A prototype closed-loop brain-machine interface for the study and treatment of pain.

Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain-machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top-down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.

The Millon Clinical Multiaxial Inventory-IV (MCMI-IV) and Millon Adolescent Clinical Inventory-II (MACI-II) in Legal Settings.

The MCMI-IV and MACI-II are the most recent iterations of the primary Millon clinical inventories and have become well-established instruments over the course of multiple editions. The MCMI, in particular in its prior editions, and to a lesser extent, the original MACI, have joined the canon of commonly-used psychological instruments in several forensic settings, though they have been met with significant controversy. This controversy is due in large part to complicated and sometimes questionable psychometric and normative referencing qualities that evaluators may find difficult to defend in a court setting. On balance, the instruments, unlike many others, are also supported by a rich though often less-than-understood theoretical backbone which lends depth and explanatory power, but which also can further complicate addressing psycho-legal questions. The authors, representing a mixed perspective on the inventories, generally conclude that while the MCMI-IV and MACI-II rely on a rich theoretical framework, the peer-reviewed literature is virtually non-existent, the need to rely on their predecessor instruments' research literatures are limiting, and the modifying indices have questionable utility in the detecting of response bias. In addition, the normative data and underreporting response styles in family court evaluations cause problems for the MCMI-IV's use in such contexts.

Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model.

Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood at the network level. In this study, we recorded local field potentials from the ACC of freely moving rats. Animals were injected with complete Freund's adjuvant (CFA) to induce persistent inflammatory pain. Mechanical stimulations were administered to the hind paw before and after CFA administration. We found a significant increase in the high-gamma band (60-100 Hz) power in response to evoked pain after CFA treatment. Ketamine, however, reduced the high-gamma band power in response to evoked pain in CFA-treated rats. In addition, ketamine had a sustained effect on the high-gamma band power lasting up to five days after a single dose administration. These results demonstrate that ketamine has the potential to alter maladaptive neural responses in the ACC induced by chronic pain.