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Biomedical subjects

Sarah H Lisanby

Publications and source records attributed to Sarah H Lisanby.

At least 19 recordsLinked to original sources
PubMed2007

Revisiting the backward masking deficit in schizophrenia: individual differences in performance and modeling with transcranial magnetic stimulation.

BACKGROUND: Deficits in backward masking have been variably reported in schizophrenia patients, but individual differences in the expression of these deficits have not been explicitly investigated. In addition, increased knowledge of the visual system has opened the door for new techniques such as transcranial magnetic stimulation (TMS) to explore these deficits physiologically. METHODS: Patients with schizophrenia and healthy controls were tested using a backward masking paradigm. In order to examine the functionality of visual pathways involved in backward masking, subjects were retested on a backward masking paradigm using single pulse TMS applied to occipital cortex in lieu of the masking stimuli. RESULTS: Compared with controls, patients had significantly delayed recovery from visual backward masking. However, 23.5% of patients (compared to 5% of controls) never recovered to levels approaching unmasked performance. When these subjects were segregated from the analysis, group differences vanished. In addition, stimulus masking with occipital TMS followed the same pattern in both patients and controls. CONCLUSIONS: Observations of individual differences in visual masking performance may identify a subgroup of schizophrenia patients. The TMS data suggest that this deficit may not localize to the occipital cortex. However, TMS can be a useful tool for localizing processing deficits in schizophrenia.

Adult↗
PubMed2007

Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of panic disorder (PD) with comorbid major depression.

BACKGROUND: Studies suggest that the dorsolateral prefrontal cortex (DLPFC) participates in neural circuitry that is dysregulated in Panic Disorder (PD) and Major Depressive Disorder (MDD). We tested whether low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of right frontal regions and thereby improve symptoms. METHODS: Six patients with PD and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for 2 weeks in this open-label trial. RESULTS: Clinical improvements were apparent as early as the first week of treatment. After the second week, 5/6 of patients showed improvements in panic and anxiety, and 4/6 showed a decrease in depression, with sustained improvement at 6 months of follow-up. Right hemisphere resting motor threshold increased significantly after rTMS. LIMITATIONS: Limitations of this study are the open design and the small sample size. CONCLUSIONS: Slow rTMS to the right DLPFC resulted in significant clinical improvement and reduction of ipsilateral motor cortex excitability. Replications in larger sample will help to clarify the relevance of this preliminary data and to define the potential role of right DLPFC rTMS in panic with major depression.

Adult↗
PubMed2006

Anesthetic considerations for magnetic seizure therapy: a novel therapy for severe depression.

Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression. However, its use is associated with significant posttreatment cognitive impairment. Magnetic seizure therapy (MST) was developed as an alternative therapy that could reduce postseizure side effects through the induction of more "focal" seizure activity. Using an open-parallel study design, we compared 20 case-matched patients undergoing a series of either ECT or MST procedures with respect to their anesthetic, muscle relaxant, and cardiovascular drug requirements, effects on cardiovascular and electroencephalographic bispectral index (BIS) values, and early recovery times. We found that MST was associated with a reduced time to orientation (4 +/- 1 versus 18 +/- 5 min; P < 0.01) compared with ECT. To minimize residual muscle paralysis after MST, a reduction in the succinylcholine dosage (38 +/- 17 versus 97 +/- 2 mg; P < 0.01) was required. The BIS values were higher before, and lower immediately after, the stimulus was applied in the MST (versus ECT) group. The Hamilton depression rating scale score was significantly reduced from the baseline value in both treatment groups; however, the posttreatment score was lower after the series of ECT treatments (6 +/- 6 versus 14 +/- 10; P < 0.05). We conclude that MST was associated with a decreased requirement for muscle relaxants, reduced variability in the BIS values after seizure induction, and a more rapid recovery of cognitive function compared with ECT. Further studies are required to evaluate the antidepressant efficacy of MST versus ECT when they are administered at comparable levels of cerebral stimulation.

Anesthesia↗
PubMed2005

Evidence for impaired cortical inhibition in patients with unipolar major depression.

BACKGROUND: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. METHODS: By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers. RESULTS: Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold. CONCLUSIONS: This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.

Adult↗
PubMed2005

Randomized controlled trial of the cognitive side-effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS).

Magnetic seizure therapy (MST) is under development as a means of improving the cognitive side-effect profile of electroconvulsive therapy (ECT) by inducing more spatially delimited seizures that spare cortical regions involved in memory. We tested whether MST had a cognitive side-effect profile distinct from electroconvulsive shock (ECS) in a non-human primate model, using the Columbia University Primate Cognitive Profile, which has been shown to be sensitive to the cognitive effects of ECS. Using a within-subject cross-over design, daily ECS, MST, and sham (anaesthesia-only) interventions were administered in 5-wk blocks. Rhesus macaques (n = 2) were trained on a long-term memory task, an anterograde learning and memory task, and a combined anterograde and retrograde task where learning and memory were evaluated for new and previously learned 3-item lists. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-h retention interval. Overall, monkeys were least accurate following ECS (p's < 0.05) compared to sham and MST. This effect was most marked for long-term memory of a constant target, short-term memory of a variable target and recall of previously learned 3-item lists. Monkeys were slowest to complete all tasks following ECS (p's = 0.0001). Time to task completion following MST did not differ from sham. These findings suggest that MST results in a more benign acute cognitive side-effect profile than ECS in this model, consistent with initial observations with human MST.

Amnesia, Anterograde↗
PubMed2005

Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS).

There is evidence that motor and premotor cortex are hyperexcitable in obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). We tested whether low-frequency repetitive transcranial magnetic stimulation (rTMS) could normalize overactive motor cortical regions and thereby improve symptoms. Subjects with OCD or TS were treated with active rTMS to the supplementary motor area (SMA) for 10 daily sessions at 1 Hz, 100% of motor threshold, 1200 stimuli/day. Suggestions of clinical improvement were apparent as early as the first week of rTMS. At the second week of treatment, statistically significant reductions were seen in the YBOCS, YGTSS, CGI, HARS, HDRS, SAD, BDI, SCL-90, and SASS. Symptoms improvement was correlated with a significant increase of the right resting motor threshold and was stable at 3 months follow-up. Slow rTMS to SMA resulted in a significant clinical improvement and a normalization of the right hemisphere hyperexcitability, thereby restoring hemispheric symmetry in motor threshold.

Adult↗
PubMed2005

Electroconvulsive therapy and repetitive transcranial magnetic stimulation in children and adolescents: a review and report of two cases of epilepsia partialis continua.

Brain stimulation for the treatment of psychiatric disorders has received increasing attention over the past decade. The introduction of experimental means to stimulate the brain noninvasively with magnetic fields not only has raised interest in these novel means of modulating brain activity but also has refocused attention on a mainstay in the treatment of severe major depression and other disorders (electroconvulsive therapy). This article reviews the current state of knowledge concerning the use electroconvulsive therapy, repetitive transcranial magnetic stimulation, and magnetic seizure therapy in children and adolescents. Two cases of medically intractable epilepsia partialis continua are presented to add to the limited literature on the use of repetitive transcranial magnetic stimulation in children and adolescents and illustrate the concept of using functional neuroimaging results to target the application of a focal intervention in an attempt to dampen hyperactive regions of the cortex.

Adolescent↗
PubMed2005

Cortical excitability in cocaine-dependent patients: a replication and extension of TMS findings.

Cortical excitability can be assessed by transcranial magnetic stimulation (TMS). Previously we observed that TMS motor threshold (MT) was elevated in abstinent cocaine-dependent subjects. In the current study we aimed at replicating our initial finding, exploring other TMS-based measures of excitability, and examining association with personality characteristics. Nineteen cocaine-dependent and 12 healthy control subjects were examined. Resting and activated motor thresholds (RMT and AMT) and duration of the cortical silent period (CSP) were examined. The Cocaine Experience Questionnaire (CEQ) was administered to assess cocaine-induced psychotic symptoms. The relationship between Minnesota Multiphasic Personality Inventory (MMPI) scales and cortical excitability measures was also examined. AMT was significantly elevated in cocaine-dependent subjects on both hemispheres. RMT was also significantly elevated on the right hemisphere. No CSP changes were noted. Patients with cocaine-induced paranoia had longer CSPs on the right hemisphere compared to subjects reporting no paranoid experiences. The patients displayed significantly elevated scores on several MMPI scales, though the scale scores did not correlate with cortical excitability measures. These data support our initial finding of decreased cortical excitability in abstinent cocaine-dependent subjects. We interpret this finding as a compensatory mechanism against the stimulating and epileptogenic effects of cocaine.

Adult↗
PubMed2005

Two-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes.

BACKGROUND: Vagus nerve stimulation (VNS) had antidepressant effects in an initial open, acute phase pilot study of 59 participants in a treatment-resistant major depressive episode (MDE). We examined the effects of adjunctive VNS over 24 months in this cohort. METHOD: Adult outpatients (N = 59) with chronic or recurrent major depressive disorder or bipolar (I or II) disorder and experiencing a treatment-resistant, nonpsychotic MDE (DSM-IV criteria) received 2 years of VNS. Changes in psychotropic medications and VNS stimulus parameters were allowed only after the first 3 months. Response was defined as > or = 50% reduction from the baseline 28-item Hamilton Rating Scale for Depression (HAM-D-28) total score, and remission was defined as a HAM-D-28 score < or = 10. RESULTS: Based on last observation carried forward analyses, HAM-D-28 response rates were 31% (18/59) after 3 months, 44% (26/59) after 1 year, and 42% (25/59) after 2 years of adjunctive VNS. Remission rates were 15% (9/59) at 3 months, 27% (16/59) at 1 year, and 22% (13/59) at 2 years. By 2 years, 2 deaths (unrelated to VNS) had occurred, 4 participants had withdrawn from the study, and 81% (48/59) were still receiving VNS. Longer-term VNS was generally well tolerated. CONCLUSION: These results suggest that patients with chronic or recurrent, treatment-resistant depression may show long-term benefit when treated with VNS.

Ambulatory Care↗
PubMed2004

Parietal cortex and representation of the mental Self.

For a coherent and meaningful life, conscious self-representation is mandatory. Such explicit "autonoetic consciousness" is thought to emerge by retrieval of memory of personally experienced events ("episodic memory"). During episodic retrieval, functional imaging studies consistently show differential activity in medial prefrontal and medial parietal cortices. With positron-emission tomography, we here show that these medial regions are functionally connected and interact with lateral regions that are activated according to the degree of self-reference. During retrieval of previous judgments of Oneself, Best Friend, and the Danish Queen, activation increased in the left lateral temporal cortex and decreased in the right inferior parietal region with decreasing self-reference. Functionally, the former region was preferentially connected to medial prefrontal cortex, the latter to medial parietal. The medial parietal region may, then, be conceived of as a nodal structure in self-representation, functionally connected to both the right parietal and the medial prefrontal cortices. To determine whether medial parietal cortex in this network is essential for episodic memory retrieval with self-representation, we used transcranial magnetic stimulation over the region to transiently disturb neuronal circuitry. There was a decrease in the efficiency of retrieval of previous judgment of mental Self compared with retrieval of judgment of Other with transcranial magnetic stimulation at a latency of 160 ms, confirming the hypothesis. This network is strikingly similar to the network of the resting conscious state, suggesting that self-monitoring is a core function in resting consciousness.

Adult↗
PubMed2004

A primate model of anterograde and retrograde amnesia produced by convulsive treatment.

A nonhuman primate model of the key cognitive effects of convulsive treatment was developed and tested. Rhesus macaques were trained on 3 tasks: a long-term memory task that required selection of a constant target from a background of distracters, an anterograde task that involved learning a new target each day against a variable number of distracters, and a task that assessed learning and memory for new and previously trained 3-item serial lists. This battery samples a range of cognitive functions, including orientation, working memory, retrograde amnesia for temporally graded stimuli, and anterograde amnesia. Using a within-subject, sham-controlled design, the amnestic effects of electroconvulsive shock (ECS) were evaluated in 2 monkeys. Significant effects of the interventions (sham and ECS) were seen on all tasks. The degree of impairment varied across tasks and as a function of task difficulty. ECS did not impair accuracy on the less difficult tasks (memory for an overlearned item and acquisition of a new item) but did increase the amount of time required to complete the tasks, consistent with a period of disorientation acutely after the intervention. This effect was progressive across the treatments. ECS impaired the acquisition and memory of new lists compatible with an anterograde memory deficit, whereas recall for old lists was relatively spared. This study developed and validated a cognitive battery to assess amnesia in nonhuman primates, providing new experimental paradigms for evaluating the cognitive effects of convulsive treatment.

Amnesia, Anterograde↗
PubMed2004

Absence of histological lesions in primate models of ECT and magnetic seizure therapy.

OBJECTIVE: The authors present preliminary findings from the first nonhuman primate neuropathological study of ECT to use perfusion fixation and adequate controls and the first to compare ECT with magnetic seizure therapy, to their knowledge. METHOD: Twelve Macaca mullata received 6 weeks of daily ECT, magnetic seizure therapy, or anesthesia alone. After perfusion fixation, their brains were examined while masked to intervention. RESULTS: No identified lesions were attributable to the interventions. Cortical and hippocampal immunoreactivity for glial fibrillary acidic protein (an astrocytic marker) was most intense in the group that received ECT. CONCLUSIONS: This small but rigorous primate study supports the view that ECT does not produce histological lesions in the brain and provides the first comparable safety data on magnetic seizure therapy.

Amygdala↗
PubMed2003

Optimization of Golgi methods for impregnation of brain tissue from humans and monkeys.

Golgi impregnation is unique in its ability to display the dendritic trees of large numbers of individual neurons. However, its reputation for inconsistency leaves many investigators reluctant to embrace this methodology, particularly for the study of formalin-fixed human brain tissue. After reviewing the literature, testing a variety of technical variations, and discussing the procedure with experienced practitioners, we have concluded that much of the unpredictability can be removed by matching the Golgi technique to the conditions that were used for fixation of the tissue. Briefly fixed tissues worked best with the rapid Golgi technique, which includes osmium during the initial chromation step, and with the Golgi-Cox method, which includes mercuric chloride during chromation. For tissues that have been fixed for several years or even for several decades, superior results are obtained with the Golgi-Kopsch technique, using multiple changes of a chromation solution that contains paraformaldehyde. In the Golgi-Kopsch technique, pH should be used to monitor the reduction of Cr6+ to Cr3+, which is a crucial determinant of successful chromation. With any Golgi technique, agitation throughout the impregnation helps to avoid precipitates and to improve the quality of impregnation. When the appropriate method is chosen, Golgi impregnation is a useful technique for the neuropathologist.

Animals↗
PubMed2003

A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life stressors.

BACKGROUND: Long-term behavioral, immunologic, and neurochemical alterations have been found in primates exposed to adverse early rearing. METHODS: Bonnet macaque (Macaca radiata) mother-infant dyads were exposed to uncertain requirements for food procurement (variable foraging demand, VFD) for a few months. Ten years later, these offspring and age- and gender-matched control subjects were studied using proton magnetic resonance spectroscopic imaging (MRSI). RESULTS: In anterior cingulate, VFD-reared subjects displayed significantly decreased N-acetylaspartate (NAA) resonance and significantly increased glutamate-glutamine-gamma-aminobutyric acid (Glx) resonance relative to the stable neurometabolite creatine (Cr). Across all subjects, NAA/Cr and Glx/Cr ratios in the anterior cingulate were negatively correlated (r = -.638, p =.014). In the medial temporal lobe, the ratio of choline-containing compounds to Cr was significantly increased in VFD subjects. CONCLUSIONS: These findings indicate that adverse early rearing in primates has an enduring impact on adult MRSI measures considered reflective of neuronal integrity and metabolism, membrane structure and glial function, and cerebral glutamate content, and that these alterations occur in the same brain regions implicated in trauma-related psychiatric disorders.

Alfaxalone Alfadolone Mixture↗
PubMed2003

Transcranial magnetic stimulation.

TMS is a powerful new tool with extremely interesting research and therapeutic potentials. Further understanding of the ways by which TMS changes neuronal function, especially as a function of its use parameters, will improve its ability to answer neuroscience questions as well as to treat diseases. Because of its noninvasiveness, it does not readily fit under the umbrella of neurosurgery. Nevertheless, it is important for neurosurgeons to be aware of TMS, because findings from TMS studies will have implications for neurosurgical approaches like DBS and VNS. Indeed, it is possible to think of using TMS as a potential noninvasive initial screening tool to identify whether perturbation of a circuit has short-term clinical effects. In the example of chronic refractory depression or OCD, which is generally a chronic illness, it might then follow that rather than having daily or weekly TMS for the rest of their lives, patients would have DBS electrodes implanted in the same circuit. Whatever road the future takes, TMS is an important new tool that will likely be of interest to neurosurgeons over the next 20 years and perhaps even longer.

Brain↗