Potential Neural Mediators of Mom Power Parenting Intervention Effects on Maternal Intersubjectivity and Stress Resilience.

Stress resilience in parenting depends on the parent's capacity to understand subjective experiences in self and child, namely intersubjectivity, which is intimately related to mimicking other's affective expressions (i. e., mirroring). Stress can worsen parenting by potentiating problems that can impair intersubjectivity, e.g., problems of "over-mentalizing" (misattribution of the child's behaviors) and "under-coupling" (inadequate child-oriented mirroring). Previously we have developed Mom Power (MP) parenting intervention to promote maternal intersubjectivity and reduce parenting stress. This study aimed to elucidate neural mechanisms underlying the effects of MP with a novel Child Face Mirroring Task (CFMT) in functional magnetic-resonance-imaging settings. In CFMT, the participants responded to own and other's child's facial pictures in three task conditions: (1) empathic mirroring (Join), (2) non-mirroring observing (Observe), and (3) voluntary responding (React). In each condition, each child's neutral, ambiguous, distressed, and joyful expressions were repeatedly displayed. We examined the CFMT-related neural responses in a sample of healthy mothers (n = 45) in Study 1, and MP effects on CFMT with a pre-intervention (T1) and post-intervention (T2) design in two groups, MP (n = 19) and Control (n = 17), in Study 2. We found that, from T1 to T2, MP (vs. Control) decreased parenting stress, decreased dorsomedial prefrontal cortex (dmPFC) during own-child-specific voluntary responding (React to Own vs. Other's Child), and increased activity in the frontoparietal cortices, midbrain, nucleus accumbens, and amygdala during own-child-specific empathic mirroring (Join vs. Observe of Own vs. Other's Child). We identified that MP effects on parenting stress were potentially mediated by T1-to-T2 changes in: (1) the left superior-temporal-gyrus differential responses in the contrast of Join vs. Observe of own (vs. other's) child, (2) the dmPFC-PAG (periaqueductal gray) differential functional connectivity in the same contrast, and (3) the left amygdala differential responses in the contrast of Join vs. Observe of own (vs. other's) child's joyful vs. distressed expressions. We discussed these results in support of the notion that MP reduces parenting stress via changing neural activities related to the problems of "over-mentalizing" and "under-coupling." Additionally, we discussed theoretical relationships between parenting stress and intersubjectivity in a novel dyadic active inference framework in a two-agent system to guide future research.

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation.

The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson's disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

Contemporary concepts of pain surgery.

Pain surgery is one of the historic foundations of neurological surgery. The authors present a review of contemporary concepts in surgical pain management, with reference to past successes and failures, what has been learned as a subspecialty over the past 50 years, as well as a vision for current and future practice. This subspecialty confronts problems of cancer pain, nociceptive pain, and neuropathic pain. For noncancer pain, ablative procedures such as dorsal root entry zone lesions and rhizolysis for trigeminal neuralgia (TN) should continue to be practiced. Other procedures, such as medial thalamotomy, have not been proven effective and require continued study. Dorsal rhizotomy, dorsal root ganglionectomy, and neurotomy should probably be abandoned. For cancer pain, cordotomy is an important and underutilized method for pain control. Intrathecal opiate administration via an implantable system remains an important option for cancer pain management. While there are encouraging results in small case series, cingulotomy, hypophysectomy, and mesencephalotomy deserve further detailed analysis. Electrical neuromodulation is a rapidly changing discipline, and new methods such as high-frequency spinal cord stimulation (SCS), burst SCS, and dorsal root ganglion stimulation may or may not prove to be more effective than conventional SCS. Despite a history of failure, deep brain stimulation for pain may yet prove to be an effective therapy for specific pain conditions. Peripheral nerve stimulation for conditions such as occipital neuralgia and trigeminal neuropathic pain remains an option, although the quality of outcomes data is a challenge to these applications. Based on the evidence, motor cortex stimulation should be abandoned. TN is a mainstay of the surgical treatment of pain, particularly as new evidence and insights into TN emerge. Pain surgery will continue to build on this heritage, and restorative procedures will likely find a role in the armamentarium. The challenge for the future will be to acquire higher-level evidence to support the practice of surgical pain management.

Neurochemical effects of motor cortex stimulation in the periaqueductal gray during neuropathic pain.

OBJECTIVE: Motor cortex stimulation (MCS) is a neurosurgical technique used to treat patients with refractory neuropathic pain syndromes. MCS activates the periaqueductal gray (PAG) matter, which is one of the major centers of the descending pain inhibitory system. However, the neurochemical mechanisms in the PAG that underlie the analgesic effect of MCS have not yet been described. The main goal of this study was to investigate the neurochemical mechanisms involved in the analgesic effect induced by MCS in neuropathic pain. Specifically, we investigated the release of γ-aminobutyric acid (GABA), glycine, and glutamate in the PAG and performed pharmacological antagonism experiments to validate of our findings. METHODS: Male Wistar rats with surgically induced chronic constriction of the sciatic nerve, along with sham-operated rats and naive rats, were implanted with both unilateral transdural electrodes in the motor cortex and a microdialysis guide cannula in the PAG and subjected to MCS. The MCS was delivered in single 15-minute sessions. Neurotransmitter release was evaluated in the PAG before, during, and after MCS. Quantification of the neurotransmitters GABA, glycine, and glutamate was performed using a high-performance liquid chromatography system. The mechanical nociceptive threshold was evaluated initially, on the 14th day following the surgery, and during the MCS. In another group of neuropathic rats, once the analgesic effect after MCS was confirmed by the mechanical nociceptive test, rats were microinjected with saline or a glycine antagonist (strychnine), a GABA antagonist (bicuculline), or a combination of glycine and GABA antagonists (strychnine+bicuculline) and reevaluated for the mechanical nociceptive threshold during MCS. RESULTS: MCS reversed the hyperalgesia induced by peripheral neuropathy in the rats with chronic sciatic nerve constriction and induced a significant increase in the glycine and GABA levels in the PAG in comparison with the naive and sham-treated rats. The glutamate levels remained stable under all conditions. The antagonism of glycine, GABA, and the combination of glycine and GABA reversed the MCS-induced analgesia. CONCLUSIONS: These results suggest that the neurotransmitters glycine and GABA released in the PAG may be involved in the analgesia induced by cortical stimulation in animals with neuropathic pain. Further investigation of the mechanisms involved in MCS-induced analgesia may contribute to clinical improvements for the treatment of persistent neuropathic pain syndromes.

Deep brain stimulation for intractable neuropathic facial pain.

OBJECTIVE Deep brain stimulation (DBS) is a well-established, evidence-based therapy with FDA approval for Parkinson's disease and essential tremor. Despite the early successful use of DBS to target the sensory thalamus for intractable facial pain, subsequent studies pursuing various chronic pain syndromes reported variable efficacy, keeping DBS for pain as an investigational and "off-label" use. The authors report promising results for a contemporary series of patients with intractable facial pain who were treated with DBS. METHODS Pain outcomes for 7 consecutive patients with unilateral, intractable facial pain undergoing DBS of the ventral posteromedial nucleus of the thalamus (VPM) and the periaqueductal gray (PAG) were retrospectively reviewed. Pain was assessed preoperatively and at multiple postoperative time points using the visual analog scale (VAS), the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and the Pain Disability Index (PDI). RESULTS VAS scores significantly decreased from a mean ± SD of 9.0 ± 1.3 preoperatively to 2.6 ± 1.5 at 1 year postoperatively (p = 0.001). PDI scores decreased from a mean total of 48.5 to 28.5 (p = 0.01). SF-MPQ-2 scores decreased from a mean of 4.6 to 2.4 (p = 0.03). Notably, several patients did not experience maximum improvement until 6-9 months postoperatively, correlating with repeated programming adjustments. CONCLUSIONS DBS of the VPM and PAG is a potential therapeutic option for patients suffering from severe, intractable facial pain refractory to other interventions. Improved efficacy may be observed over time with close follow-up and active DBS programming adjustments.

Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

OBJECTIVE: Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. METHODS: Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. RESULTS: MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. CONCLUSIONS: This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.

Chronic neuropathic pain is estimated to affect 3%-4.5% of the worldwide population. It is associated with significant loss of productive time, withdrawal from the workforce, development of mood disorders such as depression and anxiety, and disruption of family and social life. Current medical therapeutics often fail to adequately treat chronic neuropathic pain. Deep brain stimulation (DBS) targeting subcortical structures such as the periaqueductal gray, the ventral posterior lateral and medial thalamic nuclei, and the internal capsule has been investigated for the relief of refractory neuropathic pain over the past 3 decades. Recent work has identified the dorsal anterior cingulate cortex (dACC) as a new potential neuromodulation target given its central role in cognitive and affective processing. In this review, the authors briefly discuss the history of DBS for chronic neuropathic pain in the United States and present evidence supporting dACC DBS for this indication. They review existent literature on dACC DBS and summarize important findings from imaging and neurophysiological studies supporting a central role for the dACC in the processing of chronic neuropathic pain. The available neurophysiological and empirical clinical evidence suggests that dACC DBS is a viable therapeutic option for the treatment of chronic neuropathic pain and warrants further investigation.