No description available.

No description available.

Thesis (M.D.)—Boston University

This thesis represents a culmination of work which seeks to examine the prelimbic and anterior cingulate cortex (ACC) during trace fear memory across sleep and wakefulness states. In order to accomplish this task, a technical platform needed to be developed. Accordingly, the first chapter demonstrates that fear behavior can recorded utilizing neck electromyography (EMG). The second chapter examines the role of the ACC in trace fear memory, discovering that many neurons have premotor activity related to freezing behavior. Additionally, auditory-evoked potentials in the ACC demonstrate learning curves which match learning curves of fear. We suggest that the ACC is involved in affective-motor integration. The third chapter examines how genetic enhancement of trace fear learning, with calcium/calmodulin-dependent protein kinase IV (CaMKIV) over-expressed mice, can influence electro-cortical potentials during wakefulness, learning and sleep. We found that CaMKIV potentiates electro-cortical brain waves during learning and sleep. In particular 4-7.5Hz rhythms were potentiated in CaMKIV over-expressed mice during learning, and are likely to be localized to regions of the prelimbic cortex. Taken together the results of this thesis demonstrate that the trace fear memory paradigm engages the ACC and prelimbic regions, as evidenced at the single cell and cortical field potential level, for sensory-affective and premotor functions related to anticipating painful stimulation. CaMKIV appears to be a protein which modulates learning and electro-cortical potentials and may be a potential target for sleep-dependent memory consolidation in the prefrontal cortex.

This thesis represents a culmination of work which seeks to examine the prelimbic and anterior cingulate cortex (ACC) during trace fear memory across sleep and wakefulness states. In order to accomplish this task, a technical platform needed to be developed. Accordingly, the first chapter demonstrates that fear behavior can recorded utilizing neck electromyography (EMG). The second chapter examines the role of the ACC in trace fear memory, discovering that many neurons have premotor activity related to freezing behavior. Additionally, auditory-evoked potentials in the ACC demonstrate learning curves which match learning curves of fear. We suggest that the ACC is involved in affective-motor integration. The third chapter examines how genetic enhancement of trace fear learning, with calcium/calmodulin-dependent protein kinase IV (CaMKIV) over-expressed mice, can influence electro-cortical potentials during wakefulness, learning and sleep. We found that CaMKIV potentiates electro-cortical brain waves during learning and sleep. In particular 4-7.5Hz rhythms were potentiated in CaMKIV over-expressed mice during learning, and are likely to be localized to regions of the prelimbic cortex. Taken together the results of this thesis demonstrate that the trace fear memory paradigm engages the ACC and prelimbic regions, as evidenced at the single cell and cortical field potential level, for sensory-affective and premotor functions related to anticipating painful stimulation. CaMKIV appears to be a protein which modulates learning and electro-cortical potentials and may be a potential target for sleep-dependent memory consolidation in the prefrontal cortex.

Although a plethora of data exists on the role of the prefrontal cortex in memory retrieval, it has been difficult to relate specific aspects of retrieval processing to the different prefrontal regions. The present thesis consists of one behavioural experiment and three functional neuroimaging studies that aimed at elucidating the role of the mid-ventrolateral region of the prefrontal cortex in memory retrieval. We hypothesized that the mid-ventrolateral prefrontal cortex, through its anatomical connections with posterior association areas, is in a key position to exert control over posterior association areas where information is processed and stored for the active retrieval of mnemonic information. In contrast to automatic retrieval, active retrieval is necessary when a person retrieves based on his/her plans and intentions a specific memory amongst multiple related mnemonic traces. / Previously, we had demonstrated that the mid-ventrolateral prefrontal cortex in the right hemisphere controls active retrieval of non-verbal stimuli. More specifically, we reported activity increases within this region during the delay period that followed the presentation of a retrieval cue. We proposed that these activity increases reflect the top-down control exerted by the mid-ventrolateral prefrontal cortex to focus attention on relevant aspects of encoded memories in preparation for the decision. The first study of my thesis focuses on the behavioural correlates of this active retrieval process. The results indicate that the subjects' performance improves (i.e. becomes faster) with longer retrieval periods. Thus, some aspect of retrieval is initiated during the delay before the presentation of a test stimulus for the decision. The results, however, also indicate that retrieval continues after the presentation of the test stimulus. / The three event-related fMRI studies that make up chapters three, four, and five of the thesis were designed on the basis of the results obtained in the behavioural study described in chapter two. For all three fMRI studies, we used an experimental paradigm in which the retrieval cue coincided with the test stimulus presentation. The experimental design for the three neuroimaging studies was similar but examined the retrieval of mnemonic information from different sensory modalities. A separate group of subjects was tested for each study with a common hypothesis: when subjects are performing active retrieval trials, selective activity increases will be observed within the mid-ventrolateral prefrontal cortex. The study presented in chapter three examined verbal active retrieval, the study presented in chapter four examined tactile active retrieval, and the one in chapter five examined active retrieval for auditory stimuli. Selective activity increases were reported within the mid-ventrolateral prefrontal cortex during the active retrieval trials in all three studies. Activity increases were stronger in the left mid-ventrolateral prefrontal cortex when subjects retrieved verbal information. For tactile and auditory stimuli, the activity increases were bilateral. Importantly, within the prefrontal cortex, there were no other activity increases, indicating that the role of the mid-ventrolateral prefrontal cortex in memory retrieval is specific and distinct from that of other prefrontal regions. Thus it can be concluded that, across sensory modalities, the mid-ventrolateral prefrontal cortex plays a key role in the top-down control necessary for the disambiguation of information in memory during retrieval.

Thesis supervisor: Steven W. Anderson. Includes bibliographic references (p. 143-150).

Thesis (Ph. D.)--University of Texas at Austin, 2004. / Supervisor: Christine L. Duvauchelle. Vita. Includes bibliographical references.

The pedunculopontine tegmental nucleus (PPTg) has been argued to be involved in mediating neural processing relating to executive functions (Winn, 1998). Since it shares connections with fronto-striatal circuitry this proposal is not surprising. However, research examining the functions of structures within this system has frequently ignored the contribution of PPTg. The delayed spatial win-shift (DSWS) task is a task that measures spatial working memory and, as such, has been used by Phillips and colleagues to reveal the involvement of ventral striatal structures in this form of "executive" behaviour. This suggests that structures interconnected with PFC share in some way frontal functions. As might be expected from its connections, the involvement of PPTg in the same task has also been demonstrated (Keating & Winn, 2001). The current research was designed to assess further the involvement of PPTg in the DSWS task, and to compare this directly to the involvement of prefrontal cortex (PFC). In order to achieve this, rats with excitotoxic lesions of PPTg and medial PFC were assessed on the DSWS task, in addition to rats with crossed unilateral disconnection of medial PFC/PPTg. Statistically, results demonstrated both PPTg and medial PFC lesions produced similar impairments in the test phase of DSWS, characterised by increased errors, earlier error occurrence, and slower latencies. In contrast, disconnection lesions of medial PFC/PPTg produced an impairment that was fundamentally different. It was concluded that while this supports the importance of PPTg functioning within fronto-striatal systems, the pattern of impairment shown by disconnected rats suggested that this function may not be executive per se but might be necessary for executive functions to influence behaviour.

No description available.