A Comparison of Auditory Oddball Responses in Dorsolateral Prefrontal Cortex, Basolateral Amygdala, and Auditory Cortex of Macaque

Abstract

The mismatch negativity (MMN) is an ERP component seen in response to unexpected “novel” stimuli, such as in an auditory oddball task. The MMN is of wide interest and application, but the neural responses that generate it are poorly understood. This is in part due to differences in design and focus between animal and human oddball paradigms. For example, one of the main explanatory models, the “predictive error hypothesis”, posits differences in timing and selectivity between signals carried in auditory and prefrontal cortex (PFC). However, these predictions have not been fully tested because (1) noninvasive techniques used in humans lack the combined spatial and temporal precision necessary for these comparisons and (2) single-neuron studies in animal models, which combine necessary spatial and temporal precision, have not focused on higher order contributions to novelty signals. In addition, accounts of the MMN traditionally do not address contributions from subcortical areas known to be involved in novelty detection, such as the amygdala. To better constrain hypotheses and to address methodological gaps between human and animal studies, we recorded single neuron activity from the auditory cortex, dorsolateral PFC, and basolateral amygdala of two macaque monkeys during an auditory oddball paradigm modeled after that used in humans. Consistent with predictions of the predictive error hypothesis, novelty signals in PFC were generally later than in auditory cortex and were abstracted from stimulus-specific effects seen in auditory cortex. However, we found signals in amygdala that were comparable in magnitude and timing to those in PFC, and both prefrontal and amygdala signals were generally much weaker than those in auditory cortex. These observations place useful quantitative constraints on putative generators of the auditory oddball-based MMN and additionally indicate that there are subcortical areas, such as the amygdala, that may be involved in novelty detection in an auditory oddball paradigm.

Prediction error signaling explains neuronal mismatch responses in the medial prefrontal cortex

“…By contrast, only 1 repetition was enough for the initial auditory-evoked response in the mPFC to drop between >50% and >70%, and a second repetition to reach maximum suppression levels (Fig 6E, in black). Similar suppressive dynamics were reported in the orbitofrontal cortex of anesthetized and awake mice [52], in the dorsolateral PFC of alert macaques [53], as well as in human frontal sources [22].…”

“…This could provide a potential explanation for the lack of significant differences between mismatch responses across mPFC fields, despite been quite distinct from each other. The mismatch responses we recorded at the rat mPFC resembled to those recorded at the mouse orbitofrontal cortex [52] and the macaque dorsolateral PFC [53]. It is possible that non-auditory subcortical nuclei such as the hippocampus or the amygdala could compute PEs and then broadcast that signal all over the PFC for further processing and integration.…”

“…Auditory mismatch responses took about 20 ms to appear in the CA1 region of the hippocampus of freely-moving mice [66], and 30-60 ms to show in the basolateral amygdala of alert macaques [53]. Furthermore, like in the PFC, mismatch responses in the basolateral amygdala did not exhibit stimulus-dependent effects [53]. Minding the different model species, these time delays would place the hippocampus and the amygdala right between the response windows observed in the auditory pathway and those in the PFC.…”

Prediction error signaling explains neuronal mismatch responses in the medial prefrontal cortex

“…Epidural electrodes placed over the frontal cortices of awake and freely moving rats [ 40 , 45 ] recorded stronger ERPs to DEV than to CTR or STD. In awake macaques, 1 study using multichannel electrodes placed in the dorsolateral PFC found larger responses to DEV than to STD [ 53 ], while another using ECoG found strong mismatch responses in the PFC to deviant changes within a roving-standard paradigm, but not to repetitions or the many-standards control [ 54 ]. Regarding invasive research in human patients, ECoG studies have consistently proven that, in contrast with the AC, the PFC ceases responding to DEV when its occurrence can be expected [ 34 , 37 , 55 ].…”

From Description to Explanation: Integrating Across Multiple Levels of Analysis to Inform Neuroscientific Accounts of Dimensional Personality Pathology

“…For example, if an intruder detection paradigm elicited more basolateral amygdala activity during an fMRI scan, and such activity scaled with individual differences in Suspiciousness, should we conclude that the amygdala somehow encodes this trait, or that this region is computing threat? An alternative account is that amygdala activity in this paradigm reflected sensitivity to novelty (e.g., Camalier, Scarim, Mishkin, & Averbeck, 2019), not threat, and that equivalent correlations with Suspiciousness would have emerged in an auditory oddball task. To avoid such difficulties, it may be useful for personality neuroscientists to focus on developing accounts of traits whose neurobiological interface may be simpler (e.g., dopamine's role in generating motivated approach behaviors; Guitart-Masip, Duzel, Dolan, & Dayan, 2014) or more easily described in animal models (e.g., threat-related behavioral inhibition).…”