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Cognitive potentials in the basal ganglia-frontocortical circuits. An intracerebral recording study.

We studied cognitive functions related to processing sensory and motor activities in the basal ganglia (BG), specifically in the putamen and in cortical structures forming the BG-frontocortical circuits. Intracerebral recordings were made from 160 brain sites in 32 epilepsy surgery candidates. We studied P3-like potentials in five different tests evoked by auditory and visual stimuli, and two sustained potentials that are related to cognitive activities linked with movement preparation: BP (Bereitschaftspotential) and CNV (contingent negative variation). We compared the presence of a potential with a phase reversal or an amplitude gradient to the absence of a generator. All of the studied cognitive potentials were generated in the BG; the occurrence in frontal cortical areas was more selective. The frequency of all but one potential was significantly higher in the BG than in the prefrontal and in the cingulate cortices. The P3-like potentials elicited in the oddball paradigm were also more frequent in the BG than in the motor/premotor cortex, while the occurrence of potentials elicited in motor tasks (BP, CNV, and P3-like potentials in the CNV paradigm) in the motor cortex did not significantly differ from the occurrence in the BG. The processing of motor tasks fits with the model by Alexander et al. of segregated information processing in the motor loop. A variable and task-dependent internal organisation is more probable in cognitive sensory information processing. Cognitive potentials were recorded from all over the putamen. The BG may play an integrative role in cognitive information processing.

Acoustic Stimulation↗

Multi-Resolution FOCUSS: a source imaging technique applied to MEG data.

A variety of techniques are available for imaging magnetoencephalographic (MEG) data to the corresponding cortical structures. Each performs a functional optimization that includes mathematical and physical restrictions on source activity. Unlike other imaging techniques, MR-FOCUSS (Multi-Resolution FOCal Underdetermined System Solution) utilizes a wavelet statistical operator that allows spatial resolution to be chosen appropriately for focal or extended sources. Control of focal imaging properties is achieved by specifying P in an l(P) norm distribution template used to construct the wavelets. In addition, incorporation of a multi-resolution wavelet operator desensitizes the mathematical algorithm to noise, (regularization). Like the FOCUSS imaging technique, an initial estimate of cortical activity is recursively enhanced to obtain the final high resolution imaging results. Studies of model MEG data representing all regions of a realistic cortical model are performed to quantify MR-FOCUSS imaging properties. These modeled data studies included single and multiple dipole sources as well as an extended source model. Thus, MR-FOCUSS is found to be very effective for imaging language processing for pre-surgical planning and provides a high-resolution method to image sequential activation of multiple correlated sources involved in language processing.

Algorithms↗

Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system.

Immunohistochemical distribution of cannabinoid receptors in the adult rat brain was studied using specific purified antibodies against the amino-terminus of the CB1 receptor. Our results generally agree well with the previous studies using CB1 receptor autoradiography and messenger RNA in situ hybridization. However, because of its greater resolution, immunohistochemistry allowed identification of particular neuronal cells and fibers that possess cannabinoid receptors. CB1-like immunoreactivity was found in axons, cell bodies and dendrites, where it appeared as puncta in somata and processes. Both intensely and moderately or lightly stained neurons were observed. The intensely stained neurons were dispersed and only occur in cortical structures including hippocampal formation and olfactory bulb. Moderately or lightly stained neurons were found in caudate-putamen and amygdala. In the hippocampal formation only intensely stained neurons were observed. The cell bodies of pyramidal neurons in CA1 and CA3 fields appeared to be unstained but surrounded by a dense plexus of immunoreactive fibers. The granule cells in the dentate area were also immunonegative. Many intensely stained neurons were located at the base of the granule cell layer. CB1-like immunoreactive neurons and fibers were also found in the somatosensory, cingulate, perirhinal, entorhinal and piriform cortices, in claustrum, amygdaloid nuclei, nucleus accumbens and septum. Beaded immunoreactive fibers were detected in periaqueductal gray, nucleus tractus solitarius, spinal trigeminal tract and nucleus, dorsal horn and lamina X of the spinal cord. A triangular cap-like mass of immunoreactivity was found to surround the basal part of the Purkinje cell body in the cerebellum. Only small, lightly stained cells were found in the molecular layer in the cerebellum close to the Purkinje cell layer. The CB1 receptor is widely distributed in the forebrain and has a more restricted distribution in the hindbrain and the spinal cord. It appears to be expressed on cell bodies, dendrites and axons. According to the location and morphology, many, but not all, CB1-like immunoreactive neurons appear to be GABAergic. Therefore, cannabinoids and cannabinoid receptors may play a role in modulating GABAergic neurons.

Animals↗

Neurophysiology and functional neuroanatomy of pain perception.

The traditional view that the cerebral cortex is not involved in pain processing has been abandoned during the past decades based on anatomic and physiologic investigations in animals, and lesion, functional neuroimaging, and neurophysiologic studies in humans. These studies have revealed an extensive central network associated with nociception that consistently includes the thalamus, the primary (SI) and secondary (SII) somatosensory cortices, the insula, and the anterior cingulate cortex (ACC). Anatomic and electrophysiologic data show that these cortical regions receive direct nociceptive thalamic input. From the results of human studies there is growing evidence that these different cortical structures contribute to different dimensions of pain experience. The SI cortex appears to be mainly involved in sensory-discriminative aspects of pain. The SII cortex seems to have an important role in recognition, learning, and memory of painful events. The insula has been proposed to be involved in autonomic reactions to noxious stimuli and in affective aspects of pain-related learning and memory. The ACC is closely related to pain unpleasantness and may subserve the integration of general affect, cognition, and response selection. The authors review the evidence on which the proposed relationship between cortical areas, pain-related neural activations, and components of pain perception is based.

Animals↗

Hypofrontality and negative symptoms in major depressive disorder.

UNLABELLED: The purpose of the current study was to compare regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD) to that of healthy subjects and to examine the relationship between rCBF, depressive symptoms (DS) and negative symptoms (NS) in these patients. METHODS: Eleven psychiatric inpatients with diagnosed (MDD) and 15 normal control subjects were administered the scale for the assessment of negative symptoms (SANS) and the modified Hamilton rating scale for depression with items descriptive of NS excluded (HRSD-DS). Each patient underwent a SPECT scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest (ROIs) were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. RESULTS: Subjects in the MDD group had significantly lower rCBF in the frontal cortex and cinglulate gyrus (MANOVA, p = 0.038) due to differences in dorsolateral prefrontal cortex bilaterally (right F = 7.69, p = 0.01; left F = 8.41, p = 0.01) in the right orbitofrontal cortex (F = 6.79, p = 0.02) and in the cingulate gyrus (F = 5.34, p = 0.03). The MDD group also had lower rCBF in the posterior cortical structures (MANOVA, p = 0.072), which was due to decreased perfusion in the right parietal cortex (F = 7.54, p = 0.01). There were negative correlations between the SANS total score and rCBF in both the left dorsolateral prefrontal cortex (Pearson's correlation coefficient r = .-67, p < 0.05) and the left anterior temporal cortex (r = -0.71, p < 0.01) in MDD patients. Additionally, there were positive correlations between HRSD scores and rCBF in the left anterior temporal (r = 0.71, p < 0.01), left dorsolateral prefrontal (r = 0.70, p < 0.01), right frontal (r = 0.82, p < 0.01) and right posterior temporal (r = 0.74, p < 0.01) cortices. Cerebral blood flow was not correlated with either mini-mental state examination scores or age. CONCLUSION: This preliminary study replicates the finding of hypofrontality in MDD and indicates that decreased perfusion is associated specifically with negative symptom severity. These results support the hypothesis that, in MDD, negative symptoms and symptoms of depression are distinct phenomena and underscore the importance of negative symptom evaluation in neuroimaging studies of MDD and other disorders.

Adult↗

Live dynamics of Dictyostelium cofilin suggests a role in remodeling actin latticework into bundles.

Cofilin, an indispensable, actin-regulating protein represents the 'cofilin family' of actin-binding proteins existing in a wide variety of organisms. Our previous and other in vitro studies have implied that cofilin can accelerate transformation of filamentous (F)-actin and (alpha)-actinin latticework into bundles, and overexpression of cofilin induces formation of F-actin bundles in Dictyostelium. Here we expressed an Aequorea green fluorescent protein (GFP)-Dictyostelium cofilin fusion protein in Dictyostelium, and observed the live dynamics to examine the physiological function of cofilin. We show that purified GFP-cofilin binds to actin filaments and decreases the apparent viscosity of actin solution in a similar manner to authentic Dictyostelium cofilin. Expressed GFP-cofilin exhibits normal actin-binding activities in the cytoplasm as represented by incorporation into the actin rods induced with dimethyl sulfoxide. Free moving cells form a crown-like cortical structure on the dorsal surface, and GFP-cofilin exhibits dynamic assembly into actin bundles being formed beneath the cortex. During phagocytosis, GFP-cofilin accumulates into actin bundles formed in the region underlying the phagocytic cups. In cells chemotactically activated with cyclic AMP, GFP-cofilin exhibits a high level of accumulation in projecting leading edges. When the chemo-attraction is experimentally changed, the redistribution of GFP-cofilin towards the new pseudopod occurs in a matter of 30-60 seconds. These results demonstrate that cofilin plays a crucial role in vivo in rapid remodeling of the cortical actin meshwork into bundles.

Actin Depolymerizing Factors↗

Repulsive and attractive mechanisms for the formation of corticofugal projections.

Neocortical neurones project axons to subcortical and cortical structures according to their laminar location. The axon-target interactions which produce lamina-specific efferent connections were studied in an organotypic coculture of rat visual cortex with either superior colliculus (SC) or heat-treated SC. Morphological studies with fluorescent dye demonstrated that axons from upper layer neurones did not invade living SC, which receives axonal projections from layer 5, but did extend into denatured SC. In addition, the treatment considerably reduced the number of layer 5 neurones which project to the SC. These results suggest that SC contains a repulsive factor for axonal extension from the upper cortical layer as well as an attractive factor for axonal growth from layer 5 neurones.

Animals↗

Propagation of human complex-partial seizures: a correlation analysis.

Inter- and intrahemispheric propagation of ictal discharges was analysed in 7 epileptic patients having chronic intracranial electrodes. Five had temporal foci and two had frontal mesial foci. Correlation analysis of seizure discharge was used to detect the emergence of linear relationships between different structures both intra- and interhemispherically. This analysis included mesial and lateral temporal sites, cingulate gyri, anterior ventral and dorsomedial thalamic nuclei during the discharges of 13 ictal episodes. Correlation between temporal mesial structures was found to be low throughout seizure onset. Propagation of paroxysmal activity through the anterior ventral thalamic nuclei and cingulate gyri was observed in all cases with temporal or frontal mesial focus. Propagation of the discharge from the temporal lateral cortex to the contralateral homologue area was observed with a short delay during 4 complex-partial seizures originating in the temporal lobe. These results show that, even though the commissural pathways may have a role in propagation, it is a relatively unimportant one and they suggest that ictal activity during mesial temporal seizures may spread preferentially through the thalamic nuclei and cortical structures.

Adult↗

Structural imaging reveals anatomical alterations in inferotemporal cortex in congenital prosopagnosia.

Congenital prosopagnosia (CP) refers to the lifelong impairment in face recognition in individuals who have intact low-level visual processing, normal cognitive abilities, and no known neurological disorder. Although the face recognition impairment is profound and debilitating, its neural basis remains elusive. To investigate this, we conducted detailed morphometric and volumetric analyses of the occipitotemporal (OT) cortex in a group of CP individuals and matched control subjects using high-spatial resolution magnetic resonance imaging. Although there were no significant group differences in the depth or deviation from the midline of the OT or collateral sulci, the CP individuals evince a larger anterior and posterior middle temporal gyrus and a significantly smaller anterior fusiform (aF) gyrus. Interestingly, this volumetric reduction in the aF gyrus is correlated with the behavioral decrement in face recognition. These findings implicate a specific cortical structure as the neural basis of CP and, in light of the familial history of CP, target the aF gyrus as a potential site for further, focused genetic investigation.

Adult↗

Polyol determination along the rat nephron.

The polyols sorbitol and inositol were determined in single freshly microdissected tubule segments of rat kidney. Twenty different structures were separated from six different kidney zones reaching from cortex to papillary tip. Picomol amounts of sorbitol and inositol were quantitated by use of an enzymatic bioluminescence procedure. Experimental conditions (700 mosmol/kg, 4 degrees C) were chosen to assure constant polyol concentrations over 3 h dissection period. Sorbitol exhibited a concentration gradient in the collecting duct system from the outer/inner medullary border (3.9 +/- 0.5 pmol/mm) to the papillary tip (78.8 +/- 6.9 pmol/mm). In the same region descending and ascending limbs of Henle's loop contained 1.5 +/- 0.5 to 5.3 +/- 1.6 pmol/mm and 2.5 +/- 0.8 to 8.35 +/- 1.5 pmol/mm, respectively. In contrast, all outer medullary and cortical structures had lower sorbitol concentrations. Inositol amounts increased continuously in the collecting duct from cortex (5.3 +/- 0.5 pmol/mm) to inner medulla (30.7 +/- 3.8 pmol/mm). This polyol was also found in thick ascending limb of Henle's loop (6.2 +/- 1.1 pmol/mm in cortex to 11.2 +/- 1.4 pmol/mm in outer medulla) and in proximal tubules (5.6 +/- 1.2 pmol/mm in S1 and 4.5 +/- 1.5 pmol/mm in S3). When related to cellular volume measured by planimetry, intracellular sorbitol concentration was calculated to be 51 mmol/l in papillary collecting duct and inositol 28 mmol/l in outer medullary thick ascending limb cells. These data confirm the role of sorbitol in the renal concentrating process in papilla. Inositol seems to have additional function in thick ascending limb of Henle's loop and the proximal tubule.

Animals↗

T2-Weighted fast MR imaging with true FISP versus HASTE: comparative efficacy in the evaluation of normal fetal brain maturation.

OBJECTIVE: This study compares the relative efficacy of two fast T2-weighted MR imaging techniques-fast imaging with steady-state free precession (true FISP) and half-Fourier acquisition single-shot turbo spin-echo (HASTE)-in the evaluation of the normal fetal brain maturation during the second and third trimesters of gestation. SUBJECTS AND METHODS: The brain maturation of 10 normal nonsedated fetuses (5 during the second trimester and 6 during the third trimester of gestation [1 fetus underwent 2 examinations]) was examined by both techniques using a Vision+ 1.5-T MR system. We specifically looked for developing events, including white matter myelination, neuronal migration, and cortical sulcation. Image quality was graded according to the presence or absence of undesirable blurring. RESULTS: The specific absorption rate was lower for true FISP than for HASTE by a factor of 3 at equivalent imaging conditions. HASTE and true FISP provide comparable image quality in the second trimester when myelination of the cerebrum has not begun. Neuronal migration could be recognized as hypodense bands on both sequences during the second trimester. Myelination beginning at the third trimester was better delineated with true FISP than with HASTE because of point spread function-related blurring effects inherent in HASTE that hampered visualization of short-T2 structures. Cortical sulcation was well delineated by both sequences. CONCLUSION: With relatively superior image quality and significantly lower radiofrequency absorption than HASTE, true FISP is a safer and more effective alternative in the prenatal evaluation of normal fetal brain.

Basal Ganglia↗

[Neural mechanisms of anesthesia].

Positron emission tomography studies on volunteers showed that, at concentrations inducing the loss of consciousness, propofol, halothane and isoflurane reduce glucose metabolism of neocortical neurones by 20-50%. To find out whether these effects are caused by direct anaesthetic actions on cortical structures, experiments were carried out on isolated neocortical brain slices. In these investigations an excellent correlation was observed between anaesthetic concentrations causing a half-maximal depression of action potential firing in neocortical brain slices and anaesthetic blood concentrations monitored during awaking from anaesthesia in humans. Furthermore, it could be shown that, at concentrations approximately one half the MAC-value, isoflurane decreases the frequency of auditory evoked 30-40 Hz oscillations in the neocortex by 50%. Similar quantitative effects were observed on spontaneously occurring high frequency rhythms in neocortical brain slices. However, not all aspects of cerebral anaesthetic actions can be explained by direct effects on cortical neurones. The EEG synchronisation and the amplitude reduction of mid latency auditory evoked potentials are probably related to the inhibition of thalamic neurones. Halothane, isoflurane, enflurane and propofol reduced action potential firing of cortical neurones by enhancing GABAA receptor-mediated synaptic inhibition. This molecular mechanism seems also to be involved in depressing painful stimuli-induced motor responses. Nevertheless, there must be a difference between relevant anaesthetic mechanisms on the cerebral and spinal level. This follows from the observation that the relation between the concentration causing the loss of consciousness and the concentration that depresses movements considerably varies among different anaesthetic agents.

Anesthetics↗

Modular organization of finger movements by the human central nervous system.

The motor system may generate automated movements, such as walking, by combining modular spinal motor synergies. However, it remains unknown whether a modular neuronal architecture is sufficient to generate the unique flexibility of human finger movements, which rely on cortical structures. Here we show that finger movements evoked by transcranial magnetic stimulation (TMS) of the primary motor cortex reproduced distinctive features of the spatial representation of voluntary movements as identified in previous neuroimaging studies, consistent with naturalistic activation of neuronal elements. Principal component analysis revealed that the dimensionality of TMS-evoked movements was low. Principal components extracted from TMS-induced finger movements resembled those derived from end-postures of voluntary movements performed to grasp imagined objects, and a small subset of them was sufficient to reconstruct these movements with remarkable fidelity. The motor system may coordinate even the most dexterous movements by using a modular architecture involving cortical components.

Adult↗

Sensorimotor organization in patients who have undergone hemispherectomy: a study with (15)O-water PET and somatosensory evoked potentials.

To identify cortical structures that subserve residual motor and sensory function in patients with congenital hemiparesis due to a porencephalic cyst, we examined, using [(15)O]H2O, PET and somatosensory evoked potentials (SEPs) in three patients with left-sided hemiparesis who had undergone hemispherectomy. Motor stimulation of the affected hand produced ipsilateral activation in the premotor area in all patients, the SMA in two patients, and SII in two patients. Vibrotactile stimulation resulted in activation of the ipsilateral SII in all subjects. Median nerve stimulation of the affected hand produced ipsilateral long-latency SEPs in fronto-centro-parietal areas, whereas stimulation of the non-affected hand produced normal early cortical potentials in the contralateral hemisphere. Our results suggest that residual function in the paretic hand is warranted through non-primary motor and sensory areas, and higher order associative areas in the intact hemisphere.

Adult↗

ERM-Merlin and EBP50 protein families in plasma membrane organization and function.

The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regulatory molecules in linking F-actin to specific membrane proteins, especially in cell surface structures. Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function of these proteins in cortical structure, endocytic traffic, signal transduction, and growth control is discussed.

Animals↗

Calibration of BOLD fMRI using breath holding reduces group variance during a cognitive task.

The proportionality of blood oxygen level-dependent (BOLD) response during a cognitive task and that from a hypercapnic challenge was investigated in cortical structures involved in working memory (WM). Breath holding (BH) following inspiration was used to induce a BOLD response characteristic of regional vasomotor reactivity but devoid of metabolic changes. BOLD effects measured during BH were used to normalize individual subject activations during WM, which effectively reduced the confounding influence of individual- and region-specific differences in hemodynamic responsivity common to both tasks. In a study of seven subjects, the BH calibration reduced intersubject variability in WM effect amplitude by 24.8% (P < 0.03). Reduced intersubject variability resulted in a 23.7% increase in group WM activation voxel extent significant at P < 0.001, with further increases at more stringent thresholds. Because the BH task does not require CO(2) inhalation or other invasive manipulations and is broadly applicable across cortical regions, the proposed approach is simple to implement and may be beneficial for use not only in quantitative group fMRI analyses, but also for multicenter and longitudinal studies.

Adult↗

Biomechanics of bone: determinants of skeletal fragility and bone quality.

Bone fragility can be defined by biomechanical parameters, including ultimate force (a measure of strength), ultimate displacement (reciprocal of brittleness) and work to failure (energy absorption). Bone fragility is influenced by bone size, shape, architecture and tissue 'quality'. Many osteoporosis treatments build bone mass but also change tissue quality. Antiresorptive therapies, such as bisphosphonates, substantially reduce bone turnover, impairing microdamage repair and causing increased bone mineralization, which can increase the brittleness of bone. Anabolic therapies, such as parathyroid hormone (PTH-(1-84)) or teriparatide (PTH-( 1-34)), increase bone turnover and porosity, which offset some of the positive effects on bone strength. Osteoporosis therapies may also affect bone architecture by causing the redistribution of bone structure. Restructuring of bone during treatment may change bone fragility, even in the absence of drug effects on bone mineral density (BMD). This effect may explain why some drugs can affect fracture incidence disproportionately to changes in BMD. For instance, in a recent clinical trial, PTH-(1-34) therapy caused a dose-related increase in spinal BMD without any dose-dependent effect on the observed decrease in spinal fracture incidence. This apparent disassociation between spinal BMD and bone fragility is probably due to effects of PTH-(1-34) on bone architecture within vertebral bodies. While it has been shown that BMD is highly heritable, bone mineral distribution and architecture are also under strong genetic influence. Recent findings suggest that different genes regulate trabecular and cortical structures within lumbar vertebrae, producing a wide range of bone architectural designs. These findings suggest that there is no single optimal bone architecture; instead many different architectural solutions produce adequate bone strength.

Biomechanical Phenomena↗

[Characteristics of the brain lesion in experimental alcoholism in young animals].

Morphohistochemical changes in the cortical structures were studied comparatively in 56 adult and young rats during two-month alcoholization and after its discontinuation. It was demonstrated that in young animals, both compensatory processes and signs of damage were more pronounced, with various cerebral components reacting differently. Thus, the neuronal bodies displayed little change while there were marked impairments in their axons. Young animals exhibited greater vascular damage whereas their glial reaction was on the contrary more adequate to experimental conditions. Nevertheless, young animals in our model experiments showed no irreversible impairments in their cerebral cortex which could be indicative of the malignancy of juvenile alcoholism. In short-term temporary alcohol intoxication, the morphofunctional resources of the cortex can recover completely following ethanol withdrawal. Evaluating the alterations detected in the cortical nerve tissue, it appears reasonable to classify them as a manifestation of the morphohistochemical constituent of the multi-level protective compensatory syndrome in alcoholism.

Aging↗