Parkinson Disease: Amirnovin R

Gale JT, Amirnovin R, Williams ZM, Flaherty AW, Eskandar EN. · Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA. · Neurosci Biobehav Rev. · Pubmed #17466375 No free full text.

Abstract: Despite remarkable advances, the relationship between abnormal neuronal activity and the clinical manifestations of Parkinson disease (PD) remains unclear. Numerous hypotheses have emerged to explain the relationship between neuronal activity and symptoms such as tremor, rigidity and akinesia. Among these are the antagonist balance hypothesis wherein increased firing rates in the indirect pathway inhibits movement; the selectivity hypothesis wherein loss of neuronal selectivity leads to an inability to select or initiate movements; the firing pattern hypothesis wherein increased oscillation and synchronization contribute to tremor and disrupt information flow; and the learning hypothesis, wherein the basal ganglia are conceived as playing an important role in learning sensory-motor associations which is disrupted by the loss of dopamine. Deep brain stimulation (DBS) surgery provides a unique opportunity to assess these different ideas since neuronal activity can be directly recorded from PD patients. The emerging data suggest that the pathophysiologic changes include derangements in the overall firing rates, decreased neuronal selectivity, and increased neuronal oscillation and synchronization. Thus, elements of all hypotheses are present, emphasizing that the loss of dopamine results in a profound and multifaceted disruption of normal information flow through the basal ganglia that ultimately leads to the signs and symptoms of PD.

Amirnovin R, Williams ZM, Cosgrove GR, Eskandar EN. · Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Neurosurgery. · Pubmed #16543878 No free full text.

Abstract: OBJECTIVE: Subthalamic deep brain stimulation (DBS) has rapidly become the standard surgical therapy for medically refractory Parkinson disease. However, in spite of its wide acceptance, there is considerable variability in the technical approach. This study details our technique and experience in performing microelectrode recording (MER) guided subthalamic nucleus (STN) DBS in the treatment of Parkinson disease. METHODS: Forty patients underwent surgery for the implantation of 70 STN DBS electrodes. Stereotactic localization was performed using a combination of magnetic resonance and computed tomographic imaging. We used an array of three microelectrodes, separated by 2 mm, for physiological localization of the STN. The final location was selected based on MER and macrostimulation through the DBS electrode. RESULTS: The trajectory selected for the DBS electrode had an average pass through the STN of 5.6 +/- 0.4 mm on the left and 5.7 +/- 0.4 mm on the right. The predicted location was used in 42% of the cases but was modified by MER in the remaining 58%. Patients were typically discharged on the second postoperative day. Eighty-five percent of patients were sent home, 13% required short-term rehabilitation, and one patient required long-term nursing services. Seven complications occurred over 4 years. Four patients suffered small hemorrhages, one patient experienced a lead migration, one developed an infection of the pulse generator, and one patient suffered from a superficial cranial infection. CONCLUSION: Simultaneous bilateral MER-guided subthalamic DBS is a relatively safe and well-tolerated procedure. MER plays an important role in optimal localization of the DBS electrodes.

Gale JT, Shields DC, Jain FA, Amirnovin R, Eskandar EN. · Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, 15 Parkman Street, ACC-021, Boston, MA 02114, USA. · Brain Res. · Pubmed #19167367 No free full text.

Abstract: The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD were compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated - most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity.

Amirnovin R, Williams ZM, Cosgrove GR, Eskandar EN. · Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114-3117, USA. · J Neurosci. · Pubmed #15601936 links to  free full text

Abstract: There is considerable evidence that abnormal oscillatory activity in the basal ganglia contributes to the pathogenesis of Parkinson's disease. However, little is known regarding the relationship of oscillations to volitional movements. Our goal was to evaluate the dynamics of oscillatory activity at rest and during movement. We performed microelectrode recordings from the subthalamic nucleus (STN) of patients undergoing deep brain stimulation surgery. During recordings, the patients used a joystick to guide a cursor to one of four targets on a monitor. We recorded 184 cells and 47 pairs of cells in 11 patients. At rest, 26 cells (14%) demonstrated significant oscillatory activity, with a mean frequency of 18 Hz. During movement, this oscillatory activity was either reduced or completely abolished in all of the cells. At rest, 18 pairs (38%) of cells in five patients exhibited synchronized oscillatory activity, with a mean frequency of 15 Hz. In 17 of the 18 pairs, both of the cells exhibited oscillations, and, in one pair, only one of the cells was oscillatory. These synchronized oscillations were also significantly decreased with movement. There was a strong inverse correlation between firing rates and oscillatory activity. As the firing rates increased with movement, there was a decrease in oscillatory activity. These findings suggest that visually guided movements are associated with a dampening and desynchronization of oscillatory activity in STN neurons. One possible explanation for these observations is that the increased cortical drive associated with movement preparation and execution leads to a transient dampening of STN oscillations, hence facilitating movement.