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Cortical reorganization following multiple subpial transection in human brain - a study with positron emission tomography.

We investigated the cortical activation pattern in a 30-year-old woman 4 years after multiple subpial transection (MST) of the right fronto-parietal cortex and six healthy controls using positron emission tomography. Sequential finger-to-thumb opposition at the frequency of 1.5 Hertz contralateral to the operated hemisphere was used as the activation paradigm. We found preserved cortical activation in the transected fronto-parietal cortex and additional activation of the prefrontal cortex bilaterally and the inferior parietal cortex contralaterally when compared with the control group. This activation pattern indicates that MST induces a rather selective lesion leaving the cortical structures functionally intact. However, it necessitates the recruitment of additional motor areas.

Adult↗

Domain-specific distribution of working memory processes along human prefrontal and parietal cortices: a functional magnetic resonance imaging study.

This study reinvestigated the functional neuroanatomy of phonological and visual working memory in humans. Articulatory suppression was used to deprive the human subjects of species-specific verbal strategies in order to make the functional magnetic resonance imaging results more comparable to findings in non-human primates. Both phonological and visual working memory processes activated similar prefronto-parietal networks but were found to be differentially distributed along several cortical structures, in particular along the anterior and posterior parts of the intermediate frontal sulcus. These results suggest that a domain-specific topographical organization of neural working memory mechanisms in the primate brain is conserved in evolution. However, the findings also underline the critical dynamic influence that the additional availability of language may have on working memory processes and their functional implementation in the human brain.

Adult↗

Prenatal cocaine exposure produces consistent developmental alterations in dopamine-rich regions of the cerebral cortex.

Administration of cocaine to pregnant rabbits produces robust and long-lasting anatomical alterations in the dopamine-rich anterior cingulate cortex of offspring. These effects include increased length and decreased bundling of layer III and V pyramidal neuron dendrites, increases in parvalbumin expression in the dendrites of interneurons, and increases in detectable GABAergic neurons. We have now examined multiple cortical regions with varying degrees of catecholaminergic innervation to investigate regional variations in the ability of prenatal cocaine exposure to elicit these permanent changes. All regions containing a high density of tyrosine hydroxylase-immunoreactive fibers, indicative of prominent dopaminergic input, exhibited alterations in GABA and parvalbumin expression by interneurons and microtubule-associated protein-2 labeling of apical dendrites of pyramidal neurons. These regions included the medial prefrontal, entorhinal, and piriform cortices. In contrast, primary somatosensory, auditory and motor cortices exhibited little tyrosine hydroxylase staining and no measurable cocaine-induced changes in cortical structure. From these data we suggest that the presence of dopaminergic afferents contributes to the marked specificity of the altered development of excitatory pyramidal neurons and inhibitory interneurons induced by low dose i.v. administration of cocaine in utero.

Animals↗

The basolateral amygdala regulates sensorimotor gating of acoustic startle in the rat.

The acoustic startle reflex is a coordinated contraction of the skeletal musculature in response to a sudden, intense sound. One form of startle plasticity, "prepulse inhibition", is the normal suppression of the startle reflex when the intense startling stimulus is immediately preceded by a weak pre-stimulus. Prepulse inhibition is utilized as an operational measure of sensorimotor gating, and is significantly impaired in several neuropsychiatric disorders that are characterized by symptoms associated with central inhibitory deficits. In rats, prepulse inhibition is disrupted by central dopamine activation or by manipulations of limbic cortical structures including the prefrontal cortex and hippocampus. In the present study, we assessed prepulse inhibition in rats after surgical and pharmacologic manipulations of the basolateral amygdala. Quinolinic acid lesions of the basolateral amygdala significantly reduced prepulse inhibition without significantly changing startle amplitude. These lesions also blocked fear-potentiated startle, which is known to be regulated by the basolateral amygdala. The prepulse inhibition-disruptive effects of basolateral amygdala lesions were not reversed by systemic injection of the dopamine antagonist haloperidol at doses that totally restored prepulse inhibition in apomorphine-treated rats. In other studies, intra-amygdala infusion of the competitive N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovaleric acid (0, 0.15, 1.5, 4.5 microg) dose-dependently reduced prepulse inhibition. These data suggest that the basolateral amygdala regulates sensorimotor gating by mechanisms that are independent of central dopamine hyperactivity.

2-Amino-5-phosphonovalerate↗

Cortical reorganization in patients with high frequency cochlear hearing loss.

Animal research has shown that tonotopic representation in the auditory cortex is not statically fixed in the adult organism but can be altered after deafferentation. The present study examines the plasticity of the human auditory cortex in patients with high frequency cochlear hearing loss by means of magnetoencephalographic measurements. The data show that the cortical map can reorganize such that cortical neurons deprived of their usual most sensitive afferent input now respond to tone frequencies adjacent to the frequency range of the partial hearing loss. The results suggest that deafferentation due to cochlear damage in adults may lead to functional reorganization of auditory cortical structures.

Acoustic Stimulation↗

Visual evoked potentials in children with occipital epilepsies.

The objectives of this study are to see if any visual evoked potential (VEP) differences are present in two forms of occipital epilepsy, childhood epilepsy with occipital paroxysms (CEOP) and symptomatic occipital epilepsy (SOE) with respect to etiology, as CEOP is a benign age- and localization-related idiopathic epilepsy while SOE is a symptomatic form. Nineteen patients with CEOP and 13 patients with SOE were included in the study and P100 potential latency and amplitude values obtained from these patients were compared with the values recorded from normal controls. The amplitude values recorded from the patients with CEOP were significantly high (P=0.033). P100 potential latency values recorded in patients with SOE were significantly long (P=0.028). High amplitude VEP responses were mostly attributed to hyperexcitability of the occipital cortical structures whereas prolonged latency P100 responses were attributed to occipital structural changes.

Child↗

Neurophysiology of Tourette's syndrome: pathophysiological considerations.

At present the neurophysiology of Tourette's syndrome (TS) has been investigated largely from two perspectives; one for evaluation of the dysfunction of the cerebral cortex and the other for clarification of the neuronal mechanisms that underlie tics and related symptoms. For the former the following examinations have been conducted: quantitative analyses of scalp electroencephalography (EEG), premovement EEG potentials, contingent negative variation, transcranial magnetic stimulation, and neuroimaging studies, including echo-planar images and positron emission tomography scans. These explorations have revealed the likely involvement of the subcortical and the cortical structures, particularly of the basal ganglia, in the pathophysiology of TS. For the latter, surface electromyography, evoked potentials, saccadic eye movements, and polysomnographies have been performed, and again have suggested a dysfunction of the basal ganglia and the brainstem neurons in TS patients. These neurophysiological studies suggest dysfunction of both motor and non-motor basal ganglia-thalamocortical circuitries in TS patients, which is hypothesized to be caused by hypofunction of the dopamine (DA) neurons associated with DA receptor supersensitivity, a well as hypofunction of the serotonergic neurons of the brainstem. Polysomnographical examination suggests that the dysfunction of the nigrostriatal (NS)-DA neurons is not a progressive process, but that the dysfunction is closely associated with an early occurrence of the developmental decrement of the activities of the NS-DA system to mature in a normal fashion. The associated DA receptor supersensitivity is assumed to be a consequence of this developmental abnormality and not due to denervation supersensitivity.

Basal Ganglia↗

Brain stem and spinal cord impairment in Rett syndrome: somatosensory and auditory evoked responses investigations.

Six females with Rett syndrome (RS)--all seriously motor disabled with clinical symptomatology indicating not only brain but also spinal cord impairment--were investigated using auditory and somatosensory evoked responses techniques. In all patients the responses representing the pathways through the upper spinal cord were delayed suggesting an impairment of the central conduction time. The findings mean an involvement of the sub-cortical structures, the brain stem and the cervical spinal cord in the disease process. From the natural clinical course and the present findings, it is concluded that RS is also characterized by spinal cord impairment appearing with increasing age and stage of diseases.

Adolescent↗

Autism.

Autism is a neurologic disorder with impairments in language, social communication, and behavior, which may improve over time, but which persist throughout the lifetime. The evaluation of autism requires a separation of clinical and research objectives and is done best in close cooperation with professionals in the fields of communication, education, and psychology. There are no biologic markers of autism. Regression in language and social communication is present in approximately 30% of children with autism and is most likely to occur between 18 and 24 months of age. Early deficits in social communication can be identified by the assessment of joint attention, affective reciprocity, and metacognition. Current evidence suggests that deficits in social cognition and communication in autism may be related to dysfunction in the amygdala, hippocampus, and related limbic and cortical structures. Other neuroanatomic structures, such as the cerebellum, also may form part of a distributed neuronal network responsible for social cognition and communication. Genetics play a major role in autism, but what is inherited and how broad the inheritable phenotype is remain unclear. At a neurochemical level, the principal neurotransmitter implicated in autism is serotonin. Seizures and epileptiform discharges are common in autism and are linked to cognitive dysfunction. The role of medication is to target specific symptoms and open windows of opportunity that allow implementation of a multimodal individualized educational plan.

Autistic Disorder↗

Motivational responses to natural and drug rewards in rats with neonatal ventral hippocampal lesions: an animal model of dual diagnosis schizophrenia.

The high prevalence of substance use disorders in schizophrenia relative to the general population and other psychiatric diagnoses could result from developmental neuropathology in hippocampal and cortical structures that underlie schizophrenia. In this study, we tested the effects of neonatal ventral hippocampal lesions on instrumental behavior reinforced by sucrose pellets and intravenous cocaine injections. Lesioned rats acquired sucrose self-administration faster than sham-lesioned rats, but rates of extinction were not altered. Lesioned rats also responded at higher rates during acquisition of cocaine self-administration, and tended to acquire self-administration faster. Higher response rates reflected perseveration of responding during the post-injection "time-out" periods, and a greater incidence of binge-like cocaine intake, which persisted even after cocaine self-administration stabilized. In contrast to sucrose, extinction from cocaine self-administration was prolonged in lesioned rats, and reinstatement of cocaine seeking induced by cocaine priming increased compared with shams. These results suggest that neonatal ventral hippocampal lesions facilitate instrumental learning for both natural and drug rewards, and reduce inhibitory control over cocaine taking while promoting cocaine seeking and relapse after withdrawal. The findings are discussed in terms of possible developmental or direct effects of the lesions, and both positive reinforcement (substance use vulnerability as a primary disease symptom) and negative reinforcement (self-medication) theories of substance use comorbidity in schizophrenia.

Animals↗

Multimodal anatomic, functional, and metabolic brain imaging for tumor resection.

OBJECTIVE: Improvement of neurosurgical techniques with a more detailed description of brain tumors and their functional environment. METHODS: We performed: (1) anatomical magnetic resonance imaging (MRI) for reference, (2) functional sequences dedicated to the adjacent cortical structures (sensorimotor, visual, language paradigms), and (3) thallium 201 cerebral tomoscintigraphy to visualize active tumor invasion. Data were transferred to a workstation for automatic registration. RESULTS: All data were combined into one synthetic image showing the foci of high proliferative activity, which have to be completely resected, and the peritumoral functional structures, which have to be spared in order to minimize postoperative sequelae. This trimodal image is entered into a surgical neuronavigation computer for preoperative planning in order to outline tumoral target and functional risk areas. All this information is displayed in the operative microscope (Zeiss MKM) optically linked to MR images. This multimodality technique diminishes operative time by reducing electrocorticography and improves the operative short-term outcome. CONCLUSION: Multimodal imaging is useful for optimization of neurosurgical tumor resection.

Adult↗

Hippocampal volumetry in children 6 years or younger: assessment of children with and without complex febrile seizures.

PURPOSE: To study the relationship of complex febrile seizures (CFS) in the evolution of mesial temporal sclerosis. METHODS: We studied five children 22-68 (mean 44) months old with MRI volumetry 2 days-46 months after their first CFS, and compared total hippocampal volumes and right to left hippocampal volume ratios to those of 11 controls, 15-83 (mean 55) months old, who had MRI for complaints which turned out to be neurologically insignificant. RESULTS: In control children, total hippocampal volumes increased linearly with age, while right to left hippocampal volume ratios tended to decrease with age. In children with CFS total hippocampal volumes tended to be smaller than in controls. Right to left ratios were greater than 1 in all five children with CFS compared to seven of 11 controls. Hippocampal asymmetry was noted in only one child, with the right to left volume ratio exceeding two standard deviations from the control mean. The MRI of this child also demonstrated a subarachnoid cyst in the left frontocentral region, ipsilateral to the smaller hippocampus. Visual inspection of the remaining patients revealed no definite structural cortical abnormalities. None of the children developed subsequent afebrile seizures during the brief follow-up period. CONCLUSIONS: Hippocampal volumetry in controls revealed a linear increase in total hippocampal volumes and a statistically nonsignificant trend toward reduced right larger than left hippocampal ratios between 17 and 83 months old. The tendency for smaller total hippocampal volumes and larger right to left hippocampal volume ratios in children with CFS compared to controls could suggest a developmental abnormality, injury during CFS, or be age-related. The significant hippocampal asymmetry in a single child with CFS suggests that age may not be a factor in every case. Further studies are needed to collect control data in young children as well as prospectively follow children with CFS with serial imaging to better understand the relationship between CFS and the evolution of hippocampal atrophy.

Aging↗

Functional organization of the lateral premotor cortex: fMRI reveals different regions activated by anticipation of object properties, location and speed.

Previous studies have provided evidence that the lateral premotor cortex (PMC) is involved in representations triggered by attended sensory events. However, while the functional specificity of subregions of this large cortical structure has been intensively investigated in the monkey, little is known about functional differences within human lateral premotor areas. In the present study, functional magnetic resonance imaging was used to investigate if attending to object-specific (O), spatial (S), or temporal (T) properties of the same sensory event, i.e. moving objects, involves different premotor areas. We found a frontoparietal 'prehension network' comprising the pre-supplementary motor area (preSMA), the ventral PMC, and the left anterior intraparietal sulcus (aIPS) to be activated independently of the attended stimulus property, but most intensively during object-related attention. Moreover, several areas were exclusively activated according to the attended stimulus property. Particularly, different PMC regions responded to the Object (O) task (left superior ventrolateral PMC), the Spatial (S) task (dorsolateral PMC), and the Timing (T) task (frontal opercular cortex (FOP)). These results indicate that the representation of different stimulus dimensions engage distinct premotor areas and, therefore, that there is a functional specificity of lateral premotor subregions.

Adult↗

BimC motor protein KLP61F cycles between mitotic spindles and fusomes in Drosophila germ cells.

KLP61F in Drosophila is a member of the BimC family of kinesins and, as for other family members [1], is required for spindle assembly [2] [3]. KLP61F is a bipolar homotetramer that cross-links spindle microtubules [4]. It is not known, however, whether the function of KLP61F is dedicated to mitosis or whether KLP61F interacts exclusively with microtubules. Previous work suggested that KLP61F functions during interphase in proliferating germ cells [3]. Cytokinesis is incomplete in germ cells and a branched cortical structure known as a fusome extrudes through intercellular bridges called ring canals. Here I show that, in germ cells, KLP61F cycles between spindles during mitosis and fusomes during interphase. Inspection of fusome-deficient hu-li tai shao (hts) mutants indicated that KLP61F gains fusome-dependent interactions near telophase that mediate its incorporation into these structures. KLP61F proved to be maintained in fusomes by microtubule-independent, detergent-resistant interactions. Inspection of KLP61F mutants indicated that KLP61F is required to recruit fusome material to spindle midbodies near telophase and for normal fusome organization. These observations suggest that KLP61F is bifunctional in germ cells, with microtubule-dependent functions in spindle assembly and microtubule-independent functions in fusome organization. Cytological analyses with antibodies against phosphorylated Eg5 peptide [4] suggest that cycling of KLP61F might reflect phosphorylation.

Amino Acid Isomerases↗

Interindividual functional mapping: a nonlinear local approach.

Within the scope of three-dimensional brain imaging, we propose an interindividual fusion scheme to register functional activations according to anatomical cortical structures, the sulci. This paper is based on the assumption that an important part of functional intersubject variability is encoded in anatomical variability. The aim of this paper is therefore to propose a generic framework to register functional activations according to the relevant anatomical landmarks. Compared to "classical" interindividual fusion schemes, this approach is local. It relies on a statistical sulci shape model accounting for the interindividual variability of a population of subjects and providing deformation modes relative to a reference shape (a mean sulcus). The deformation field obtained between a given sulcus and the reference sulcus is extended to a neighborhood of the given sulcus by using the thin-plate spline interpolation. It is then applied to functional activations located in the vicinity of this sulcus. This approach is compared with rigid and nonrigid registration methods. In this paper, we present results on MEG somatosensory data acquired on 18 subjects. We show that the nonlinear local fusion scheme significantly reduces the observed functional variability.

Adult↗

Spectrotemporal features of the auditory cortex: the activation in response to dynamic ripples.

Functional MRI was used to investigate the characteristics of the human cerebral response to dynamic ripples. Dynamic ripples are sound stimuli containing regular spectrotemporal modulations, which are of major importance in speech processing; however, in contrast to speech, dynamic ripples can be characterized fully by a limited number of parameters. Extensive activation consisting of multiple separate regions was found bilaterally in the auditory cortex, particularly along the Heschl's gyri. This agrees with the presence of a structural cortical subdivision into functional fields. The level and the extent of activation were measured and correlated highly (R(2) = 0.97). Both measures depended strongly on the spectral density, temporal frequency, and amplitude of the modulations and matched the perceptual discernibility of the spectrotemporal modulations. The largest responses occurred for parameter values near the optimal human sensitivity. The drift direction of the modulations did not influence the activation. No quantitative differences were found between the two hemispheres. Average brain activation levels proved to be separable with regard to the spectral density and temporal frequency of the modulations. Topographic mappings of the modulation density and frequency onto the cortical surface were shown, approximately in posterolateral-to-anteromedial and lateral-to-medial directions, respectively. Posterolateral regions were most sensitive to spectrotemporal features at a scale similar to phonemes. Anteromedial regions, however, were also relatively sensitive to smaller scale acoustic features. This spatially dependent sensitivity suggests a functional topographic and hierarchical organization of the auditory cortex.

Acoustic Stimulation↗

Determination of activation areas in the human auditory cortex by means of synthetic aperture magnetometry.

In this study we applied synthetic aperture magnetometry (SAM) to investigate active cortical areas associated with magnetically recorded transient and steady-state auditory evoked responses. For transient evoked responses, SAM images reveal an activated volume of cortical tissue within the lateral aspect of the superior temporal plane. The volume of cortical activation for steady-state responses was located more medially than that for transient evoked responses. Additionally, SAM also reveals a small overlap of activated areas between transient and steady-state evoked responses, which has not be demonstrated when using equivalent current dipole (ECD) source modeling. Source waveforms from SAM and ECD analyses show comparable temporal information. Results from this study suggest that SAM is a useful technique for imaging cortical structures involved in processing perceptual information.

Acoustic Stimulation↗

Quantitative Brain PET. Comparison of 2D and 3D Acquisitions on the GE Advance Scanner.

PURPOSE: Recent developments in the design of positron emission tomography (PET) scanners have made three-dimensional (3D) data acquisition attractive because of significantly higher sensitivity compared to the conventional 2D mode (with lead/tungsten septa extended). However, the increased count rate in 3D mode comes at the cost of increased scatter, randoms, and dead time. Several schemes to correct for these effects have been proposed and validated in phantom studies. In this study, we evaluated the overall improvement afforded by 3D imaging in quantitative human brain PET studies carried out at our institution.METHODS: Subjects were studied using sequential/interleaved 2D and 3D data acquisition with a GE Advance scanner. We calculated regional and global cerebral glucose metabolism with [(18)F]flourodeoxyglucose (FDG) and estimated rate constants for striatal [(18)F]fluorodopa (FDOPA) uptake.RESULTS: FDG: Global mean glucose metabolic rates were in almost complete agreement (within 1%) between the two modes whereas the regional differences ranged from -7.7% to +9% for all cortical structures. However, for small regions (<2 cm(2)) like caudate nuclei, the maximum difference was 14.7%. FDOPA: A significant improvement in image quality was evident in 3D mode and there was complete agreement between the estimated parameters in the two scanning modes for the same noise equivalent counts: Striatal-to-occipital ratio (SOR) and striatal FDOPA uptake (K(i)(FD)) had mean differences of less than 2% and 5%, respectively.CONCLUSIONS: 3D FDG studies can be done with either half the injected dose or half the scan duration to a comparable 2D study. 3D PET imaging has distinct advantages over 2D in the quantitative fluorodopa studies.

Journal Article↗