Biomedical subjects

Mark S George

Publications and source records attributed to Mark S George.

At least 37 records · Page 2Linked to original sources

PubMed2005

Functional neuroanatomy of subcomponent cognitive processes involved in verbal working memory.

Recent research has used functional magnetic resonance imaging (fMRI) to examine brain regions related to specific subcomponent cognitive processes of verbal working memory, which include initial encoding of material, maintenance of the information over a brief delay interval, and later retrieval of the information. The present study examined each of these subcomponents in 14 healthy adults using a Sternberg verbal working memory task and fMRI. Group analysis revealed several brain regions active during all subcomponent processes, which included dorsolateral and ventrolateral prefrontal, parietal, hippocampal, and premotor cortex. Several other brain regions showed activation limited to specific subcomponent processes.

Adult↗

PubMed2005

Brain damage and cortical compensation in foreign accent syndrome.

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.

Brain Injuries↗

PubMed2005

SPECT study of Chinese schizophrenic patients suggests that cerebral hypoperfusion and laterality exist in different ethnic groups.

Hypofrontality is a common finding in schizophrenia in many countries. To date, there have been few studies on Chinese patients with schizophrenia. We thus wondered whether hypofrontality exists in Chinese patients with schizophrenia. We investigated 45 patients with schizophrenia and 21 healthy controls using brain perfusion single photon emission computed tomography (SPECT). Subjects were also administered the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Halstead-Reitan Neuropsychological Battery (HRNB) and the Wechsler Memory Scale-Revised (WMS-R). Images were analyzed using a semi-quantitative reading and a quantified region of interest analysis. We found that schizophrenic patients showed hypoperfusion in the frontal and temporal lobes and hyperperfusion in the basal ganglia. Schizophrenic patients with both negative and positive symptoms showed asymmetric perfusion in the temporal lobe. Schizophrenic patients with prominent negative symptoms also showed asymmetric perfusion in the prefrontal lobes. Negative symptoms showed a significantly negative correlation with regional cerebral blood flow (rCBF) in the left frontal lobe. Improved memory quotient (MQ) was significantly correlated with increased rCBF in the left temporal lobe. These findings from Chinese patients confirm a similar regional neuroanatomic dysfunction as in Western patients with the disease.

Adolescent↗

PubMed2005

Decreased cortical response to verbal working memory following sleep deprivation.

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.

Adolescent↗

PubMed2005

Decreased brain activation during a working memory task at rested baseline is associated with vulnerability to sleep deprivation.

STUDY OBJECTIVE: To examine whether differences in patterns of brain activation under baseline conditions relate to the differences in sleep-deprivation vulnerability. DESIGN: Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging, we scanned 33 healthy young men while they performed the Sternberg working memory task following a normal night of sleep and again following 30 hours of sleep deprivation. From this initial group, based on their Sternberg working memory task performance, we found 10 subjects resilient to sleep deprivation (sleep deprivation-resilient group) and then selected 10 age- and education-matched subjects vulnerable to sleep deprivation (sleep deprivation-vulnerable group). SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Data from 10 young men (mean age 27.8 +/- 1.7 years) in the sleep deprivation-resilient group and 10 young men (mean age 28.2 +/- 1.9 years) in the sleep deprivation-vulnerable group were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared functional magnetic resonance imaging BOLD signal at rested baseline and sleep deprivation states in the 2 groups. As hypothesized, following sleep deprivation, both groups showed significant decreases in global brain activation compared to their rested group baseline. At rested baseline and in the sleep-deprivation state, the sleep deprivation-resilient group had significantly more brain activation than did the sleep deprivation-vulnerable group. There were also differences in functional circuits within and between groups in response to sleep deprivation. CONCLUSIONS: These preliminary data suggest that patterns of brain activation during the Sternberg working memory task at the rested baseline and the sleep-deprivation state, differ across individuals as a function of their sleep-deprivation vulnerability.

Adolescent↗

PubMed2005

An increased precision comparison of TMS-induced motor cortex BOLD fMRI response for image-guided versus function-guided coil placement.

OBJECTIVE: To examine with high precision the differences between function-guided and image-guided transcranial magnetic stimulation (TMS). METHOD: Using a calibrated TMS coil holder/positioner, interleaved TMS/functional magnetic resonance imaging (fMRI), and individualized anatomy-based regional normalization, we conducted a two-phase study of TMS coil positioning guided by either function (elicited thumb motion) or image-based targeting of the "hand knob," the anatomy associated with fMRI activation during thumb motion. RESULTS: In every case, image-guided TMS coil placement produced a thumb movement response at thresholds similar to those found under function guidance. Unexpectedly, function-guided coil locations clustered bimodally over central and precentral sulci. Image-guided locations clustered as anticipated toward the targeted gyral crown. Despite these differences, blood oxygenation level-dependent (BOLD) activation locations and magnitude for the two methods displayed no consistent differences in mean or variance between or within subjects. Image guidance produced more consistent coil placement from subject to subject relative to targeted anatomy. Surprisingly, BOLD time courses from image-guided experiments showed significantly slower return to baseline after TMS than was observed under function guidance. CONCLUSIONS: The results demonstrate the effectiveness and precision of image-guided positioning of TMS coils combined with a precisely adjustable holder/positioner and regional normalization. Image guidance provides an accurate TMS placement relative to individual anatomy when no external sign is available.

Adult↗

PubMed2005

Vagus nerve stimulation affects pain perception in depressed adults.

BACKGROUND: Previous research suggests that vagus nerve stimulation (VNS) affects pain perception in epilepsy patients, with acute VNS decreasing pain thresholds and chronic VNS treatment increasing pain thresholds. However, no studies have investigated the effects of VNS on pain perception in chronically depressed adults, nor have controlled, systematic investigations been published on the differential effects of certain VNS device parameters on pain perception. OBJECTIVES: The present study tried to replicate the results of previous research showing acute pronociceptive effects of VNS and determine the effects of various device parameter settings on pain tolerance. The present study also investigated the relationship among patients' levels of depression, duration of VNS treatment and VNS-induced changes in pain perception. METHODS: A thermal pain challenge task was used to determine pain tolerance during VNS device activation using different combinations of VNS device parameter settings within subjects undergoing VNS therapy for chronic depression. RESULTS: Significant pronociceptive effects were found for acute VNS activation. Individual differences were found with respect to the VNS settings associated with the largest changes in pain perception. Severity of depression was inversely related to baseline pain tolerance, but depression severity was unrelated to VNS-induced acute changes in pain tolerance, as was the length of time participants had been undergoing VNS treatment. CONCLUSIONS: VNS appears to affect pain perception in depressed adults. Different VNS parameter settings may be associated with unique effects from patient to patient. More studies are needed to determine the long-term effects of VNS on pain perception.

Acute Disease↗

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

Neural correlates of speech anticipatory anxiety in generalized social phobia.

Patients with generalized social phobia fear embarrassment in most social situations. Little is known about its functional neuroanatomy. We studied BOLD-fMRI brain activity while generalized social phobics and healthy controls anticipated making public speeches. With anticipation minus rest, 8 phobics compared to 6 controls showed greater subcortical, limbic, and lateral paralimbic activity (pons, striatum, amygdala/uncus/anterior parahippocampus, insula, temporal pole)--regions important in automatic emotional processing--and less cortical activity (dorsal anterior cingulate/prefrontal cortex)--regions important in cognitive processing. Phobics may become so anxious, they cannot think clearly or vice versa.

Adult↗

PubMed2004

A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations.

The aim of this study was to evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on the left and right temporoparietal cortex compared with sham stimulation in schizophrenic patients with treatment-refractory auditory hallucinations (AH). Thirty-nine patients with schizophrenia with treatment-refractory AH were allocated randomly to one of three groups: daily left, right, and sham rTMS groups. rTMS was applied to the TP3 or 4 regions with the aid of the electroencephalography 10-20 international system at 1 Hz for 20 min per day for 10 treatment days. Symptoms were evaluated using the Auditory Hallucination Rating Scale (AHRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression--Severity (CGI-S), and Clinical Global Impression--Improvement (CGI-I) scale. For the time effect (within-subject comparison), there were significant changes in the frequency of AHs, positive symptoms of PANSS, and CGI-I. A between-group comparison revealed significant differences in the positive symptoms of PANSS, and CGI-I scores. Post hoc analysis revealed that both the right- and left-side rTMS treatment groups exhibited better CGI-I scores compared to the sham-stimulated group. This study suggests that 10 days of low-frequency rTMS applied daily for 20 min to either temporoparietal cortex significantly reduces the symptoms in patients with schizophrenia who are having refractory AH, but the left sided rTMS is not superior to right or sham rTMS.

Adolescent↗

PubMed2004

Acute left prefrontal transcranial magnetic stimulation in depressed patients is associated with immediately increased activity in prefrontal cortical as well as subcortical regions.

BACKGROUND: Focal prefrontal cortex repetitive transcranial magnetic stimulation (rTMS) was originally investigated as a potential antidepressant under the assumption that in depressed patients, prefrontal cortex stimulation would produce changes in connected limbic regions involved in mood regulation. METHODS: Fourteen adult patients with depression were scanned in a 1.5-T scanner using interleaved rTMS (1 Hz) applied on the left prefrontal cortex over 7.35 min. Images were analyzed with Statistical Parametric Mapping 2b and principal component analysis. RESULTS: Over the left prefrontal cortex, 1-Hz TMS was associated with increased activity at the site of stimulation as well as in connected limbic regions: bilateral middle prefrontal cortex, right orbital frontal cortex, left hippocampus, mediodorsal nucleus of the thalamus, bilateral putamen, pulvinar, and insula (t = 3.85, p <.001). Significant deactivation was found in the right ventromedial frontal cortex. CONCLUSIONS: In depressed patients, 1-Hz TMS at 100% motor threshold over the left prefrontal cortex induces activation underneath the coil, activates frontal-subcortical neuronal circuits, and decreases activity in the right ventromedial cortex. Further work is needed to understand whether these immediate changes vary as a function of TMS use parameters (intensity, frequency, location) and whether they relate to neurobiologic effects and antidepressant mechanisms of TMS.

Acute Disease↗

PubMed2004

Acute vagus nerve stimulation using different pulse widths produces varying brain effects.

BACKGROUND: Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VNS /functional magnetic resonance imaging (fMRI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PW studies. METHODS: Twelve adult patients with major depression, treated with VNS, underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 micros, 250 micros, or 500 micros). The data were analyzed with SPM2. RESULTS: Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both significantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs. CONCLUSIONS: The data confirm our hypothesis that VNS at PW 500 globally produces no more activation than does PW 250, and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects.

Adult↗

PubMed2004

Safety and benefits of distance-adjusted prefrontal transcranial magnetic stimulation in depressed patients 55-75 years of age: a pilot study.

In contrast to the effects seen in younger adults, depressed elderly subjects have shown more modest antidepressant responses to transcranial magnetic stimulation (TMS). We theorized that higher stimulation intensities in older depressed subjects with prefrontal atrophy might be needed to stimulate underlying cortex. In an open design with patients on stable baseline medications, we treated 18 treatment-resistant elderly depressed subjects (mean age 61.2 +/- 7.3) with 15 rTMS sessions over 3 weeks. We adjusted the delivered TMS intensity to account for MRI measured prefrontal atrophy. The skull to prefrontal cortex distance increased with age, whereas the skull to motor cortex distance did not. All subjects tolerated the higher doses well. The average intensity used was 114% of motor threshold (MT) with a range from 103-141% MT. There was an average 35% decline over the 3 weeks in HRSD scores. After 3 weeks of treatment, 27% (5/18) met response criteria (> 50% improvement), with four of these five also meeting criteria for remission (exit Hamilton Depression Score < 8). These initial pilot findings support the need for blinded studies using prefrontal TMS in an elderly population, testing whether TMS, delivered at stimulation intensities calculated to overcome atrophy, is more effective than TMS without adjusting for atrophy.

Aged↗

PubMed2004

Can left prefrontal rTMS be used as a maintenance treatment for bipolar depression?

Numerous studies have examined the acute antidepressant effects of prefrontal transcranial magnetic stimulation (TMS). However, there is little information on whether TMS can be used as a maintenance treatment to maintain normal mood once subjects have responded. We describe seven adults with bipolar depression who responded acutely to TMS and were then treated with TMS weekly for up to 1 year. TMS was carried out over the left prefrontal cortex at 110% motor threshold, 5 Hz for 8 s for 40 trains. Three subjects completed 1 full year of weekly TMS with an average Hamilton Rating Scale for Depression of 13 (sd = 5.9) over the year. These data suggest but do not prove that TMS might eventually be used as an adjunctive maintenance treatment for at least some patients with bipolar depression. Much work remains.

Adult↗

PubMed2004

A replication study of the neural correlates of deception.

The authors attempted to replicate prior group brain correlates of deception and improve on the consistency of individual results. Healthy, right-handed adults were instructed to tell the truth or to lie while being imaged in a 3T magnetic resonance imaging (MRI) scanner. Blood oxygen level-dependent functional MRI significance maps were generated for subjects giving a deceptive answer minus a truthful answer (lie minus true) and the reverse (true minus lie). The lie minus true group analysis (n = 10) revealed significant activation in 5 regions, consistent with a previous study (right orbitofrontal, inferior frontal, middle frontal cortex, cingulate gyrus, and left middle frontal), with no significant activation for true minus lie. Individual results of the lie minus true condition were variable. Results show that functional MRI is a reasonable tool with which to study deception.

Adolescent↗

PubMed2004

Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving.

Using fMRI, our group previously found that after a sip of alcohol and exposure to alcohol beverage pictures, alcoholics compared to social drinkers had increased differential brain activity in the prefrontal cortex and anterior thalamus. This study extends this earlier work with several improvements including imaging the entire brain (rather than the anterior half previously) and recording craving, while the subjects viewed images within the scanner. In a Philips 1.5 T MRI scanner, 10 nontreatment-seeking alcoholics and 10 age-matched healthy social drinkers were given a sip of alcohol before viewing a 12 min randomized presentation of pictures of alcoholic beverages, nonalcoholic beverages, and two different visual control tasks. During picture presentation, changes in regional brain activity were measured in 15 transverse T2(*)-weighted blood oxygen level dependent slices. Subjects rated their urge to drink after each picture sequence. After a sip of alcohol, while viewing alcohol cues compared to viewing other beverage cues, the alcoholics, but not social drinkers, reported higher craving ratings and had increased activity in the prefrontal cortex and anterior limbic regions. Brain activity in the left nucleus accumbens, anterior cingulate, and left orbitofrontal cortex significantly correlated with subjective craving ratings in alcohol subjects but not in control subjects. This study suggests, as did our earlier study, that alcoholics and not social drinkers, when exposed to alcohol cues, have increased brain activity in areas that reportedly subserve craving for other addictive substances.

Adult↗

PubMed2004

Interleaved transcranial magnetic stimulation/functional MRI confirms that lamotrigine inhibits cortical excitability in healthy young men.

Little is known about how lamotrigine (LTG) works within brain circuits to achieve its clinical effects. We wished to determine whether the new technique of interleaved transcranial magnetic stimulation (TMS)/functional magnetic resonance imaging (fMRI) could be used to assess the effects of LTG on activated motor or prefrontal/limbic circuits. We carried out a randomized, double-blind, crossover trial involving two visits 1 week apart with TMS measures of cortical excitability and blood oxygen level-dependent TMS/fMRI. Subjects received either a single oral dose of 325 mg of LTG or placebo on each visit. In all, 10 subjects provided a complete data set that included interleaved TMS/fMRI measures and resting motor threshold (rMT) determinations under both placebo and LTG conditions. A further two subjects provided only rMT data under the two drug conditions. LTG caused a 14.9+/-9.6% (mean+/-SD) increase in rMT 3 h after the drug, compared with a 0.6+/-10.9% increase 3 h after placebo (t=3.41, df =11, p<0.01). fMRI scans showed that LTG diffusely inhibited cortical activation induced by TMS applied over the motor cortex. In contrast, when TMS was applied over the prefrontal cortex, LTG increased the TMS-induced activation of limbic regions, notably the orbitofrontal cortex and hippocampus. These results suggest that LTG, at clinically relevant serum concentrations, has a general inhibitory effect on cortical neuronal excitability, but may have a more complex effect on limbic circuits. Furthermore, the interleaved TMS/fMRI technique may be a useful tool for investigating regional brain effects of psychoactive compounds.

Adolescent↗

PubMed2004

The maximum-likelihood strategy for determining transcranial magnetic stimulation motor threshold, using parameter estimation by sequential testing is faster than conventional methods with similar precision.

BACKGROUND: The resting motor threshold (rMT) is the basic unit of transcranial magnetic stimulation (TMS) dosing. Traditional methods of determining rMT involve finding a threshold of either visible movement or electromyography (EMG) motor-evoked potentials, commonly approached from above and below and then averaged. This time-consuming method typically uses many TMS pulses. Mathematical programs can efficiently determine a threshold by calculating the next intensity needed based on the prior results. Within our group of experienced TMS researchers, we sought to perform an illustrative study to compare one of these programs, the Maximum-Likelihood Strategy using Parameter Estimation by Sequential Testing (MLS-PEST) approach, to a modification of the traditional International Federation of Clinical Neurophysiology (IFCN) method for determining rMT in terms of the time and pulses required and the rMT value. METHODS: One subject participated in the study. Five researchers determined the same subject's rMT on 4 separate days-twice using EMG and twice using visible movement. On each visit, researchers used both the MLS-PEST and the IFCN methods, in alternating order. RESULTS: The MLS-PEST approach was significantly faster and used fewer pulses to estimate rMT. For EMG-determined rMT, MLS-PEST and IFCN derived similar rMT, whereas for visible movement MLS-PEST rMT was higher than for IFCN. CONCLUSIONS: The MLS-PEST algorithm is a promising alternative to traditional, time-consuming methods for determining rMT. Because the EMG-PEST method is totally automated, it may prove useful in studies using rMT as a quickly changing variable, as well as in large-scale clinical trials. Further work with PEST is warranted.

Algorithms↗