Jay Nierenberg - Academia.edu (original) (raw)
Papers by Jay Nierenberg
JAMA network open, Dec 28, 2018
Although the negative effects of substance use disorders on our society are enormous and health c... more Although the negative effects of substance use disorders on our society are enormous and health care systems have struggled in the effort to integrate prevention, treatment, and recovery services, progress has been made. 1 A core challenge to managing substance use disorders is reducing the high
Alzheimers & Dementia, Jul 1, 2017
Advances in behavioral biology, 1998
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.
Experimental Neurology, May 1, 1998
The perirhinal cortex (PRh) has been suggested as a substrate for the expression of generalized c... more The perirhinal cortex (PRh) has been suggested as a substrate for the expression of generalized clonic seizures in the late stages of kindling development (stages 4-5). Using the induction of Fos as a marker of neuronal activation, the PRh region was investigated after kindling or nonkindling electrical stimulation. Nonkindling electrical stimulation of the PRh elicited stimulus-locked behaviors, without afterdischarge. These behaviors were characterized by rearing and bilateral forelimb clonus which were terminated upon electrical stimulus offset in half of the rats displaying this behavior (with the other half expressing self-sustained seizures). In these animals, Fos immunoreactivity was found throughout neocortical and subcortical structures in the hemisphere ipsilateral to the stimulating electrode. By contrast, Fos-immunoreactivity in the contralateral hemisphere was localized primarily in the PRh and frontal motor cortex. Likewise, similar patterns of Fos immunoreactivity were observed in both hemispheres of rats following kindling to one generalized clonic seizure from several limbic and paleocortical structures. These results suggest that the bilateral involvement of the PRh is critical in producing the bilateral behaviors associated with generalized clonic seizure expression. In support of this interpretation, infusion of 3 M KCl directly into the contralateral PRh of rats kindled to a single stage 4-5 (generalized clonic) seizure from the ipsilateral amygdala reduced seizure manifestations from a generalized clonic seizure (stage 4-5) to a unilateral clonic seizure (stage 3) without affecting measures of focal excitability. Taken together, these data indicate a role for the bilateral involvement of the PRh in generalized clonic seizure expression whether evoked from the naive or kindled state. These results further indicate that bilateral behaviors require the bilateral involvement of the structures necessary for the expression of these behaviors. 1998 Academic Press
Translational Psychiatry, Mar 1, 2016
Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalit... more Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age-and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N = 28; age-and gender-matched comparison group, N = 19) at baseline and 3-year follow-up (MDD group, N = 19; comparison group, N = 17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by highperformance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β 42, amyloid-β 40 , and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.
Drug and Alcohol Dependence, Feb 1, 2012
Introduction-Extensive evidence demonstrates that current cocaine abusers show hypoactivity in an... more Introduction-Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequalae of long-term abstinence in cocaine addicts. Methods-Here, we use a GO-NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short-and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks, respectively). Results-We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation. Conclusions-Differences between the short-and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence.
Brain Imaging and Behavior, Feb 17, 2010
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.
Brain Research, Sep 1, 1989
The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality w... more The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine-and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine-or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.
Epilepsia, Mar 1, 1992
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.
American Journal of Psychiatry, Aug 1, 2005
Objective-Research suggests that the normal left-greater-than-right angular gyrus volume asymmetr... more Objective-Research suggests that the normal left-greater-than-right angular gyrus volume asymmetry is reversed in chronic schizophrenia. The authors examined whether angular gyrus volume and asymmetry were abnormal in patients with first-episode schizophrenia. Method-Magnetic resonance imaging scans were obtained from 14 inpatients at their first hospitalization for psychosis and 14 normal comparison subjects. Manual editing was undertaken to delineate postcentral, supramarginal, and angular gyri gray matter volumes. Results-Group comparisons revealed that the left angular gyrus gray matter volume in patients was 14.8% less than that of the normal subjects. None of the other regions measured showed significant group volume or asymmetry differences. Conclusions-Patients with new-onset schizophrenia showed smaller left angular gyrus volumes than normal subjects, consistent with other studies showing parietal lobe volume abnormalities in schizophrenia. Angular gyrus pathology in first-episode patients suggests that the angular gyrus may be a neuroanatomical substrate for the expression of schizophrenia. Angular and supramarginal gyri form the inferior parietal lobule, a heteromodal association neocortical region that is part of the neuroanatomical circuitry for language comprehension (1). Consistent with their role in language, these structures are left-lateralized (2), and functional neuroimaging studies (3) show lateralized activation of these areas in normal subjects performing language tasks. Such functional lateralization appears to be diminished in schizophrenia (4). Volume reductions in the inferior parietal lobule (5) and supramarginal gyrus (6) have been reported in schizophrenia. Moreover, reversal of the normal left-greater-than-right angular gyrus asymmetry has been reported in chronic schizophrenia (7,8), consistent with the notion that abnormalities of normal hemispheric asymmetry are the primary neurogenetic deficit in Address correspondence and reprint requests to Drs.
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.
Alzheimers & Dementia, Jul 1, 2019
Alzheimers & Dementia, Jul 1, 2017
Alzheimers & Dementia, Jul 1, 2015
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
Alzheimers & Dementia, Jul 1, 2015
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.
American Journal of Medical Genetics - Neuropsychiatric Genetics, Jun 5, 2006
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...
Alzheimers & Dementia, Jul 1, 2012
Neuroreport, Aug 3, 2016
Risk of Alzheimer's disease (AD) can be predicted by volumetric analyses of MRI data in the media... more Risk of Alzheimer's disease (AD) can be predicted by volumetric analyses of MRI data in the medial temporal lobe. The present study compared a volumetric measurement of the hippocampus to a novel measure of hippocampal integrity derived from the ratio of parenchyma volume over total volume. Participants were cognitively intact and aged 60 or older at baseline, and were tested twice, roughly three years apart. Participants had been recruited for a study on late-life major depression (LLMD) and were evenly split between depressed and controls. Linear regression models were applied to the data with a cognitive composite score as outcome, and hippocampal integrity (HI) and volume (HV), together or separately, as predictors. Subsequent cognitive performance was predicted well by models that include an interaction between HI and LLMD-status, such that lower HI scores predicted more cognitive decline in depressed subjects. More research is needed, but tentative results from this study appear to suggest that the newly introduced measure HI is an effective tool for the purpose of predicting future changes in general cognitive ability, and especially so in individuals with LLMD.
JAMA network open, Dec 28, 2018
Although the negative effects of substance use disorders on our society are enormous and health c... more Although the negative effects of substance use disorders on our society are enormous and health care systems have struggled in the effort to integrate prevention, treatment, and recovery services, progress has been made. 1 A core challenge to managing substance use disorders is reducing the high
Alzheimers & Dementia, Jul 1, 2017
Advances in behavioral biology, 1998
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.
Experimental Neurology, May 1, 1998
The perirhinal cortex (PRh) has been suggested as a substrate for the expression of generalized c... more The perirhinal cortex (PRh) has been suggested as a substrate for the expression of generalized clonic seizures in the late stages of kindling development (stages 4-5). Using the induction of Fos as a marker of neuronal activation, the PRh region was investigated after kindling or nonkindling electrical stimulation. Nonkindling electrical stimulation of the PRh elicited stimulus-locked behaviors, without afterdischarge. These behaviors were characterized by rearing and bilateral forelimb clonus which were terminated upon electrical stimulus offset in half of the rats displaying this behavior (with the other half expressing self-sustained seizures). In these animals, Fos immunoreactivity was found throughout neocortical and subcortical structures in the hemisphere ipsilateral to the stimulating electrode. By contrast, Fos-immunoreactivity in the contralateral hemisphere was localized primarily in the PRh and frontal motor cortex. Likewise, similar patterns of Fos immunoreactivity were observed in both hemispheres of rats following kindling to one generalized clonic seizure from several limbic and paleocortical structures. These results suggest that the bilateral involvement of the PRh is critical in producing the bilateral behaviors associated with generalized clonic seizure expression. In support of this interpretation, infusion of 3 M KCl directly into the contralateral PRh of rats kindled to a single stage 4-5 (generalized clonic) seizure from the ipsilateral amygdala reduced seizure manifestations from a generalized clonic seizure (stage 4-5) to a unilateral clonic seizure (stage 3) without affecting measures of focal excitability. Taken together, these data indicate a role for the bilateral involvement of the PRh in generalized clonic seizure expression whether evoked from the naive or kindled state. These results further indicate that bilateral behaviors require the bilateral involvement of the structures necessary for the expression of these behaviors. 1998 Academic Press
Translational Psychiatry, Mar 1, 2016
Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalit... more Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age-and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N = 28; age-and gender-matched comparison group, N = 19) at baseline and 3-year follow-up (MDD group, N = 19; comparison group, N = 17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by highperformance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β 42, amyloid-β 40 , and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.
Drug and Alcohol Dependence, Feb 1, 2012
Introduction-Extensive evidence demonstrates that current cocaine abusers show hypoactivity in an... more Introduction-Extensive evidence demonstrates that current cocaine abusers show hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond poorly relative to drug-naïve controls on tests of executive function. Relatively little is known about the cognitive sequalae of long-term abstinence in cocaine addicts. Methods-Here, we use a GO-NOGO task in which successful performance necessitated withholding a prepotent response to assay cognitive control in short-and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks, respectively). Results-We report significantly greater activity in prefrontal, cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for both successful response inhibitions and errors of commission. Moreover, this relative hyperactivity was present in both abstinent groups, which, in the presence of comparable behavioral performance, suggests a functional compensation. Conclusions-Differences between the short-and long-abstinence groups in the patterns of functional recruitment suggest different cognitive control demands at different stages in abstinence. Short-term abstinence showed increased inhibition-related dorsolateral and inferior frontal activity indicative of the need for increased inhibitory control while long-term abstinence showed increased error-related ACC activity indicative of heightened behavioral monitoring. The results suggest that the integrity of prefrontal systems that underlie cognitive control functions may be an important characteristic of successful long-term abstinence.
Brain Imaging and Behavior, Feb 17, 2010
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.
Brain Research, Sep 1, 1989
The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality w... more The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine-and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine-or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.
Epilepsia, Mar 1, 1992
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.
American Journal of Psychiatry, Aug 1, 2005
Objective-Research suggests that the normal left-greater-than-right angular gyrus volume asymmetr... more Objective-Research suggests that the normal left-greater-than-right angular gyrus volume asymmetry is reversed in chronic schizophrenia. The authors examined whether angular gyrus volume and asymmetry were abnormal in patients with first-episode schizophrenia. Method-Magnetic resonance imaging scans were obtained from 14 inpatients at their first hospitalization for psychosis and 14 normal comparison subjects. Manual editing was undertaken to delineate postcentral, supramarginal, and angular gyri gray matter volumes. Results-Group comparisons revealed that the left angular gyrus gray matter volume in patients was 14.8% less than that of the normal subjects. None of the other regions measured showed significant group volume or asymmetry differences. Conclusions-Patients with new-onset schizophrenia showed smaller left angular gyrus volumes than normal subjects, consistent with other studies showing parietal lobe volume abnormalities in schizophrenia. Angular gyrus pathology in first-episode patients suggests that the angular gyrus may be a neuroanatomical substrate for the expression of schizophrenia. Angular and supramarginal gyri form the inferior parietal lobule, a heteromodal association neocortical region that is part of the neuroanatomical circuitry for language comprehension (1). Consistent with their role in language, these structures are left-lateralized (2), and functional neuroimaging studies (3) show lateralized activation of these areas in normal subjects performing language tasks. Such functional lateralization appears to be diminished in schizophrenia (4). Volume reductions in the inferior parietal lobule (5) and supramarginal gyrus (6) have been reported in schizophrenia. Moreover, reversal of the normal left-greater-than-right angular gyrus asymmetry has been reported in chronic schizophrenia (7,8), consistent with the notion that abnormalities of normal hemispheric asymmetry are the primary neurogenetic deficit in Address correspondence and reprint requests to Drs.
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.
Alzheimers & Dementia, Jul 1, 2019
Alzheimers & Dementia, Jul 1, 2017
Alzheimers & Dementia, Jul 1, 2015
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
Alzheimers & Dementia, Jul 1, 2015
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.
American Journal of Medical Genetics - Neuropsychiatric Genetics, Jun 5, 2006
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...
Alzheimers & Dementia, Jul 1, 2012
Neuroreport, Aug 3, 2016
Risk of Alzheimer's disease (AD) can be predicted by volumetric analyses of MRI data in the media... more Risk of Alzheimer's disease (AD) can be predicted by volumetric analyses of MRI data in the medial temporal lobe. The present study compared a volumetric measurement of the hippocampus to a novel measure of hippocampal integrity derived from the ratio of parenchyma volume over total volume. Participants were cognitively intact and aged 60 or older at baseline, and were tested twice, roughly three years apart. Participants had been recruited for a study on late-life major depression (LLMD) and were evenly split between depressed and controls. Linear regression models were applied to the data with a cognitive composite score as outcome, and hippocampal integrity (HI) and volume (HV), together or separately, as predictors. Subsequent cognitive performance was predicted well by models that include an interaction between HI and LLMD-status, such that lower HI scores predicted more cognitive decline in depressed subjects. More research is needed, but tentative results from this study appear to suggest that the newly introduced measure HI is an effective tool for the purpose of predicting future changes in general cognitive ability, and especially so in individuals with LLMD.