Perirhinal and postrhinal, but not lateral entorhinal, cortices are essential for acquisition of trace eyeblink conditioning.

The acquisition of temporal associative tasks such as trace eyeblink conditioning is hippocampus-dependent, while consolidated performance is not. The parahippocampal region mediates much of the input and output of the hippocampus, and perirhinal (PER) and entorhinal (EC) cortices support persistent spiking, a possible mediator of temporal bridging between stimuli. Here we show that lesions of the perirhinal or postrhinal cortex severely impair the acquisition of trace eyeblink conditioning, while lateral EC lesions do not. Our findings suggest that direct projections from the PER to the hippocampus are functionally important in trace acquisition, and support a role for PER persistent spiking in time-bridging associations.

Emotional responses to unpleasant music correlates with damage to the parahippocampal cortex.

Music is typically a pleasurable experience. But under certain circumstances, music can also be unpleasant, for example, when a young child randomly hits piano keys. Such unpleasant musical experiences have been shown to activate a network of brain structures involved in emotion, mostly located in the medial temporal lobe: the parahippocampal gyrus, amygdala, hippocampus and temporal pole. However, the differential roles of these regions remain largely unknown. In this study, pleasant and unpleasant music was presented to 17 patients with variable excisions of the medial temporal lobe, as well as to 19 matched controls. The pleasant music corresponded to happy and sad selections taken from the classical instrumental repertoire; the unpleasant music was the dissonant arrangement of the same selections. Only patients with substantial resections of the left or right parahippocampal cortex (PHC) gave highly abnormal judgements to dissonant music; they rated dissonant music as slightly pleasant while controls found it unpleasant. This indifference to dissonance was correlated with the remaining volume in the PHC, but was unrelated to the volume of the surrounding structures. The impairment was specific: the same patients judged consonant music to be pleasant, and were able to judge music as happy or sad. Furthermore, this lack of responsiveness to unpleasantness was not due to a perceptual disorder, because all patients were able to detect intentional errors in the musical excerpts. Moreover, the impairment differed from that induced by amygdala damage alone. These findings are consistent with a two-dimensional model of defensive responses to aversive stimuli, in which the PHC and the amygdala subserve different roles.

Imaging visual recognition memory network by PET in the baboon: perirhinal cortex heterogeneity and plasticity after perirhinal lesion.

We recently mapped the visual recognition memory network in the behaving baboon using a positron emission tomography (PET) activation paradigm with 18F-fluoro-deoxyglucose during a visual delayed matching-to-sample task. This study confirmed the key role of the perirhinal cortex and documented an unexpected left-sided advantage. Specific contribution of each subdivision of the perirhinal cortex has, however, never been investigated. Furthermore, although alteration to the perirhinal cortex has been implicated in several brain disorders, putative plasticity within the entire brain network after perirhinal damage remains largely unknown. To confirm our previous data and to investigate these latter issues, we used our PET activation paradigm on a second healthy baboon before and after 16 months after bilateral excitotoxic lesions of the perirhinal cortex. Activation common to our two healthy baboons occurred only in the left rostroventral perirhinal cortex (i.e., areas 36pm and rostral 36r) and insular cortex. Although histologic analysis disclosed that the perirhinal lesions achieved in the present baboon were essentially caudal to this preoperatively activated area, memory performance was severely impaired. Concomitant with this long-lasting cognitive deficit, changes in the neural network implicated in the task were observed, involving disappearance of the preoperative activations and appearance of a significant activation of the frontal and occipital cortices. However, different activation patterns were found in the first and last eight postoperative months. These findings highlight the functional heterogeneity of the perirhinal cortex and evidence progressive plasticity after perirhinal cortex damage.

Comparison of the effects of damage to the perirhinal and parahippocampal cortex on transverse patterning and location memory in rhesus macaques.

Monkeys with damage to the parahippocampal (TH/TF) or perirhinal (PRh) cortex were tested on two sets of the transverse patterning (TP) problem (A+/B-, B+/C-, C+/A- and D+/E-, E+/F-, F+/D-) and delayed nonmatching-to-location paradigm (DNML), with delays ranging from 10 to 600 s. Damage to either area impaired acquisition and performance of TP but not of linear discriminations (e.g., A>B>C>X). Damage to areas TH/TF impaired performance of the DNML at all delays but only affected memory for objects at the longest delay, as measured by a delayed nonmatching-to-sample task (DNMS) (Nemanic et al., 2004). Damage to the PRh impaired performance of the DNMS but not of the DNML. The results present a dissociation in object and place memory for these two cortical regions and suggest a role for each in the cortical circuitry supporting configural/relational memory.

Theta- and movement velocity-related firing of hippocampal neurons is disrupted by lesions centered on the perirhinal cortex.

The hippocampus is critically involved in spatial memory and navigation. It has previously been proposed that, as part of this process, the hippocampus might have access to self-motion information. The possibility that some of this information may originate from the perirhinal cortex, a region involved in high-order multimodal processing, was tested in the present study by recording the responses of hippocampal complex-spike (place cells) and theta cells (putative interneurons) to movement velocity and to the movement-related theta rhythm EEG while rats with bilateral ibotenic acid lesions centered on the perirhinal cortex (n = 5), or control surgeries (n = 5), foraged in a rectangular environment. Perirhinal cortex lesions altered several characteristics of place and theta cell firing. First, the proportion of theta cells recorded was significantly lower in perirhinal lesion animals (8/39 units) compared to controls (22/53 units). Second, the firing of place cells recorded from lesion animals was phase-shifted so as to occur significantly earlier during the theta rhythm cycle than in place cells from controls (mean difference = 48.73 degrees). Third, the firing rates of a significantly lower proportion of place cells from lesion animals were modulated by the movement velocity of the animal compared to place cells from controls. These results indicate that the perirhinal cortex contributes to the responses of hippocampal CA1 place cells by providing information about self-movement and by controlling the timing of firing of these cells. This information may normally be utilized by the hippocampus during spatial memory and navigation processes.