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Binaural specialisation in human auditory cortex: an fMRI investigation of interaural correlation sensitivity.

A listener's sensitivity to the interaural correlation (IAC) of sound plays an important role in several phenomena in binaural hearing. Although IAC has been examined humans, little is known about the neural basis of sensitivity to IAC in humans. The present study employed functional magnetic resonance imaging to measure blood oxygen level-dependent (BOLD) activity in auditory brainstem and cortical structures in human listeners during presentation of band-pass noise stimuli between which IAC was varied systematically. The stimuli evoked significant bilateral activation in the inferior colliculus, medial geniculate body, and auditory cortex. There was a significant positive relationship between BOLD activity and IAC which was confined to a distinct subregion of primary auditory cortex located bilaterally at the lateral extent of Heschl's gyrus. Comparison with published anatomical data indicated that this area may also be cytoarchitecturally distinct. Larger differences in activation were found between levels of IAC near unity than between levels near zero. This response pattern is qualitatively compatible with previous measures of psychophysical and neurophysiological sensitivity to IAC. extensively in neurophysiological studies in animals and in psychophysical studies in

Acoustic Stimulation↗

Contrasting metabolic impairment in frontotemporal degeneration and early onset Alzheimer's disease.

[18F]FDG positron emission tomography (PET) scans of 14 patients comprising the clinical prototypes of dementias that are considered to be associated with frontotemporal lobar degeneration (FTLD) were compared to a population of 15 patients with early onset Alzheimer's disease (EOAD). The FTLD group included patients with frontotemporal dementia (FTD), semantic dementia (SD), and primary progressive aphasia (PPA). A voxel to voxel group comparison identified metabolic impairment in the bilateral ventromedial frontal area, the left anterior insula, and inferior frontal cortex, and indicated the right middle temporal gyrus to exhibit increased activity in FTLD compared to EOAD patients. All identified cortical structures are considered to be critically involved in neuropsychological features associated with FTLD (altered social behavior, aphasia) and EOAD (impaired linguistic and visuo-constructive abilities). In conjunction with recent insights from neuropathologic investigations, these results implicate that the a priori heterogeneous prototypes of FTLD (FTD, SD, PPA) may share more common ground than previously assumed, and therefore would become distinguishable as an entire group from EOAD.

Age of Onset↗

Mindboggle: a scatterbrained approach to automate brain labeling.

Mindboggle (http://www.binarybottle.com/mindboggle.html) is a fully automated, feature matching approach to label cortical structures and activity anatomically in human brain MRI data. This approach does not assume that the existence of component structures and their relative spatial relationship is preserved from brain to brain, but instead disassembles a labeled atlas and reassembles its pieces to match corresponding pieces in an unlabeled subject brain before labeling. Mindboggle: (1) converts linearly coregistered subject and atlas MRI data into sulcus pieces, (2) matches each atlas piece with a combination of subject pieces by minimizing a cost function, (3) transforms atlas label boundaries to the matching subject pieces, (4) warps atlas labels to their transformed boundaries, and (5) propagates labels to fill remaining gaps in a mask derived from the subject brain. We compared Mindboggle with four registration methods: linear registration, and nonlinear registration using SPM2, AIR, and ANIMAL. Automated labeling by all of the nonlinear methods was found to be at least comparable with linear registration. Mindboggle outperformed every other method, as measured by the agreement between overlapping atlas labels and manually assigned subject labels, with respect to the union or the intersection of voxels. After applying the same procedure that Mindboggle uses to fill a subject's segmented gray matter mask with labels (step 5), the results of the other methods improved. However, after performing a one-way ANOVA (and Tukey's honestly significant difference criterion) in a multiple comparison between the results obtained by the different methods, Mindboggle was still found to be the only nonlinear method whose labeling performance was significantly better than that of linear registration or SPM2. Further advantages to Mindboggle include a high degree of robustness against image artifacts, poor image quality, and incomplete brain data. We tested the latter hypothesis by conducting all of the tests again, this time registering the atlas to an artificially lesioned version of itself, and found that Mindboggle was the only method whose performance did not degrade significantly as the lesion size increased.

Animals↗

Spatial auditory compensation in early-blind humans: involvement of eye movements and/or attention orienting?

Several studies have reported that the early-blind displays higher auditory spatial abilities than the sighted. Although many studies have attempted to delineate the cortical structures that undergo functional reorganization in blind people, few have tried to determine which auditory or non-auditory processes mediate these increased auditory spatial abilities. The aim of this paper is to investigate the role of eye movements and orientation of attention in auditory localization in blind humans. Although we found, in a first experiment, that the influence of eye movements on auditory spatial localization is preserved in spite of congenital visual deprivation, the saccade influence on spatial hearing is not more pronounced in the blind than in the sighted. In a second experiment, early-blind and sighted subjects undertook a task involving discrimination of sound elevation in which auditory targets followed uninformative auditory cues on either side with an intermediate elevation. When sounds were emitted from the frontal hemifield, both groups showed similar auditory localization performance. Although the auditory cue did not affect discrimination accuracy in both groups, early-blind subjects exhibited shorter reaction times than sighted subjects when sound sources were placed at far-lateral locations. Attentional cues, however, had similar effects on both groups of subjects, suggesting that improved auditory spatial abilities are not mediated by attention orienting mechanisms.

Adaptation, Physiological↗

Visual spatial and visual pattern working memory: neuropsychological evidence for a differential role of left and right dorsal visual brain.

According to neurophysiological, neuroimaging, and behavioural evidence, visual working memory (WM) can be separated into a "what" and a "where" component, reflecting the duality of visual processing. Whereas a wealth of empirical data suggests a right-sided fronto-parietal network critical for the maintenance of spatial information, the cortical structures underlying maintenance of object information have remained controversial. Although visual object processing depends on ventral, inferior temporal areas, recent neuroimaging results suggest that maintenance of visual object information involves a left-sided or bilateral fronto-parietal network. The aim of the present study is to further clarify the role of the left and right parietal lobes for pattern and spatial visual WM. Seven patients with left-sided, seven with right-sided parietal brain injury, and two age-matched healthy control groups performed a delayed-matching-to-sample task using either pattern (shape) or spatial (location) information or both. In addition, eight patients with left-sided injury sparing parietal areas were tested to further examine the specific role of the left parietal cortex in pattern WM. Left parietal injury resulted in pattern WM impairment, only, while right parietal injury was associated with pattern and spatial WM deficits. Non-parietal injury was not associated with comparable deficits. These results suggest that visual spatial WM depends critically on right parietal areas; in contrast, pattern WM depends on both, left and right parietal areas.

Adult↗

The effect of low arousal on visuo-spatial attention.

Clinical and experimental evidence suggests a special role of the right hemisphere for alerting and orienting. However, it is not clear whether these attentional aspects should be taken to be independent or interacting. At least on the functional neuroanatomical level there seems to be an overlap in right parietal and frontal cortical structures. In this sleep deprivation study we examined the effect of different levels of arousal on covert orienting of attention repeatedly over a period of 28 h in 11 healthy subjects. The main finding is a disproportionate and significant slowing of responses to stimuli presented to the left visual hemifield that could only be observed in a state of maximally reduced arousal at 5:00 a.m. Furthermore, a facilitation of attentional shifts to the right could be observed in invalid trials when attention had to be reoriented. These results suggest an interaction of arousal and orienting, at least in situations of maximally reduced activation when attentional asymmetries could be provoked even in healthy subjects. The findings are compatible with a right hemisphere dominance for alerting and orienting, and they are discussed in the light of theoretical accounts of visual orienting.

Adult↗

Cortical correlates of TMS-induced phantom hand movements revealed with concurrent TMS-fMRI.

We studied an amputee patient who experiences a conscious sense of movement (SoM) in her phantom hand, without significant activity in remaining muscles, when transcranial magnetic stimulation (TMS) is applied at appropriate intensity over the corresponding sector of contralateral motor cortex. We used the novel methodological combination of TMS during fMRI to reveal the neural correlates of her phantom SoM. A critical contrast concerned trials at intermediate TMS intensities: low enough not to produce overt activity in remaining muscles; but high enough to produce a phantom SoM on approximately half such trials. Comparing trials with versus without a phantom SoM reported phenomenally, for the same intermediate TMS intensities, factored out any non-specific TMS effects on brain activity to reveal neural correlates of the phantom SoM itself. Areas activated included primary motor cortex, dorsal premotor cortex, anterior intraparietal sulcus, and caudal supplementary motor area, regions that are also involved in some hand movement illusions and motor imagery in normals. This adds support to proposals that a conscious sense of movement for the hand can be conveyed by activity within corresponding motor-related cortical structures.

Adult↗

Alterations in working memory as a function of leukoaraiosis in dementia.

Dementia research suggests executive dysfunction is best understood within the context of disease-specific neuropathology. Leukoaraiosis (LA) results in executive dysfunction yet little is known about its impact on specific aspects of working memory (WM). This study aimed to investigate the relationship between MRI LA severity and WM in dementia. A visual rating scale was used to assign patients with dementia into groups with minimal-mild LA (Low LA; n=34) and moderate-severe LA (High LA; n=32). A modified Digit Span Backward Task consisting of 3-, 4-, and 5-span trials measured specific components of WM. Short-term storage and rehearsal in WM were assessed by the total number of digits reported regardless of recall order (ANY-ORDER; e.g., 47981 recalled '18943', score=4). Mental manipulation in the form of disengagement and temporal re-ordering was assessed by the total number of digits recalled in correct position (SERIAL-ORDER; e.g., 47981 recalled '18943', score=3). There was no difference between LA groups on ANY-ORDER comparisons. The High LA group obtained lower SERIAL-ORDER scores than the Low LA group. Stepwise regression analyses were conducted that first entered MMSE scores then composite z-scores reflecting executive functioning, language and memory. ANY-ORDER performance variance was explained solely by dementia severity. SERIAL-ORDER performance variance was further explained by executive dysfunction. Results suggest that high degrees of LA do not interfere with immediate (digit) recall but do interfere with disengagement and temporal re-ordering. LA may disconnect the frontal lobes from subcortical and cortical structures that form the neuronal networks critical for these WM functions.

Aged↗

Neural substrates of choice selection in adults and adolescents: development of the ventrolateral prefrontal and anterior cingulate cortices.

A heightened propensity for risk-taking and poor decision-making underlies the peak morbidity and mortality rates reported during adolescence. Delayed maturation of cortical structures during the adolescent years has been proposed as a possible explanation for this observation. Here, we test the hypothesis of adolescent delayed maturation by using fMRI during a monetary decision-making task that directly examines risk-taking behavior during choice selection. Orbitofrontal/ventrolateral prefrontal cortex (OFC/VLPFC) and dorsal anterior cingulate cortex (ACC) were examined selectively since both have been implicated in reward-related processes, cognitive control, and resolution of conflicting decisions. Group comparisons revealed greater activation in the OFC/VLPFC (BA 47) and dorsal ACC (BA 32) in adults than adolescents when making risky selections. Furthermore, reduced activity in these areas correlated with greater risk-taking performance in adolescents and in the combined group. Consistent with predictions, these results suggest that adolescents engage prefrontal regulatory structures to a lesser extent than adults when making risky economic choices.

Adolescent↗

Olfactory bulb networks revealed by lateral olfactory tract stimulation in the in vitro isolated guinea-pig brain.

Olfactory information processing is mediated by synaptic connections between the olfactory bulbs (OBs) and piriform-limbic cortices. Limited accessibility using common in vivo and in vitro preparations has hindered previous attempts to define these synaptic interactions. We utilized the isolated guinea-pig brain preparation to overcome these experimental limitations. Previous studies demonstrated extensive functional preservation in this preparation maintained in vitro by arterial perfusion. Field potential laminar profiles were performed with multi-channel probes in the OB following stimulation of both the lateral olfactory tract (LOT) and the anterior piriform cortex (APC). Current-source density analysis was carried out on laminar profiles to reconstruct current sinks/sources associated with intrinsic synaptic activities. LOT stimulation induced sequentially i) an antidromic population spike (at 2.66+/-0.39 ms) located in the mitral cell layer that was resistant to 100 Hz high-frequency stimulation (HFS) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM), ii) a component located in the external plexiform layer at 3.85+/-0.63 ms that was unaffected by HFS, iii) a large amplitude potential (peak amplitude at 5.84+/-0.58 ms) generated in the external plexiform layer, abolished by HFS and CNQX, but not by bicuculline (50 microM), iv) a late response (onset at 20.00+/-2.94 ms) abolished by CNQX and enhanced by bicuculline. Stimulation of the APC also induced a late potential abolished by HFS and CNQX. Both APC-evoked and late LOT-evoked responses were abolished by a transverse cut to separate OB from APC. These results demonstrate in an isolated mammalian brain preparation the presence of reciprocal synaptic interactions between the OB and piriform cortical structures.

2-Amino-5-phosphonovalerate↗

Pharmacogenetics of antipsychotic-induced weight gain.

Weight gain appears to be a serious side effect encountered during treatment with many antipsychotic drugs. Although the propensities of inducing weight gain vary considerably between antipsychotics, weight gain is mostly observed in atypical antipsychotics, increasingly prescribed for a variety of psychiatric disorders. Beside the psychological consequences weight gain may influence patients' compliance and secondary medical comorbidities related to being overweight may arise, including diabetes, hypertonia, respiratory problems, and some types of cancer. Obesity research generally suggests that a complex system of neurotransmitters, neuropeptides, hormones and immune related factors interact in neural circuits involving at least the hypothalamus, the solitary tract and cortical structures to regulate energy homeostasis and body weight. Antipsychotics that have weight gain inducing properties may disrupt associated pathways at any of these levels, although it remains unclear what the mechanisms of action might be. Given the potential deleterious effects of weight gain, individual predictors of weight gain would be extremely helpful at the beginning of pharmacological treatment with atypical antipsychotics, allowing obesity to be avoided or for counteractive steps such as dietary restrictions to be taken in predisposed individuals. So far, only a few predictors to detect individuals at high risk have been reported and these have limited power. It is likely that genetic factors play a major role in determining individual response to antipsychotics as well as their side effect profile. In this article, we have reviewed literature related to antipsychotic-induced weight gain and have discussed the major issues, before updating the reader on current obesity research findings. Finally, we emphasize previous studies relating to the pharmacogenetics of antipsychotic-induced weight gain.

Animals↗

Renal cortex remodeling in streptozotocin-induced diabetic spontaneously hypertensive rats treated with olive oil, palm oil and fish oil from Menhaden.

We studied the effects of edible oils intake on the renal cortical structure of streptozotocin-induced diabetic (Db) and non-diabetic spontaneously hypertensive rats (SHR). Male SHR divided into 5 groups were studied during 6 weeks: one non-diabetic SHR group and four diabetic SHR groups (three groups received by gavage olive, palm or fish oil). Kidneys were analyzed by light microscopy and stereology. Oils intake did not change the plasma glucose levels. The blood pressure (BP) was lower in SHR-Db than in SHR, but SHR-Db-fish oil showed the lowest BP. Creatinine clearance was different between diabetic SHR and non-diabetic SHR, but not between treated SHR-Db and untreated SHR-Db. The renal cortex showed scars surrounding obsolete glomeruli with inflammatory infiltrate mainly in untreated SHR-Db. The olive oil, palm oil and mainly fish oil intake retard the usual loss of glomeruli and attenuate the renal cortex adverse remodeling of Db and non-Db SHR.

Animals↗

Interactions between volitional and automatic breathing during respiratory apraxia.

The sites and forms of interactions between voluntary breathing acts and automatic respiratory rhythm generation are the subject of considerable research interest. We report here observations of the control of breathing in a patient suffering from an advanced form of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). This patient demonstrated a severely compromised ability to perform volitional respiratory acts upon command, despite exacerbated behavioural and automatic control of respiration. The presence of residual volitional control of breathing in this patient provided interesting insights concerning the interaction between the automatic and the voluntary control of respiration. We observed that (1) when the subjects was asked to inspire voluntarily he could at best mobilize a volume similar to spontaneous VT and only very slowly; (2) automatic breathing movements persisted, superimposed onto the active voluntary movements, with an amplitude that decreased when the inspiratory activity, albeit weak, reached its maximal level; (3) during breath holding both the amplitude and the frequency of the basal spontaneous rhythmic activity were depressed. This observation therefore supports the idea of a strong interaction between volitional and automatic breathing in the form of an inhibition of automatic activity during voluntary breathing. Although, the site of interaction (spinal versus supraspinal) could not be determined during volitional inspiration, the effect of breath holding on the frequency of the spontaneous breathing activity supports the view that a volitional breathing arrest has some inhibitory effects on the respiratory oscillator at the medullary level. Finally, in an attempt to reconcile the persistence of a rhythmic activity during voluntary inspiration and expiration with previous data from the literature, it is proposed that the normal suppression of the automatic activity during voluntary inspiration relies on cortical and sub-cortical structures involved in the planning, i.e. the praxic component, of a respiratory task rather than on projections originating from the primary motor cortex.

Aged↗

Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin.

Layilin is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. We have identified merlin, the neurofibromatosis type 2 tumor suppressor protein and radixin, as other interactors with the carboxy-terminal domain of layilin. We show that the carboxy-terminal domain of layilin is capable of binding to the amino-terminal domain of radixin. An interdomain interaction between the amino- and the carboxy-terminal domains of radixin inhibits its ability to bind to layilin. In the presence of acidic phospholipids, the interdomain interaction of radixin is inhibited and layilin can bind to full-length radixin. In contrast, layilin binds both full-length and amino-terminal merlin-GST fusion proteins without a requirement for phospholipids. Furthermore, layilin antibody can immunoprecipitate merlin, confirming association in vivo between these two proteins, which also display similar subcellular localizations in ruffling membranes. No interaction was observed between layilin and ezrin or layilin and moesin. These findings expand the known binding partners of layilin to include other members of the talin/band 4.1/ERM (ezrin, radixin, and moesin) family of cytoskeletal-membrane linker molecules. This in turn suggests that layilin may mediate signals from extracellular matrix to the cell cytoskeleton via interaction with different intracellular binding partners and thereby be involved in the modulation of cortical structures in the cell.

3T3 Cells↗

Ischemic stroke: relation of age, lesion location, and initial neurologic deficit to functional outcome.

OBJECTIVE: Establish the relation between age, gender, initial neurologic deficit, stroke location, prior stroke, hemisphere of stroke, and functional outcome in ischemic stroke. DESIGN: Single group, multivariate, repeated measures design with 327 persons having ischemic stroke recruited from 20 participating centers. SETTING: Twenty European stroke centers. PATIENTS: Consecutive admissions of men and women between the ages of 40 and 85 yrs with a hemispheric stroke caused by middle cerebral artery ischemia and a Unified Neurological Stroke Scale score of 5 to 24. INTERVENTIONS: Inpatients enrolled in the trial received traditional rehabilitation therapies including physical therapy, occupational therapy, and speech therapy when appropriate. MAIN OUTCOME MEASURES: Barthel Index computed at 7 to 10 days and 3 months poststroke. RESULTS: Positive functional outcomes were significantly related to the absence of prior strokes, a younger age, a less severe initial neurologic deficit, stroke involving cortical structures, and dominant (left hemisphere) lesions. CONCLUSIONS: Despite some inconsistencies in existing literature, standardized prospective examination of outcome after stroke clearly demonstrated the effect of age, initial severity of stroke, and lesion location as predictors of functional outcome.

Activities of Daily Living↗

Emotion, motivation, and anxiety: brain mechanisms and psychophysiology.

The organization of response systems in emotion is founded on two basic motive systems, appetitive and defensive. The subcortical and deep cortical structures that determine primary motivated behavior are similar across mammalian species. Animal research has illuminated these neural systems and defined their reflex outputs. Although motivated behavior is more complex and varied in humans, the simpler underlying response patterns persist in affective expression. These basic phenomena are elucidated here in the context of affective perception. Thus, the research examines human beings watching uniquely human stimuli--primarily picture media (but also words and sounds) that prompt emotional arousal--showing how the underlying motivational structure is apparent in the organization of visceral and behavioral responses, in the priming of simple reflexes, and in the reentrant processing of these symbolic representations in the sensory cortex. Implications of the work for understanding pathological emotional states are discussed, emphasizing research on psychopathy and the anxiety disorders.

Animals↗

Fos expression in the rat brain after exposure to gravito-inertial force changes.

The immediate-early genes constitute useful neurobiological tools for mapping brain functional activity after sensory stimulation. We immunohistochemically investigated Fos protein expression in the brain of rats exposed to gravito-inertial force changes. Experiments were performed in hypergravity rats born and housed for 60 days in terrestrian gravity (1xg) and thereafter exposed for 90 min to 2xg or 4xg in a centrifuge, and in hypogravity rats born and housed for 60 days at 2xg and submitted for 90 min to 1xg. Data from these two experimental groups were quantified by light microscopy and compared to those from two groups of control rats born and permanently housed in either 1xg or 2xg environments that never had to adapt to novel gravito-inertial environments. Results showed a low basal Fos expression in the controls and a strong Fos staining in the experimental rats. Only the hypergravity rats displayed Fos-positive cells in vestibular-related brainstem regions (medial, inferior, and superior vestibular nuclei (VN); group y; dorsomedial cell column (DMCC) of the inferior olive (IO)). By contrast, many suprabulbar areas were strongly labeled in both the hyper- and hypogravity rats, as shown by the numerous Fos-positive cells in mesencephalic (colliculus, laterodorsal periaqueductal gray, autonomic nuclei), diencephalic (hypothalamic and thalamic nuclei), and telencephalic (parietal, temporal, entorhinal and visual cortices) structures. These spatial patterns of Fos expression suggest that an increase in gravito-inertial force activates otolith-vestibulo-olivar pathways and various suprabulbar structures underlying the corticovestibular interactions, which govern the multiple representations of vestibular information in the cortex. A decrease in gravito-inertial force has the opposite effects on the vestibulo-olivar structures as a result of otolith system disfacilitation which, in turn, modifies the activity of complex neural pathways. Exposure to both hyper- and hypogravity environments likely induces neurovegetative and/or stress effects that could account for Fos labeling in autonomic nuclei and in nervous structures involved in the hypothalamo-pituitary-adrenal axis.

Animals↗

Effects of single and dual administration of cocaine and ethanol on opioid and ORL1 receptor expression in rat CNS: an autoradiographic study.

The co-abuse of cocaine and ethanol is common among human addicts and has been reported to produce a stronger increase of euphoria as compared to either drug given alone. Both cocaine and ethanol increase the extracellular dopamine concentration in the nucleus accumbens, a terminal region in the mesolimbic dopamine pathway. In addition, both cocaine and ethanol affect the endogenous opioid system, which in turn alters the activity of the mesolimbic dopamine pathway. We have carried out quantitative autoradiography mapping of the opioid receptors as well as the opioid receptor-like 1 receptor in the brains of rats treated with both single and dual cocaine and ethanol. Rats received acute cocaine, ethanol or both drugs in combination. Ethanol alone or in combination with cocaine modulated the receptor densities in rat central nervous system. The kappa receptor densities were generally decreased, while both the mu and the opioid receptor-like 1 receptors were up-regulated. The mu opioid receptor levels were mainly increased in non-cortical regions, whereas the opioid receptor-like 1 receptors were increased in cortical structures. No changes in delta opioid receptors were observed. Cocaine alone did not influence the receptor levels in any of the treatment groups.

Anesthetics, Local↗