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Showing papers on "Temporal cortex published in 1995"


Journal ArticleDOI
TL;DR: The results suggest that IT neurons can develop a complex receptive field organization as a consequence of extensive training in the discrimination and recognition of objects, and support the idea that a population of neurons tuned to a different object aspect, and each showing a certain degree of invariance to image transformations--may encode at least some types of complex three-dimensional objects.

956 citations


Journal ArticleDOI
TL;DR: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions, which have implications for understanding the neural substrates of both normal and pathological emotion.
Abstract: Objective: The specifit brain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if H 2 15 O position emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women. Method: Eleven healthy and never mentally ill adult women were scanned, by using PET and H 2 15 O, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human fates. Results: Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of signifitantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right prefrontal and bilateral temporal-parietal regions. Conclusions: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion

761 citations


Journal ArticleDOI
14 Jul 1995-Science
TL;DR: Age-related impairments of memory may be due to a failure to encode the stimuli adequately, which is reflected in the lack of cortical and hippocampal activation during encoding.
Abstract: The participation of the medial temporal cortex and other cerebral structures in the memory impairment that accompanies aging was examined by means of positron emission tomography. Cerebral blood flow (rCBF) was measured during encoding and recognition of faces. Young people showed increased rCBF in the right hippocampus and the left prefrontal and temporal cortices during encoding and in the right prefrontal and parietal cortex during recognition. Old people showed no significant activation in areas activated during encoding in young people but did show right prefrontal activation during recognition. Age-related impairments of memory may be due to a failure to encode the stimuli adequately, which is reflected in the lack of cortical and hippocampal activation during encoding.

672 citations


Journal ArticleDOI
TL;DR: Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers with specific connections with visual‐, somatosensory‐, olfactory‐, gustatory‐, and visceral‐related structures.
Abstract: Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers. Restricted areas of the lateral and posterior orbital cortex had specific connections with visual-, somatosensory-, olfactory-, gustatory-, and visceral-related structures. More medial areas received few direct sensory inputs. Within the lateral and posterior orbital cortex, area 12l received a substantial projection from visual areas in the inferior temporal cortex (TE). Area 12m received somatosensory input from face, digit, or forelimb regions in the opercular part of area 1-2, in area 7b, in the second somatosensory area (SII), and in the anterior infraparietal area (AIP). Areas 13m and 13l also received a projection from the opercular part of areas 1-2 and 3b. The posteromedial and lateral agranular insular areas (Iapm and Ial, respectively) received fibers from the ventral part of the parvicellular division of the ventroposterior medial nucleus of the thalamus (VPMpc) that may represent a visceral afferent system. The dorsal part of VPMpc projected to the adjacent gustatory cortex. These restricted inputs from several sensory modalities and the convergent corticocortical connections to orbital areas 13l and 13m suggest a network related to feeding. The OMPFC was also connected to premotor cortex in ventral area 6 (areas 6va and 6vb), in cingulate area 24c, and probably in the supplementary eye field. Area 6va projected to area 12m, whereas a region of area 6vb projected to area 13l. The region of the supplementary eye field projected to areas 12l, 12o, and 12r. Area Ial received fibers from area 24c. Lighter and more diffuse projections also reached wider areas of the OMPFC. For example, injections in several orbital areas labeled a few cells scattered through the anterior part of area TE and the superior temporal gyrus. There was also a projection to the intermediate agranular insular area (Iai) and to areas 13a and 12o from the apparently multimodal areas in the superior temporal sulcus and gyrus.

648 citations


Journal ArticleDOI
TL;DR: This work investigated the topographic organization of visual cortex connections with frontal eye field (FEF), the final stage of cortical processing for saccadic eye movements in individual macaque monkeys.
Abstract: The primate visual system consists of at least two processing streams, one passing ventrally into temporal cortex that is responsible for object vision, and the other running dorsally into parietal cortex that is responsible for spatial vision How information from these two streams is combined for perception and action is not understood Visually guided eye movements require information about both feature identity and location, so we investigated the topographic organization of visual cortex connections with frontal eye field (FEF), the final stage of cortical processing for saccadic eye movements Multiple anatomical tracers were placed either in parietal and temporal cortex or in different parts of FEF in individual macaque monkeys Convergence from the dorsal and ventral processing streams occurred in lateral FEF but not in medial FEF Certain extrastriate areas with retinotopic visual field organizations projected topographically onto FEF The dorsal bank of the superior temporal sulcus projected to medial FEF; the ventral bank, to lateral FEF, and the fundus, throughout FEF Thus, lateral FEF, which is responsible for generating short saccades, receives visual afferents from the foveal representation in retinotopically organized areas, from areas that represent central vision in inferotemporal cortex and from other areas having no retinotopic order In contrast, medial FEF, which is responsible for generating longer saccades, is innervated by the peripheral representation of retinotopically organized areas, from areas that emphasize peripheral vision or are multimodal and from other areas that have no retinotopic order or are auditory

631 citations


Journal ArticleDOI
TL;DR: The concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients is strongly supported.
Abstract: Apolipoprotein E (apoE) is critical in the modulation of cholesterol and phospholipid transport between cells of different types. Human apoE is a polymorphic protein with three common alleles, APO epsilon 2, APO epsilon 3, and APO epsilon 4. ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD). Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects. To characterize the possible impact of the apoE4 allele on cholinergic markers in AD, we examined the effect of apoE4 allele copy number on pre- and postsynaptic markers of cholinergic activity. ApoE4 allele copy number showed an inverse relationship with residual brain ChAT activity and nicotinic receptor binding sites in both the hippocampal formation and the temporal cortex of AD subjects. AD cases lacking the apoE4 allele showed ChAT activities close or within age-matched normal control values. The effect of the apoE4 allele on cholinomimetic drug responsiveness was assessed next in a group (n = 40) of AD patients who completed a double-blind, 30-week clinical trial of the cholinesterase inhibitor tacrine. Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline. These results strongly support the concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients.

613 citations


Journal ArticleDOI
TL;DR: Data support the notion that neocortical neuronal degeneration, as indicated by NFT formation, is a critical determinant of the clinical progression of Alzheimer's disease and suggest that medial temporal lobe structures may represent the initial site of NFT Formation.
Abstract: Objective: To determine the relationships between dementia severity and the extent of histopathologic lesions in a variety of brain regions. Neocortical and hippocampal ratings for neurofibrillary tangles (NFTs) and senile plaques (SPs) were compared in 70 cases of clinically and neuropathologically confirmed Alzheimer's disease. Design: Neuropathologic case series. Dementia severity was assessed by postmortem chart review with use of the extended Clinical Dementia Rating Scale (CDR). Linear association between CDR scores and NFT and SP scores were assessed by partial correlation, controlling for age at death. Setting: Studies were conducted at the Alzheimer's Disease Research Center of the Mount Sinai Medical Center, New York, NY. Main Outcome Measure: Association between CDR scores and neuropathologic changes assessed with the Consortium to Establish a Registry for Alzheimer's Disease semiquantitative scale. Results: Among these lesion scores, only NFTs showed a significant association with CDR score, and only for neocortical regions. In particular, NFT densities in the superior temporal cortex were most strongly correlated with dementia severity, followed by those in the inferior parietal and midfrontal cortex. No such correlations were apparent for the amygdala, hippocampus, or entorhinal cortex. Medial temporal lobe structures displayed high NFT scores, even in cases of mild dementia. Senile plaques did not correlate significantly with CDR score in any region. Conclusions: These data support the notion that neocortical neuronal degeneration, as indicated by NFT formation, is a critical determinant of the clinical progression of Alzheimer's disease and suggest that medial temporal lobe structures may represent the initial site of NFT formation. While SP density correlates with age at death, there is no correlation between SP counts and dementia severity. These results further suggest that the clinical presentation of dementia may be closely related to neurodegeneration in neocortical regions within the temporal lobe.

509 citations


Journal ArticleDOI
TL;DR: Chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and they fail to show the expected reductions of activity in the superior temporal cortex, which may reflect abnormal functional connectivity between frontal and temporal cortex.
Abstract: BACKGROUND This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

420 citations


Journal ArticleDOI
TL;DR: Results indicate that heme oxygenase‐1 is significantly overexpressed in neurons and astrocytes of AD hippocampus and cerebral cortex relative to control brains.
Abstract: Heme oxygenase-1 is a cellular stress protein expressed in brain and other tissues in response to oxidative challenge and other noxious stimuli. Using immunohistochemistry and immunofluorescent labeling in conjunction with laser scanning confocal microscopy, we observed intense immunoreactivity of heme oxygenase-1 in neurons of the hippocampus and temporal cortex of Alzheimer-diseased (AD) brain relative to age-matched control specimens. Furthermore, we demonstrated consistent colocalization of heme oxygenase-1 to glial fibrillary acidic protein-positive astrocytes, neurofibrillary tangles, and senile plaques in the AD specimens. In AD hippocampus, approximately 86% of glial fibrillary acidic protein-positive astrocytes expressed heme oxygenase-1, whereas only 6.8% of hippocampal astrocytes in normal senescent control specimens were immunopositive for heme oxygenase-1 (p 0.05). Robust 32-kd bands corresponding to heme oxygenase-1 were observed by Western blotting of protein extracts derived from AD temporal cortex and hippocampus after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Heme oxygenase-1 bands were very faint or absent in protein extracts prepared from control specimens. These results indicate that heme oxygenase-1 is significantly overexpressed in neurons and astrocytes of AD hippocampus and cerebral cortex relative to control brains. Upregulation of heme oxygenase-1 in AD brain supports the contention that the affected tissues are experiencing chronic oxidative stress. In addition, the excessive generation of carbon monoxide, a metabolite of heme degradation, may participate in the pathogenesis of AD.

360 citations


Journal ArticleDOI
TL;DR: The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group, and the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics.
Abstract: Magnetic resonance imaging was used to quantify the volume of the hippocampus in 47 men with chronic alcoholism and 72 healthy male control subjects. The subjects ranged in age from 21 to 70 years, thus permitting a test of whether older alcoholics suffer greater brain tissue volume reduction than do younger ones. Comparison brain regions included temporal lobe gray matter, white matter, and cerebrospinal fluid, as well as measures of the lateral ventricles, third ventricle, and temporal horns. The results of this cross-sectional study showed that the anterior, but not the posterior, portions of the hippocampus in both hemispheres were significantly smaller in the alcoholic than the healthy control group. Furthermore, the bilateral anterior hippocampal volume loss was greater in older than younger alcoholics. Despite the hippocampal volume deficit, these alcoholics did not demonstrate an explicit memory impairment; furthermore, memory test scores did not correlate significantly with hippocampal volumes. In the alcoholics, the age-related volume loss, which was over and above that expected in normal aging, was also evident in the temporal cortex and white matter. Likewise, alcoholic ventricular enlargement was age-related. Analysis of covariance revealed that the anterior hippocampal deficit persisted after accounting for the temporal lobe gray matter volume deficit. Multiple regression analysis revealed that the age-related brain volume abnormalities observed in the alcoholics could not be attributed to duration of alcoholism or total lifetime consumption of alcohol.

337 citations


Journal ArticleDOI
TL;DR: The results suggest that the cortical functional unit has a different ratio of input and output components in men and women which could have implications for the sex differences in cognition and behavior.
Abstract: Cytoarchitectonic area TA1 (von Economo) in the cortex of the planum temporale within the Sylvian fissure, which is auditory association cortex and documented to be part of the neural substrate of language functions, was studied quantitatively in the brain specimens of five women and four men (mean age of 50 year). All cases were documented to be medically and cognitively normal, and consistently right-handed. We investigated the possibility that the difference in brain size between men and women is reflected in differences in the numerical density of neurons in area TA1, an area associated with morphologic and psychological sex differences. Neuron counts were made directly through cell differentiation under the microscope from Nissl-stained sections. Cortical depth, the number of neurons through the depth of cortex under 1 mm2 of cortical surface (Nc), and the number of neurons per unit volume (Nv) were obtained for the total cortex and for each of the six layers in each hemisphere. For total cortex in both hemispheres, depth and Nc were similar, but Nv was greater by 11% in women, with no overlap of scores between the sexes. The sex difference in Nv was attributable to layers II and IV; in contrast, Nv did not differ between the sexes in layers III, V, and VI. This is the first report of such a sex difference in human cortex. The results suggest that the cortical functional unit has a different ratio of input and output components in men and women which could have implications for the sex differences in cognition and behavior. Due to the small sample size and the homogeneity of the cases studied, generalizability of the results requires replication by other studies. In addition, cytoarchitectonic mapping indicated that area TA1 also occurs in the vertical posterior wall of the Sylvian fissure, providing evidence that anatomical definition of the planum temporale should include the posterior vertical wall of the superior temporal gyrus.

Journal ArticleDOI
TL;DR: Positron emission tomography was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and thoserelated to actual recovery of stored information (ecphory).
Abstract: Positron emission tomography (PET) was used to identify brain regions associated with two component processes of episodic retrieval; those related to thinking back in subjective time (retrieval mode) and those related to actual recovery of stored information (ecphory). Healthy young subjects recognized words that had been encoded with respect to meaning or the speaker's voice. Regardless of how the information had been encoded, recognition was associated with increased activation in regions in right prefrontal cortex, left anterior cingulate, and cerebellum. These activations reflect retrieval mode. Recognition following meaning encoding was specifically associated with increased activation in left temporal cortex, and recognition following voice encoding involved regions in right orbital frontal and parahippocampal cortex. These activations reflect ecphory of differentially encoded information.

Journal ArticleDOI
17 Aug 1995-Nature
TL;DR: It is shown that increases in blood flow in inferior temporal regions are associated with object decisions about possible but not impossible objects, and that there are increases in the vicinity of the hippocampal formation associated with episodic recognition of possible objects.
Abstract: An object's global, three-dimensional structure may be represented by a specialized brain system involving regions of inferior temporal cortex1–3. This system's role in object representation can be understood by experiments in which people study drawings of novel objects with possible or impossible three-dimensional structures, and later make either possible/impossible object decisions or old/ new recognition decisions about briefly flashed studied and non-studied objects. Although object decisions about possible objects are facilitated by prior study, there is no corresponding facilitation for impossible objects, thereby implicating a system that is specifically involved in the representation of structurally coherent visual objects4. Here we show, by positron emission tomography (PET), that increases in blood flow in inferior temporal regions are associated with object decisions about possible but not impossible objects, and that there are increases in the vicinity of the hippocampal formation associated with episodic recognition of possible objects.

Journal ArticleDOI
TL;DR: The results suggest that anxiety associated with the simple phobia symptomatic state is mediated by paralimbic structures and activation of somatosensory cortex may reflect tactile imagery as one component of the phobic symptomatic condition.
Abstract: Background: The goal of this study was to determine the mediating neuroanatomy of simple phobic symptoms. Methods: Positron emission tomography and oxygen 15 were used to measure normalized regional cerebral blood flow in seven subjects with simple phobia during control and provoked states. Stereotactic transformation and statistical parametric mapping techniques were employed to determine the locations of significant activation. Results: Statistical parametric maps demonstrated significant increases in normalized regional blood flow for the symptomatic state compared with the control state in the anterior cingulate cortex, the insular cortex, the anterior temporal cortex, the somatosensory cortex, the posterior medial orbitofrontal cortex, and the thalamus. Conclusions: The results suggest that anxiety associated with the simple phobic symptomatic state is mediated by paralimbic structures. Moreover, activation of somatosensory cortex may reflect tactile imagery as one component of the phobic symptomatic condition.

Journal ArticleDOI
TL;DR: Volumes of temporal lobe sulcal CSF and the ventricular system (temporal horns and lateral and third ventricles) significantly increased with age and were related to enlargement of the three ventricular regions, which may be indicative of age-related atrophy of the adjacent cortex but not the hippocampus, at least up to age 70 years.

Journal ArticleDOI
TL;DR: It is possible that neurofilament protein is crucial for the unique capacity of certain subsets of neurons to perform the highly precise mapping functions of the monkey visual system.
Abstract: Visual function in monkeys is subserved at the cortical level by a large number of areas defined by their specific physiological properties and connectivity patterns. For most of these cortical fields, a precise index of their degree of anatomical specialization has not yet been defined, although many regional patterns have been described using Nissl or myelin stains. In the present study, an attempt has been made to elucidate the regional characteristics, and to varying degrees boundaries, of several visual cortical areas in the macaque monkey using an antibody to neurofilament protein (SMI32). This antibody labels a subset of pyramidal neurons with highly specific regional and laminar distribution patterns in the cerebral cortex. Based on the staining patterns and regional quantitative analysis, as many as 28 cortical fields were reliably identified. Each field had a homogeneous distribution of labeled neurons, except area V1, where increases in layer IVB cell and in Meynert cell counts paralleled the increase in the degree of eccentricity in the visual field representation. Within the occipitotemporal pathway, areas V3 and V4 and fields in the inferior temporal cortex were characterized by a distinct population of neurofilament-rich neurons in layers II-IIIa, whereas areas located in the parietal cortex and part of the occipitoparietal pathway had a consistent population of large labeled neurons in layer Va. The mediotemporal areas MT and MST displayed a distinct population of densely labeled neurons in layer VI. Quantitative analysis of the laminar distribution of the labeled neurons demonstrated that the visual cortical areas could be grouped in four hierarchical levels based on the ratio of neuron counts between infragranular and supragranular layers, with the first (areas V1, V2, V3, and V3A) and third (temporal and parietal regions) levels characterized by low ratios and the second (areas MT, MST, and V4) and fourth (frontal regions) levels characterized by high to very high ratios. Such density trends may correspond to differential representation of corticocortically (and corticosubcortically) projecting neurons at several functional steps in the integration of the visual stimuli. In this context, it is possible that neurofilament protein is crucial for the unique capacity of certain subsets of neurons to perform the highly precise mapping functions of the monkey visual system.

Journal ArticleDOI
10 Aug 1995-Nature
TL;DR: Psychophysical evidence for the existence of neural mechanisms in human vision that integrate motion signals along complex trajectories is provided, showing that whereas motion-sensitive neurons in primary visual cortex respond best to local translation, many neurons in the medial superior temporal cortex have large receptive fields tuned to radial, circular or spiral motion.
Abstract: As we move through our environment, the flow of the deforming images on our retinae provides rich information about ego motion and about the three-dimensional structure of the external world. Flow-fields comprise five independent compenents, including radial and circular motion1a¤-3. Here we provide psychophysical evidence for the existence of neural mechanisms in human vision that integrate motion signals along these complex trajectories. Signal-to-noise sensitivity for discriminating the direction of radial, circular and translational motion increased predictably with the number of exposed sectors, implying the existence of specialized detectors that integrate motion signals of different directions from different locations. However, contrast sensitivity for complex motion did not increase greatly with sector number, implying that the specialized detectors are preceded by a first stage of local-motion mechanisms that impose a contrast threshold. These findings fit well with recent electrophysiological evidence in monkey4a¤-7 showing that whereas motion-sensitive neurons in primary visual cortex respond best to local translation, many neurons in the medial superior temporal cortex have large receptive fields tuned to radial, circular or spiral motion.

Journal ArticleDOI
TL;DR: The study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.
Abstract: The purpose of the present study was to investigate by using positron emission tomography (PET) whether the cortical pathways that are involved in visual perception of spatial location and object identity are also differentially implicated in retrieval of these types of information from episodic long-term memory. Subjects studied a set of displays consisting of three unique representational line drawings arranged in different spatial configurations. Later, while undergoing PET scanning, subjects' memory for spatial location and identity of the objects in the displays was tested and compared to a perceptual baseline task involving the same displays. In comparison to the baseline task, each of the memory tasks activated both the dorsal and the ventral pathways in the right hemisphere but not to an equal extent. There was also activation of the right prefrontal cortex. When PET scans of the memory tasks were compared to each other, areas of activation were very circumscribed and restricted to the right hemisphere: For retrieval of object identity, the area was in the inferior temporal cortex in the region of the fusiform gyrus (area 37), whereas for retrieval of spatial location, it was in the inferior parietal lobule in the region of the supramarginal gyrus (area 40). Thus, our study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.

Journal ArticleDOI
TL;DR: Typical cerebral glucose metabolism was examined with positron-emission tomography as a measure of neuronal activation during performance of the classically conditioned eyeblink response in 12 young adult subjects to support a role for the hippocampus in conditioning and suggest that the ventral striatum may also be involved.
Abstract: Relative cerebral glucose metabolism was examined with positron-emission tomography (PET) as a measure of neuronal activation during performance of the classically conditioned eyeblink response in 12 young adult subjects. Each subject received three sessions: (i) a control session with PET scan in which unpaired presentations of the tone conditioned stimulus and corneal airpuff unconditioned stimulus were administered, (ii) a paired training session to allow associative learning to occur, and (iii) a paired test session with PET scan. Brain regions exhibiting learning-related activation were identified as those areas that showed significant differences in glucose metabolism between the unpaired control condition and well-trained state in the 9 subjects who met the learning criterion. Areas showing significant activation included bilateral sites in the inferior cerebellar cortex/deep nuclei, anterior cerebellar vermis, contralateral cerebellar cortex and pontine tegmentum, ipsilateral inferior thalamus/red nucleus, ipsilateral hippocampal formation, ipsilateral lateral temporal cortex, and bilateral ventral striatum. Among all subjects, including those who did not meet the learning criterion, metabolic changes in ipsilateral cerebellar nuclei, bilateral cerebellar cortex, anterior vermis, contralateral pontine tegmentum, ipsilateral hippocampal formation, and bilateral striatum correlated with degree of learning. The localization to cerebellum and its associated brainstem circuitry is consistent with neurobiological studies in the rabbit model of eyeblink classical conditioning and neuropsychological studies in brain-damaged humans. In addition, these data support a role for the hippocampus in conditioning and suggest that the ventral striatum may also be involved.

Journal ArticleDOI
TL;DR: The findings support previous reports that ADPD cases are more likely to manifest extrapyramidal dysfunction and show plaque predominance at autopsy.
Abstract: Although extrapyramidal signs such as rigidity, bradykinesia, and postural impairment frequently occur in patients with Alzheimer's disease (AD), the correlation of these parkinsonian manifestations with the neuropathologic changes of Parkinson's disease (PD) has not been well established. Previous clinicopathologic studies addressing this issue have been largely retrospective or have consisted of relatively small numbers of cases. We examined the neuropathologic correlates of clinical parkinsonism in 78 cases with autopsy-confirmed AD prospectively enrolled in the Consortium to Establish a Registry for Alzheimer's Disease. Sixteen (20.5%) of the 78 AD cases showed concomitant PD pathology (AD/PD) as evidenced by the presence of nigral degeneration and Lewy bodies at any site. There were neocortical Lewy bodies in eight of these 16 cases. Two or more clinical manifestations of extrapyramidal dysfunction were present in eight (50.0%) of the 16 cases of AD/PD versus 11 (17.7%) of the 62 cases of AD alone (p < 0.01). Although semiquantitative ratings of the frequency of neuritic plaques showed no differences between the two groups, neurofibrillary tangles in the AD/PD group were less frequent in the midfrontal (p < 0.001) and superior temporal cortex (p < 0.05). These findings support previous reports that AD/PD cases are more likely to manifest extrapyramidal dysfunction and show plaque predominance at autopsy.

Journal ArticleDOI
TL;DR: The results indicate that right frontal and left frontal, parietal, and temporal areas all participate in face working memory, but that left hemisphere areas are associated with a more durable working memory representation or strategy that subjects rely on increasingly with longer retention intervals.
Abstract: Neural systems that participate in working memory for faces were investigated in an experiment designed to distinguish face perception areas from working memory areas. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) while subjects performed a sensorimotor control task, a face perception control task, and five working memory tasks with parametrically varied retention intervals, ranging from 1 to 21 sec. Striate and ventral occipitotemporal extrastriate areas demonstrated a simple negative correlation between rCBF and retention delay, indicating that these areas participate principally in perceptual operations performed during visual stimulation. By contrast, right and left frontal areas demonstrated rCBF increases that were significantly more sustained across delays than were increases in ventral extrastriate areas, but the relation between rCBF and retention interval differed significantly by hemisphere. Whereas right frontal rCBF showed a nonsignificant tendency to diminish at longer delays, left inferior frontal, middle frontal, and anterior cingulate cortex, as well as left parietal and inferior temporal cortex, demonstrated their largest rCBF increases at the longest delays. These results indicate that right frontal and left frontal, parietal, and temporal areas all participate in face working memory, but that left hemisphere areas are associated with a more durable working memory representation or strategy that subjects rely on increasingly with longer retention intervals. One possible explanation for this hemispheric difference is that left hemisphere activity is associated with a face representation that embodies the result of more analysis and elaboration, whereas right frontal activity is associated with a simpler, icon-like image of a face that is harder to maintain in working memory. © 1995 Wiley-Liss, Inc.

Journal ArticleDOI
01 Jun 1995-Brain
TL;DR: The results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration, as conscious visual experience appears to occur without activation of the primary visual cortex.
Abstract: In a small proportion of the normal population, stimulation in one modality can lead to perceptual experience in another, a phenomenon known as synaesthesia. In the most common form of synaesthesia, hearing a word can result in the experience of colour. We have used the technique of PET, which detects brain activity as changes of regional cerebral blood flow (rCBF), to study the physiology of colour-word synaesthesia in a group of six synaesthete women. During rCBF measurements synaesthetes and six controls were blindfolded and were presented with spoken words or pure tones. Auditory word, but not tone, stimulation triggered synaesthesia in synaesthetes. In both groups word stimulation compared with tone stimulation activated the classical language areas of the perisylvian regions. In synaesthetes, a number of additional visual associative areas, including the posterior inferior temporal cortex and the parieto-occipital junctions, were activated. The former has been implicated in the integration of colour with shape and in verbal tasks which require attention to visual features of objects to which words refer. Synaesthetes also showed activations in the right prefrontal cortex, insula and superior temporal gyrus. By contrast, no significant activity was detected in relatively lower visual areas, including areas V1, V2 and V4. These results suggest that colour-word synaesthesia may result from the activity of brain areas concerned with language and visual feature integration. In the case of colour-word synaesthesia, conscious visual experience appears to occur without activation of the primary visual cortex.

Journal ArticleDOI
TL;DR: It is shown that reliable discrimination of briefly presented shapes by single neurons depends on the temporal integration of the response, and provides direct neurophysiological evidence for the "interruption theory" of backward masking.
Abstract: The perception of a briefly presented shape is strongly impaired when it is followed by another pattern, a phenomenon called backward masking. We found that the vast majority of a sample of shape-selective neurons in the macaque inferior temporal cortex respond selectively to backward-masked shapes, although these shapes could not be discriminated by human and monkey subjects. However, this selective response was brief, since it was either interrupted by the mask or overridden by a response to the mask itself. We show that reliable discrimination of briefly presented shapes by single neurons depends on the temporal integration of the response. Presentation of the mask, however, reduces the number of spikes available for integration, explaining backward masking. These results also provide direct neurophysiological evidence for the "interruption theory" of backward masking.

Journal ArticleDOI
01 Mar 1995-Cortex
TL;DR: It is concluded that right hippocampal regions are involved in a largely automatic, primary processing of faces, while left hippocampal areas are additionally involved when explicit memory for faces is required.

Journal ArticleDOI
TL;DR: The cellular expression of Fos protein in rat brain has been studied after groups of rats were either shown sets of novel or highly familiar objects, or were exposed to the same pattern of illumination without objects being shown.

Journal ArticleDOI
TL;DR: Information concerning stimulus repetition and familiarity is separably encoded at the single neuron level in the rat cortex as in the monkey cortex; such information is of importance to recognition memory, working memory and priming memory.
Abstract: This study was conducted to discover whether the rat cortex contains neurons that signal information concerning the previous occurrence of stimuli, as has been found in the primate. Recordings of the activity of 396 single neurons were made while unanaesthetized rats were shown objects. The effects on neuronal responsiveness of stimulus repetition and of the relative familiarity of the stimuli were sought. The areas sampled were the rhinal (entorhinal and perirhinal) cortex, area TE of the temporal cortex, the lateral occipital cortex and the hippocampal formation. The response to the first presentations of objects was significantly different from that to their second presentations for 63 (34%) of the 185 responsive neurons; for 39 of the neurons the response was smaller when the stimulus was repeated, whereas for 24 it was larger. The incidence of decremental responses was higher in the non-hippocampal cortex than in the hippocampal formation, while the incidence of incremental responses was higher in the hippocampal formation than other cortical areas. The response to unfamiliar objects was significantly different from that to highly familiar objects for 15 (22%) of 67 responsive neurons so tested; for 12 of the neurons the response was smaller when the stimulus was repeated, and for three it was larger; most of these neurons were found in area TE. The responses of ten familiarity neurons varied significantly with the relative familiarity of the stimuli but not with stimulus repetition; the responses of seven recency neurons varied significantly upon stimulus repetition but not with the relative familiarity of the stimuli. Thus information concerning stimulus repetition and familiarity is separably encoded at the single neuron level in the rat cortex. The results demonstrate that in the rat cortex as in the monkey cortex there are neurons that signal information concerning the prior occurrence of stimuli; such information is of importance to recognition memory, working memory and priming memory.

Journal ArticleDOI
TL;DR: A heterogeneous distribution of 5‐HT4 receptors in human brain, with high to moderate densities in basal ganglia and limbic structures is suggested, given the lack of change observed in Parkinson's disease.
Abstract: 1 The distribution, pharmacology and effects of neurodegenerative diseases on 5-HT4 receptors in human brain have been characterized in vitro 2 The 5-HT4 receptor in post mortem human brain tissue was specifically labelled with [3H]-GR 113808 In human putamen, this ligand labelled a homogeneous population of sites, with an apparent affinity (-log Kd) of 101 and a density (Bmax) of 573 fmol mg-1 tissue The pharmacology of this site was characterized by use of a series of displacing ligands, and the following rank order of apparent affinities (with mean +/- sd -log Ki values in parentheses) was generated: GR113808 (1005 +/- 004) > SDZ 205,557 (865 +/- 008) > DAU 6285 (795 +/- 004) > BIMU-1 (781 +/- 006) > DAU 6215 (742 +/- 023) > tropisetron (739 +/- 023) > 5-HT (732 +/- 100) > BIMU-8 (725 +/- 004) > (R)-zacopride (582 +/- 004) The Hill coefficients were not significantly different from unity, consistent with an interaction at a single site A comparison of the affinities of these compounds with those obtained from guinea-pig striatum indicated no evidence of species differences 3 The regional distribution of 5-HT4 receptors was assessed by determining the density of binding sites for [3H]-GR 113808 The distribution were as follows (with mean +/- sd Bmax values, fmol mg-1 tissue, in parentheses): caudate nucleus (87 +/- 15), lateral pallidum (86 +/- 55), putamen (57 +/- 30), medial pallidum (38 +/- 09), temporal cortex (26 +/- 06), hippocampus (24 +/- 08), amygdala (23 +/-11), frontal cortex (17 +/- 05), cerebellar cortex (<10) In these studies, the affinities of GR 113808 were not significantly different4 The density of 5-HT4 receptors selected from regions of post mortem brains of patients with Parkinson's disease, Huntington's disease and Alzheimer's disease were compared to age-matched controls In Parkinson's disease, there was no significant difference between control or patient values(mean +/- sd Bmax values, fmol mg-1 tissue; putamen, control 474 +/- 007, patient 586 +/- 148; substantia nigra, control 421 +/- 256, patient 557 +/- 010) In Huntington's disease, there was a significant decrease in putamen (control 533 +/- 108, patient 268 +/- 108), while in Alzheimer's disease, there was a marked loss of receptors in hippocampus (control 234 +/- 062, patient 078 +/- 061), in frontal cortex (control,176 +/- 019, patient 130 +/- 022) Receptor density in temporal cortex showed a decrease, but did not achieve statistical significance (control 206 +/- 021, patient 144 +/- 064)5 These data suggest a heterogeneous distribution of 5-HT4 receptors in human brain, with high to moderate densities in basal ganglia and limbic structures These receptors may not be principally co-localized on dopaminergic cell bodies or terminals, given the lack of change observed in Parkinson's disease The loss of 5-HT4 receptors in the putamen in Huntington's disease raises the possibility of their presence on intrinsic striatal GABAergic or cholinergic neurones The marked loss of receptors in hippocampal and cortical regions in the brains from patients with Alzheimer's disease is consistent with a role for the 5-HT4 receptor in cognitive processing

Journal ArticleDOI
TL;DR: Good agreement of histological presentation of infarct with the total area of decreased ADC was demonstrated and no significant change was noted in proton density during the observation period.
Abstract: The quantitative NMR parameters T1, T2, rho, and apparent diffusion coefficient (ADC) were determined during the 7 h after middle cerebral artery occlusion in rats. In the normal caudate-putamen (CP), 869 +/- 145 ms and 72 +/- 2 ms for T1 and for T2, respectively, were found; the corresponding values for cortex were 928 +/- 117 ms and 73 +/- 2 ms. The ADC showed significant dependence on gradient direction: diffusion along x resulted in 534 +/- 53 microns 2/s (CP) and 554 +/- 62 microns 2/s (cortex), and along y in 697 +/- 58 microns 2/s (CP) and 675 +/- 53 microns 2/s (cortex). In the ischemic territory, a continuous increase over time of both relaxation times was observed in the CP, leading to an increase of 29 +/- 20% (T1) and 51 +/- 41% (T2) above control level. ADC dropped to 63 +/- 15% of control in the CP and to 74 +/- 4% of control in the temporal cortex. No significant change was noted in proton density during the observation period. Strongest ADC reduction was in the center of the ischemic territory (< or = 60% of control) surrounded by a region of lesser reduction (< or = 80% of control). During the early part of the study, the area of reduced ADC was larger than that of elevated relaxation times. Toward the end of the experiment, the area of increased relaxation times approached that of decreased ADC at < or = 80% of control. Good agreement of histological presentation of infarct with the total area of decreased ADC (< or = 80%) was demonstrated.

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TL;DR: The intracranially recorded MMN was found to be attention independent and modality specific, and was confined to a rather small area in temporal cortex, which was different from the structures where attention-dependent N2 and P3 responses to the frequency change could be recorded.
Abstract: Mismatch negativity (MMN) is an event-related potential (ERP) component elicited by any discernible change in a repetitive sound even in the absence of attention. Previous studies have established that MMN is generated by change detection in a process comparing the deviant sensory input with the neural memory trace encoding the physical features of the repetitive sound. In the present study, we recorded MMNs to tonal frequency changes directly from the human temporal cortex of patients with electrodes implanted in the brain for diagnosis and therapy. The intracranially recorded MMN was found to be attention independent and modality specific. It was confined to a rather small area in temporal cortex, which was different from the structures where attention-dependent N2 and P3 responses to the frequency change could be recorded.

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TL;DR: Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients, and adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in post operative memory performance.
Abstract: Summary We examined the relationship of age of onset of epilepsy, chronological age at time of operation, and adequacy of preoperative memory performance to pre- to postoperative verbal memory decline. Patients who underwent left (n = 50) or right (n = 51) anterior temporal lobectomy (ATL) were administered tests of verbal episodic (list learning, paragraph recall) and semantic memory (visual naming, vocabulary), both preoperatively and 6 months postoperatively. As a group, left ATL patients showed the classic selective decrease on measures of episodic but not semantic memory. However, examination of episodic memory outcome showed considerable individual variability. Stepwise regression analyses indicated that both later age at onset and older chronologic age were significant and selective predictors of episodic memory decrease for left ATL patients. Adequacy of preoperative memory performance was a nonspecific predictor, associated with decrease in postoperative memory performance for both left and right ATL patients and for multiple types of memory indices. The clinical and theoretical implications are discussed.