Today’s students around the world are striking deals to buy and sell the drug methylphenidate (MPD) for cognitive enhancement. Our knowledge on the effects of MPD on the brain is very limited. The present study was designed to investigate the acute and chronic effect of MPD on the prefrontal cortex (PFC) neurons. On experimental day 1 (ED1) recordings were obtained following saline injections and after 2.5 mg/kg MPD. On ED2 through ED6, daily single 2.5 mg/kg MPD was given followed by 3 washout days (ED7 to 9). On ED10, neuronal recordings were resumed from the same animal after saline and MPD injection similar to that obtained at ED1. Ninety PFC units were recorded, all responded to the initial MPD injection, 66 units (73%) increased their activity At ED10. Recordings were resumed for the 66 units that increased their firing rate at ED1, and following MPD injection 54 units (82%) exhibited significant increases in their baseline firing rates compared to ED1 baseline. When these 54 units were rechallenged (chronic effect) with MPD, 39/54 (72%) exhibited reduction in their firing rate which can be interpreted as tolerance. From the 24 (27%) units that responded to MPD at ED1 by decreasing their activity, 14 units (58%) exhibited a decrease in their baseline firing rates at ED10 compared to ED1 baseline. However, following MPD rechallenge of these 14 units, 11 units (79%) exhibited an increase in their firing rate which is interpreted as sensitization. In conclusion, all PFC units modified their neural baseline activity.

Aggressiveness, defined as violent and angry behavior, is a special and challenging condition that is encountered in medicine. There is frequently involvement of the patient with self-aggressiveness and automutilation, and there may be a history in relatives. Allied health personal and others may be affected by injuries and trauma caused by the patient. Lesioning of the posterior hypothalamus (PHyp) is a technique that was used successfully to control aggressiveness 40 years ago. Deep brain stimulation (DBS) has been recently used for treatment of motor symptoms of movement disorders as well as for some psychiatric diseases, and groups have also suggested that it may be useful for aggressive behavior in select circumstances. This chapter reports the case of a patient with uncontrollable aggressiveness and the implantation of DBS in the PHyp. In this case, the DBS also helped to control epilepsy and to focus attention.