Travis Stoub - Academia.edu (original) (raw)

Papers by Travis Stoub

Objective: To determine whether depressive and /or anxiety disorders alter the volumes of mesial ... more Objective: To determine whether depressive and /or anxiety disorders alter the volumes of mesial temporal structures in patients with epilepsy (PWE). Background: Mood and anxiety disorders are the most common psychiatric co-morbidities in PWE. Hippocampal atrophy has been documented in patients with primary mood disorders and is a common finding in temporal lobe epilepsy. The purpose of this study is to establish if PWE and comorbid mood and/or anxiety disorders are more likely to have smaller hippocampal and amygdala volumes than in PWE without psychiatric comorbidity. Design/Methods: Manual quantitative volumetric measurements of hippocampus and amygdala were performed in 3 Tesla high-resolution brain MRI studies of 40 PWE (TLE, n = 25 [MTS, n = 11]); extratemporal focal epilepsy, n = 15). Psychiatric diagnoses were established with the MINI International Neuropsychiatric Interview. In addition, patients completed self-rating scales, the Generalized Anxiety Disorder- 7 (GAD-7) and...

Objective: To investigate an association between mesial temporal, thalamic and orbitofrontal cort... more Objective: To investigate an association between mesial temporal, thalamic and orbitofrontal cortical volumes and history of pre-surgical and/or post-surgical mood and anxiety disorders in subjects with TLE who underwent laser ablation (LA) of mesial temporal structures. Background: Larger volumes of the amygdala have been associated with symptoms of depression and anxiety in TLE. Whether smaller cortical thickness and smaller volume of thalamic nuclei have the same effect is yet to be established. Design/Methods: 26 patients who underwent a LA, had a psychiatric evaluation before and at 1, 4, 12, 24 and 52 weeks after surgery. Automated quantitative volumetric measurements of hippocampi, amygdalae, thalamic nuclei, insula and orbitofrontal cortices as well as manual measurements of amygdala and hippocampus were performed in 3 Tesla high-resolution brain MRI studies. Results: Among the 26 (12 females) their mean age was 45 years old (range: 25 to 72) and the mean post-surgical follo...

Epilepsy & behavior : E&B, Jan 8, 2018

A quarter of patients with newly diagnosed epilepsy are older, yet they are less likely to be off... more A quarter of patients with newly diagnosed epilepsy are older, yet they are less likely to be offered resective surgery potentially because of clinical bias that they incur increased surgical risks. There are few peer-reviewed case series that address this cohort and their outcomes. In the context of current literature, the objective of this study was to report on all epilepsy surgeries in patients aged 50 years or older from a tertiary care center over 15 years with an average follow-up period of 6 years. Patients with epilepsy who underwent surgery between 2001 and 2016 were reviewed retrospectively. Inclusion criteria were age > 50 at surgery, availability of presurgical evaluation data, and minimum one year of follow-up data. We identified 34 patients. Seizure outcome was evaluated using the Engel classification system. Thirty-four patients aged 50 years and older out of 276 underwent epilepsy surgery. Average age at time of surgery was 55 years, and average duration of epile...

Neurobiology of learning and memory, Jan 12, 2018

Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however... more Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however, are misregulated in several neurological disorders, causing both gain- and loss-of-function channelopathies in neurons. Using several transgenic mouse models of Alzheimer's disease (AD), we find that sub-threshold voltage signals strongly influenced by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels progressively deteriorate over chronological aging in hippocampal CA1 pyramidal neurons. The progressively degraded signaling via HCN channels in the transgenic mice is accompanied by an age-related global loss of their non-uniform dendritic expression. Both the aberrant signaling via HCN channels and their mislocalization could be restored using a variety of pharmacological agents that target the endoplasmic reticulum (ER). Our rescue of the HCN channelopathy helps provide molecular details into the favorable outcomes of ER-targeting drugs on the pathogenesis and sy...

Motricité Cérébrale : Réadaptation, Neurologie du Développement

Hippocampus

A deficit in declarative memory function is common among individuals with temporal lobe epilepsy.... more A deficit in declarative memory function is common among individuals with temporal lobe epilepsy. The purpose of this study is to evaluate the relationship between the volume of the hippocampus, entorhinal cortex along with the surrounding parahippocampal white matter and memory performance in those with temporal lobe epilepsy. T1 weighted MRI scans were acquired using a 3-D pulse sequence in 50 individuals with temporal lobe epilepsy. Hippocampal and entorhinal cortex volumes were derived by manually tracing consecutive coronal slices aligned perpendicular to the long axis of the hippocampus. In addition, parahippocampal white matter volumes were determined using voxel based morphometry. Finally, declarative memory was assessed using immediate and delayed verbal and visual memory tests from the Wechsler Memory Scale third edition. Significant correlations were seen between right and left hippocampal volumes and delayed verbal memory test scores. In addition, left parahippocampal white matter showed positive correlations with immediate and delayed verbal and visual recall. Furthermore, regression models found that the right hippocampus and left parahippocampal white matter were the best predictors of immediate and delayed verbal and visual memory performance. These results show that a decrease in white matter fibers projecting to the hippocampus may cause a disruption of incoming multi-modal sensory information, contributing to the memory decline seen in individuals with temporal lobe epilepsy.

Seizure, 2016

There is significant variation in how patients respond to cortical electrical stimulation. It has... more There is significant variation in how patients respond to cortical electrical stimulation. It has been hypothesized that individual demographic and pathologic factors, such as age, sex, disease duration, and MRI findings, may explain this discrepancy. The purpose of our study is to identify specific patient characteristics and their effect on cortical stimulation, and discover the extent of variation in behavioral responses that exists among patients with epilepsy. Method: We retrospectively analyzed data from 92 patients with medically intractable epilepsy who had extra-operative cortical electrical stimulation. Mapping records were evaluated and information gathered about demographic data, as well as the thresholds of stimulation for motor, sensory, speech, and other responses; typical seizure behavior; and the induction of afterdischarges. Results: Ninety-two patient cortical stimulation mapping reports were analyzed. The average of the minimum thresholds for motor response was 4.15 mA AE 2.67. The average of the minimum thresholds for sensory response was 3.50 mA AE 2.15. The average of the minimum thresholds for speech response was 4.48 mA AE 2.42. The average of the minimum thresholds for afterdischarge was 4.33 mA AE 2.37. Most striking were the degree of variability and wide range of thresholds seen between patients and within the different regions of the same patient. Conclusion: Wide ranges of thresholds exist for the different responses between patients and within different regions of the same patient. With multivariate analysis in these series, no clinical or demographic factors predicted physiological response or afterdischarge threshold levels. Published by Elsevier Ltd on behalf of British Epilepsy Association.

Journal of neurosurgery, Dec 18, 2016

OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection ... more OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection outcomes obtained by presurgical subtracted ictal SPECT in patients with lesional (MRI positive) and nonlesional (MRI negative) refractory extratemporal lobe epilepsy (ETLE) and temporal lobe epilepsy (TLE). Specifically, outcomes were compared between partial versus complete resection of the regions of transient hyperperfusion identified using subtraction ictal SPECT coregistered to MRI (SISCOM) in relation to the ictal onset zone (IOZ) that was confirmed by electrocorticography (ECoG). That is, SISCOM was used to understand the long-term postsurgical outcomes following resection of the IOZ that overlapped with 1 or more regions of ictal onset-associated transient hyperperfusion. METHODS The study cohort included 44 consecutive patients with refractory ETLE or TLE who were treated between 2002 and 2013 and underwent presurgical evaluation using SISCOM. Concordance was determined between...

Progress in brain research, 2007

Quantitative imaging techniques allow the in vivo investigation of age and disease related change... more Quantitative imaging techniques allow the in vivo investigation of age and disease related changes in the brain and their relation to cognitive function. In this chapter we review imaging evidence indicating that the entorhinal cortex and hippocampus show atrophy very early in Alzheimer's disease (AD) and in individuals who are at risk of developing AD compared to age appropriate controls. Furthermore, the extent and rate of atrophy of the entorhinal cortex, a brain region pathologically involved very early in the disease process, can predict who among the elderly will develop AD. Techniques that assess the integrity of white matter further demonstrate that alterations in the parahippocampal white matter in the region that includes the perforant path could partially disconnect the dentate gyrus and other hippocampal subfields from incoming sensory information. Such partial disconnection and degradation in transmission of sensory information in people at risk of AD and in patient...

Neurobiology of aging, 2004

With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to ... more With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In the present study, 27 patients diagnosed with mild cognitive impairment (MCI) received a high-resolution MRI scan at baseline and were followed with yearly clinical evaluations. Ten of the 27 patients converted to AD during a 36-month period following the baseline clinical evaluation. Hippocampal and entorhinal cortex volumes derived from the baseline scan were compared to determine which of these two regions, known to be pathologically involved very early in the course of AD, could best differentiate MCI converters from non-converters. Although both entorhinal and hippocampal volumes were found to be independent predictors of the likelihood of conversion to AD, it was the right hemisphere entorhinal volume that best predicted conversion with a concorda...

Pain physician

The number of neuroimaging studies that examine chronic pain are relatively small, and it is clea... more The number of neuroimaging studies that examine chronic pain are relatively small, and it is clear that different chronic pain conditions activate diverse regions of the brain. Cancer patients presenting for diagnostic positron emission tomography (PET) imaging were asked to rate their spontaneous baseline pain score. Twenty patients with either no pain (NRS = 0) or with moderate to severe pain (NRS = 4) were invited to participate in this study to determine the difference in brain activity in cancer patients with moderate to severe chronic pain versus no pain. Prospective, non-randomized, observational report. Academic medical center. Patients had a 2-D PET scan with the radionuclide 18F-fluoro-2-deoxyglucose (FDG) at a dose of approximately 20 mCi. Each individual raw PET scan was coregistered and normalized to standard stereotactic space. Differences in regional glucose metabolism were then statistically compared between patients with moderate-to-severe pain and patients with no ...

Behavioral Neuroscience, 2003

PloS one, 2012

The functions of HCN channels in neurons depend critically on their subcellular localization, req... more The functions of HCN channels in neurons depend critically on their subcellular localization, requiring fine-tuned machinery that regulates subcellular channel trafficking. Here we provide evidence that regulatory mechanisms governing axonal HCN channel trafficking ...

Pain …, 2010

Background: The number of neuroimaging studies that examine chronic pain are relatively small, an... more Background: The number of neuroimaging studies that examine chronic pain are relatively small, and it is clear that different chronic pain conditions activate diverse regions of the brain. Objective: Cancer patients presenting for diagnostic positron emission tomography (PET) imaging were asked to rate their spontaneous baseline pain score. Twenty patients with either no pain (NRS = 0) or with moderate to severe pain (NRS ≥ 4) were invited to participate in this study to determine the difference in brain activity in cancer patients with moderate to severe chronic pain versus no pain.

Progress in brain research, 2007

Quantitative imaging techniques allow the in vivo investigation of age and disease related change... more Quantitative imaging techniques allow the in vivo investigation of age and disease related changes in the brain and their relation to cognitive function. In this chapter we review imaging evidence indicating that the entorhinal cortex and hippocampus show atrophy very early in Alzheimer's disease (AD) and in individuals who are at risk of developing AD compared to age appropriate controls. Furthermore, the extent and rate of atrophy of the entorhinal cortex, a brain region pathologically involved very early in the disease process, can predict who among the elderly will develop AD. Techniques that assess the integrity of white matter further demonstrate that alterations in the parahippocampal white matter in the region that includes the perforant path could partially disconnect the dentate gyrus and other hippocampal subfields from incoming sensory information. Such partial disconnection and degradation in transmission of sensory information in people at risk of AD and in patients with very mild AD could contribute to the memory dysfunction associated with the early stages of the disease.

Journal of Neuroscience, 2011

Output properties of neurons are greatly shaped by voltage-gated ion channels, whose biophysical ... more Output properties of neurons are greatly shaped by voltage-gated ion channels, whose biophysical properties and localization within axodendritic compartments serve to significantly transform the original input. The hyperpolarization-activated current, I h , is mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and plays a fundamental role in influencing neuronal excitability by regulating both membrane potential and input resistance. In neurons such as cortical and hippocampal pyramidal neurons, the subcellular localization of HCN channels plays a critical functional role, yet mechanisms controlling HCN channel trafficking are not fully understood. Because ion channel function and localization are often influenced by interacting proteins, we generated a knockout mouse lacking the HCN channel auxiliary subunit, tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b). Eliminating expression of TRIP8b dramatically reduced I h expression in hippocampal pyramidal neurons. Loss of I h-dependent membrane voltage properties was attributable to reduction of HCN channels on the neuronal surface, and there was a striking disruption of the normal expression pattern of HCN channels in pyramidal neurondendrites.Inheterologouscellsandneurons,absenceofTRIP8bincreasedHCNsubunittargetingtoanddegradationbylysosomes.Mice lacking TRIP8b demonstrated motor learning deficits and enhanced resistance to multiple tasks of behavioral despair with high predictive validity for antidepressant efficacy. We observed similar resistance to behavioral despair in distinct mutant mice lacking HCN1 or HCN2. These data demonstrate that interaction with the auxiliary subunit TRIP8b is a major mechanism underlying proper expression of HCN channels and I h in vivo, and suggest that targeting I h may provide a novel approach to treatment of depression.

Objective: To determine whether depressive and /or anxiety disorders alter the volumes of mesial ... more Objective: To determine whether depressive and /or anxiety disorders alter the volumes of mesial temporal structures in patients with epilepsy (PWE). Background: Mood and anxiety disorders are the most common psychiatric co-morbidities in PWE. Hippocampal atrophy has been documented in patients with primary mood disorders and is a common finding in temporal lobe epilepsy. The purpose of this study is to establish if PWE and comorbid mood and/or anxiety disorders are more likely to have smaller hippocampal and amygdala volumes than in PWE without psychiatric comorbidity. Design/Methods: Manual quantitative volumetric measurements of hippocampus and amygdala were performed in 3 Tesla high-resolution brain MRI studies of 40 PWE (TLE, n = 25 [MTS, n = 11]); extratemporal focal epilepsy, n = 15). Psychiatric diagnoses were established with the MINI International Neuropsychiatric Interview. In addition, patients completed self-rating scales, the Generalized Anxiety Disorder- 7 (GAD-7) and...

Objective: To investigate an association between mesial temporal, thalamic and orbitofrontal cort... more Objective: To investigate an association between mesial temporal, thalamic and orbitofrontal cortical volumes and history of pre-surgical and/or post-surgical mood and anxiety disorders in subjects with TLE who underwent laser ablation (LA) of mesial temporal structures. Background: Larger volumes of the amygdala have been associated with symptoms of depression and anxiety in TLE. Whether smaller cortical thickness and smaller volume of thalamic nuclei have the same effect is yet to be established. Design/Methods: 26 patients who underwent a LA, had a psychiatric evaluation before and at 1, 4, 12, 24 and 52 weeks after surgery. Automated quantitative volumetric measurements of hippocampi, amygdalae, thalamic nuclei, insula and orbitofrontal cortices as well as manual measurements of amygdala and hippocampus were performed in 3 Tesla high-resolution brain MRI studies. Results: Among the 26 (12 females) their mean age was 45 years old (range: 25 to 72) and the mean post-surgical follo...

Epilepsy & behavior : E&B, Jan 8, 2018

A quarter of patients with newly diagnosed epilepsy are older, yet they are less likely to be off... more A quarter of patients with newly diagnosed epilepsy are older, yet they are less likely to be offered resective surgery potentially because of clinical bias that they incur increased surgical risks. There are few peer-reviewed case series that address this cohort and their outcomes. In the context of current literature, the objective of this study was to report on all epilepsy surgeries in patients aged 50 years or older from a tertiary care center over 15 years with an average follow-up period of 6 years. Patients with epilepsy who underwent surgery between 2001 and 2016 were reviewed retrospectively. Inclusion criteria were age > 50 at surgery, availability of presurgical evaluation data, and minimum one year of follow-up data. We identified 34 patients. Seizure outcome was evaluated using the Engel classification system. Thirty-four patients aged 50 years and older out of 276 underwent epilepsy surgery. Average age at time of surgery was 55 years, and average duration of epile...

Neurobiology of learning and memory, Jan 12, 2018

Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however... more Voltage-gated ion channels are critical for neuronal integration. Some of these channels, however, are misregulated in several neurological disorders, causing both gain- and loss-of-function channelopathies in neurons. Using several transgenic mouse models of Alzheimer's disease (AD), we find that sub-threshold voltage signals strongly influenced by hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels progressively deteriorate over chronological aging in hippocampal CA1 pyramidal neurons. The progressively degraded signaling via HCN channels in the transgenic mice is accompanied by an age-related global loss of their non-uniform dendritic expression. Both the aberrant signaling via HCN channels and their mislocalization could be restored using a variety of pharmacological agents that target the endoplasmic reticulum (ER). Our rescue of the HCN channelopathy helps provide molecular details into the favorable outcomes of ER-targeting drugs on the pathogenesis and sy...

Motricité Cérébrale : Réadaptation, Neurologie du Développement

Hippocampus

A deficit in declarative memory function is common among individuals with temporal lobe epilepsy.... more A deficit in declarative memory function is common among individuals with temporal lobe epilepsy. The purpose of this study is to evaluate the relationship between the volume of the hippocampus, entorhinal cortex along with the surrounding parahippocampal white matter and memory performance in those with temporal lobe epilepsy. T1 weighted MRI scans were acquired using a 3-D pulse sequence in 50 individuals with temporal lobe epilepsy. Hippocampal and entorhinal cortex volumes were derived by manually tracing consecutive coronal slices aligned perpendicular to the long axis of the hippocampus. In addition, parahippocampal white matter volumes were determined using voxel based morphometry. Finally, declarative memory was assessed using immediate and delayed verbal and visual memory tests from the Wechsler Memory Scale third edition. Significant correlations were seen between right and left hippocampal volumes and delayed verbal memory test scores. In addition, left parahippocampal white matter showed positive correlations with immediate and delayed verbal and visual recall. Furthermore, regression models found that the right hippocampus and left parahippocampal white matter were the best predictors of immediate and delayed verbal and visual memory performance. These results show that a decrease in white matter fibers projecting to the hippocampus may cause a disruption of incoming multi-modal sensory information, contributing to the memory decline seen in individuals with temporal lobe epilepsy.

Seizure, 2016

There is significant variation in how patients respond to cortical electrical stimulation. It has... more There is significant variation in how patients respond to cortical electrical stimulation. It has been hypothesized that individual demographic and pathologic factors, such as age, sex, disease duration, and MRI findings, may explain this discrepancy. The purpose of our study is to identify specific patient characteristics and their effect on cortical stimulation, and discover the extent of variation in behavioral responses that exists among patients with epilepsy. Method: We retrospectively analyzed data from 92 patients with medically intractable epilepsy who had extra-operative cortical electrical stimulation. Mapping records were evaluated and information gathered about demographic data, as well as the thresholds of stimulation for motor, sensory, speech, and other responses; typical seizure behavior; and the induction of afterdischarges. Results: Ninety-two patient cortical stimulation mapping reports were analyzed. The average of the minimum thresholds for motor response was 4.15 mA AE 2.67. The average of the minimum thresholds for sensory response was 3.50 mA AE 2.15. The average of the minimum thresholds for speech response was 4.48 mA AE 2.42. The average of the minimum thresholds for afterdischarge was 4.33 mA AE 2.37. Most striking were the degree of variability and wide range of thresholds seen between patients and within the different regions of the same patient. Conclusion: Wide ranges of thresholds exist for the different responses between patients and within different regions of the same patient. With multivariate analysis in these series, no clinical or demographic factors predicted physiological response or afterdischarge threshold levels. Published by Elsevier Ltd on behalf of British Epilepsy Association.

Journal of neurosurgery, Dec 18, 2016

OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection ... more OBJECTIVE The purpose of this study was to assess the positive predictive value of postresection outcomes obtained by presurgical subtracted ictal SPECT in patients with lesional (MRI positive) and nonlesional (MRI negative) refractory extratemporal lobe epilepsy (ETLE) and temporal lobe epilepsy (TLE). Specifically, outcomes were compared between partial versus complete resection of the regions of transient hyperperfusion identified using subtraction ictal SPECT coregistered to MRI (SISCOM) in relation to the ictal onset zone (IOZ) that was confirmed by electrocorticography (ECoG). That is, SISCOM was used to understand the long-term postsurgical outcomes following resection of the IOZ that overlapped with 1 or more regions of ictal onset-associated transient hyperperfusion. METHODS The study cohort included 44 consecutive patients with refractory ETLE or TLE who were treated between 2002 and 2013 and underwent presurgical evaluation using SISCOM. Concordance was determined between...

Progress in brain research, 2007

Quantitative imaging techniques allow the in vivo investigation of age and disease related change... more Quantitative imaging techniques allow the in vivo investigation of age and disease related changes in the brain and their relation to cognitive function. In this chapter we review imaging evidence indicating that the entorhinal cortex and hippocampus show atrophy very early in Alzheimer's disease (AD) and in individuals who are at risk of developing AD compared to age appropriate controls. Furthermore, the extent and rate of atrophy of the entorhinal cortex, a brain region pathologically involved very early in the disease process, can predict who among the elderly will develop AD. Techniques that assess the integrity of white matter further demonstrate that alterations in the parahippocampal white matter in the region that includes the perforant path could partially disconnect the dentate gyrus and other hippocampal subfields from incoming sensory information. Such partial disconnection and degradation in transmission of sensory information in people at risk of AD and in patient...

Neurobiology of aging, 2004

With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to ... more With high-resolution quantitative magnetic resonance imaging (MRI) techniques, it is possible to examine alterations in brain anatomy in vivo and to identify regions affected in the earliest stages of Alzheimer's disease (AD). In the present study, 27 patients diagnosed with mild cognitive impairment (MCI) received a high-resolution MRI scan at baseline and were followed with yearly clinical evaluations. Ten of the 27 patients converted to AD during a 36-month period following the baseline clinical evaluation. Hippocampal and entorhinal cortex volumes derived from the baseline scan were compared to determine which of these two regions, known to be pathologically involved very early in the course of AD, could best differentiate MCI converters from non-converters. Although both entorhinal and hippocampal volumes were found to be independent predictors of the likelihood of conversion to AD, it was the right hemisphere entorhinal volume that best predicted conversion with a concorda...

Pain physician

The number of neuroimaging studies that examine chronic pain are relatively small, and it is clea... more The number of neuroimaging studies that examine chronic pain are relatively small, and it is clear that different chronic pain conditions activate diverse regions of the brain. Cancer patients presenting for diagnostic positron emission tomography (PET) imaging were asked to rate their spontaneous baseline pain score. Twenty patients with either no pain (NRS = 0) or with moderate to severe pain (NRS = 4) were invited to participate in this study to determine the difference in brain activity in cancer patients with moderate to severe chronic pain versus no pain. Prospective, non-randomized, observational report. Academic medical center. Patients had a 2-D PET scan with the radionuclide 18F-fluoro-2-deoxyglucose (FDG) at a dose of approximately 20 mCi. Each individual raw PET scan was coregistered and normalized to standard stereotactic space. Differences in regional glucose metabolism were then statistically compared between patients with moderate-to-severe pain and patients with no ...

Behavioral Neuroscience, 2003

PloS one, 2012

The functions of HCN channels in neurons depend critically on their subcellular localization, req... more The functions of HCN channels in neurons depend critically on their subcellular localization, requiring fine-tuned machinery that regulates subcellular channel trafficking. Here we provide evidence that regulatory mechanisms governing axonal HCN channel trafficking ...

Pain …, 2010

Background: The number of neuroimaging studies that examine chronic pain are relatively small, an... more Background: The number of neuroimaging studies that examine chronic pain are relatively small, and it is clear that different chronic pain conditions activate diverse regions of the brain. Objective: Cancer patients presenting for diagnostic positron emission tomography (PET) imaging were asked to rate their spontaneous baseline pain score. Twenty patients with either no pain (NRS = 0) or with moderate to severe pain (NRS ≥ 4) were invited to participate in this study to determine the difference in brain activity in cancer patients with moderate to severe chronic pain versus no pain.

Progress in brain research, 2007

Quantitative imaging techniques allow the in vivo investigation of age and disease related change... more Quantitative imaging techniques allow the in vivo investigation of age and disease related changes in the brain and their relation to cognitive function. In this chapter we review imaging evidence indicating that the entorhinal cortex and hippocampus show atrophy very early in Alzheimer's disease (AD) and in individuals who are at risk of developing AD compared to age appropriate controls. Furthermore, the extent and rate of atrophy of the entorhinal cortex, a brain region pathologically involved very early in the disease process, can predict who among the elderly will develop AD. Techniques that assess the integrity of white matter further demonstrate that alterations in the parahippocampal white matter in the region that includes the perforant path could partially disconnect the dentate gyrus and other hippocampal subfields from incoming sensory information. Such partial disconnection and degradation in transmission of sensory information in people at risk of AD and in patients with very mild AD could contribute to the memory dysfunction associated with the early stages of the disease.

Journal of Neuroscience, 2011

Output properties of neurons are greatly shaped by voltage-gated ion channels, whose biophysical ... more Output properties of neurons are greatly shaped by voltage-gated ion channels, whose biophysical properties and localization within axodendritic compartments serve to significantly transform the original input. The hyperpolarization-activated current, I h , is mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and plays a fundamental role in influencing neuronal excitability by regulating both membrane potential and input resistance. In neurons such as cortical and hippocampal pyramidal neurons, the subcellular localization of HCN channels plays a critical functional role, yet mechanisms controlling HCN channel trafficking are not fully understood. Because ion channel function and localization are often influenced by interacting proteins, we generated a knockout mouse lacking the HCN channel auxiliary subunit, tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b). Eliminating expression of TRIP8b dramatically reduced I h expression in hippocampal pyramidal neurons. Loss of I h-dependent membrane voltage properties was attributable to reduction of HCN channels on the neuronal surface, and there was a striking disruption of the normal expression pattern of HCN channels in pyramidal neurondendrites.Inheterologouscellsandneurons,absenceofTRIP8bincreasedHCNsubunittargetingtoanddegradationbylysosomes.Mice lacking TRIP8b demonstrated motor learning deficits and enhanced resistance to multiple tasks of behavioral despair with high predictive validity for antidepressant efficacy. We observed similar resistance to behavioral despair in distinct mutant mice lacking HCN1 or HCN2. These data demonstrate that interaction with the auxiliary subunit TRIP8b is a major mechanism underlying proper expression of HCN channels and I h in vivo, and suggest that targeting I h may provide a novel approach to treatment of depression.