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Abstract

It is widely believed that the prefrontal cortex contributes to adap-tive control over prepotent or habitual behaviors. One of the proposedmeans of implementing control involves directed “top-down” inhibi-tion of actions. While this descriptive model is helpful, much work re-mains to be done to explain the distinct neural mechanisms by whichsuch top-down control alters action selection. In a recent report, Alegreet al. (2013) provide evidence that the cortex and subthalamic nucleus(STN) of the basal ganglia interact to both enable and inhibit behaviorby exchanging information across different oscillatory frequency bands.The STN are small subcortical nuclei that lie between the brainstemand the pallidum. Long considered a part of the cortico-striatal indirectpathway, they have been implicated as a part of an inhibitory systemthat prevents motor gating, acting in antagonism to the facilitatory di-rect pathway (Alexander and Crutcher, 1990; Mink, 1996). However,morerecenthistological (Nambuet al.,2002,2012), functionalconnec-tivity (Aron et al., 2007),and computational (Frank,2006) descriptionsof thecortico-basalganglia systemsuggestthat theSTNparticipate in athird extra-striatal information processing stream: the “hyperdirect”pathway. In this role, motor and premotor cortex project directly tothe STN (bypassing the striatum altogether), which projects to basalganglia output in order to act a global brake on striatal output. Thishyperdirect system is thus a compelling candidate “hold-your horses”mechanism by which high-level premotor areas of frontal cortex (suchasthemidcingulatecortexorpre-supplementalmotorarea)couldrapid-ly delay motor output due to signals of con flict between competing re-sponse options, buying time so the best decision can be made ( Frank,2006). While functional MRI studies show STN activation during re-sponse inhibition (e.g.,Aron et al., 2007), a better understanding ofthe detailed neuronal dynamics within the STN is needed to under-standhow this systemprocesses information andhowit cango awryin Parkinson's disease.Given the pathology of akinesia and bradykinesia in Parkinsonism,it should be apparent that removal of this STN brake on motor outputcan provide increased motor fluidity to patients, such that relativelyless amount of direct pathway activity is needed. Moreover, dopa-mine depletion can cause the STN to function aberrantly, increasingoscillatory coupling between the STN and globus pallidus and leadingtomotortremor(Bergman et al., 1998; Levy et al., 2000; Raz et al.,2000). Ameliorative treatment can be provided by interfering withSTN function via lesions (Bergman et al., 1990)ordeepbrainstimu-lation, which alters neuronal output and provides tremendous symp-tom relief including abolishment o f tremor. However, this procedurehas some unfortunate side effects in vulnerable individuals, where itcan increase impulsivity and induce poor decision making ( Frank et al.,2007;Halbigetal.,2009).Clearly,athoroughunderstandingofthisneu-ral system will not only have important implications for understandingbasic mechanisms of action selection, but also for optimizing treatmentfor Parkinsonism and other motor disorders.In their recent report, Alegre et al. (2013) capitalize on the abilityto record from the STN after implantation of deep brain stimulationelectrodes in Parkinsonian patients. In order to assess adaptive inhib-itory control, patients performed a stop signal task where a ‘go’ cueindicates the need for action, unless it is followed (at varying delays)by a ‘stop’ cue that indicates a need to cancel the action. Recordingswere supplemented by simultaneous scalp EEG over motor cortex, andwere performed both on and off dopaminergic medication. Given thatprevious reports have suggested that dorsal (motor) and ventral (cogni-tiveandaffective)areasoftheSTNmaydifferentiallycontributetoactionselection (Greenhouse et al., 2011; Hershey et al., 2010; Weinbergeret al., 2006), the spatial speci ficity of these recordings were considered,including the hemisphericlaterality of any potentialeffects.The findingsrevealed that different action selection processes were not only spatiallydistinct, but were also represented in different frequency bands in theEEG. Field oscillations at different frequencies allow neurons to ‘tune in’to different networks in order to communicate different types of infor-mation. In the case of EEG, Alegre et al. (2013) revealed that the theta(~4–6Hz),beta(~12–25 Hz)andgamma(~55–75 Hz)bandseachcon-tributedtodistinctaspectsofactionselectioninthecortico-STNnetwork.Neuronal activities in the beta band are thought to reflect a typeof active inhibition (e.g. “preserving the status quo”: Engel and Fries,2010). A diminishment in beta power during action readiness is thusobservedinbothcortexandSTN,possiblyduetodopaminergicin fluence(JenkinsonandBrown,2011).Dopaminedepletioncontributestoexces-sive synchronization of beta activities in STN ( Marceglia et al., 2011;Weinbergeretal.,2006),aswellaswithinnetworksincludingtheexter-nalglobuspallidus(Malletetal.,2008a),andcortex(Eusebioetal.,2009;Malletetal.,2008b),suggestingthatitenhancesthefunctionalroleofac-tive inhibition to a maladaptive degree. Conversely, activity in the thetaand gamma bands are thought to reflect active information processing(Fries,2009;Womelsdorfetal.,2010),whichsometimesinteracttogeth-er to facilitate information transfer across long distances or timescales(Canolty et al., 2006). The spectral width of each of these frequenciesalso appears to relate to the specificity of information content. Theta