Biomedical subjects

Jing-Yu Chang

Publications and source records attributed to Jing-Yu Chang.

12 recordsLinked to original sources

PubMed2006

Temporal sequence of ictal discharges propagation in the corticolimbic basal ganglia system during amygdala kindled seizures in freely moving rats.

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However, no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures.

Amygdala↗

PubMed2006

Basal ganglia neural responses during behaviorally effective deep brain stimulation of the subthalamic nucleus in rats performing a treadmill locomotion test.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). In spite of proven therapeutic success, the mechanism underlying the benefits of DBS has not been resolved. A multiple-channel single-unit recording technique was used in the present study to investigate basal ganglia (BG) neural responses during behaviorally effective DBS of the STN in a rat model of PD. Rats underwent unilateral dopamine (DA) depletion by injection of 6-hydroxyDA (6-OHDA) into one side of the medial forebrain bundle and subsequently developed a partial akinesia, which was assessed during the treadmill locomotion task. High frequency stimulation (HFS) of the STN restored normal treadmill locomotion behavior. Simultaneous recording of single unit activity in the striatum (STR), globus pallidus (GP), substantia nigra pars reticulata (SNr), and STN revealed a variety of neural responses during behaviorally effective HFS of the STN. Predominant inhibitory responses appeared in the STN stimulation site. Nearly equal numbers of excitatory and inhibitory responses were found in the GP and SNr, whereas more rebound excitatory responses were found in the STR. Mean firing rate did not change significantly in the STR, GP, and SNr, but significantly decreased in both sides of STN during DBS. A decrease in firing rate in the contralateral side of STN provides neural substrate for the clinical observation that unilateral DBS produces bilateral benefits in patients with PD. In addition to the firing rate changes, a decrease in burst firing was observed in the GP and STN. The present study indicates that DBS induces complex modulations of the BG circuit and further suggests that BG network reorganization, rather than a simple excitation or inhibition, may underlie the therapeutic effects of DBS in patients with PD.

Adrenergic Agents↗

PubMed2006

Deep brain stimulation of the substantia nigra pars reticulata exerts long lasting suppression of amygdala-kindled seizures.

Deep brain stimulation (DBS) has been used to treat a variety of neurological disorders including epilepsy. However, we have limited knowledge about effective target areas, optimal stimulation parameters, and long-term effect of DBS on epileptic seizures. Here we examined the effects of DBS of the substantia nigra pars reticulata (SNr) on amygdala-kindled seizures. Microwire electrodes were implanted into the SNr and amygdala of adult male rats. When stage 5-kindled seizures were achieved by daily amygdala kindling, high frequency stimulation was delivered to the SNr bilaterally 1 s after cessation of kindling. Our DBS protocol completely blocked kindled seizures in 10 out of 23 (43.5%) rats studied. Furthermore, when the same amygdala kindling procedure was performed 24 h later without DBS, the kindling failed to elicit any seizure signs in 6 of these 10 rats. Some of the post-DBS period of seizure suppression lasted for up to 4 days. In other 3 rats, only mild stage 1 to 2 seizures appeared following amygdala kindling. Only 1 of the 10 rats for which DBS had blocked kindled seizures exhibited full-scale 5 stage-kindled seizures 24 h after DBS. These results suggest that highly plastic neural networks are involved in amygdala-kindled seizures and that DBS, if well timed with the onset of amygdala kindling, may exert long lasting effects on the networks that may prevent the recurrence of kindled seizures.

Amygdala↗

PubMed2006

Dynamic neuronal responses in cortical and thalamic areas during different phases of formalin test in rats.

Although formalin-induced activity in primary afferent fibers and spinal dorsal horn is well described, the forebrain neural basis underlying each phase of behavior in formalin test has not yet been clarified. The present study was designed to investigate the cortical and thalamic neuronal responses and interactions among forebrain areas during different phases after subcutaneous injection of formalin. Formalin-induced neuronal activities were simultaneously recorded from primary somatosensory cortex (SI), anterior cingulate cortex (ACC) and medial dorsal (MD) and ventral posterior (VP) thalamus during different phases (i.e., first phase, interphase, second phase and third recovery phase starting from 70 min after injection) of formalin test, using a multi-channel, single-unit recording technique. Our results showed that, (i) unlike the responses in primary afferent fibers and spinal dorsal horn, many forebrain neurons displayed monophasic excitatory responses in the first hour after formalin injection, except a small portion of neurons which exhibited biphasic responses; (ii) the response patterns of many cortical and thalamic neurons changed from excitatory to inhibitory at the end of the second phase; (iii) the direction of information flow also changed dramatically, i.e., from cortex to thalamus and from the medial to the lateral pathway in the first hour, but reversed in phase 3. These results indicate that the changes of activity pattern in forebrain networks may underlie the emerging and subsiding of central sensitization-induced pain behavior in the second phase of formalin test.

Action Potentials↗

PubMed2005

Neural responses in multiple basal ganglia regions following unilateral dopamine depletion in behaving rats performing a treadmill locomotion task.

To investigate basal ganglia (BG) neural responses to dopamine (DA) depletion, multiple channel, single unit recording was carried out in freely moving rats performing a treadmill locomotion task. Single unit activity from 64 microelectrodes in the striatum (STR), globus pallidus (GP), subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) was recorded simultaneously before and after a unilateral DA lesion induced by microinjection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The DA lesion resulted in an impairment of treadmill walking manifested by a significant decrease in swing time of both forelimbs. The stance time, however, increased significantly only in ipsilateral (good) forelimbs, reflecting compensatory changes in the good limb for motor deficits. Neural activity in the STR and GP ipsilateral to the lesion decreased during the 7-day period following the DA lesion. Conversely, an increase in spike discharges appeared in the ipsilateral SNr and STN several days after the DA lesion. Changes in the type of neural response associated with treadmill locomotion were also found in some neurons after DA depletion. Such changes were most prominent in the STR. Limb movement-related neural activity increased significantly mainly in the SNr. Additionally, neural responses to the tone cue associated with the onset of the treadmill diminished greatly in the lesioned side of the BG. Increased activity in SNr neurons is consistent with the concept that inhibition of thalamus contributes to hypokinesis in the absence of DA. Substantial decrease in striatal activity supports a concept that DA loss leads to a global suppression of recurrent cortical striatal thalamic activity that degrades normal information flow in Parkinson's diseases.

Action Potentials↗

PubMed2005

Coding of peripheral electrical stimulation frequency in thalamocortical pathways.

Frequency information of the environment is an important feature for sensory perception. It has been demonstrated that cortical and thalamic neurons exhibited frequency-specific responses to peripheral stimulation. In the present study, we investigated the effects of 1-100 Hz peripheral electrical stimulations on various thalamic and cortical areas in awake rats. We used chronically implanted microelectrode arrays to record neural activities from the anterior cingulate cortex, primary somatosensory cortex, and medial dorsal and ventral posterior thalamus. The results revealed that cortical and thalamic neurons exhibited frequency-specific responses at both single-neuron and ensemble levels. Clusters of neurons responded to different frequency ranges with changes of both the peak firing rates and the phases of the peak responses in a stimulation cycle. Partial directed coherence analysis showed that information flowing between these recorded areas is also enhanced or inhibited in some frequency-specific pattern during stimulation. These evidences suggest that central nervous system may code environmental frequency information mainly with the activation of selected neural circuits according to their own intrinsic electrical properties. These properties, in turn, may facilitate or inhibit their responses when stimulation with specific frequency information arrives.

Animals↗

PubMed2004

Differential modulation of nociceptive neural responses in medial and lateral pain pathways by peripheral electrical stimulation: a multichannel recording study.

It is well accepted that peripheral electrical stimulation (PES) can produce an analgesic effect in patients with acute and chronic pain. However, the neural basis underlying stimulation-induced analgesia remains unclear. In the present study, we examined the pain-related neural activity modified by peripheral stimulation in rats. The stimulation frequency of pulses applied to needle electrodes in the hindlimb was 2 Hz alternating with 100 Hz, with 0.6 ms pulse width for 2 Hz and 0.2 ms for 100 Hz. The intensity of the stimulation was increased stepwise from 1 to 3 mA with each 1-mA step lasting for 10 min. The nociceptive neural and behavioral responses were examined immediately after the termination of stimulation. Using a multiple-channel recording technique, we simultaneously recorded the activity of many single neurons located in the primary somatosensory and anterior cingulate cortex (ACC), as well as the ventral posterior and medial dorsal thalamus in behaving rats. Our results showed that peripheral electrical stimulation significantly reduced the nociceptive responses in ventroposterior thalamus and somatosensory cortex, indicating an inhibition of nociceptive processing. In contrast, the analgesic stimulation produced a significant increase in mediodorsal thalamus while a less significant decrease in cingulate cortex, reflecting a complicated effect associated with combined antinociceptive activation and nociceptive suppression. These results support the idea that peripheral electrical stimulation can ultimately alter the pain perception by specifically inhibiting the nociceptive transmission in the sensory pathway while mobilizing the antinociceptive action in the affective pathway, thus to produce pain relief.

Animals↗

PubMed2004

High-frequency stimulation of the subthalamic nucleus reverses limb-use asymmetry in rats with unilateral 6-hydroxydopamine lesions.

Deep brain stimulation (DBS) is a widely used clinical treatment for Parkinson's disease (PD). A rodent model of DBS is a necessary tool for understanding the neural mechanisms of this method. Our previous study showed that high-frequency stimulation (HFS) of the subthalamic nucleus (STN) improved treadmill locomotion in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of nigrostriatal dopamine (DA) neurons. The present study tested DBS effects on limb-use asymmetry (LUA) during vertical/lateral exploration in a cylindrical chamber in rats with similar unilateral nigrostriatal DA lesions. Limb-use asymmetry assessment has been used to detect functional capacity over a wide range of dopamine depletion. Before lesioning, rats exhibited regular rearing activity and used both forelimbs equally often to support weight during exploration of the walls of the cylinder. After unilateral nigrostriatal DA lesioning, rats displayed reduced rearing activity and predominant use of the ipsilateral (good) forelimb to touch the wall. HFS of the STN, but not of other nearby regions surrounding the STN, in the lesioned rats restored normal rearing activity and reversed the limb-use asymmetry caused by the unilateral DA depletion. This study is consistent with the possibility that there can be beneficial effects of STN-DBS on behavioral impairments in unilateral DA-depleted rats and may suggest an appropriate rodent model for DBS study.

Animals↗

PubMed2004

Brain stimulation for neurological and psychiatric disorders, current status and future direction.

Interest in brain stimulation therapies has been rejuvenated over the last decade and brain stimulation therapy has become an alternative treatment for many neurological and psychiatric disorders, including Parkinson's disease (PD), dystonia, pain, epilepsy, depression, and schizophrenia. The effects of brain stimulation on PD are well described, and this treatment has been widely used for such conditions worldwide. Treatments for other conditions are still in experimental stages and large-scale, well controlled studies are needed to refine the treatment procedures. In the treatment of intractable brain disorders, brain stimulation, especially transcranial magnetic stimulation (TMS), is an attractive alternative to surgical lesioning as it is relatively safe, reversible, and flexible. Brain stimulation, delivered either via deeply implanted electrodes or from a surface-mounted transcranial magnetic device, can alter abnormal neural circuits underlying brain disorders. The neural mechanisms mediating the beneficial effects of brain stimulation, however, are poorly understood. Conflicting theories and experimental data have been presented. It seems that the action of stimulation on brain circuitry is not limited to simple excitation or inhibition. Alterations of neural firing patterns and long-term effects on neurotransmitter and receptor systems may also play important roles in the therapeutic effects of brain stimulation. Future research on both the basic and clinical fronts will deepen our understanding of how brain stimulation works. Real-time computation of neural activity allows for integration of brain stimulation signals into ongoing neural processing. In this way abnormal circuit activity can be adjusted by optimal therapeutic brain stimulation paradigms.

Electric Stimulation↗

PubMed2004

Nociceptive responses of anterior cingulate cortical ensembles in behaving rats.

OBJECTIVE: To confirm the role of anterior cingulated cortices (ACC) in the coding of pain affect by exploring the neural ensemble coding pattern within the anterior cingulate cortex in behaving rats with a multichannel recording technique. METHODS: In five adult male Sprague-Dawley rats, two arrays of eight stainless steel microwires were bilaterally implanted into ACC. Noxious radiant heat stimulation was applied to the tail, bilateral fore-paws and hind-paws of freely moving rats. Neuroelectric signals were obtained from the microwires and sent to a multichannel recording device via cables and connectors. The time stamps of neuronal activities were stored on a personal computer for off-line analysis. RESULTS: Noxious heat stimuli evoked predominantly excitatory and sustained neural activity within ACC, reflecting the processing of pain unpleasantness; pain-related anticipatory responses could be seen near the stimulation start, indicating the behavioral preparation for escape; ACC neurons had broad receptive fields by showing quite similar pain-related responses to stimuli on either side of the hind-paw, suggesting that they are not eligible for the localization of a stimulus. CONCLUSION: ACC has played a major role in processing the affective-motivational aspect of pain.

Animals↗

PubMed2003

Parallel pain processing in freely moving rats revealed by distributed neuron recording.

The present study was designed to examine the possible differential roles of the medial and lateral pain systems in pain perception. We used a microwire array recording technique to record the pain-evoked neural activity of multiple neurons in freely moving rats. Noxious radiant heat was delivered to either hind-paw in a randomized order. A total of 256 single units were recorded in primary somatosensory cortex (SI), anterior cingulate cortex (ACC), and medial dorsal (MD) and ventral posterior (VP) thalamus during the painful stimulation. The results showed that SI neurons displayed a strong pain-related excitatory response with short duration and significant contralateral bias; VP had very similar functional patterns to that of SI. This suggested that SI, together with VP, participate in the processing of the sensory-discriminative aspect of pain. In contrast, ACC and MD shared common characteristics of moderate and longer-lasting increase of neural activity, bilateral receptive fields without contralateral preference, as well as the anticipatory response at the start of a painful stimulus, corresponding to the specific role of ACC and MD in the affective-motivational aspects of pain. The results provide an initial demonstration of distributed activity patterns within different pain systems in awake and freely moving rats, hence, providing confirmation of the existence of the dual pain pathways.

Action Potentials↗

PubMed2003

High frequency stimulation of the subthalamic nucleus improves treadmill locomotion in unilateral 6-hydroxydopamine lesioned rats.

This study investigated the influence of electrical stimulation of the subthalamic nucleus (STN) on motor impairment induced by unilateral 6-hydroxydopamine (6-OHDA) lesions in the medial forebrain bundle. Rats were trained to walk on a treadmill and then implanted with microelectrode arrays in and near the STN. The neurotoxin 6-OHDA was injected into the medial forebrain bundle (MFB) unilaterally to produce a targeted lesion of the dopaminergic system. Successful lesions produced impaired treadmill walking behavior. High frequency stimulation (HFS) of the STN improved treadmill walking immediately and restored normal walking patterns. The same HFS failed to evoke visible side effects such as stepping, turning, raising of the head or facial muscle contraction in the absence of treadmill movement, or to change rotational behaviors elicited by the dopamine (DA) agonist apomorphine in unilateral lesioned rats. This suggests that the stimulation did not cause movement by an activation of brainstem locomotor regions or an increase attention leading to movement. Apomorphine-induced rotation may represent an imbalance of dopaminergic activation which remains during HFS. This work may provide a rodent model for deep brain stimulation (DBS) in patients with Parkinson's disease, and be suitable for further investigation of the neural mechanisms underlying the therapeutic effects of DBS.

Animals↗