Kindling is a powerful model of epilepsy.11,29 It is the best model we have of mesial temporal lo... more Kindling is a powerful model of epilepsy.11,29 It is the best model we have of mesial temporal lobe epilepsy (MTLE), which is the most devastating type of human epilepsy, accounting for the vast majority of people with medically intractable epilepsy. More than 0.5 million people in the USA are afflicted with MTLE and continue to have seizures despite the best available medical treatment. It has been the hope of investigators that understanding the mechanisms underlying kindling will provide insight into treatment for MTLE. In nearly thirty years of research, however, kindling has yet to give up its most fundamental secrets.
Schizophrenia has a strong genetic component that is relevant to the understanding of the pathoph... more Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.
Carbamazepine (CBZ) blocks the development of local anesthetic seizures kindled by cocaine and li... more Carbamazepine (CBZ) blocks the development of local anesthetic seizures kindled by cocaine and lidocaine. Cocaine and lidocaine release corticotropin-releasing hormone (CRH) in hypothalamic cell cultures, and this effect is also blocked by CBZ. Because CRH administered intracerebroventricularly (i.c.v.) can produce seizures, its potential role in the development of cocaine seizures and in the anticonvulsant effects of CBZ was studied. CRH (at doses of 5, 10, and 100 micrograms) potentiated cocaine-kindled seizure development and lethality in a dose-related fashion. CRH also reversed the effects of CBZ on cocaine kindling and lethality, but only at the highest doses, which also affected cocaine kindling. Thus, a selective role for CRH in the anticonvulsant effects of CBZ was not demonstrated. The findings suggest a potentially important role for CRH in exacerbating cocaine-seizure evolution and its associated lethality and confirm the inhibition of cocaine kindling and lethality by CBZ.
MRI studies suggest that chronic psychostimulant abuse is associated with changes in white matter... more MRI studies suggest that chronic psychostimulant abuse is associated with changes in white matter integrity and striatal volume. We tested 12 HIV-negative, and 5 HIV-positive, patients with methamphetamine dependence and 17 age matched healthy controls.  MRI scans included eight-direction Diffusion Tensor Imaging (DTI), T2-weighted spin echo and FLAIR (Fluid Attenuated Inversion Recovery) and T1-weighted 3D volumetric scan.  T1 weighted images were used for volume determinations and in intersubject registrations of the DTI data for voxelwise analyses. Fractional anisotropy (FA), a measure of white matter integrity, was analyzed using voxelwise t tests with false discovery rate correction. Computerized cognitive tests using the Cogtest® battery were used to evaluate attention, response inhibition, facial emotion recognition, verbal working memory, spatial working memory, set shift and tapping speed. Combined volume of caudate and nucleus accumbens was similar across groups and no gross white matter damage was noted based on the presence of white matter hyperintensities (FLAIR). However, methamphetamine patients showed significantly lower FA in the white matter of the corpus callosum and superior longitudinal fasciculi bilaterally as well as in the left superior frontal and fusiform gyri and the right posterior cingulate gyrus. Methamphetamine patients also showed significantly higher FA in the left ventral tegmental area and mediodorsal thalamus and in the right subcallosal fasciculus.  Methamphetamine patients showed cognitive deficits in attention, set shift, spatial and verbal memory, and finger tapping speed. Lower voxelwise FA in methamphetamine users in the corpus callosum and fasciculi paralleled findings in active cocaine abusers. Correlations of cognitive deficits with changes in FA will be presented.
P2-211 THE ASSOCIATION OF OUTPUT ORDER AND VARIABILITY IN FREE RECALLWITH COGNITIVE ABILITYAND HI... more P2-211 THE ASSOCIATION OF OUTPUT ORDER AND VARIABILITY IN FREE RECALLWITH COGNITIVE ABILITYAND HIPPOCAMPAL VOLUME IN ELDERLY INDIVIDUALS Davide Bruno, Michel J. Grothe, Jay Nierenberg, John Sidtis, Stefan J. Teipel, Nunzio Pomara, Liverpool Hope University, Liverpool, United Kingdom; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Nathan Kline Institute, Orangeburg, NY, USA; German Center for Neurodegenerative Disease (DZNE), Rostock, Germany; New York University-Langone Medical Center, New York, NY, USA. Contact e-mail: brunod@hope.ac.uk
P1⁄40.00153). According to the cognitive impairment level, a moderate positive correlation was ob... more P1⁄40.00153). According to the cognitive impairment level, a moderate positive correlation was observed in the MCI level (FAST stage: 2-3) (r1⁄40.310, t1⁄42.62, P1⁄40.0109), but no correlation was noted in the dementia level ( FAST stage 4) (r1⁄4-0.0771, t1⁄4-0.604, P1⁄40.548). Conclusions: Since the results of this study indicated that the Z score tends to increase with the FAST stage, the degree of atrophy of the medial temporal region is considered to increase with the severity of Alzheimer’s disease. While the Z score increased with the FAST stage in the MCI group, no correlation was observed between the FAST stage and Z score in the Alzheimer’s disease group. Therefore, the VSRAD was suggested to be useful as an index for the follow-up of patients with MCI.
Sprague-Dawley rats (175-225g) were chronically exposed to thermogenic doses (SAR = 27.4 W/kg) of... more Sprague-Dawley rats (175-225g) were chronically exposed to thermogenic doses (SAR = 27.4 W/kg) of microwave (..mu..W) irradiation (2.45 GHz, 80 mW/cm², cw, 30 min/day x 4 days), and subsequently shown to have an altered bile flow rate (BFR) at normothermic temperatures. Sham exposed animals had a BFR of 2.05 ..mu..g bile/min/g liver while ..mu..W exposed animals had a BFR of 1.75 ..mu..g bile/min/g liver at 37âC. An examination of BFR vs body temperature in both groups of animals demonstrated linear relationships (r² > 0.95), with sham exposed animals demonstrating a ..delta..BFR of 0.16 ..mu..g bile/min/g liver/°C versus 0.21 ..mu..g bile/min/g liver/°C in ..mu..W exposed animals. A projection of their respective regression lines collected over the temperature range of 36 to 41°C resulted in their intersection at 44.0°C. Previous work has suggested that the alteration in BFR was secondary to decreases in Ca/sup 2 +/-Mg/sup 2 +/ and Mg/sup 2 +/ ATPase function rather than t...
Kindling is a powerful model of epilepsy.11,29 It is the best model we have of mesial temporal lo... more Kindling is a powerful model of epilepsy.11,29 It is the best model we have of mesial temporal lobe epilepsy (MTLE), which is the most devastating type of human epilepsy, accounting for the vast majority of people with medically intractable epilepsy. More than 0.5 million people in the USA are afflicted with MTLE and continue to have seizures despite the best available medical treatment. It has been the hope of investigators that understanding the mechanisms underlying kindling will provide insight into treatment for MTLE. In nearly thirty years of research, however, kindling has yet to give up its most fundamental secrets.
Schizophrenia has a strong genetic component that is relevant to the understanding of the pathoph... more Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.
Carbamazepine (CBZ) blocks the development of local anesthetic seizures kindled by cocaine and li... more Carbamazepine (CBZ) blocks the development of local anesthetic seizures kindled by cocaine and lidocaine. Cocaine and lidocaine release corticotropin-releasing hormone (CRH) in hypothalamic cell cultures, and this effect is also blocked by CBZ. Because CRH administered intracerebroventricularly (i.c.v.) can produce seizures, its potential role in the development of cocaine seizures and in the anticonvulsant effects of CBZ was studied. CRH (at doses of 5, 10, and 100 micrograms) potentiated cocaine-kindled seizure development and lethality in a dose-related fashion. CRH also reversed the effects of CBZ on cocaine kindling and lethality, but only at the highest doses, which also affected cocaine kindling. Thus, a selective role for CRH in the anticonvulsant effects of CBZ was not demonstrated. The findings suggest a potentially important role for CRH in exacerbating cocaine-seizure evolution and its associated lethality and confirm the inhibition of cocaine kindling and lethality by CBZ.
MRI studies suggest that chronic psychostimulant abuse is associated with changes in white matter... more MRI studies suggest that chronic psychostimulant abuse is associated with changes in white matter integrity and striatal volume. We tested 12 HIV-negative, and 5 HIV-positive, patients with methamphetamine dependence and 17 age matched healthy controls.  MRI scans included eight-direction Diffusion Tensor Imaging (DTI), T2-weighted spin echo and FLAIR (Fluid Attenuated Inversion Recovery) and T1-weighted 3D volumetric scan.  T1 weighted images were used for volume determinations and in intersubject registrations of the DTI data for voxelwise analyses. Fractional anisotropy (FA), a measure of white matter integrity, was analyzed using voxelwise t tests with false discovery rate correction. Computerized cognitive tests using the Cogtest® battery were used to evaluate attention, response inhibition, facial emotion recognition, verbal working memory, spatial working memory, set shift and tapping speed. Combined volume of caudate and nucleus accumbens was similar across groups and no gross white matter damage was noted based on the presence of white matter hyperintensities (FLAIR). However, methamphetamine patients showed significantly lower FA in the white matter of the corpus callosum and superior longitudinal fasciculi bilaterally as well as in the left superior frontal and fusiform gyri and the right posterior cingulate gyrus. Methamphetamine patients also showed significantly higher FA in the left ventral tegmental area and mediodorsal thalamus and in the right subcallosal fasciculus.  Methamphetamine patients showed cognitive deficits in attention, set shift, spatial and verbal memory, and finger tapping speed. Lower voxelwise FA in methamphetamine users in the corpus callosum and fasciculi paralleled findings in active cocaine abusers. Correlations of cognitive deficits with changes in FA will be presented.
P2-211 THE ASSOCIATION OF OUTPUT ORDER AND VARIABILITY IN FREE RECALLWITH COGNITIVE ABILITYAND HI... more P2-211 THE ASSOCIATION OF OUTPUT ORDER AND VARIABILITY IN FREE RECALLWITH COGNITIVE ABILITYAND HIPPOCAMPAL VOLUME IN ELDERLY INDIVIDUALS Davide Bruno, Michel J. Grothe, Jay Nierenberg, John Sidtis, Stefan J. Teipel, Nunzio Pomara, Liverpool Hope University, Liverpool, United Kingdom; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany; Nathan Kline Institute, Orangeburg, NY, USA; German Center for Neurodegenerative Disease (DZNE), Rostock, Germany; New York University-Langone Medical Center, New York, NY, USA. Contact e-mail: brunod@hope.ac.uk
P1⁄40.00153). According to the cognitive impairment level, a moderate positive correlation was ob... more P1⁄40.00153). According to the cognitive impairment level, a moderate positive correlation was observed in the MCI level (FAST stage: 2-3) (r1⁄40.310, t1⁄42.62, P1⁄40.0109), but no correlation was noted in the dementia level ( FAST stage 4) (r1⁄4-0.0771, t1⁄4-0.604, P1⁄40.548). Conclusions: Since the results of this study indicated that the Z score tends to increase with the FAST stage, the degree of atrophy of the medial temporal region is considered to increase with the severity of Alzheimer’s disease. While the Z score increased with the FAST stage in the MCI group, no correlation was observed between the FAST stage and Z score in the Alzheimer’s disease group. Therefore, the VSRAD was suggested to be useful as an index for the follow-up of patients with MCI.
Sprague-Dawley rats (175-225g) were chronically exposed to thermogenic doses (SAR = 27.4 W/kg) of... more Sprague-Dawley rats (175-225g) were chronically exposed to thermogenic doses (SAR = 27.4 W/kg) of microwave (..mu..W) irradiation (2.45 GHz, 80 mW/cm², cw, 30 min/day x 4 days), and subsequently shown to have an altered bile flow rate (BFR) at normothermic temperatures. Sham exposed animals had a BFR of 2.05 ..mu..g bile/min/g liver while ..mu..W exposed animals had a BFR of 1.75 ..mu..g bile/min/g liver at 37âC. An examination of BFR vs body temperature in both groups of animals demonstrated linear relationships (r² > 0.95), with sham exposed animals demonstrating a ..delta..BFR of 0.16 ..mu..g bile/min/g liver/°C versus 0.21 ..mu..g bile/min/g liver/°C in ..mu..W exposed animals. A projection of their respective regression lines collected over the temperature range of 36 to 41°C resulted in their intersection at 44.0°C. Previous work has suggested that the alteration in BFR was secondary to decreases in Ca/sup 2 +/-Mg/sup 2 +/ and Mg/sup 2 +/ ATPase function rather than t...
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