Interictal psychiatric disturbance is a well-documented occurrence in temporal lobe epilepsy (TLE). Recent work has identified the presence of negative symptoms in a distinct subset of TLE patients. Research in other neurological populations supports that negative symptoms are related to damage to the basal ganglia resulting in system-wide disruption in behavior. The present study's purpose was threefold. The first objective entailed a comparison of brain volumes in TLE subjects with negative symptoms (NEG) to a TLE group without negative symptoms (NoNEG), and an age and gender matched control group (C). Second, we examined longitudinal changes in basal ganglia and the anterior cingulate in TLE over a four-year period. Third, group differences on neuropsychological measures that rely on intact functioning of subcortical structures were compared with group differences on neuropsychological measures which have not demonstrated such dependence. We hypothesized that negative symptoms in TLE results from a system-wide disruption in an integrated neural network including the caudate, putamen, globus pallidus, nucleus accumbens, and anterior cingulate. Moreover, we expected volume loss greater over time in the NEG group and group differences on neuropsychological measures dependent on subcortical integrity. Findings were generally supportive of this hypothesis. The negative symptom group showed significantly reduced volumes compared to both control and the epilepsy no negative symptom groups in two regions of interest within the network, the putamen and globus pallidus. In addition, both structures contributed increased predictive discrimination on the negative symptom group from the other two groups. Contrary to expectations, cognitive abnormality in the no negative symptom group was evident across a wide range of measures rather than being restricted to "subcortical measures," and there was no evidence for increased volume reduction over the four year interval (i.e., group x time interaction). In summary, in our sample, it appears that specific nodes (i.e., globus pallidus and putamen) within the broader anterior-medial frontal system contribute to the phenomenon of negative symptoms in TLE. We suggest that these two subcortical structures may play an important role in the expression of a system-wide disruption in a default-mode network that is associated with negative symptoms.