Residual haptic sensation following stroke using ipsilateral stimulation.

In 1987, Weiskrantz and Zhang described a stroke patient with severe somatosensory loss who, nevertheless, demonstrated impressive residual sensory performance when required to touch the affected limb with her ipsilesional hand (self touch; ST). The current study set out to ascertain the prevalence and characteristics of self-touch enhancement (STE) in patients with unilateral stroke and hemihypaesthesia. Thirty-nine stroke patients who were referred with hemihypaesthesia fulfilled the criteria. STE was defined where a patient showed a statistically significant increase (p<0.05) in performance for (i) detection, (ii) localisation and/or (iii) perceived intensity during touch with their ipsilesional hand, compared with standard experimenter elicited sensory performance. Group comparisons between the conventional touch versus ST conditions revealed significant differences for detection (p<0.01), intensity estimation (p<0.01) and localisation (p<0.001) using ST. Twenty-two of the 39 patients (56.4%) showed STE on at least one assessment mode. In detection, 16 (41%) patients showed STE; for localisation, 12 patients (31%) showed STE and for intensity, 17 patients (44%) showed STE. Out of the 22 patients with STE, 17 had right hemisphere lesions. In summary, more than half of the stroke patients showed reliable and significant improvements in somatosensory performance when using their unaffected hand as the source of tactile stimulation. This striking phenomenon suggests that the threshold for the impaired hand is affected by active involvement of the contralateral (ipsilesional) limb when delivering the stimulus contact. Possible mechanisms to explain these findings are discussed.

Impulsivity, time perception, emotion and reinforcement sensitivity in patients with orbitofrontal cortex lesions.

Damage to the orbitofrontal cortex (OFC) in humans has been associated with disinhibited or socially inappropriate behaviour and emotional changes. Some of the changes may be related to difficulty in responding correctly to rewards and punishers, in that these patients have difficulty in learning to correct their choice of a visual stimulus when it is no longer associated with reward. We extend this fundamental approach by investigating the relationship between frontal dysfunction and impulsive behaviour, the behavioural, emotional and personality changes seen in patients with prefrontal cortex damage, and thus in addition illuminate the cognitive and biological processes that are impaired in impulsive people. OFC patients (n = 23) performed more impulsively on both self-report and cognitive/behavioural tests of impulsivity, reported more inappropriate 'frontal' behaviours, and performed worse on a stimulus-reinforcement association reversal task, than non-OFC prefrontal cortex lesion control (n = 20) and normal control (n = 39) participants. Further, OFC patients experienced more subjective anger than non-OFC and normal participants, and less subjective happiness than normals; and had a faster subjective sense of time (overestimated and underproduced time intervals) than normal controls, while non-OFC patients did not differ from normals. Finally, both OFC and non-OFC patients were less open to experience than normal participants. There were no differences between OFC patients, non-OFC lesion patients and normal controls on all other personality traits, most notably extraversion. In a spatial working memory task, the non-OFC group, most of whom had dorsolateral prefrontal cortex lesions, were impaired in that they repeatedly returned to previously chosen empty locations ('within errors'), whereas OFC patients were not impaired on this measure. Thus there is a dissociation between the effects of OFC damage which does not affect this measure of spatial working memory but does affect impulsive and inappropriate behaviour, reversal, personality, time perception and emotion; and dorsolateral prefrontal cortex damage which does affect this measure of spatial working memory, but not impulsive and inappropriate behaviour, reversal, personality, time perception and emotion. The effects of OFC damage on impulsive and related behaviours described here have implications for understanding impulsive behaviour.

The Frontal Lobe Score: part I: construction of a mental status of frontal systems.

OBJECTIVE: To develop a bedside mental status examination to assess the behavioural effects of damage to the frontal lobes. DESIGN: A prospective clinical comparison of patients with cerebral lesions of different locations. SUBJECTS: A total of 118 subjects were examined: 27 patients with cerebral lesions confined to the frontal lobes, 25 patients with cerebral lesions without involvement of the frontal lobes, 18 patients with mixed frontal/nonfrontal lesions, and 48 normal control subjects. MEASURES: Twenty-three mental status tests, clinical examinations and rating scales that had been reported as indicative of frontal lobe function were brought together. By statistical analysis, 12 tests and a neurobehavioural rating scale were selected. These constitute the Frontal Lobe Score (FLS). RESULTS: The FLS detected pure frontal lesions with a sensitivity of 77.7%. It discriminated patients with frontal lesions from normal control subjects with a specificity of 100%. Differentiation from patients with nonfrontal lesions was obtained with a specificity of 84%. CONCLUSION: The Frontal Lobe Score is a useful screening instrument for the clinical detection of effects of frontal lobe damage.

The Frontal Lobe Score: part II: evaluation of its clinical validity.

OBJECTIVE: To evaluate the ability of the Frontal Lobe Score (FLS) to differentiate patients with frontal lobe lesions from those with nonfrontal lesions and normal controls. DESIGN: In a prospective, blind setup, the sensitivity and specificity of the Frontal Lobe Score was compared with the Wisconsin Card Sorting Test (WCST) and the Stroop Test. PATIENTS: A sample of 108 subjects (26 patients with cerebral lesions confined to the frontal lobes, 28 patients with cerebral lesions without involvement of the frontal lobes, 31 patients with mixed frontal/nonfrontal lesions, 23 controls without cerebral lesions) was examined. MEASURES: Frontal Lobe Score, Wisconsin Card Sorting Test, Stroop Test. RESULTS: The Frontal Lobe Score detected pure frontal lesions with a sensitivity of 92.3%. It discriminated patients with frontal lesions from normal controls with a specificity of 100%; differentiation from patients with nonfrontal lesions was obtained with a specificity of 75.0%. For the WCST, sensitivity for detection of pure frontal lesions was 65.4%, while specificity was 60.9% compared with normal controls and 53.6% compared with nonfrontal lesions. The Stroop Test showed a sensitivity of 30.8%, a specificity compared with normal controls of 95.7% and compared with nonfrontal lesions of 92.9%. CONCLUSION: The Frontal Lobe Score has clinical usefulness for screening of effects of frontal lobe damage superior to that of the WCST and the Stroop Test.

Temporal profile of release of interleukin-1beta in neurotrauma.

Timing and extent of trauma-induced release of interleukin-1beta (IL-1beta) in extracellular fluid of the CNS were analyzed. In brain tissue perfusates obtained by in vivo microdialysis a marked release of IL-1beta was unexpectedly detected within less than 60 min. At such an early stage of neurotrauma, mRNA expression of IL-1beta was detected whereas immunoreactivity for the IL-1beta protein was negative. Concentrations of extracellularly secreted IL-1beta protein gradually increased, peaked at day 2 and decreased thereafter. Drugs acting on mononuclear phagocytes significantly modulated IL-1beta secretion. This so far unrecognized acuity of IL-1beta release demonstrated here, may represent a precondition for the orchestrating role of this mediator in the cascade of inflammatory host response.

Modulation of striatal acetylcholine concentrations by NMDA and the competitive NMDA receptor-antagonist AP-5: an in vivo microdialysis study.

The effects of local perfusion with the competitive NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP-5) and the glutamate receptor agonist N-methyl-D-aspartate (NMDA) on release of extracellular acetylcholine (ACh) and choline (Ch) in the dorsolateral striatum were studied using in vivo microdialysis in freely moving rats. AP-5 caused a dose-dependent decrease in ACh release that was counteracted by the addition of NMDA. Perfusion with AP-5 also decreased Ch levels. Local perfusion with NMDA induced an elevation of ACh release in low (10(-5) M), but not high (10(-2) M and 10(-3) M) concentrations, that were associated with massive cellular death. These inhibitory effects of AP-5 and the stimulatory effect of NMDA in non-neurotoxic dosages on ACh release provide further evidence for a tonic stimulation of striatal cholinergic interneurons by glutamatergic neurons via NMDA receptors.

Dynamic pattern of brain activation during sequencing of word strings evaluated by fMRI.

An impaired ability to recite highly automated word strings (e.g., the names of the months of the year) in reverse order concomitant with preserved production of the conventional sequence has been considered a salient sign of frontal lobe dysfunction. Using functional magnetic resonance imaging (fMRI), the spatial and temporal pattern of brain activation during covert performance of these tasks was evaluated in healthy subjects. As compared to the response obtained during forward recitation, re-sequencing of the word string yielded additional activation of the bilateral middle and inferior frontal gyri, the posterior parietal cortex and the left anterior cingulate gyrus. The prefrontal responses are in accordance with the clinical findings referred to. However, the set of activated areas, as a whole, presumably reflects contribution of the various components of the working memory system to the sequencing of word strings. During successive periods of task administration, subjects showed a linear increase of production speed. Analysis of corresponding dynamic changes of regional hemodynamic responses revealed a significant increase at the level of the left inferior parietal cortex and a decrease within the mesial aspect of the left superior frontal gyrus. Presumably, the former finding reflects increasing demands on the phonological short-term memory store, due to faster updating of its content under increased word production rate. Decreasing activation within the superior frontal gyrus might indicate contribution of this area to the initiation of the cognitive processes subserving the sequencing of verbal items. These findings demonstrate the capability of fMRI as a powerful tool for the analysis of dynamic brain activation.

[Functional magnetic resonance tomography in psychopathological research]. / Funktionelle Magnetresonanztomographie in der psychopathologischen Forschung.

Mental disorders are characterised by psychopathological symptoms which correspond to functional brain states. Functional magnetic resonance imaging (fMRI) is used for the non-invasive study of cerebral activation patterns in man. First of all, the neurobiological principles and presuppositions of the method are outlined. Results from the Heidelberg imaging lab on several simple sensorimotor tasks as well as higher cognitive functions, such as working and semantic memory, are then presented. Thereafter, results from preliminary fMRI studies of psychopathological symptoms are discussed, with emphasis on hallucinations, psychomotoric phenomena, emotions, as well as obsessions and compulsions. Functional MRI is limited by the physics underlying the method, as well as by practical constraints regarding its use in conjunction with mentally ill patients. Within this framework, the problems of signal-to-noise ratio, data analysis strategies, motion correction, and neurovascular coupling are considered. Because of the rapid development of the field of fMRI, maps of higher cognitive functions and their respective pathology seem to be coming within easy reach.

Functional magnetic resonance imaging of category-specific cortical activation: evidence for semantic maps.

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of cortical activity during a picture naming task. Subjects (n=12) had to covertly name either animals or furniture items. Functional scanning was performed using a conventional 1.5-Tesla whole-body MRI system. Images obtained during naming the two categories were compared using a non-parametric test. The study revealed evidence for domain-specific lexical regions in left middle, right middle and inferior frontal areas, as well as in superior and middle temporal areas. The results corroborate neuropsychological data and demonstrate directly and non-invasively in human volunteers that semantic representations in frontal and temporal areas are, to some degree, localized and possibly implemented as multiple maps. A completely distributed storage of semantic information is rendered unlikely.

Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: association with cerebral inflammation.

OBJECTIVE: To investigate the association between affective and neuroendocrine abnormalities, commonly observed in multiple sclerosis, with inflammatory disease activity. DESIGN: Cross-sectional design. Twenty-three patients with definite relapsing-remitting multiple sclerosis and age- and sex-matched control subjects were investigated. Depression and anxiety were assessed using structured interviews, self-report measures, and Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria. Neurologic impairment was assessed by the Kurtzke Expanded Disability Status Scale and function of hypothalamic-adrenal-pituitary axis was analyzed using a corticotropin-releasing hormone stimulation test after dexamethasone suppression. Inflammatory disease activity was evaluated first by routine and experimental laboratory tests, and second by magnetic resonance assessment of gadolinium uptake of multiple sclerotic plaques. SETTING: University hospital, a major provider of acute neurologic care. RESULTS: Compared with controls, patients with multiple sclerosis had higher scores on depression and anxiety scales and exhibited a failure of suppression of cortisol release after dexamethasone pretreatment. Both affective symptoms and neuroendocrine abnormalities were correlated with cerebrospinal fluid white blood cell counts and presence of gadolinium-enhancing lesions on magnetic resonance images; however, no association with the degree of neurologic impairment was observed. CONCLUSION: Affective and neuroendocrine disorders were related to inflammatory disease activity but not to degree of disability, supporting the hypothesis that these symptoms are causally associated with brain injury.

[Frontal-subcortical neuronal circuits]. / Frontal-subkortikale neuronale Schaltkreise.

Recent findings on frontal and subcortical circuitry provide an uniform and integral view of numerous neurological and psychiatric disorders. Frontal cortical areas, the basal ganglia and the thalamus are linked in parallel circuits, which can be related to specific mental and motor functions and pathologies. In particular, five such circuits can be distinguished: (1) motor, (2) oculomotor, (3) dorsolateral-pre-frontal, (4) lateral orbitofrontal, and (5) mediofrontal limbic. The anatomy of these circuits as well as the involved neurotransmitters provide a comprehensive framework for understanding the symptoms of neurological diseases such as frontal lobe infarctions, Parkinson's, Huntington's, and Binswanger's disease, as well as psychiatric diseases such as schizophrenic, affective, and obsessive-compulsive disorder.

Endothelial-derived adhesion molecules in bacterial meningitis: association to cytokine release and intrathecal leukocyte-recruitment.

The release of circulating isoforms of selectin- (L-selectin, ELAM-1) and immunoglobulin-type- (ICAM-1) adhesion molecules, responsible for accumulation of leukocytes at sites of tissue injury was studied in CSF and serum of 21 patients with bacterial meningitis and in healthy subjects. Their concentrations were compared with the intrathecal leukocyte recruitment and release of inflammatory cytokines. In contrast to serum concentrations of the leukocyte-derived adhesion molecule, sL-selectin, serum concentrations of endothelial-derived adhesion molecules, sELAM-1 and sICAM-1, were significantly increased in meningitis. No intrathecal synthesis of these adhesion molecules was observed. Serum levels of sELAM-1 were associated with extent of CSF pleocytosis and with concentrations of proinflammatory cytokines IL-1beta and TNF alpha in CSF, but not in serum. Therefore, expression of endothelial adhesion molecules i.e. ELAM-1 may be responsible for the massive intrathecal recruitment of potentially harmful leukocytes in patients with bacterial meningitis. Intrathecally released proinflammatory cytokines may represent the inducing signals for their endothelial upregulation.

Dopaminergic modulation of semantic network activation.

In order to examine the effect of dopamine on semantic processing, we performed a double-blind, placebo-controlled study. Healthy volunteers (n = 31) were tested in a lexical decision paradigm after ingestion of either L-dopa 100 mg with benserazide 25 mg or placebo. While direct semantic priming was influenced only marginally by L-dopa, the indirect priming effects was reduced significantly. These data support the hypothesis that dopamine increases the signal-to-noise ratio in semantic networks by reducing the spread of semantic processing, thereby leading to a focussing of activation.

Functional MR imaging of semantic information processing and learning-related effects using psychometrically controlled stimulation paradigms.

Functional magnetic resonance imaging (fMRI), in conjunction with carefully designed, psychometrically optimized stimulation procedures, was used to investigate the relation between brain activation and the processing of word associations. A semantic discrimination task of word-pair similarity was performed by normal subjects (n = 17) within a clinical 1.5-Tesla whole-body MRI system. A color similarity task of psychometrically equivalent difficulty, as indicated by behavioral data acquired online during fMRI, served as active control condition. Comparisons between tasks dramatically improved results compared to comparisons between task and resting condition. The language paradigm selectively activated left frontal and left fronto-temporal areas. Cortical activation during the semantic task decreased significantly over three runs of the same word list and was paralleled by decreased reaction times. No such changes were observed in the active control condition indicating selective learning of the language task only. When combined with psychological activation schemes and the acquisition of behavioral data, fMRI represents a powerful tool for the study of brain-behavior interaction.

[Cerebral findings following cervical spine distortion caused by acceleration mechanism (whiplash injury). Assessment of current diagnostic methods in nuclear medicine]. / Zerebrale Befunde nach Halswirbelsäulendistorsion durch Beschleunigungsmechanismus (HWS-Schleudertrauma). Standortbestimmung zu neuen diagnostischen Methoden der Nuklearmedizin.

In any grade of distortion of the cervical spine as a result of acceleration forces in addition to cervical symptoms cerebral symptoms like headache, vertigo, auditory disturbances, tinnitus, disturbances in concentration and memory, difficulties in swallowing, impaired vision and temporo-mandibular dysfunctions may appear. These symptoms can persist and become invalidating. Cerebral single-photon emission tomography (SPECT) and positron emission tomography (PET) enable new diagnostic horizons for neurotraumatology. In this article we summarize the actual findings of these nuclear medical methods in neuropsychologically deficient patients with distortion of the cervical spine as a result of acceleration forces. Especially the latest results of the group of Basle (University Hospital Basle, Clinic of Rehabilitation Rheinfelden, Switzerland) are illustrated. This group found parieto-occipital hypoperfusion by relative quantitation using SPECT and bicisate (Neurolite, ECD). A first pilot study using PET and F-18-fluoro-deoxyglucose (FDG) could verify the above observation. The group's working hypothesis is that parieto-occipital hypoperfusion may be caused by activation of nociceptive afferences from the upper cervical spine. A critical approach to interpreting new functional methods and, on the other hand, openness in new scientific findings may contribute to answering the lasting controversial medico-legal discussion with more objectivity.

Alien hand syndrome of the dominant hand and ideomotor apraxia of the nondominant hand.

Following an extended infarction in the territory of the left anterior cerebral artery including the anterior corpus callosum, a 66-year-old right-handed man exhibited an alien hand syndrome on the right side and an ideomotor apraxia of the left hand. In addition to other typical symptoms of frontal lobe lesions, he presented with an interesting difference in the manifestation of perseveration in either hand. In the right hand, the perseveration was part of the alien hand syndrome, whereas in the left hand perseveration showed in the inability to switch promptly from one movement to another on instruction during praxis testing.

Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke.

BACKGROUND AND PURPOSE: Cellular adhesion molecules mediate adhesion between endothelial cells and leukocytes as a precondition for extravasation of leukocytes at sites of tissue injury. The pattern of release of circulating adhesion molecules has been characterized in patients with acute ischemic stroke. METHODS: Serum concentrations of soluble selectin-type adhesion molecules (solube endothelial leukocyte adhesion molecule-1 [sELAM-1], soluble lymph node homing receptor [sL-selectin]) and immunoglobulin-type adhesion molecules (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1]) were serially determined (at hours 4, 8, and 10 and at days 1, 3, and 5) in 22 patients with acute ischemic stroke. As control subjects, age- and sex-matched individuals with (n = 40) and without (n = 22) vascular risk factors were studied. RESULTS: We observed increased concentrations of sICAM-1 and decreased levels of sL-selectin in patients with risk factors even in the absence of stroke. Patients with acute stroke had, in addition, an initial transient increase of sELAM-1 and a persistent increase of sVCAM-1. CONCLUSIONS: The results suggest a chronic alteration of expression of adhesion molecules sICAM-1 and sL-selectin in subjects with risk factors for atherosclerosis; they also indicate acute changes of levels of sELAM-1 and sVCAM-1 in response to acute ischemic stroke. Determination of soluble adhesion molecules could allow in vivo monitoring of the initial steps of leukocyte-mediated brain damage in acute ischemic stroke.

A neural network model of phantom limbs.

This paper presents a detailed clinical description of phantom limbs and a neuronal network model that provides a comprehensive and parsimonious explanation of otherwise inexplicable or at least unrelated phenomena. Simulations of self-organizing feature maps (Kohonen networks) that had been trained to recognize input patterns were deprived of parts of their input in order to simulate partial deafferentation. This leads to reorganization processes that are shown to be driven by input noise. In patients with an amputated limb, this noise is generated by dorsal root ganglion sensory neurons which are known to fire irregularly upon laceration. According to this model, the long-standing debate concerning non-cortical vs. cortical contributions to the generation of the phenomenon of phantom limbs can be resolved in that it is the peripherally generated noise that causes cortical reorganization. The model can be tested and may have therapeutic implications.

Choline enhances scopolamine-induced acetylcholine release in dorsal hippocampus of conscious, freely-moving rats.

We examined the effects of exogenous choline (30, 60, 120 mg/kg, i.p.) on basal and scopolamine-evoked acetylcholine (ACh) release in awake animals, using in vivo microdialysis. After collection of 3-4 baseline dialysate samples (15 min each), rats received either saline or choline chloride and 4 additional samples were collected. All animals then received scopolamine hydrochloride (0.5 mg/kg, i.p.) and 6 additional samples were collected. Basal ACh release in animals receiving choline did not differ from that in rats given saline, nor from ACh release prior to choline administration. Scopolamine alone increased average ACh levels in dialysates from 1.22 +/- 0.54 to 11.18 +/- 3.07 pmol/15 min (mean +/- SD; p = 0.001); administration of 60 mg/kg or 120 mg/kg of choline chloride significantly enhanced maximal scopolamine responses by about 55%. These results suggest that supplemental choline enhances evoked ACh release in hippocampus of freely-moving rats.