Biomedical subjects

G F Molnar

Publications and source records attributed to G F Molnar.

5 recordsLinked to original sources

PubMed2006

Changes in motor cortex excitability with stimulation of anterior thalamus in epilepsy.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for movement disorders and pain. Recently, bilateral DBS of the anterior nucleus of thalamus (AN) was performed for the treatment of intractable epilepsy. This surgery reduced seizure frequency in an initial group of patients. However, its physiologic effects on the cortex and mechanisms of action remain poorly understood. Different classes of antiepileptic drugs (AEDs) have distinct effects on the excitatory and inhibitory circuits in the motor cortex, which can be studied noninvasively by transcranial magnetic stimulation (TMS). OBJECTIVE: To examine the effects of bilateral AN DBS on motor cortex excitability in epilepsy and compare these to the known effects of AEDs. METHODS: Cortical excitability was assessed in five medicated epilepsy patients with bilateral stimulators implanted in the anterior thalamus and nine healthy controls. Single and paired TMS were used to examine cortical inhibitory and facilitatory circuits. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex. Patients were studied during DBS turned off (OFF condition), DBS with cycling stimulation mode (1 minute on, 5 minutes off; CYCLE), and DBS with continuous stimulation (CONTINUOUS) in random order on 3 consecutive days. RESULTS: Motor thresholds were increased in the patients regardless of DBS condition. Active short-interval intracortical inhibition (SICI) was significantly reduced in the OFF and CYCLE conditions but returned toward normal levels in the CONTINUOUS condition. Rest SICI, long interval intracortical inhibition, and silent period duration were unchanged. CONCLUSIONS: Increased short-interval intracortical inhibition with continuous deep brain stimulation (DBS) suggests that thalamic DBS might drive cortical inhibitory circuits, similar to antiepileptic drugs that enhance gamma-aminobutyric acid inhibition.

Adult↗

PubMed2005

Changes in cortical excitability with thalamic deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for several movement disorders. However, its mechanism of action is largely unknown. Both lesioning and DBS of the ventralis intermedius (VIM) nucleus of thalamus improve essential tremor. Although DBS was initially thought to inhibit the target neurons, recent studies suggest that DBS activates neurons. OBJECTIVE: To test the hypothesis that thalamic DBS activates the target area in patients with essential tremor. METHODS: Cortical excitability was assessed in seven unmedicated patients with essential tremor using unilateral stimulators implanted in the VIM of the dominant hemisphere and in 11 healthy controls using transcranial magnetic stimulation (TMS). Patients were studied during optimal DBS (ON condition), half the optimal frequency (HALF), and with DBS off (OFF) in random order. Tremor was assessed after a change in DBS setting. Electromyography was recorded from the dominant hand, and TMS was applied over the contralateral motor cortex using single and paired pulses to elicit motor evoked potentials (MEPs). MEP recruitment was determined using stimulus intensities from 100% to 150% of motor threshold. RESULTS: Tremor scores were significantly improved with DBS ON. Analysis of variance showed a significant interaction between condition (ON, HALF, OFF, Normal) and stimulus intensity on MEP amplitude. During DBS ON MEP amplitudes were significantly higher compared with controls at high but not at low TMS intensities. CONCLUSION: Because the ventralis intermedius (VIM) projects directly to the motor cortex, the high motor evoked potential amplitude with deep brain stimulation ON suggests that VIM DBS activates rather than inhibits the target area.

Adult↗

PubMed2005

Differences in neuronal firing rates in pallidal and cerebellar receiving areas of thalamus in patients with Parkinson's disease, essential tremor, and pain.

The motor symptoms of Parkinson's disease (PD) are thought to result from increased inhibitory outflow from the basal ganglia to the pallidal receiving areas of thalamus (ventral oral anterior and posterior-Voa,Vop). To test this hypothesis, we examined the firing rates of neurons in pallidal and cerebellar receiving areas of thalamus in five PD patients and compared them to those of neurons in comparable regions of motor thalamus in two other patient groups where hyperactivity of GPi is not believed to occur [essential tremor (ET), pain]. Neuronal recordings were made during microelectrode-guided functional stereotactic neurosurgery. The mean spontaneous firing rate (MSFR) of neurons classified as voluntary neurons and presumed to be in pallidal receiving areas of thalamus in PD patients [7.4 +/- 1.0 (SE) Hz] was significantly lower (P < 0.01) than in the ET (18.1 +/- 3.0 Hz) and pain (19.0 +/- 1.9Hz) groups. In contrast, the MSFR of neurons classified as kinesthetic and presumed to be primarily in the cerebellar receiving area of thalamus (ventral intermediate-Vim), although some are probably in the deep shell region of the ventrocaudal nucleus (VPLa), was significantly greater in ET patients (25.8 +/- 3.5 Hz) than in the PD (14.3 +/- 1.6 Hz; P < 0.01) and pain (16.1 +/- 1.5 Hz; P < 0.05) groups. Similar findings were obtained when the neurons were grouped according to their estimated locations in Voa/Vop and Vim of motor thalamus. These data provide support for the prediction of the classical pathophysiological model of PD and moreover suggest that pathophysiology in the cerebello-thalamo-cortical pathway may be a possible cause of tremor in ET patients.

Action Potentials↗

PubMed2004

Thalamic deep brain stimulation activates the cerebellothalamocortical pathway.

To investigate the mechanism of action of deep brain stimulation (DBS), the authors studied the effects of thalamic DBS on the cerebellothalamocortical (CTC) pathway. With DBS turned off, excitability of the CTC pathway was reduced. Turning DBS on resulted in facilitation of the CTC pathway. Therefore, thalamic DBS appears to activate rather than inhibit the target area.

Adult↗

PubMed1998

Protein kinase C is required for long-lasting synaptic enhancement by the neuropeptide DRNFLRFamide in crayfish.

The FMRFamide-related neuropeptide AspArgAsnPheLeuArgPhe-NH2 (DRNFLRFamide, DF2) induces a long-lasting enhancement of synaptic transmission at neuromuscular junctions on the crayfish deep abdominal extensor muscles. Here we investigated the function of protein kinase C (PKC) in this effect because PKC has been implied in the control of long-term synaptic modulation in other systems. The general kinase antagonist staurosporine reduced both the initial increase in excitatory postsynaptic potential (EPSP) amplitude and the duration of synaptic enhancement. Unlike staurosporine, the selective PKC inhibitors, chelerythrine and bisindolylmaleimide, augmented the initial EPSP increase. However, like staurosporine, they also reduced the duration of synaptic enhancement. The PKC activator, phorbol-12-myristate 13-acetate, induced a long-lasting synaptic enhancement that was blocked by chelerythrine. These results show that synaptic enhancement by DF2 is mediated by different intracellular signaling systems that act in temporal sequence. The initial increase in EPSP amplitudes is negatively regulated by PKC and involves another, staurosporine-sensitive, kinase; whereas, the maintenance of synaptic enhancement requires PKC.

Alkaloids↗