james fallon | University of California, Irvine (original) (raw)
Papers by james fallon
Neuroscience Letters, 1977
ABSTRACT
Experimental Neurology, 1975
The Journal of Comparative Neurology, 1982
An analysis of the cells and their processes within the island of Calleja complexes (ICC) was mad... more An analysis of the cells and their processes within the island of Calleja complexes (ICC) was made in light and electron microscopic preparations to determine synaptic relationships within this part of the basal forebrain. The light microscopic preparations showed that the ICC contained two cell types, granule cells and large cells. In electron microscopic preparations, the somata of granule cells were grouped together and were directly apposed to other somata of granule cells. Specialized junctions (4-6 nm wide) that occurred at sites of somal apposition suggested ephaptic coupling of granule cells. The granule cell somata had nuclei that contained clumps of heterochromatin adjacent to smooth nuclear envelopes. The perikaryal cytoplasm of these cells consisted of a relatively thin rim containing few organelles. Spinous dendrites of small diameter were occasionally found in continuity with these cells. Axon terminals rarely formed synapses with the somata of granule cells, but were more frequently found to synapse on their dendrites and dendritic spines. These features for granule cells are similar to those for medium-sized spiny neurons in the neostriatum. The somata of the large cells were found either within the core or along the dorsal margin of the ICC. The large cells had infolded nuclei and an abundant perikaryal cytoplasm that contained many organelles. Large diameter dendrites that tapered down to smaller diameters emanated in many directions from these somata. Axon terminals covered nearly the entire surface of these somata and dendrites where they commonly formed symmetric synaptic junctions. These characteristics of large cells indicate a resemblance to the large cells in the globus pallidus and ventral pallidum. Therefore, the ICC have ultrastructural features found in both the neostriatum and globus pallidus.
For many models of the cerebral cortex, particularly developmental ones, knowledge of cortical st... more For many models of the cerebral cortex, particularly developmental ones, knowledge of cortical structure is essential to a proper understanding of its functional capacities. We have studied the microscopic neuroanatomic changes of the postnatal human cerebral cortex during its development from birth to 72 mo. The microscopic structural changes we have identified to date are complex, yet well organized, and mathematically describable. The discoveries to date arising from analyses of the Conel data include: 1. That the total number of cortical neurons increases by 1/3 from term birth to 3 mo, then decreases back to the birth value by 15 mo, then increases by approximately 70% above the birth value from 15 to 72 mo. 2. Based on 35 cortical areas, the mean number of neurons under 1 mm2 of cortical surface extending the depth of the cortex decreases by 50% from term birth to 15 mo, then from 15 to 72 mo, increases by 70% above the value at 15 mo. Both of the previous findings provided the first evidence for postnatal mammalian (human) neocortical neurogenesis. These findings have received subsequent support from studies demonstrating cortical neurogenesis in adult macaque monkeys. 3. That changes in total cortical neuron number from birth to 72 mo inversely correlate strongly (ρ = −0.73) with the number of new behaviors acquired during this time. The correlation appears strongest when there is a time delay, suggesting that changes in cortical neuron number precede the appearance of newly acquired behaviors. 4. That each of 35 cortical areas analyzed show characteristic increases and decreases in neuron number in a wave-like fashion from birth to 72 mo, suggesting local regulatory control of both neuronal cell death and neurogenesis. The changes in neuron number appear to follow gradients that correspond to functional cortical systems, including frontal (motor, dorsolateral prefrontal, and orbitofrontal, separately), visual (ventral and dorsal streams, separately), and auditory systems. 5. That within any given cortical area from birth to 72 mo, there are functionally related shifts in the relative numbers of neurons in the six cortical layers. Since each of the six cortical layers has a specific function with specific communication to other layers, the neocortex can create 720 variations (6!) in its function just by changing the relative power of the six cortical layers in all possible permutations. The data clearly show that only a few of these permutations are actually used. It appears that the function of secondary association neocortical areas or higher are most developed when layers III and VI have the most neurons, and that the function of primary sensory, 1st order association, or transitional (i.e., cingulate) neocortical areas are most developed when layers III and IV have the most neurons. Layer III is primarily responsible for long distance cortico-cortical communication; layer IV is primarily responsible for receiving thalamic sensory information from the environment plus feedforward cortico-cortical communication; and layer VI is primarily responsible for sending cortical information back to the thalamus and receiving feedback cortico-cortical information. In this chapter, we present the data and studies that formed the basis for the above discoveries in postnatal human cerebral cortex from birth to 72 mo. These data have particular relevance to those interested in building computational models of cortical development and provide a basis for concomitant cortical electrophysiological and behavioral developmental changes. Computational models incorporating such knowledge may provide a mechanistic understanding of how the brain develops and how it functions.
Neurocomputing, 2000
ABSTRACT Cortical connectivity for human cerebral cortex was estimated for 31 cortical areas usin... more ABSTRACT Cortical connectivity for human cerebral cortex was estimated for 31 cortical areas using microscopic anatomical data of the number of neurons, myelinated axon density, and dendrite fiber density. Estimated connections agree with known connections derived from imaging and tracing studies. Also some unusual connections, which have been recently confirmed by other studies, were estimated.
Neurocomputing, 2000
... Additional context-sensitive features to accommodate segment retraction, differential growth ... more ... Additional context-sensitive features to accommodate segment retraction, differential growth rates in adjacent dendritic arbors, and the synchronized growth of neuronal forests are being examined. ... A neuron visualizer allows a 3D interactive display of neurons in the ...
Psychiatry Research: Neuroimaging, 2015
The Journal of Neuroscience, 1986
Neurocomputing, 2000
We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebr... more We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebral cortical areas from 0 to 72 months. These data have yielded important findings, such as overturning the dogma of no postnatal neurogenesis in humans. To facilitate their use in computational models, the data are being interfaced with GENESIS.
Neurocomputing, 2000
We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebr... more We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebral cortical areas from 0 to 72 months. These data have yielded important findings, such as overturning the dogma of no postnatal neurogenesis in humans. To facilitate their use in computational models, the data are being interfaced with GENESIS.
Pediatric and Developmental Pathology, 1999
From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of the developing h... more From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of the developing human cerebral cortex and published the findings in eight volumes. We have constructed a database using his neuroanatomical measurements (neuronal packing density, myelinated large fiber density, large proximal dendrite density, somal breadth and height, and total cortical and cortical layer thickness) at the eight age periods (0 [term birth], 1, 3, 6, 15, 24, 48, and 72 postnatal months) he studied. In this report, we examine changes in neuron numbers over the eight age-points for 35 von Economo areas for which Conel gave appropriate data. From birth to 3 months postnatal age, total cortical neuron number increases 23–30%, then falls to within 3.5% of the birth value at 24 months, supporting our previous work showing that the observed decrease in the number of neurons per column of cortex under a 1-mm2 cortical surface from birth to 15 months is almost entirely due to cortical surface ex...
…, 1998
A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but... more A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but this concept has been based primarily on indirect evidence from psychopharmacology and analogies with animal research. Diffusion tensor imaging, a new MRI technique that permits direct assessment of the large axon masses stretching from the prefrontal cortex to the striatum, was used to study white matter axon bundles. Diffusion tensor images, high-resolution structural MRI and positron emission tomography scans with 18-fluorodexoyglucose were obtained on five patients with schizophrenia and six age- and sex-matched normal controls. Significantly lower diffusion anisotropy in the white matter of the prefrontal cortex in schizophrenic patients than in normal controls was observed in statistical probability maps. Co-registered PET scans revealed significantly lower correlation coefficients between metabolic rates in the prefrontal cortex and striatum in patients than in controls. These twin findings provide convergent evidence for diminished fronto-striatal connectivity in schizophrenia.
Brain Sciences
System-specific brain responses—time-locked to rapid eye movements (REMs) in sleep—are characteri... more System-specific brain responses—time-locked to rapid eye movements (REMs) in sleep—are characteristically widespread, with robust and clear activation in the primary visual cortex and other structures involved in multisensory integration. This pattern suggests that REMs underwrite hierarchical processing of visual information in a time-locked manner, where REMs index the generation and scanning of virtual-world models, through multisensory integration in dreaming—as in awake states. Default mode network (DMN) activity increases during rest and reduces during various tasks including visual perception. The implicit anticorrelation between the DMN and task-positive network (TPN)—that persists in REM sleep—prompted us to focus on DMN responses to temporally-precise REM events. We timed REMs during sleep from the video recordings and quantified the neural correlates of REMs—using functional MRI (fMRI)—in 24 independent studies of 11 healthy participants. A reanalysis of these data reveal...
The Journal of comparative neurology, Jan 15, 2016
Epigenetic programming and reprogramming are at the heart of cellular differentiation and represe... more Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms in both germline and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate on how geno...
Methods of assigning quantitative phenotype measurement summary statistics to differential brain ... more Methods of assigning quantitative phenotype measurement summary statistics to differential brain image information associated with neuropsychiatric disorders are provided. Summary statistics are correlated to genotype information to identify loci that correlate with differential brain image phenotypes. Methods of identifying modulators of genes at the loci are provided, as well as modulators identified by the methods. Systems for correlating polymorphisms and differential brain image phenotypes, for identifying modulators and for ...
The American Journal of Psychiatry, 2002
Positron emission tomography (PET) was used to compare cerebral metabolic patterns in schizophren... more Positron emission tomography (PET) was used to compare cerebral metabolic patterns in schizophrenic subjects with predominantly negative symptoms (alogia, affective flattening, avolition, and attentional impairment) and in those with predominantly positive symptoms. Fourteen right-handed male subjects with DSM-IV schizophrenia were assigned to groups with predominantly negative or predominantly positive symptoms on the basis of their post-drug-washout scores on the Positive and Negative Syndrome Scale. The patients were compared to seven age- and gender-matched normal volunteers. PET scans with [(18)F]fluorodeoxyglucose were obtained during a degraded Continuous Performance Task to measure absolute glucose metabolic rates. Statistical parametric mapping was used to estimate the regional metabolic differences between groups. The subjects with predominantly negative symptoms had significant differences in glucose metabolic rates, compared to both the subjects with predominantly positive symptoms and the normal subjects. Negative symptom subjects had a lower glucose metabolic rate in the right hemisphere, especially in the temporal and ventral prefrontal cortices, compared to the other groups, and higher metabolic rates in the cerebellar cortex and in the lower deep cerebellar nuclei. Negative symptom subscale scores were negatively correlated with glucose metabolic rates for most of the brain areas that differentiated subjects with predominantly negative symptoms from those with predominantly positive symptoms. Schizophrenic subjects with predominantly negative symptoms have greater metabolic abnormalities than subjects with predominantly positive symptoms, particularly in frontal, temporal, and cerebellar circuitry. These results are consistent with abnormalities in corticocortical, corticobasal ganglia, mesocortical dopamine, and cerebellar-thalamic-prefrontal circuits, which may underlie the negative symptoms of schizophrenia.
Neuroscience Letters, 1977
ABSTRACT
Experimental Neurology, 1975
The Journal of Comparative Neurology, 1982
An analysis of the cells and their processes within the island of Calleja complexes (ICC) was mad... more An analysis of the cells and their processes within the island of Calleja complexes (ICC) was made in light and electron microscopic preparations to determine synaptic relationships within this part of the basal forebrain. The light microscopic preparations showed that the ICC contained two cell types, granule cells and large cells. In electron microscopic preparations, the somata of granule cells were grouped together and were directly apposed to other somata of granule cells. Specialized junctions (4-6 nm wide) that occurred at sites of somal apposition suggested ephaptic coupling of granule cells. The granule cell somata had nuclei that contained clumps of heterochromatin adjacent to smooth nuclear envelopes. The perikaryal cytoplasm of these cells consisted of a relatively thin rim containing few organelles. Spinous dendrites of small diameter were occasionally found in continuity with these cells. Axon terminals rarely formed synapses with the somata of granule cells, but were more frequently found to synapse on their dendrites and dendritic spines. These features for granule cells are similar to those for medium-sized spiny neurons in the neostriatum. The somata of the large cells were found either within the core or along the dorsal margin of the ICC. The large cells had infolded nuclei and an abundant perikaryal cytoplasm that contained many organelles. Large diameter dendrites that tapered down to smaller diameters emanated in many directions from these somata. Axon terminals covered nearly the entire surface of these somata and dendrites where they commonly formed symmetric synaptic junctions. These characteristics of large cells indicate a resemblance to the large cells in the globus pallidus and ventral pallidum. Therefore, the ICC have ultrastructural features found in both the neostriatum and globus pallidus.
For many models of the cerebral cortex, particularly developmental ones, knowledge of cortical st... more For many models of the cerebral cortex, particularly developmental ones, knowledge of cortical structure is essential to a proper understanding of its functional capacities. We have studied the microscopic neuroanatomic changes of the postnatal human cerebral cortex during its development from birth to 72 mo. The microscopic structural changes we have identified to date are complex, yet well organized, and mathematically describable. The discoveries to date arising from analyses of the Conel data include: 1. That the total number of cortical neurons increases by 1/3 from term birth to 3 mo, then decreases back to the birth value by 15 mo, then increases by approximately 70% above the birth value from 15 to 72 mo. 2. Based on 35 cortical areas, the mean number of neurons under 1 mm2 of cortical surface extending the depth of the cortex decreases by 50% from term birth to 15 mo, then from 15 to 72 mo, increases by 70% above the value at 15 mo. Both of the previous findings provided the first evidence for postnatal mammalian (human) neocortical neurogenesis. These findings have received subsequent support from studies demonstrating cortical neurogenesis in adult macaque monkeys. 3. That changes in total cortical neuron number from birth to 72 mo inversely correlate strongly (ρ = −0.73) with the number of new behaviors acquired during this time. The correlation appears strongest when there is a time delay, suggesting that changes in cortical neuron number precede the appearance of newly acquired behaviors. 4. That each of 35 cortical areas analyzed show characteristic increases and decreases in neuron number in a wave-like fashion from birth to 72 mo, suggesting local regulatory control of both neuronal cell death and neurogenesis. The changes in neuron number appear to follow gradients that correspond to functional cortical systems, including frontal (motor, dorsolateral prefrontal, and orbitofrontal, separately), visual (ventral and dorsal streams, separately), and auditory systems. 5. That within any given cortical area from birth to 72 mo, there are functionally related shifts in the relative numbers of neurons in the six cortical layers. Since each of the six cortical layers has a specific function with specific communication to other layers, the neocortex can create 720 variations (6!) in its function just by changing the relative power of the six cortical layers in all possible permutations. The data clearly show that only a few of these permutations are actually used. It appears that the function of secondary association neocortical areas or higher are most developed when layers III and VI have the most neurons, and that the function of primary sensory, 1st order association, or transitional (i.e., cingulate) neocortical areas are most developed when layers III and IV have the most neurons. Layer III is primarily responsible for long distance cortico-cortical communication; layer IV is primarily responsible for receiving thalamic sensory information from the environment plus feedforward cortico-cortical communication; and layer VI is primarily responsible for sending cortical information back to the thalamus and receiving feedback cortico-cortical information. In this chapter, we present the data and studies that formed the basis for the above discoveries in postnatal human cerebral cortex from birth to 72 mo. These data have particular relevance to those interested in building computational models of cortical development and provide a basis for concomitant cortical electrophysiological and behavioral developmental changes. Computational models incorporating such knowledge may provide a mechanistic understanding of how the brain develops and how it functions.
Neurocomputing, 2000
ABSTRACT Cortical connectivity for human cerebral cortex was estimated for 31 cortical areas usin... more ABSTRACT Cortical connectivity for human cerebral cortex was estimated for 31 cortical areas using microscopic anatomical data of the number of neurons, myelinated axon density, and dendrite fiber density. Estimated connections agree with known connections derived from imaging and tracing studies. Also some unusual connections, which have been recently confirmed by other studies, were estimated.
Neurocomputing, 2000
... Additional context-sensitive features to accommodate segment retraction, differential growth ... more ... Additional context-sensitive features to accommodate segment retraction, differential growth rates in adjacent dendritic arbors, and the synchronized growth of neuronal forests are being examined. ... A neuron visualizer allows a 3D interactive display of neurons in the ...
Psychiatry Research: Neuroimaging, 2015
The Journal of Neuroscience, 1986
Neurocomputing, 2000
We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebr... more We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebral cortical areas from 0 to 72 months. These data have yielded important findings, such as overturning the dogma of no postnatal neurogenesis in humans. To facilitate their use in computational models, the data are being interfaced with GENESIS.
Neurocomputing, 2000
We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebr... more We introduce a database of the microscopic, laminar development of ∼73% of postnatal human cerebral cortical areas from 0 to 72 months. These data have yielded important findings, such as overturning the dogma of no postnatal neurogenesis in humans. To facilitate their use in computational models, the data are being interfaced with GENESIS.
Pediatric and Developmental Pathology, 1999
From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of the developing h... more From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of the developing human cerebral cortex and published the findings in eight volumes. We have constructed a database using his neuroanatomical measurements (neuronal packing density, myelinated large fiber density, large proximal dendrite density, somal breadth and height, and total cortical and cortical layer thickness) at the eight age periods (0 [term birth], 1, 3, 6, 15, 24, 48, and 72 postnatal months) he studied. In this report, we examine changes in neuron numbers over the eight age-points for 35 von Economo areas for which Conel gave appropriate data. From birth to 3 months postnatal age, total cortical neuron number increases 23–30%, then falls to within 3.5% of the birth value at 24 months, supporting our previous work showing that the observed decrease in the number of neurons per column of cortex under a 1-mm2 cortical surface from birth to 15 months is almost entirely due to cortical surface ex...
…, 1998
A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but... more A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but this concept has been based primarily on indirect evidence from psychopharmacology and analogies with animal research. Diffusion tensor imaging, a new MRI technique that permits direct assessment of the large axon masses stretching from the prefrontal cortex to the striatum, was used to study white matter axon bundles. Diffusion tensor images, high-resolution structural MRI and positron emission tomography scans with 18-fluorodexoyglucose were obtained on five patients with schizophrenia and six age- and sex-matched normal controls. Significantly lower diffusion anisotropy in the white matter of the prefrontal cortex in schizophrenic patients than in normal controls was observed in statistical probability maps. Co-registered PET scans revealed significantly lower correlation coefficients between metabolic rates in the prefrontal cortex and striatum in patients than in controls. These twin findings provide convergent evidence for diminished fronto-striatal connectivity in schizophrenia.
Brain Sciences
System-specific brain responses—time-locked to rapid eye movements (REMs) in sleep—are characteri... more System-specific brain responses—time-locked to rapid eye movements (REMs) in sleep—are characteristically widespread, with robust and clear activation in the primary visual cortex and other structures involved in multisensory integration. This pattern suggests that REMs underwrite hierarchical processing of visual information in a time-locked manner, where REMs index the generation and scanning of virtual-world models, through multisensory integration in dreaming—as in awake states. Default mode network (DMN) activity increases during rest and reduces during various tasks including visual perception. The implicit anticorrelation between the DMN and task-positive network (TPN)—that persists in REM sleep—prompted us to focus on DMN responses to temporally-precise REM events. We timed REMs during sleep from the video recordings and quantified the neural correlates of REMs—using functional MRI (fMRI)—in 24 independent studies of 11 healthy participants. A reanalysis of these data reveal...
The Journal of comparative neurology, Jan 15, 2016
Epigenetic programming and reprogramming are at the heart of cellular differentiation and represe... more Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms in both germline and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate on how geno...
Methods of assigning quantitative phenotype measurement summary statistics to differential brain ... more Methods of assigning quantitative phenotype measurement summary statistics to differential brain image information associated with neuropsychiatric disorders are provided. Summary statistics are correlated to genotype information to identify loci that correlate with differential brain image phenotypes. Methods of identifying modulators of genes at the loci are provided, as well as modulators identified by the methods. Systems for correlating polymorphisms and differential brain image phenotypes, for identifying modulators and for ...
The American Journal of Psychiatry, 2002
Positron emission tomography (PET) was used to compare cerebral metabolic patterns in schizophren... more Positron emission tomography (PET) was used to compare cerebral metabolic patterns in schizophrenic subjects with predominantly negative symptoms (alogia, affective flattening, avolition, and attentional impairment) and in those with predominantly positive symptoms. Fourteen right-handed male subjects with DSM-IV schizophrenia were assigned to groups with predominantly negative or predominantly positive symptoms on the basis of their post-drug-washout scores on the Positive and Negative Syndrome Scale. The patients were compared to seven age- and gender-matched normal volunteers. PET scans with [(18)F]fluorodeoxyglucose were obtained during a degraded Continuous Performance Task to measure absolute glucose metabolic rates. Statistical parametric mapping was used to estimate the regional metabolic differences between groups. The subjects with predominantly negative symptoms had significant differences in glucose metabolic rates, compared to both the subjects with predominantly positive symptoms and the normal subjects. Negative symptom subjects had a lower glucose metabolic rate in the right hemisphere, especially in the temporal and ventral prefrontal cortices, compared to the other groups, and higher metabolic rates in the cerebellar cortex and in the lower deep cerebellar nuclei. Negative symptom subscale scores were negatively correlated with glucose metabolic rates for most of the brain areas that differentiated subjects with predominantly negative symptoms from those with predominantly positive symptoms. Schizophrenic subjects with predominantly negative symptoms have greater metabolic abnormalities than subjects with predominantly positive symptoms, particularly in frontal, temporal, and cerebellar circuitry. These results are consistent with abnormalities in corticocortical, corticobasal ganglia, mesocortical dopamine, and cerebellar-thalamic-prefrontal circuits, which may underlie the negative symptoms of schizophrenia.