Temporal integration as “common currency” of brain and self‐scale‐free activity in resting‐state EEG correlates with temporal delay effects on self‐relatedness

The self is a multifaceted phenomenon that integrates information and experience across multiple time scales. How temporal integration on the psychological level of the self is related to temporal integration on the neuronal level remains unclear. To investigate temporal integration on the psychological level, we modified a well‐established self‐matching paradigm by inserting temporal delays. On the neuronal level, we indexed temporal integration in resting‐state EEG by two related measures of scale‐free dynamics, the power law exponent and autocorrelation window. We hypothesized that the previously established self‐prioritization effect, measured as decreased response times or increased accuracy for self‐related stimuli, would change with the insertion of different temporal delays between the paired stimuli, and that these changes would be related to temporal integration on the neuronal level. We found a significant self‐prioritization effect on accuracy in all conditions with delays, indicating stronger temporal integration of self‐related stimuli. Further, we observed a relationship between temporal integration on psychological and neuronal levels: higher degrees of neuronal integration, that is, higher power‐law exponent and longer autocorrelation window, during resting‐state EEG were related to a stronger increase in the self‐prioritization effect across longer temporal delays. We conclude that temporal integration on the neuronal level serves as a template for temporal integration of the self on the psychological level. Temporal integration can thus be conceived as the “common currency” of neuronal and psychological levels of self.     

Catatonia and neuroleptic malignant syndrome: psychopathology and pathophysiology

Summary. Catatonia was originally described as a psychomotor syndrome in the 19^th century by Kahlbaum including motor, affective and behavioral symptoms. Later, at the beginning of the 20th century, catatonia was rather considered as the motoric manifestation of schizophrenia. Accordingly, neuropathological research focused predominantly on those neuroanatomical substrates, i.e. the basal ganglia being primarily involved in the generation of movements. Even though some authors observed minor alterations in the basal ganglia, consistent findings in these subcortical structures could not be obtained. Since neuroleptics can induce catatonic-like symptoms i.e. neuroleptic malignant syndrome (NMS), there has been a recent re-emergence in clinical and scientific interest in catatonia. However, exact psychopathological and pathophysiological characterization of both NMS and catatonia remains unclear. Clinically, catatonia and NMS show more or less similar motor symptoms i.e. akinesia. These may be accounted for by dysregulation in cortical-subcortical circuits between motor/premotor cortex and basal ganglia i.e. the so-called “motor loop”. While in NMS the “motor loop” may be dysregulated by neuroleptic blockade of subcortical striatal D-2 receptors one may rather assume cortical gaba-ergic alteration in catatonia. The premotor/motor cortex and consecutively the “motor loop” may be dysregulated by gaba-ergic abnormalities in orbitofrontal cortex. Gaba-ergic cortical dysfunction may account for affective and behavioural abnormalities in catatonia which cannot be observed as such in NMS. Consequently, one may characterize catatonia as a cortical “psychomotor syndrome” while NMS may rather be regarded as subcortical “motor syndrome”. Received January 10, 2002; accepted May 15, 2002 Published online July 26, 2002 Author's address: G. Northoff, MD, PhD, PhD, Harvard University, Beth Israel Deaconnes Medical Center, Department of Behavioral Neurology, Kirstein Building KS 454, 330 Brookline Avenue, 02215 Boston, Ma, USA, e-mail: gnorthof@caregroup.harvard.edu     

Increased interleukin-6 in collected drainage blood after total knee arthroplasty: an association with febrile reactions during retransfusion

We determined interleukin-6 (IL-6) concentrations in collected shed drainage blood intended for retransfusion in a prospective study in 81 patients after total knee replacement. We found large increases in IL-6 levels, averaging 6.5 (SD 3.9) ng/mL, in shed blood collected in the first 6 postoperative hours. 3 patients had febrile reactions after collected blood was retransfused. The IL-6 levels in the drainage blood of these patients were very high (9.6-13.4 ng/mL). In the blood collected after 6 hours, IL-6 concentrations increased to 47 (SD 33) ng/mL (p < 0.001). These results suggest a relation between increased interleukin-6 concentrations in shed drainage blood and the occurrence of febrile reactions after retransfusion of such blood.     

Catatonia: short-term response to lorazepam and dopaminergic metabolism

Therapeutic response to lorazepam and dopaminergic metabolism were investigated in 18 neuroleptically naive acute catatonic patients. They were diagnosed as catatonic according to criteria by Lohr and Rosebush and treated exclusively with lorazepam (2–4 mg) during the first 24 h. Dopaminergic metabolism (plasma HVA, plasma MHPG), anxiety (HAM-A) and parkinsonic/dyskinetic movements (SEPS, AIMS) were measured under standard conditions before initial treatment with lorazepam (day 0) and 24 h after initial treatment (day 1). On day 0 responders to lorazepam treatment (complete remission of catatonic syndrome after 24 h according to Rosebush and Lohr) showed significantly higher (P=0.004) plasma HVA (130.4±51.2 pmol/ml; means ± SD) than non-responders (no remission of catatonic syndrome after 24 h; 73.2±40.5 pmol/ml; means ± SD). On day 1 plasma HVA did not differ any more significantly between both groups Clinically, responders showed significantly higher HAM-A (P=0.025) and AIMS (P=0.022) scores as well as significantly lower SEPS (P=0.049) scores than non-responders on day 0. Hence catatonic short-term responders and non-responders to lorazepam can be distinguished with regard to plasma HVA, anxiety and dyskinetic/parkinsonic movements.     

How do we modulate our emotions? Parametric fMRI reveals cortical midline structures as regions specifically involved in the processing of emotional valences

One of the major problems in affective neuroscience of healthy subjects as well as of patients with emotional dysfunctions is to disentangle emotional core functions and non-emotional processes. Emotional valence is considered an emotional key process. The present study employed a parametric functional magnetic resonance imaging (fMRI) study to address this question. Thirteen healthy volunteers were scanned during emotional stimulus processing (International Affective Picture System). The presented pictures covered the entire range of emotional valences. The fMRI data were consecutively subjected to a preliminary categorical (valence-independent) and a detailed parametric analysis, the latter using individual valence ratings as regressor. The parametric analysis revealed a linear valence-dependent modulation of the BOLD signal in the orbito- and dorsomedial prefrontal cortex (OMPFC, DMPFC), medial parietal cortex (MPC), and insula. In addition, we observed that emotional valence exerts its effects predominantly via modulation of signal decreases. We conclude that the psychological concept of emotional valence may be related to neural processing in cortical midline regions.     

Deficit in decision making in catatonic schizophrenia: an exploratory study

Catatonic schizophrenia can be distinguished from paranoid schizophrenia by prominent behavioral and motor anomalies. As demonstrated in recent imaging studies, behavioral symptoms may be related to dysfunction in the ventral prefrontal cortex. However, the neuropsychological correlates of ventral prefrontal cortical dysfunction remain unclear. In an exploratory study, we investigated eight patients with catatonic schizophrenia and compared them with 19 patients with paranoid schizophrenia and 26 healthy subjects. The Iowa Gambling Task (IGT) and the Object Alternation Task (OAT) served as measures of ventral prefrontal cortical function. In addition, other prefrontal cortical tests such as a visual working memory task, a Go-NoGo task, and the Wisconsin Card Sorting Test, as well as attentional tasks, were included in the test battery. Catatonic patients showed significant deficits in the IGT characterized by an inability to shift from the initial preference for high-risk cards to a more advantageous strategy with low-risk cards. Moreover, catatonic patients showed significant deficits in the OAT. In conclusion, our preliminary results suggest a specific deficit in catatonic schizophrenia in those neuropsychological measures that are associated with ventral prefrontal cortical function.     

Orbitofrontal cortical dysfunction in akinetic catatonia: a functional magnetic resonance imaging study during negative emotional stimulation

Catatonia is a psychomotor syndrome characterized by concurrent emotional, behavioral, and motor anomalies. Pathophysiological mechanisms of psychomotor disturbances may be related to abnormal emotional-motor processing in prefrontal cortical networks. We therefore investigated prefrontal cortical activation and connectivity patterns during emotional-motor stimulation using functional magnetic resonance imaging (FMRI). We investigated 10 akinetic catatonic patients in a postacute state and compared them with 10 noncatatonic postacute psychiatric controls (age-, sex-, diagnosis-, and medication-matched) and 10 healthy controls. Positive and negative pictures from the International Affective Picture System were used for emotional stimulation. FMRI measurements covered the whole frontal lobe, activation signals in various frontal cortical regions were obtained, and functional connectivity between the different prefrontal cortical regions was investigated using structural equation modeling. Catatonic patients showed alterations in the orbitofrontal cortical activation pattern and in functional connectivity to the premotor cortex in negative and positive emotions compared to psychiatric and healthy controls. Catatonic behavioral and affective symptoms correlated significantly with orbitofrontal activity, whereas catatonic motor symptoms were rather related to medial prefrontal activity. It is concluded that catatonic symptoms may be closely related to dysfunction in the orbitofrontal cortex and consequent alteration in the prefrontal cortical network during emotional processing. Because we investigated postacute patients, orbitofrontal cortical alterations may be interpreted as a trait marker predisposing for development of catatonic syndrome in schizophrenic or affective psychosis.     

Characterization and functional analysis of granulocyte concentrates collected from donors after repeated G-CSF stimulation

BACKGROUND: Neutropenic patients often develop bacterial or fungal infections not responding to broad-spectrum antibacterial or antifungal agents. Clinical efforts were made with transfusion of granulocyte concentrates; however, functions of granulocytes after multiple G-CSF stimulations and after apheresis are not yet investigated and described sufficiently. STUDY DESIGN AND METHODS: The aim of this study was to characterize functional and immunologic variables of granulocytes in blood samples drawn from donors before and after each stimulation episode with G-CSF, in the resulting granulocyte concentrates and in the patients 8 hours after transfusion. RESULTS: Chemotaxis was not influenced, neither by G-CSF application nor by apheresis. Multiple G-CSF stimulations enhanced oxidative burst and phagocytosis of Escherichia coli in donor granulocytes. These values returned to basal levels in granulocyte concentrates. Expression of granulocytic surface antigens was downregulated after application of G-CSF but returned to normal and in part enhanced values in concentrates. A clinically relevant increase of proinflammatory cytokines could not be detected. Leukotriene B4 production was reduced after the fourth G-CSF stimulation in the donor blood and enhanced in the granulocyte concentrate after apheresis. Results in recipients indicate that changes of granulocyte function noted in concentrates were only transient. CONCLUSION: Stimulation of healthy donors with repeated G-CSF injections and subsequent granulocyte apheresis does not dramatically change decisive functions of granulocytes.