Burning mouth syndrome (BMS) is a burning oral sensation without any corresponding abnormal findi... more Burning mouth syndrome (BMS) is a burning oral sensation without any corresponding abnormal findings. In some cases, BMS is refractory to pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex induces analgesic effect in both acute and chronic pain. However, its effect for BMS has not been evaluated. The aim of this randomized, controlled, single-blind study was to assess the efficacy of prefrontal rTMS for BMS. Twenty patients with BMS were recruited and randomized to receive 30,000 pulses in total at 10 Hz TMS (n = 12) or sham TMS (n = 8). We assessed the change of BMS pain condition, functional status and mood until 2 months after the beginning of treatment. In the real group, the BMS pain intensity decreased 67%, and 75% of the patients reported >50% pain decrease on final assessment compared to baseline, without heavy side effects. There was significant pain reduction in subjects in the real group immediately after 1 week of treatment, whereas there was none in those in the sham group. Similar tendency was confirmed in change of functional status. Mood and the affective aspect of pain were not changed in this study. BMS pain was significantly improved with 2 weeks of treatment of high frequency rTMS over left DLPFC compared to sham stimulation. Further study is needed to refine and improve TMS as a potential treatment of BMS.
Disruptions in motor control are often overlooked features of chronic cocaine users. During a sim... more Disruptions in motor control are often overlooked features of chronic cocaine users. During a simple sensorimotor integration task, for example, cocaine users activate a larger area of cortex than controls but have lower functional connectivity between the cortex and dorsal striatum, which is further correlated with poor performance. The purpose of this study was to determine whether abnormal cortical excitability in cocaine users was related to disrupted inhibitory or excitatory mechanisms, as measured by transcranial magnetic stimulation (TMS). A battery of TMS measures were acquired from 87 individuals (50 cocaine dependent, 37 controls). Functional MRI data were acquired from a subset of 28 individuals who performed a block-design finger tapping task. TMS measures revealed that cocaine users had significantly higher resting motor thresholds and higher intracortical cortical facilitation (ICF) than controls. There was no between-group difference in either measure of cortical inhi...
Vulnerability to drug related cues is one of the leading causes for continued use and relapse amo... more Vulnerability to drug related cues is one of the leading causes for continued use and relapse among substance dependent individuals. Using drugs in the face of cues may be associated with dysfunction in at least two frontal-striatal neural circuits: (1) elevated activity in medial and ventral areas that govern limbic arousal (including the medial prefrontal cortex (MPFC) and ventral striatum) or (2) depressed activity in dorsal and lateral areas that govern cognitive control (including the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum). Transcranial magnetic stimulation (TMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. To date however, nearly all repetitive TMS studies in addiction have focused on amplifying activity in frontal-striatal circuits that govern cognitive control. This manuscript reviews recent work using TMS as a tool to decrease craving for multiple substances and provides a theoretical...
Interventional psychiatry offers substantial therapeutic benefits in some neuropsychiatric disord... more Interventional psychiatry offers substantial therapeutic benefits in some neuropsychiatric disorders and enormous potential in treating others. However, as interventional diagnostics and therapeutics require specialized knowledge and skill foreign to many psychiatrists, the emerging subspecialty of interventional psychiatry must be more formally integrated into the continuum of psychiatric training to ensure both safe application and continued growth. By establishing training paradigms for interventional psychiatry, academic medical centers can help fill this knowledge gap. The cultivation of a properly trained cohort of interventional psychiatrists will better meet the challenges of treatment-resistant psychiatric illness through safe and ethical practice, while facilitating a more informed development and integration of novel neuromodulation techniques.
Background: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area wh... more Background: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial corticalsubcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment.
Interventional psychiatry is an emerging subspecialty that uses a variety of procedural neuromodu... more Interventional psychiatry is an emerging subspecialty that uses a variety of procedural neuromodulation techniques in the context of an electrocircuit-based view of mental dysfunction as proximal causes for psychiatric diseases. The authors propose the development of an interventional psychiatry-training paradigm analogous to those found in cardiology and neurology. The proposed comprehensive training in interventional psychiatry would include didactics in the theory, proposed mechanisms, and delivery of invasive and noninvasive brain stimulation. The development and refinement of this subspecialty would facilitate safe, effective growth in the field of brain stimulation by certified and credentialed practitioners within the field of psychiatry while also potentially improving the efficacy of current treatments.
BACKGROUND: Several recent studies suggest that repetitive transcranial magnetic stimulation can ... more BACKGROUND: Several recent studies suggest that repetitive transcranial magnetic stimulation can temporarily reduce pain perception in neuropathic pain patients and in healthy adults using laboratory pain models. No studies have investigated the effects of prefrontal cortex stimulation using transcranial magnetic stimulation on postoperative pain.METHODS: Twenty gastric bypass surgery patients were randomly assigned to receive 20 min of either active or sham left prefrontal repetitive transcranial magnetic stimulation immediately after surgery. Patient-controlled analgesia pump use was tracked, and patients also rated pain and mood twice per day using visual analog scales.RESULTS: Groups were similar at baseline in terms of body mass index, age, mood ratings, pain ratings, surgery duration, time under anesthesia, and surgical anesthesia methods. Significant effects were observed for surgery type (open vs. laparoscopic) and condition (active vs. sham transcranial magnetic stimulation) on the cumulative amount of patient-delivered morphine during the 44 h after surgery. Active prefrontal repetitive transcranial magnetic stimulation was associated with a 40% reduction in total morphine use compared with sham during the 44 h after surgery. The effect seemed to be most prominent during the first 24 h after cortical stimulation delivery. No effects were observed for repetitive transcranial magnetic stimulation on mood ratings.CONCLUSIONS: A single session of postoperative prefrontal repetitive transcranial magnetic stimulation was associated with a reduction in patient-controlled analgesia pump use in gastric bypass surgery patients. This is important because the risks associated with postoperative morphine use are high, especially among obese patients who frequently have obstructive sleep apnea, right ventricular dysfunction, and pulmonary hypertension. These preliminary findings suggest a potential new noninvasive method for managing postoperative morphine use.
Therapeutics and Clinical Risk Management, Oct 1, 2008
Short term immobilization of the lower limb is associated with increased corticospinal excitabili... more Short term immobilization of the lower limb is associated with increased corticospinal excitability at 24 hours post cast removal. We wondered whether daily stimulation of the motor cortex might decrease brain reorganization during casting. We tested the feasibility of this approach. Using transcranial magnetic stimulation (TMS), resting motor threshold and recruitment curves were obtained at baseline in 6 healthy participants who then had leg casts placed for 10 days. On 7 of the 10 days subjects received 20 minutes of 1 Hz repetitive TMS (rTMS). TMS measures were then recorded immediately after and 24 hours post cast removal. Four of 6 subjects completed the study. At the group level there were no changes in excitability following cast removal. At the individual level, two participants did not show any change, 1 participant had higher and one lower excitability 24 hours after cast removal. Daily rTMS over motor cortex is feasible during casting and may modify neuroplastic changes occurring during limb disuse. A prospective double blind study is warranted to test whether daily rTMS might improve outcome in subjects undergoing casting, and perhaps in other forms of limb disuse such as those following brain injury or weightlessness in space flight.
Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological ... more Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5). Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (p<0.005, threshold 15 voxels). Interestingly the ventral striatum activation significantly correlated with the days since the last use of meth (r=-0.76, p=0.017). No significant activity was found in healthy control group....
Foreign Accent Syndrome (FAS) is a well-known neurological deficit whose underlying cause has rem... more Foreign Accent Syndrome (FAS) is a well-known neurological deficit whose underlying cause has remained obscure despite almost a century of study. Combining structural and functional imaging, our studies suggest that FAS represents a compensatory response to impaired motor regulation of speech. We describe a patient who acquired FAS as a result of an ischemic stroke in the left basal ganglia. In addition to this case being exceptionally clean, we were able to confirm a specific lesion location as well as provide strong evidence that impaired motor speech regulation resulted in compensation by other areas of the cortical motor speech network.
Single photon emission tomography allows the imaging of dynamic brain functioning. The use of cer... more Single photon emission tomography allows the imaging of dynamic brain functioning. The use of cerebral activating procedures within the scan protocol enables investigation of the mechanisms involved in specific brain functions in health and disease. Activation studies involve the comparison of at least two data sets describing brain activity generated in conditions that differ for the specific function in question. When designing an activation study, decisions regarding methodology include: the nature of the activation regime, the tracer-ligand utilized, the SPET instrument and the manner of subsequent data analysis. These issues are discussed in this review, both theoretically and with reference to published studies. Means of activating particular cerebral structures and functions are reviewed, as are the limitations of the techniques with respect to temporal and spatial resolution and the potentially confounding nature of preconceived ideas regarding the mechanisms of brain function.
Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somat... more Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somatic clinical intervention for treatment-resistant depression (TRD). Long-term open data suggest a sustainable antidepressant response over time. Here we review the clinical data that exist so far and their limitations. We also discuss guidelines that may inform the clinical utilization of this procedure. Further clinical studies, in addition to prospective cost utilization and health economic investigations, are needed to better understand VNS therapy and the impact it holds on TRD care.
Recent advances in single photon emission computed tomography (SPECT) have allowed improved image... more Recent advances in single photon emission computed tomography (SPECT) have allowed improved image resolution with lower doses of labelled tracer. Capitalizing on these improvements, the authors have developed a new SPECT protocol for imaging neuronal activation. We outline this technique and describe how it can demonstrate increased human motor cortex activity in normal subjects performing a motor task. The ability to accurately demonstrate neuronal activation with SPECT using this method may have important scientific and clinical implications.
The relationship between reaction time and both state and trait personality variables was investi... more The relationship between reaction time and both state and trait personality variables was investigated in 37 participants after 30 h of sleep deprivation. Regression analyses suggested that endorsement of greater Novelty Seeking, anger/hostility, and depression/dejection, and less confusion, was associated with greater reaction time declines on one Multi-Attribute Task Battery index after sleep deprivation. Further, greater Novelty Seeking and depression/dejection, and less vigor/activity, was associated with greater reaction time declines after sleep deprivation on another Multi-Attribute Task Battery index. Additional correlational analyses indicated that better reaction times were associated with greater Novelty Seeking and lower anger/hostility prior to sleep deprivation, and less confusion/bewilderment following sleep deprivation. Findings suggest that both state and trait personality variables are associated with reaction time performance following sleep deprivation.
Burning mouth syndrome (BMS) is a burning oral sensation without any corresponding abnormal findi... more Burning mouth syndrome (BMS) is a burning oral sensation without any corresponding abnormal findings. In some cases, BMS is refractory to pharmacologic treatments. Repetitive transcranial magnetic stimulation (rTMS) over left prefrontal cortex induces analgesic effect in both acute and chronic pain. However, its effect for BMS has not been evaluated. The aim of this randomized, controlled, single-blind study was to assess the efficacy of prefrontal rTMS for BMS. Twenty patients with BMS were recruited and randomized to receive 30,000 pulses in total at 10 Hz TMS (n = 12) or sham TMS (n = 8). We assessed the change of BMS pain condition, functional status and mood until 2 months after the beginning of treatment. In the real group, the BMS pain intensity decreased 67%, and 75% of the patients reported &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% pain decrease on final assessment compared to baseline, without heavy side effects. There was significant pain reduction in subjects in the real group immediately after 1 week of treatment, whereas there was none in those in the sham group. Similar tendency was confirmed in change of functional status. Mood and the affective aspect of pain were not changed in this study. BMS pain was significantly improved with 2 weeks of treatment of high frequency rTMS over left DLPFC compared to sham stimulation. Further study is needed to refine and improve TMS as a potential treatment of BMS.
Disruptions in motor control are often overlooked features of chronic cocaine users. During a sim... more Disruptions in motor control are often overlooked features of chronic cocaine users. During a simple sensorimotor integration task, for example, cocaine users activate a larger area of cortex than controls but have lower functional connectivity between the cortex and dorsal striatum, which is further correlated with poor performance. The purpose of this study was to determine whether abnormal cortical excitability in cocaine users was related to disrupted inhibitory or excitatory mechanisms, as measured by transcranial magnetic stimulation (TMS). A battery of TMS measures were acquired from 87 individuals (50 cocaine dependent, 37 controls). Functional MRI data were acquired from a subset of 28 individuals who performed a block-design finger tapping task. TMS measures revealed that cocaine users had significantly higher resting motor thresholds and higher intracortical cortical facilitation (ICF) than controls. There was no between-group difference in either measure of cortical inhi...
Vulnerability to drug related cues is one of the leading causes for continued use and relapse amo... more Vulnerability to drug related cues is one of the leading causes for continued use and relapse among substance dependent individuals. Using drugs in the face of cues may be associated with dysfunction in at least two frontal-striatal neural circuits: (1) elevated activity in medial and ventral areas that govern limbic arousal (including the medial prefrontal cortex (MPFC) and ventral striatum) or (2) depressed activity in dorsal and lateral areas that govern cognitive control (including the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum). Transcranial magnetic stimulation (TMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. To date however, nearly all repetitive TMS studies in addiction have focused on amplifying activity in frontal-striatal circuits that govern cognitive control. This manuscript reviews recent work using TMS as a tool to decrease craving for multiple substances and provides a theoretical...
Interventional psychiatry offers substantial therapeutic benefits in some neuropsychiatric disord... more Interventional psychiatry offers substantial therapeutic benefits in some neuropsychiatric disorders and enormous potential in treating others. However, as interventional diagnostics and therapeutics require specialized knowledge and skill foreign to many psychiatrists, the emerging subspecialty of interventional psychiatry must be more formally integrated into the continuum of psychiatric training to ensure both safe application and continued growth. By establishing training paradigms for interventional psychiatry, academic medical centers can help fill this knowledge gap. The cultivation of a properly trained cohort of interventional psychiatrists will better meet the challenges of treatment-resistant psychiatric illness through safe and ethical practice, while facilitating a more informed development and integration of novel neuromodulation techniques.
Background: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area wh... more Background: The prefrontal cortex (PFC) is an anatomically and functionally heterogeneous area which influences cognitive and limbic processing through connectivity to subcortical targets. As proposed by the lateral and medial aspects of the PFC project to distinct areas of the striatum in parallel but functionally distinct circuits. The purpose of this preliminary study was to determine if we could differentially and consistently activate these lateral and medial corticalsubcortical circuits involved in executive and limbic processing though interleaved transcranial magnetic stimulation (TMS) in the MR environment.
Interventional psychiatry is an emerging subspecialty that uses a variety of procedural neuromodu... more Interventional psychiatry is an emerging subspecialty that uses a variety of procedural neuromodulation techniques in the context of an electrocircuit-based view of mental dysfunction as proximal causes for psychiatric diseases. The authors propose the development of an interventional psychiatry-training paradigm analogous to those found in cardiology and neurology. The proposed comprehensive training in interventional psychiatry would include didactics in the theory, proposed mechanisms, and delivery of invasive and noninvasive brain stimulation. The development and refinement of this subspecialty would facilitate safe, effective growth in the field of brain stimulation by certified and credentialed practitioners within the field of psychiatry while also potentially improving the efficacy of current treatments.
BACKGROUND: Several recent studies suggest that repetitive transcranial magnetic stimulation can ... more BACKGROUND: Several recent studies suggest that repetitive transcranial magnetic stimulation can temporarily reduce pain perception in neuropathic pain patients and in healthy adults using laboratory pain models. No studies have investigated the effects of prefrontal cortex stimulation using transcranial magnetic stimulation on postoperative pain.METHODS: Twenty gastric bypass surgery patients were randomly assigned to receive 20 min of either active or sham left prefrontal repetitive transcranial magnetic stimulation immediately after surgery. Patient-controlled analgesia pump use was tracked, and patients also rated pain and mood twice per day using visual analog scales.RESULTS: Groups were similar at baseline in terms of body mass index, age, mood ratings, pain ratings, surgery duration, time under anesthesia, and surgical anesthesia methods. Significant effects were observed for surgery type (open vs. laparoscopic) and condition (active vs. sham transcranial magnetic stimulation) on the cumulative amount of patient-delivered morphine during the 44 h after surgery. Active prefrontal repetitive transcranial magnetic stimulation was associated with a 40% reduction in total morphine use compared with sham during the 44 h after surgery. The effect seemed to be most prominent during the first 24 h after cortical stimulation delivery. No effects were observed for repetitive transcranial magnetic stimulation on mood ratings.CONCLUSIONS: A single session of postoperative prefrontal repetitive transcranial magnetic stimulation was associated with a reduction in patient-controlled analgesia pump use in gastric bypass surgery patients. This is important because the risks associated with postoperative morphine use are high, especially among obese patients who frequently have obstructive sleep apnea, right ventricular dysfunction, and pulmonary hypertension. These preliminary findings suggest a potential new noninvasive method for managing postoperative morphine use.
Therapeutics and Clinical Risk Management, Oct 1, 2008
Short term immobilization of the lower limb is associated with increased corticospinal excitabili... more Short term immobilization of the lower limb is associated with increased corticospinal excitability at 24 hours post cast removal. We wondered whether daily stimulation of the motor cortex might decrease brain reorganization during casting. We tested the feasibility of this approach. Using transcranial magnetic stimulation (TMS), resting motor threshold and recruitment curves were obtained at baseline in 6 healthy participants who then had leg casts placed for 10 days. On 7 of the 10 days subjects received 20 minutes of 1 Hz repetitive TMS (rTMS). TMS measures were then recorded immediately after and 24 hours post cast removal. Four of 6 subjects completed the study. At the group level there were no changes in excitability following cast removal. At the individual level, two participants did not show any change, 1 participant had higher and one lower excitability 24 hours after cast removal. Daily rTMS over motor cortex is feasible during casting and may modify neuroplastic changes occurring during limb disuse. A prospective double blind study is warranted to test whether daily rTMS might improve outcome in subjects undergoing casting, and perhaps in other forms of limb disuse such as those following brain injury or weightlessness in space flight.
Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological ... more Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5). Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (p<0.005, threshold 15 voxels). Interestingly the ventral striatum activation significantly correlated with the days since the last use of meth (r=-0.76, p=0.017). No significant activity was found in healthy control group....
Foreign Accent Syndrome (FAS) is a well-known neurological deficit whose underlying cause has rem... more Foreign Accent Syndrome (FAS) is a well-known neurological deficit whose underlying cause has remained obscure despite almost a century of study. Combining structural and functional imaging, our studies suggest that FAS represents a compensatory response to impaired motor regulation of speech. We describe a patient who acquired FAS as a result of an ischemic stroke in the left basal ganglia. In addition to this case being exceptionally clean, we were able to confirm a specific lesion location as well as provide strong evidence that impaired motor speech regulation resulted in compensation by other areas of the cortical motor speech network.
Single photon emission tomography allows the imaging of dynamic brain functioning. The use of cer... more Single photon emission tomography allows the imaging of dynamic brain functioning. The use of cerebral activating procedures within the scan protocol enables investigation of the mechanisms involved in specific brain functions in health and disease. Activation studies involve the comparison of at least two data sets describing brain activity generated in conditions that differ for the specific function in question. When designing an activation study, decisions regarding methodology include: the nature of the activation regime, the tracer-ligand utilized, the SPET instrument and the manner of subsequent data analysis. These issues are discussed in this review, both theoretically and with reference to published studies. Means of activating particular cerebral structures and functions are reviewed, as are the limitations of the techniques with respect to temporal and spatial resolution and the potentially confounding nature of preconceived ideas regarding the mechanisms of brain function.
Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somat... more Vagus nerve stimulation (VNS) therapy is the first US Food and Drug Administration-approved somatic clinical intervention for treatment-resistant depression (TRD). Long-term open data suggest a sustainable antidepressant response over time. Here we review the clinical data that exist so far and their limitations. We also discuss guidelines that may inform the clinical utilization of this procedure. Further clinical studies, in addition to prospective cost utilization and health economic investigations, are needed to better understand VNS therapy and the impact it holds on TRD care.
Recent advances in single photon emission computed tomography (SPECT) have allowed improved image... more Recent advances in single photon emission computed tomography (SPECT) have allowed improved image resolution with lower doses of labelled tracer. Capitalizing on these improvements, the authors have developed a new SPECT protocol for imaging neuronal activation. We outline this technique and describe how it can demonstrate increased human motor cortex activity in normal subjects performing a motor task. The ability to accurately demonstrate neuronal activation with SPECT using this method may have important scientific and clinical implications.
The relationship between reaction time and both state and trait personality variables was investi... more The relationship between reaction time and both state and trait personality variables was investigated in 37 participants after 30 h of sleep deprivation. Regression analyses suggested that endorsement of greater Novelty Seeking, anger/hostility, and depression/dejection, and less confusion, was associated with greater reaction time declines on one Multi-Attribute Task Battery index after sleep deprivation. Further, greater Novelty Seeking and depression/dejection, and less vigor/activity, was associated with greater reaction time declines after sleep deprivation on another Multi-Attribute Task Battery index. Additional correlational analyses indicated that better reaction times were associated with greater Novelty Seeking and lower anger/hostility prior to sleep deprivation, and less confusion/bewilderment following sleep deprivation. Findings suggest that both state and trait personality variables are associated with reaction time performance following sleep deprivation.
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