry during auditory language processing and tone discrimination in schizophrenic patients.

Syntactic and semantic processing in the healthy and aphasic human brain.

A syntactic and a semantic task were performed by German-speaking healthy subjects and aphasics with lesions in the dominant left hemisphere. In both tasks, pictures of objects were presented that had to be classified by pressing buttons. The classification was into grammatical gender in the syntactic task (masculine or feminine gender?) and into semantic category in the semantic task (man- or nature made?). Behavioral data revealed a significant Group by Task interaction, with aphasics showing most pronounced problems with syntax. Brain event-related potentials 300-600 ms following picture onset showed different task-dependent laterality patterns in the two groups. In controls, the syntax task induced a left-lateralized negative ERP, whereas the semantic task produced more symmetric responses over the hemispheres. The opposite was the case in the patients, where, paradoxically, stronger laterality of physiological brain responses emerged in the semantic task than in the syntactic task. We interpret these data based on neuro-psycholinguistic models of word processing and current theories about the roles of the hemispheres in language recovery.

Source distribution of neuromagnetic slow waves and MEG-delta activity in schizophrenic patients.

BACKGROUND: Schizophrenic patients exhibit more activity in the electroencephalographic delta and theta frequency range than do control subjects. Using magnetic source imaging (MSI) our study aimed to explore this phenomenon in the magnetoencephalogram (MEG), the distribution of its sources, and associations between symptom profiles and sources of low-frequency activity in the brain. METHODS: Whole-head MEG recordings were obtained from 28 schizophrenic patients and 20 healthy control subjects during a resting condition. The generators of the focal magnetic slow waves were located employing a single moving dipole model. Distributed or multiple delta and theta sources were captured by the minimum norm estimate. RESULTS: Both localization procedures showed slow wave activity to be enhanced in schizophrenic patients compared with control subjects. Focal slow wave activity differed most between groups in frontotemporal and in posterior regions. Slow wave activity was associated with symptom characteristics in that positive symptoms varied with frontal delta and theta activity. CONCLUSIONS: Results indicate that activity in low-frequency bands in schizophrenic patients exceeds the activity of control subjects in distinct areas, and that this focal clustering of neuromagnetic slow waves may be related to psychopathologic characteristics.

Constraint-induced therapy of chronic aphasia after stroke.

Patients with chronic aphasia were assigned randomly to a group to receive either conventional aphasia therapy or constraint-induced (CI) aphasia therapy, a new therapeutic technique requiring intense practice over a relatively short period of consecutive days. CI aphasia therapy is realized in a communicative therapeutic environment constraining patients to practice systematically speech acts with which they have difficulty. Patients in both groups received the same amount of treatment (30 to 35 hours) as 10 days of massed-practice language exercises for the CI aphasia therapy group (3 hours per day minimum; 10 patients) or over a longer period of approximately 4 weeks for the conventional therapy group (7 patients). CI aphasia therapy led to significant and pronounced improvements on several standard clinical tests, on self-ratings, and on blinded-observer ratings of the patients' communicative effectiveness in everyday life. Patients who received the control intervention failed to achieve comparable improvements. Data suggest that the language skills of patients with chronic aphasia can be improved in a short period by use of an appropriate massed-practice technique that focuses on the patients' communicative needs.

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia.

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.

Increased semantic and repetition priming in schizophrenic patients.

Positive and negative priming (PP and NP) in schizophrenia were studied with a lexical-decision task. Probe words, presented 800 ms after the response to the prime (containing a word and a nonword), were either identical to, semantically related to, or unrelated to the prime target word (PP) or to the prime distractor word (NP). Schizophrenic patients displayed stronger semantic and repetition PP than controls after controlling for their slower responses. Significant NP was observed in both groups for word repetition only. The PP findings contrast with results from studies with similar prime-probe intervals but without prime responses. It is proposed that schizophrenic patients, because of impaired (controlled) processes of response selection, strongly benefit from (or rely on) the automatic retrieval of processing episodes containing response information. Related findings indicating automatic response facilitation in schizophrenia are discussed.

Event-related potential correlates of verbal and pictorial feature comparison in aphasics and controls.

Event-related potentials (ERPs) were recorded from 19 aphasic patients and 18 controls in four versions of a feature comparison task, in which the verbal or pictorial representation of a first stimulus (S1) had to be compared with the verbal or pictorial representation of a second stimulus (S2) presented 2 s later. These tasks were designed to cover some of the discriminatory variance of the token test (TT) including the analytical isolation, encoding and short-term storage of individual features of objects, independent of auditory verbal comprehension. Aphasics made more errors and had longer response latencies than controls in all four tasks, performance being poorest when verbal stimuli had to be processed. ERP analyses - restricted to subjects performing well above chance and to trials with correct responses - were confined to the slow wave (SW) (250-750 ms post-S1-onset) and the contingent negative variation (CNV) preceding the S2. There was no overall group difference that would have suggested that the patients activated different cortical areas than controls on correct performance. A left-hemispheric predominance of the negative SW was found in all four tasks and in both groups, although it was more pronounced in aphasics, and more pronounced in non-fluent than in fluent aphasics. The CNV was characterized by a left-hemispheric accentuation which was more pronounced in controls than in aphasics, particularly in tasks with a verbal S2. Results indicate that successful feature comparisons in the present tasks activate primarily left-anterior cortical areas. During encoding and short-term storage this activation is more pronounced in aphasics than in controls.

Event-related potentials in a working-memory task in schizophrenics and controls.

Event-related potentials (ERPs) were recorded from 65 channels in 12 schizophrenics and 12 age- and sex-matched controls during a delayed matching-to-sample design with variation of working-memory (WM) challenge: following a 500 ms visual sample stimulus (called S1, two diamonds varying in size, rotation angle and vertical position), the same pattern was either presented throughout a 6s retention interval (no challenge) or a diamond pattern differing from the first one in at least one dimension was presented during this interval (WM challenge). The 500 ms matching stimulus (called S2) comprised one diamond, which had to be matched for identity to either the left or the right diamond of the sample stimulus. The topographical distribution of ERPs during an interval of 500 ms after S1-onset, 5s of the retention interval, a 500 ms-interval preceding the S2, and a 1s postimperative interval were evaluated. No WM challenge during the retention interval induced a right-posterior accentuation of the slow negative potentials in either group, while WM challenge evoked a tendency for left-hemispheric negativity in controls, but not in patients. Patients exhibited a postimperative negative variation (PINV) with left-anterior focus irrespective of the preceding WM challenge, while in controls, the left-anterior PINV was found only following WM challenge. In schizophrenic patients the lack of a left-anterior accentuation of negative ERPs under WM challenge might be related to WM dysfunction, and the condition-independent PINV might be considered either the consequence of this dysfunction or indication of processes related more to the diagnoses than to WM-challenge and -dysfunction.

Interhemispheric cooperation during word processing: evidence for callosal transfer dysfunction in schizophrenic patients.

Functional lateralization and interhemispheric interaction during word processing were investigated in schizophrenic patients (n=12) and matched healthy controls (n=18). Words and phonologically regular pseudowords were presented tachistoscopically either in the left or right visual field (unilateral conditions), or simultaneously in both visual hemifields (bilateral condition). Consistent with earlier findings, healthy controls showed a right visual field advantage (RVFA), indicating left-hemispheric dominance for language. The patients showed a RVFA similar to that of controls, consistent with normal left-hemispheric language dominance. Importantly, controls performed much better on words presented in the bilateral condition, when two copies of the same word appeared twice, compared to stimulation in only one of the visual hemifields. This bilateral advantage, which has been interpreted as evidence for cooperation between the hemispheres, was absent in schizophrenics. These data show that schizophrenic patients can exhibit similar lateralization patterns as healthy controls. Their specific functional deficit may be a lack of cooperation between the hemispheres.

MEG gamma band activity in schizophrenia patients and healthy subjects in a mental arithmetic task and at rest.

OBJECTIVES: High frequency oscillations have been suggested as a correlate of cognitive processes and have recently also been implicated in aberrant forms of information processing. The present study investigated whether magnetoencephalographic (MEG) gamma band activity (20-71 Hz) can serve as an index of cognitive processes in the absence of external stimulation and to what extent gamma activity differs between healthy people and schizophrenia patients. METHODS: The amount and topography of MEG power in the gamma band range was examined in 15 schizophrenia patients and 15 healthy comparison subjects while performing a complex mental arithmetic task and at rest. RESULTS: In healthy subjects a left frontal and left fronto-temporal increase in gamma power was observed during mental arithmetic. Schizophrenia patients either failed to display such a task effect (30-45 Hz) or had reversed lateralization with enhanced activity over right frontal and right fronto-temporal regions under cognitive demands (45-71 Hz). In the frequency band from 60 to 71 Hz patients showed less gamma at fronto-temporal, posterio-temporal and occipital sites irrespective of the task. CONCLUSIONS: These results indicate, first, that gamma topography can index cognitive activation in a very complex and purely internal task. Second, groups differed in the pattern of activation during the task, a result which may be consistent with working memory dysfunction in schizophrenia. Third, the general topographic difference between healthy subjects and patients is in line with the notion of abnormalities in the thalamocortical circuit in schizophrenia.

Statistical control of artifacts in dense array EEG/MEG studies.

With the advent of dense sensor arrays (64-256 channels) in electroencephalography and magnetoencephalography studies, the probability increases that some recording channels are contaminated by artifact. If all channels are required to be artifact free, the number of acceptable trials may be unacceptably low. Precise artifact screening is necessary for accurate spatial mapping, for current density measures, for source analysis, and for accurate temporal analysis based on single-trial methods. Precise screening presents a number of problems given the large datasets. We propose a procedure for statistical correction of artifacts in dense array studies (SCADS), which (1) detects individual channel artifacts using the recording reference, (2) detects global artifacts using the average reference, (3) replaces artifact-contaminated sensors with spherical interpolation statistically weighted on the basis of all sensors, and (4) computes the variance of the signal across trials to document the stability of the averaged waveform. Examples from 128-channel recordings and from numerical simulations illustrate the importance of careful artifact review in the avoidance of analysis errors.

EEG brain mapping of phonological and semantic tasks in Italian and German languages.

OBJECTIVES: Event-related potential correlates of phonological encoding - as compared with lexical access and semantic categorization - were measured in two studies involving two groups of 14 German and 14 Italian subjects. METHODS: A two stimulus reaction time paradigm was used. Stimulus pairs presented one-by-one with 2 s inter-stimulus intervals (ISI) had to be matched with respect to lexical identity (word-picture) in a word comprehension task or with respect to the phonological representative of objects in a rhyming task. A semantic categorization task was added for the Italian sample. In both studies, the EEG was recorded from 26 scalp electrodes according to the 10-20 system. The slow negative potential during the ISI (CNV) was determined as the electrocortical correlate of preparation for and activation of the specific language-related task. RESULTS: In both samples, phonological encoding (rhyming) evoked a more pronounced CNV over the left- compared with the right-frontal area, while less lateralized central dominance of the CNV was found in the word comprehension task. Semantic categorization was accompanied by the least asymmetry of activity. CONCLUSIONS: Results indicate that the different degree of asymmetry induced by phonological and semantic processing may be determined from the scalp distribution of slow cortical potentials with cross-lingual reliability.