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Functional brain imaging of olfactory processing in monkeys.

As a step toward bridging the gap between human and animal studies of olfactory brain systems, we report results from an fMRI study of olfaction in squirrel monkeys. High-resolution fMRI images at 3 T with 1.25 x 1.25 x 1.2 mm(3) voxels were obtained covering the whole brain using an 8-cm-diameter birdcage coil and a gradient-echo spiral pulse sequence. Data were acquired from six sedated adult males using a standard block design. All fMRI data were spatially normalized to a common template and analyzed at the individual and group levels with statistical parametric and nonparametric methods. Robust odorant-induced activations were detected in several brain regions previously implicated in conscious human olfactory processing, including the orbitofrontal cortex, cerebellum, and piriform cortex. Consistent with human data, no stimulus intensity effects were observed in any of these regions. Average signal changes in these regions exceeded 0.6%, more than three times the expected signal change based on human fMRI studies of olfaction adjusting for differences in voxel size. These results demonstrate the feasibility of studying olfaction in sedated monkeys with imaging techniques commonly used at 3 T in humans and help promote direct comparisons between humans and nonhuman primates. Our findings, for example, provide novel support for the hypothesis that the cerebellum is involved in sensory acquisition. More broadly, this study suggests that olfactory processing in sedated monkeys and nonsedated humans shares similar neural substrates both within and beyond the primary olfactory system.

Animals↗

Religious thought and behaviour as by-products of brain function.

Religious concepts activate various functionally distinct mental systems, present also in non-religious contexts, and 'tweak' the usual inferences of these systems. They deal with detection and representation of animacy and agency, social exchange, moral intuitions, precaution against natural hazards and understanding of misfortune. Each of these activates distinct neural resources or families of networks. What makes notions of supernatural agency intuitively plausible? This article reviews evidence suggesting that it is the joint, coordinated activation of these diverse systems, a supposition that opens up the prospect of a cognitive neuroscience of religious beliefs.

Journal Article↗

Insight: its relationship with cognitive function, brain volume and symptoms in schizophrenia.

BACKGROUND: Lack of insight is frequently observed in schizophrenia. Relationships have been noted between poor insight, clinical symptoms and cognitive impairments but the findings are inconsistent. There have been some recent attempts to relate poor insight to neuro-anatomical measures. METHOD: We assessed insight, positive and negative symptoms of schizophrenia, cognitive performance, and whole brain volumes in a sample of 78 DSM-IV male schizophrenics and 36 normal male comparison subjects matched for age and IQ. Subjects underwent a dual-echo MRI brain scan to establish grey, white and whole brain volumes. RESULTS: Poor Wisconsin Card Sorting Test performance inversely correlated with insight in schizophrenic patients, as did the symptoms alogia, anhedonia, avolition/apathy, affective flattening, inappropriate affect, thought disorder and delusions. The presence of inappropriate affect, delusions and thought disorder, showed the most significant impact on insight levels. There were no significant correlations between whole brain, white and grey matter volume and degree of insight. CONCLUSIONS: The results suggest that poor insight is significantly related to schizophrenic psychopathology, and confirm that there is a relationship between insight and executive performance. Awareness of illness is not related to any global brain measures, suggesting future investigations should pay attention to more specific cortical regions such as the frontal cortex.

Adult↗

Functional brain imaging with single-photon emission computed tomography in the diagnosis of Alzheimer's disease.

High-resolution single-photon emission computed tomography (SPECT) with brain-retained technetium-99m (99mTc)-labeled tracers may be used for 3-dimensional measurements of regional cerebral blood flow (rCBF). This article summarizes important findings in SPECT studies of Alzheimer's disease (AD). There are three distinct potential applications of SPECT in diagnosing AD: (a) as a diagnostic adjunct in patients with mild cognitive or behavioral symptoms, suggesting a possible dementia disorder; (b) as a diagnostic adjunct for demented patients in whom the history, physical examination, and laboratory studies are in agreement with a diagnosis of probable AD; and (c) for determining the relative contributions of degenerative and vascular pathology to the clinical picture in demented patients with mixed disease. A clinical diagnosis of probable AD is associated with focal perfusion deficits as measured by SPECT. Characteristically, hypoperfusion is observed in the frontal and temporoparietal association areas, whereas other brain regions are relatively spared. The changes are present in the early phases of AD. The topography of rCBF deficits displays a marked heterogeneity among patients and correlates with cognitive profiles. In patients with mild cognitive complaints, the presence of focal hypoperfusion on SPECT may increase the accuracy of the diagnosis by confirming the presence of brain disease. In patients with probable AD, the presence of temporoparietal rCBF deficits on SPECT increases the accuracy of the clinical diagnosis, in particular when associated with medial temporal lobe atrophy on cranial X-ray computed tomography (CT). The role of SPECT in diagnosing patients with mixed disease remains to be clarified.

Alzheimer Disease↗

Evaluation of photodynamic therapy near functional brain tissue in patients with recurrent brain tumors.

INTRODUCTION: Photodynamic therapy (PDT) involves the selective retention of a photosensitizer that upon activation with light mediates tumor cell destruction via the production of singlet oxygen. This study evaluates the toxicity of PDT and a new light-delivery device based on light-emitting diode (LED) technology in selected patients with brain tumors. METHODS: Twenty patients with recurrent malignant brain tumors received 22 treatments with PDT. Sixteen tumors were supratentorial and four tumors were infratentorial. Patients received IV Photofrin 24 h prior to light exposure starting at 0.75 mg kg(-1). Laser and LED arrays were used to deliver 100 J cm(-2) of light to the sensitized tumors. Fourteen patients received PDT with a laser-balloon adapter, two via interstitial optical fibers and five patients had LED based PDT. At the maximum Photofrin dose of 2.0 mg kg(-1) five patients received laser-balloon adapter light and five patients received LED light. In addition, three patients received LED light with 0.25 mg kg(-1) of Visudine, a benzoporphyrin derivative (BPD). Quantitative analysis of toxicity and time to progression was performed. RESULTS: Two patients had toxicity consisting of ataxia and facial weakness after treatment with interstitial fibers. Escalating doses of Photofrin were tolerated to the maximum dose of 2.0 mg kg(-1). BPD did not result in additional toxicity. PDT in the posterior fossa or near eloquent brain was tolerated using the LED or laser-balloon adapter. All patients had tumor responses as documented by MRI scan and the mean time to tumor progression after PDT was 67 weeks. CONCLUSION: PDT with LED balloon adapters (also tunable dye laser) has acceptable toxicity in brain tumor patients. Future studies using more effective photosensitizers could improve local recurrence control.

Adolescent↗

[The control of gaze (2): cortical control of ocular saccades: functional brain imaging data].

Saccades are very rapid eye movements allowing us to explore the visual world. Although most of the time unconscious, the programming of each saccade implies a complex decision which depends upon both the perceptual context and the intentions of the subject. The cerebral cortex is critically involved in deciding where, when and in which sequence we move the eyes. Using sophisticated experimental designs, such as the learning of sequences of saccades, has revealed that besides a core fronto-parietal circuit, prefrontal, cingulate, and mediotemporal regions seem critically involved in higher level oculomotor control. Understanding precisely the cortical networks associated to different components of ocular movements can certainly be very useful to characterize, test, and eventually detect various kinds of neurological pathology.

Attention↗

Anterior insular cortex: linking intestinal pathology and brain function in autism-spectrum subgroups.

Autism includes deficits in communications skills and is associated with intestinal pathology. Numerous parents and some physicians report that an autistic child's attention and language improve in response to treatments which eliminate certain dietary antigens and/or which improve intestinal health. For at least some autism-spectrum children, the link between intestinal pathology, attention, and language may derive from shared neuroanatomic pathways within the anterior insular cortex (aIC); from a neurotrophic virus such as herpes simplex (HSV) migrating within afferents to the insular cortex; and/or from synaptic exhaustion in the aIC as induced by chronically inappropriate neuronal activity in the enteric nervous system and/or its vagal efferents.

Autistic Disorder↗

Psychostimulants, analeptics, nootropics: an attempt to differentiate and assess drugs designed for the treatment of impaired brain functions.

The common characteristic properties of psychostimulants, analeptics, and nootropics are excitatory and disinhibitory effects on the central nervous system. The differences lie in the type of excitatory effect. Psychostimulants produce a general, yet nonphysiologic, activation with subsequent sedation. They generally act in a destabilising manner, disturbing the homoeostatic functions of centrally regulated reactions. Nootropics produce a physiological activation of disturbed or reduced adaptation functions. They have a stabilising effect, increasing the homoeostatic functions of the centrally regulated reactions that have become susceptible to disturbances. Analeptics differ from psychostimulants and nootropics. The effects of neuronal excitation or disinhibition are mainly restricted to the respiratory and circulatory systems. In high dosages they produce convulsions and corresponding motor reactions. No conclusive evidence for a general efficacy in the treatment of organic mental disorders has been furnished for any of the three drug classes. Yet there is sufficient proof that nootropics, unlike psychostimulants and analeptics, can produce therapeutic results in at least some patients, even if it is not yet clear under what conditions they can be meaningfully applied. There is a fundamental difference between the three groups with regard to the potential for abuse. While tolerance and extreme physiological dependence can occur rapidly under treatment with psychostimulants, such risks are not a typical feature of nootropics or analeptics.

Animals↗

Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging.

The hippocampal formation contains a distinct population of neurons organized into separate anatomical subregions. Each hippocampal subregion expresses a unique molecular profile accounting for their differential vulnerability to mechanisms of memory dysfunction. Nevertheless, it remains unclear which hippocampal subregion is most sensitive to the effects of advancing age. Here we investigate this question by using separate imaging techniques, each assessing different correlates of neuronal function. First, we used MRI to map cerebral blood volume, an established correlate of basal metabolism, in the hippocampal subregions of young and old rhesus monkeys. Second, we used in situ hybridization to map Arc expression in the hippocampal subregions of young and old rats. Arc is an immediate early gene that is activated in a behavior-dependent manner and is correlated with spike activity. Results show that the dentate gyrus is the hippocampal subregion most sensitive to the effects of advancing age, which together with prior studies establishes a cross-species consensus. This pattern isolates the locus of age-related hippocampal dysfunction and differentiates normal aging from Alzheimer's disease.

Aging↗