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Biomedical subjects

S H Lisanby

Publications and source records attributed to S H Lisanby.

At least 19 recordsLinked to original sources

Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: frequency- and time-dependent effects.

Although improvements in performance due to TMS have been demonstrated with some cognitive tasks, performance improvement has not previously been demonstrated with working memory tasks. In the present study, a delayed match-to-sample task was used in which repetitive TMS (rTMS) at 1, 5, or 20 Hz was applied to either left dorsolateral prefrontal or midline parietal cortex during the retention (delay) phase of the task. Only 5 Hz stimulation to the parietal site resulted in a significant decrease in reaction time (RT) without a corresponding decrease in accuracy. This finding was replicated in a second experiment, in which 5 Hz rTMS at the parietal site was applied during the retention phase or during presentation of the recognition probe. Significant speeding of RT occurred in the retention phase but not the probe phase. This finding suggests that TMS may improve working memory performance, in a manner that is specific to the timing of stimulation relative to performance of the task, and to stimulation frequency.

Adult↗

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials.

Testing the therapeutic potential of transcranial magnetic stimulation (TMS) in controlled trials requires a valid sham condition. Sham TMS is typically administered by tilting the coil 45--90 degrees off the scalp, with one or two wings of the coil touching the scalp. Lack of cortical effects has not been verified. We compared sham manipulations in their thresholds for eliciting motor-evoked potentials (MEPs) in human volunteers and in intracerebral measurements of voltage induced in the prefrontal cortex of a rhesus monkey. Three types of sham (one-wing 45 degrees and 90 degrees and two-wing 90 degrees tilt) induced much lower voltage in the brain than active TMS (67--73% reductions). However, the two-wing 45 degrees sham induced values just 24% below active TMS. This sham was about half as potent in inducing MEPs over the motor cortex as active TMS. Some sham TMS conditions produce substantial cortical stimulation, making it critical to carefully select the sham manipulation for clinical trials.

Adult↗

Elevated motor threshold in drug-free, cocaine-dependent patients assessed with transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) provides a noninvasive method of examining cortical inhibitory and excitatory processes and cortical excitability in awake subjects. There is evidence from clinical and electroencephalographic (EEG) data that cortical excitability may be abnormal in some psychiatric populations. Chronic cocaine abuse influences a number of neurotransmitters that are involved in the excitatory/inhibitory balance of the cerebral cortex. This pilot study was conducted to ascertain the possible utility of TMS in examining cortical excitability in a population of chronic cocaine abusers. METHODS: The right and left motor thresholds of ten cocaine-dependent subjects, according to DSM-IV, and ten normal control subjects were examined using single pulse TMS. RESULTS: The resting motor thresholds resulting from stimulation of the right or the left motor cortical regions were significantly elevated in cocaine-dependent subjects compared with matched control subjects. CONCLUSIONS: These pilot data suggest that chronic cocaine use significantly alters cortical excitability in the direction of increased inhibition or decreased excitability. We hypothesize that this observation reflects adaptation to those effects of cocaine intoxication that promote cortical excitability and seizures.

Adult↗

Transcranial magnetic stimulation differentially affects speed and direction judgments.

This study was conducted to determine whether humans' judgments about the speed and direction of moving stimuli was differentially affected by transcranial magnetic stimulation (TMS). Subjects viewed two successively presented moving stimuli that differed from each other both in speed and direction of motion. Single-pulse TMS was applied either medially (approximately 2 cm above the inion) or laterally (approximately 5 cm lateral to and 4 cm above the inion), while subjects judged the speed and direction differences. The physical stimulation (visual and TMS) was identical on the two tasks, as was discriminability (d') when TMS was not applied. We found significant criterion (beta) shifts on the speed discrimination task at both stimulation sites. Specifically, on TMS trials the proportion of "slower" judgments increased significantly, consistent with subjective reports that stimuli often appeared to slow when TMS was applied. The subjective reports indicated no corresponding change in perceived direction. We also found that speed discriminability was impaired significantly more than direction discriminability, but only when TMS was applied medially. Indeed, after controlling for TMS-related changes in reaction time, speed discriminability was impaired significantly, while direction discriminability remained largely intact. This dissociation suggests that the sensory response constraining speed discrimination is at least partially independent from the sensory response constraining direction discrimination. Combined with previous psychophysical data, the present data suggest a double dissociation between speed and direction discrimination in humans.

Adult↗

Repetitive transcranial magnetic stimulation to SMA worsens complex movements in Parkinson's disease.

OBJECTIVES: To evaluate the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) for Parkinson's disease (PD) by delivering stimulation at higher intensity and frequency over longer time than in previous research. Promising beneficial effects on movement during or after rTMS have been reported. METHODS: Ten patients with idiopathic PD were enrolled in a randomized crossover study comparing active versus sham rTMS to the supplementary motor area (SMA). Assessments included reaction and movement times (RT/MT), quantitative spiral analysis, timed motor performance tests, United Parkinson's Disease Rating Scale (UPDRS), patient self-report and guess as to stimulation condition. RESULTS: Two of 10 patients could not tolerate the protocol. Thirty to 45 min following stimulation, active rTMS as compared with sham stimulation worsened spiral drawing (P=0.001) and prolonged RT in the most affected limb (P=0.030). No other significant differences were detected. CONCLUSIONS: We sought clinically promising improvement in PD but found subclinical worsening of complex and preparatory movement following rTMS to SMA. These results raise safety concerns regarding the persistence of dysfunction induced by rTMS while supporting the value of rTMS as a research tool. Studies aimed at understanding basic mechanisms and timing of rTMS effects are needed.

Aged↗

Therapeutic application of repetitive transcranial magnetic stimulation: a review.

Transcranial magnetic stimulation (TMS), a non-invasive means of electrically stimulating neurons in the human cerebral cortex, is able to modify neuronal activity locally and at distant sites when delivered in series or trains of pulses. Data from stimulation of the motor cortex suggest that the type of effect on the excitability of the cortical network depends on the frequency of stimulation. These data, as well as results from studies in rodents, have been generalized across brain areas and species to provide rationales for using repetitive TMS (rTMS) to treat various brain disorders, most notably depression. Research into clinical applications for TMS remains active and has the potential to provide useful data, but, to date, the results of blinded, sham-controlled trials do not provide clear evidence of beneficial effects that replace or even match the effectiveness of conventional treatments in any disorder. In this review, we discuss the clinical and scientific bases for using rTMS as treatment, and review the results of trials in psychiatric and neurological disorders to date.

Animals↗

Protein kinase a in major depression: the link between hypothalamic-pituitary-adrenal axis hyperactivity and neurogenesis.

The latest and most generative biological theories of major depression center on two major hypotheses. The first focuses on the concept that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis leads to many of the pathological changes in the brain that accompany major depression. The second posits that neurogenesis leads to the repair of depression-related injuries. These two hypotheses are complementary: the former alludes to the etiology or consequences of depression, while the latter suggests mechanisms of antidepressant action. Significant crosstalk occurs between these two systems at many levels. Protein kinase A (PKA) may play an important role in this crosstalk at the intracellular level of signaling cascades. PKA is involved in the formation of long-term potentiation and fear conditioning in response to stress. Chronic stress leads to the suppression of hippocampal activity, which may cause the hyperactivity of the HPA axis during melancholic depression. PKA is also involved in the stimulation of hippocampal neurogenesis after antidepressant treatment. In theory, neurogenesis may lead to the restoration of hippocampal function, and this may be the mechanism that leads to antidepressant-mediated normalization of HPA hyperactivity. Thus, PKA is active during processes that potentially lead to depression and other processes that lead to the resolution of the illness. These opposing processes may be mediated by separate PKA isozymes that activate two distinct pathways. This review highlights the dual role of this enzyme in two biological hypotheses pertaining to depression and its treatment.

Journal Article↗

ECT in bipolar and unipolar depression: differences in speed of response.

OBJECTIVES: There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT. METHODS: Over three double-blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n = 162) or BP depression (n = 66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post-ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length. RESULTS: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT. CONCLUSIONS: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.

Adult↗

Focal prefrontal seizures induced by bilateral ECT.

INTRODUCTION: It has been proposed that the greater efficacy of bilateral (BL) over right unilateral (RUL) electroconvulsive therapy (ECT) at low stimulus intensity is due to differences in site of seizure initiation. We hypothesized that focal prefrontal seizures are more common with BL than RUL administration. METHOD: Records were reviewed of the 1,007 ECT treatments of 84 consecutive patients randomized to RUL or BL electrode placement. RESULTS: Eight events were identified in which there was an electroencephalographic seizure without motor manifestation. All of these events occurred at titration sessions and with BL stimuli (p = 0.002). These events were more likely to occur later in the course of treatment. DISCUSSION: We suggest that BL ECT may induce focal seizures in prefrontal areas and that these seizures are more likely to occur later in the treatment course.

Adult↗

ECT in the treatment of status epilepticus.

INTRODUCTION: Owing to its potent anticonvulsant actions, electroconvulsive therapy (ECT) has been proposed as an intervention for treatment-resistant seizure disorders. METHOD: We review the literature on the use of ECT in treatment-resistant epilepsy and status epilepticus (SE) and present a case of a patient who was in nonconvulsive SE for 26 days and then treated with ECT after all standard pharmacological strategies were exhausted. Because of skull defects, a novel electrode placement was used. RESULTS: Owing to massively elevated seizure threshold attributable to concomitant anticonvulsant medications, extraordinarily high electrical dosage was needed for ECT to elicit generalized seizures. Status was terminated after three successful ECT-induced seizures. However, the long-term functional outcome of the patient was poor. DISCUSSION: The role of ECT in the treatment algorithm for SE is discussed.

Adult↗

The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression.

BACKGROUND: Chronic vagus nerve stimulation (VNS) is effective in the management of treatment-resistant epilepsy. Open-trial evidence suggests that VNS has clinically significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes. However, limited information regarding the effects of VNS on neurocognitive performance exists. OBJECTIVE: The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration. METHOD: A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS. Thirteen neurocognitive tests sampled the domains of motor speed, psychomotor function, language, attention, memory, and executive function. RESULTS: No evidence of deterioration in any neurocognitive measure was detected. Relative to baseline, improvement in motor speed (finger tapping), psychomotor function (digit-symbol test), language (verbal fluency), and executive functions (logical reasoning, working memory, response inhibition, or impulsiveness) was found. For some measures, improved neurocognitive performance correlated with the extent of reduction in depressive symptoms, but VNS output current was not related to changes in cognitive performance. CONCLUSIONS: Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function, primarily among patients who show clinical improvement. Controlled investigation is needed to rule out the contribution of practice effects.

Adolescent↗

A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities.

BACKGROUND: Controversy persists about the use of right unilateral (RUL) and bilateral (BL) electroconvulsive therapy (ECT). While RUL ECT results in less severe short-term and long-term cognitive effects, there is concern that it is less efficacious than BL ECT. METHODS: In a double-blind study, 80 depressed patients were randomized to RULECT, with electrical dosages 50%, 150%, or 500% above the seizure threshold, or BL ECT, with an electrical dosage 150% above the threshold. Depression severity and cognitive functioning were assessed before, during, immediately after, and 2 months after ECT. Compared with baseline, responders had at least a 60% reduction in symptom scores 1 week after ECT, and were monitored for relapse for 1 year. RESULTS: High-dosage RUL and BL ECT were equivalent in response rate (65%) and approximately twice as effective as low-dosage (35%) or moderate-dosage (30%) unilateral ECT. During the week after the randomized phase, BL ECT resulted in greater impairment than any dosage of unilateral ECT in several measures of anterograde and retrograde memory. Two months after ECT, retrograde amnestic deficits were greatest among patients treated with BL ECT. Thirty-three (53%) of the 62 patients who responded to ECT relapsed, without treatment group differences. The relapse rate was greater in patients who had not responded to adequate pharmacotherapy prior to ECT and who had more severe depressive symptoms after ECT. CONCLUSION: Right unilateral ECT at high dosage is as effective as a robust form of BL ECT, but produces less severe and persistent cognitive effects.

Amnesia↗

The effects of electroconvulsive therapy on memory of autobiographical and public events.

BACKGROUND: Retrograde amnesia is the most persistent cognitive adverse effect of electroconvulsive therapy (ECT); however, it is not known whether ECT has differential effects on autobiographical vs impersonal memories. This study examined the short- and long-term effects of differing forms of ECT on memory of personal and impersonal (public) events. METHODS: Fifty-five patients with major depression were randomly assigned to right unilateral (RUL) or bilateral (BL) ECT, each at either low or high electrical dosage. The Personal and Impersonal Memory Test was administered by blinded raters at baseline, during the week after ECT, and at the 2-month follow-up. Normal controls were tested at matched intervals. RESULTS: Shortly after ECT, patients recalled fewer events and event details than controls, with the deficits most marked for impersonal compared with personal events. Bilateral ECT caused more marked amnesia for events and details than RUL ECT, and especially for impersonal memories. These effects were independent of electrical dosage and clinical outcome. At the 2-month follow-up, patients had reduced retrograde amnesia, but continued to show deficits in recalling the occurrence of impersonal events and the details of recent impersonal events. CONCLUSIONS: The amnestic effects of ECT are greatest and most persistent for knowledge about the world (impersonal memory,) compared with knowledge about the self (personal memory), for recent compared with distinctly remote events, and for less salient events. Bilateral ECT produces more profound amnestic effects than RUL ECT, particularly for memory of impersonal events.

Amnesia↗

Animal models of the mechanisms of action of repetitive transcranial magnetic stimulation (RTMS): comparisons with electroconvulsive shock (ECS).

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive means of brain stimulation with a broad range of basic neuroscience and potential future clinical applications. Recent animal studies have shed some light on the mechanisms of action of rTMS, and broadened our understanding of how this intervention affects brain functioning acutely and chronically. Differences in the physical properties of magnetic and electrical stimulation result in marked disparities in the amount and distribution of electrical current induced in the brain; nevertheless, rTMS shares many of the behavioral and biochemical actions of electroconvulsive shock (ECS) and other antidepressant treatments. rTMS reduces immobility in the Porsolt swim task and enhances apomorphine-induced stereotypy, as does ECS. Although rTMS can induce a seizure when given at high enough doses, most studies have found subconvulsive levels of rTMS to be anticonvulsant. rTMS acutely modulates dopamine and serotonin content and turnover rates. Chronic rTMS modulates cortical beta-adrenergic receptors, reduces frontal cortex 5-HT2 receptors, increases 5-hydroxytryptamine1A receptors in frontal cortex and cingulate, and increases N-methyl-D-aspartate receptors in the ventromedial hypothalamus, basolateral amygdala, and parietal cortex. More work will be needed to clarify and explore the mechanism behind the early suggestions that rTMS may exert long-term-potentiation-like or long-term-depression-like action on hippocampal activity. Finally, rTMS is emerging as yet another intervention, like ECS and other antidepressants, that can regulate gene expression and may have an impact on neuronal viability and synaptic plasticity.

Animals↗