Frontal-Occipital Interactions during Visual Memory

Lay Summary

Imaging may yield a biomarker for visual memory deficits of dementia, stroke, traumatic brain injury

Imaging techniques in patients and healthy volunteers may identify a biomarker for diagnosing and assessing treatments for frontal lobe diseases and injuries that produce visual memory problems, such as Alzheimer’s and other dementing diseases, and brain injuries including stroke and brain chronic traumatic encephalopathy (CTE).

Visual memories, such as remembering where to turn to drive home, seem effortless unless retrieval is compromised by dementing illnesses or injuries affecting the brain’s frontal lobes (at the front of the brain). Studies have shown that both the frontal lobe and the occipital lobe (at the back of the brain) are critical in retrieving visual memories. But just how and when the brain’s frontal lobe affects this visual sensory region at the back of the brain during memory processes remains a mystery. The researchers have found, however, that when people remember an object’s previous spatial location, the brain is activated as if the person were actually seeing that object in its previous location. This finding supports the notion that memory is a constructive process where various brain regions reactivate details from a previous experience and the combined information creates a memory. That is, unless this process is disrupted.

The investigators hypothesize that disruption of the left prefrontal lobe, such as by dementing illness or brain injuries, impairs spatial memory accuracy and decreases the magnitude of the earliest visual sensory activity involved in memory processes. They will combine three imaging techniques to investigate this hypothesis . The first study will involve 32 healthy volunteers, where investigators will use reversible methods to identify and disrupt electrical activity in the key area of the left prefrontal lobe involved in spatial memory and assess consequences to memory processes. Then, in the second study, investigators will identify 16 patients who have a stroke in that exact left prefrontal area and study their visual memory activity. Specifically:

Study 1. While healthy volunteers observe an object, investigators will: 1) use fMRI to locate the frontal lobe region that is activated during spatial memory; 2) then temporarily disturb electrical activity in that region by using non-invasive transcranial magnetic stimulation (TMS, where magnetic coils placed above the head disrupt electrical impulses); and 3) determine whether this frontal lobe disruption produces abnormal activity in the brain’s occipital lobe during spatial memory. To assess this, they will use another non-invasive technique called event-related potential (ERP) recording. This measures brain waves associated with the visual response.

Study 2. Investigators then will measure ERPs in 16 patients who have had a stroke damaging that exact left prefrontal lobe area, compared to a new group of 16 healthy participants, to see whether patients have resultant abnormal occipital lobe activity during spatial memory. Investigators anticipate that the findings will demonstrate that damage to this left prefrontal area disrupts visual sensory ERP activity in the occipital area. If so, disrupted ERP activity could be a biomarker used to identify, early on, not only brain injuries that affect the left prefrontal lobe but also degenerative diseases, such as Alzheimer’s, and CTE.

Significance: The biomarker of disrupted ERP activity for visual memory could be used at the earliest stage of neurodegenerative diseases and injuries to track progression and to assess responses to experimental therapies.

Again, we only use three imaging techniques for the healthy young participants.

Abstract

Frontal-occipital interactions during visual memory

The broad goal of the proposed research is to investigate the causal mechanisms of spatial memory. The ultimate aim is to develop a marker of early disease affecting spatial memory (including Alzheimer’s disease) that can be used not only to signal disease but also to track disease progression and assess effectiveness of therapies. It is known that the frontal lobe and the occipital lobe are both critical during visual memory retrieval. However, there is no causal evidence detailing how and when the frontal cortex modulates visual sensory regions during memory. We will integrate three brain imaging techniques: functional magnetic resonance imaging (fMRI, a technique with excellent spatial resolution but limited temporal resolution), transcranial magnetic stimulation (TMS, a technique that can be used to temporarily deactivate a cortical region of interest in unimpaired participants), and event-related potentials (ERPs, a technique with excellent temporal resolution but limited spatial resolution). The combinations of fMRI and TMS or TMS and ERPs have been used to study visual perception and attention; however, these pairs of techniques have not been used to study memory or other higher level mental functions and no studies have integrated all three of these techniques. Our recent fMRI, ERP, and TMS findings indicate that memory for visual object features (i.e., spatial location, color, shape, and motion) activates the same regions of the visual sensory cortex that are activated during perception of these features. For instance, when participants remember an object’s previous spatial location, the brain is activated as if they were seeing that object in the previous spatial location. Such visual sensory effects support the view that memory is a constructive process, where the details from a previous experience are reactivated in different brain regions and this information is combined to create a memory. In the proposed research, the effect of left prefrontal cortex disruption will be investigated in healthy young participants using fMRI activity to guide the location of TMS application and in older stroke patients with a focal lesion in this region. The nature and timing of the resultant visual sensory ERP effects in the occiptial cortex will then be evaluated. The first aim is to determine the time(s) at which visual sensory ERP effects in the occipital cortex are modulated following disruption of the left prefrontal cortex. The second aim is to evaluate the occipital ERP effects following disruption of the left prefrontal cortex to determine whether the frontal-occipital interactions are facilitatory or inhibitory. The third aim is to develop a novel fMRI guided TMS-ERP methodology that will serve as a framework for future studies to investigate the causal mechanisms in the brain during other cognitive processes. Most importantly, the visual sensory ERP effects identified may serve as markers to improve human health. Our preliminary TMS-ERP results suggest that disruption of the left frontal cortex using TMS impairs spatial memory accuracy and decreases the magnitude of the earliest visual sensory ERP activity (i.e., the magnitude of the earliest occipital ERP component, between 50-250 milliseconds, was diminished while later occipital ERP components were not affected). The findings are likely to have a number of direct clinical applications. Many brain injuries and diseases affect the prefrontal cortex, including stroke, traumatic brain injury, Alzheimer’s disease and other forms of dementia, schizophrenia, and depression. Patients with these disorders often have spatial memory deficits, and thus it is plausible that such patients will also have disruption of the visual sensory ERP component described above. Disruption of this visual sensory ERP component could be used as a marker of early disease and could also be used to track disease progression. In addition, an ERP marker of frontal lobe injury or disease could be used to measure the effectiveness of therapies. Finally, the techniques developed in the project could be used to assess whether disruption of the frontal cortex or other brain regions (e.g., the parietal cortex) selectively disrupts ERP activity and impairs other mental functions (e.g., attention or language). Such ERP components could similarly be used as markers to diagnose, track, and evaluate therapy for a range of brain injuries or diseases and greatly improve human health. In short, this project will use a novel combination of brain imaging techniques and patient evidence to identify a marker of frontal lobe disease affecting spatial memory.