A comparison of auditory oddball responses in dorsolateral prefrontal cortex, basolateral amygdala and auditory cortex of macaque

Abstract

The mismatch negativity (MMN) is an event-related potential 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. 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 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 prefrontal cortex, 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 prefrontal cortex 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 prefrontal cortex, 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

“…Whereas AC responses to pure tones take just a few milliseconds to emerge [38,39], evoked responses in the mPFC take hundreds of milliseconds to appear, both at spike activity ( Figs 2D, 4B, 5C and 6B) and LFP recordings ( Figs 4C, 4D, 5D, 5E and 6D). Prefrontal response delays over 100 ms with respect to the AC have also been reported in the lateral and ventral orbitofrontal cortex of anesthetized and awaked mice [52], as well as in the dorsolateral PFC of alert macaques [53]. Entire AC responses could fit within the latency of the auditory-evoked responses found in the PFC (Fig 6B and 6C).…”

“…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].…”

Correlates of auditory decision making in prefrontal, auditory, and basal lateral amygdala cortical areas

“…Particularly, dlPFC showed a reduction of responses to the cue and delay activity and an abolishment of target related activity compared to the active task condition. This is consistent with data from the same animals and areas during a passive oddball task in which dlPFC activity was later (~100 ms) and weaker than in AC (Camalier, Scarim et al 2019). Taken together it suggests that the strength and timing of the information transfer between AC and dlPFC can be flexibly allocated and is dependent on task demands.…”

“…If the response was incorrect, there was a long "timeout" period before the next trial could be initiated. As in our previous work (Camalier, Scarim et al 2019) the use of square waves (which contain odd harmonics) allowed for wideband stimulation that was perceptually distinct, but whose broad spectral signature robustly activated large swaths of AC in a way that pure tones would not. Thus, similar to human paradigms, the stimuli could be kept identical across all sessions, independent of where recordings were carried out in AC, and data could be collapsed.…”

“…1B; dorsal bank of the principal sulcus extending ventral, >1mm away from arcuate sulcus, roughly 46/8Ad), the basal and lateral portions of the amygdala (entire dorsoventral extent), and auditory cortex (primarily A1 but including small portions of lateral belt areas). Recording areas were verified through a T1 scan of grid coverage with respect to underlying anatomical landmarks, combined with maps of frequency reversals and response latencies of single neurons to determine A1 location and extent (Camalier, D'Angelo et al 2012, Camalier, Scarim et al 2019. Recordings were mainly carried out in simultaneous AC and PFC sessions, with BLA sessions occurring later in the experiment, but some data included were from just one, or even three simultaneously recorded areas in a given session.…”