Lateral Frontal Activity Research Articles

Attenuated frontotemporal brain activation during cognitive tasks is associated with lower succinate dehydrogenase protein levels in patients with major depressive disorder

BackgroundPrevious studies have shown a lower hemodynamic response in patients with major depressive disorder (MDD) during cognitive tasks. However, the mechanism underlying impaired hemodynamic and neural responses to cognitive tasks in MDD patients remains unclear. Succinate dehydrogenase (SDH) is a key biomarker of mitochondrial energy generation, and it can affect the hemodynamic response via the neurovascular coupling effect. In the current study, cerebral hemodynamic responses were detected during verbal fluency tasks (VFTs) via functional near-infrared spectroscopy (fNIRS) and SDH protein levels were examined in serum from MDD patients to quickly identify whether these hemodynamic alterations were related to mitochondrial energy metabolism. MethodsFifty patients with first-episode drug-naïve MDD and 42 healthy controls (HCs) were recruited according to inclusion and exclusion criteria. The 17-item Hamilton Depression Rating Scale (17-HDRS), Hamilton Anxiety Rating Scale (HAMA) and Inventory of Depressive Symptomatology-Self Report (IDS-SR) were used to assess the clinical symptoms of the patients. All participants underwent fNIRS measurements to evaluate cerebral hemodynamic responses in the frontal and temporal cortex during VFTs; moreover, SDH protein levels were measured using an enzyme-linked immunosorbent assay. ResultsActivation in the frontal-temporal brain region during the VFTs was lower in patients with MDD than in HCs. The SDH level in the serum of MDD patients was also significantly lower than that in HCs (p = 0.003), which significantly affected right lateral frontal (p = 0.025) and right temporal (p = 0.022) lobe activation. Both attenuated frontal-temporal activation during the VFTs (OR = 1.531) and lower SDH levels (OR = 1.038) were risk factors for MDD. ConclusionsMDD patients had lower cerebral hemodynamic responses to VFTs; this was associated with mitochondrial dysfunction, as indicated by SDH protein levels. Furthermore, attenuated hemodynamic responses in frontotemporal regions and lower SDH levels increased the risk for MDD. LimitationsThe sample size is relatively small. SDH protein levels in peripheral blood may not necessarily reflect mitochondrial energy generation in the central nervous system.

Learning Cognitive Flexibility: Neural Substrates of Adapting Switch-Readiness to Time-varying Demands.

An individual's readiness to switch tasks (cognitive flexibility) varies over time, in part, as the result of reinforcement learning based on the statistical structure of the world around them. Consequently, the behavioral cost associated with task-switching is smaller in contexts where switching is frequent than where it is rare, but the underlying brain mechanisms of this adaptation in cognitive flexibility are not well understood. Here, we manipulated the likelihood of switches across blocks of trials in a classic cued task-switching paradigm while participants underwent fMRI. As anticipated, behavioral switch costs decreased as the probability of switching increased, and neural switch costs were observed in lateral and medial frontoparietal cortex. To study moment-by-moment adjustments in cognitive flexibility at the neural level, we first fitted the behavioral RT data with reinforcement learning algorithms and then used the resulting trial-wise prediction error estimate as a regressor in a model-based fMRI analysis. The results revealed that lateral frontal and parietal cortex activity scaled positively with unsigned switch prediction error and that there were no brain regions encoding signed (i.e., switch- or repeat-specific) prediction error. Taken together, this study documents that adjustments in cognitive flexibility to time-varying switch demands are mediated by frontoparietal cortex tracking the likelihood of forthcoming task switches.

Motivated cognitive control during cued anticipation and receipt of unfamiliar musical themes: An fMRI study

Principal themes, particularly choruses in pop songs, hold a central place in human music. Singing along with a familiar chorus tends to elicit pleasure and a sense of belonging, especially in group settings. These principal themes, which frequently serve as musical rewards, are commonly preceded by distinctive musical cues. Such cues guide listeners' attention and amplify their motivation to receive the impending themes. Despite the significance of cue-theme sequences in music, the neural mechanisms underlying the processing of these sequences in unfamiliar songs remain underexplored. To fill this research gap, we employed fMRI to examine neural activity during the cued anticipation of unfamiliar musical themes and the subsequent receipt of their opening phrase. Twenty-three Taiwanese participants underwent fMRI scans while listening to excerpts of Korean slow pop songs unfamiliar to them, with lyrics they could not understand. Our findings revealed distinct temporal dynamics in lateral frontal activity, with posterior regions being more active during theme anticipation and anterior regions during theme receipt. During anticipation, participants reported substantial increases in arousal levels, aligning with the observed enhanced activity in the midbrain, ventral striatum, inferior frontal junction, and premotor regions. We posit that when motivational musical cues are detected, the ventral striatum and inferior frontal junction played a role in attention allocation, while premotor regions may be engaged in monitoring the theme's entry. Notably, both the anticipation and receipt of themes were associated with pronounced activity in the frontal eye field, dorsolateral prefrontal cortex, posterior parietal cortex, dorsal caudate, and salience network. Overall, our results highlight that within a naturalistic music-listening context, the dynamic interplay between the frontoparietal, dopaminergic midbrain-striatal, and salience networks could allow for precise adjustments of control demands based on the cue-theme structure in unfamiliar songs.

The Differential Weights of Motivational and Task Performance Measures on Medial and Lateral Frontal Neural Activity.

Behavioral adaptations are triggered by different constraints given by rules, and are informed by outcomes, or motivational changes. Neural activity in multiple frontal areas is modulated during behavioral adaptations, but the source of these modulations and the nature of the mechanisms involved are unclear. Here we tested how different variables related to changes in task performance and to behavioral adaptation impact the amplitude of event-related local field potentials (LFPs) in the lateral prefrontal and midcingulate cortex of male rhesus macaques. We found that the behavioral task used induced consistently different types of performance modulation: in relation to task difficulty (imposed by the experimental setup), to successes and errors, and to the time spent in the task. Difficulty had a significant effect on monkeys' accuracy and reaction times. Interestingly, there is also a strong interaction between difficulty and trial success on the reaction times variation. However, LFP modulations were mostly related to reaction times, touch position, feedback valence and time-in-session, with little, if any, effect of difficulty. Hence, difficulty modulated performance but not LFP activity. This suggests that, in our experimental design, execution, regulation, and motivation-related factors are the main factors influencing medial and lateral frontal activity.SIGNIFICANCE STATEMENT Adapting decisions might be determined by several mechanisms and might be driven by motivational factors and/or factors inherent to the task at hand. Multiple frontal areas contribute to behavioral adaptations. One current challenge is to understand which information they process contributes to behavioral changes. Diverging views have emerged on whether task demands, like the decision difficulty, or factors linked to incentives to adapt, are driving frontal activity. Here we show that task difficulty had a strong effect on performance (accuracy and reaction times) but little effect on LFP recorded in monkey lateral prefrontal and midcingulate cortex. However, information related to actions, outcome valence, and time-in-session had major influences. Thus, task difficulty modulated performance but not LFP activity in frontal areas.

Brain correlates of impaired goal management in bipolar mania.

Although executive impairment has been reported in mania, its brain functional correlates have been relatively little studied. This study examined goal management, believed to be more closely related to executive impairment in daily life than other executive tasks, using a novel functional magnetic resonance imaging (fMRI) paradigm in patients in this illness phase. Twenty-one currently manic patients with bipolar disorder and 30 matched healthy controls were scanned while performing the Computerized Multiple Elements Test (CMET). This requires participants to sequentially play four simple games, with transition between games being made either voluntarily (executive condition) or automatically (control condition). CMET performance was impaired in the manic patients compared to the healthy controls. Manic patients failed to increase activation in the lateral frontal, cingulate and inferior parietal cortex when the executive demands of the task increased, while this increase was observed in the healthy controls. Activity in these regions was associated with task performance. Manic patients show evidence of impaired goal management, which is associated with a pattern of reduced medial and lateral frontal and parietal activity.

T155. SEPARABLE AND REPLICABLE NEURAL STRATEGIES DURING SOCIAL BRAIN FUNCTION IN PEOPLE WITH AND WITHOUT SEVERE MENTAL ILLNESS

BackgroundThe case-control design and disease heterogeneity may be major limiting factors impeding biomarker discovery in brain disorders, including serious mental illness such as schizophrenia spectrum disorder (SSD) or bipolar disorder (BPD). We propose that this heterogeneity represents an opportunity for discovery by uncovering relevant biologically driven sub-types within disorders. Individuals with schizophrenia spectrum disorder (SSD) have deficits in social cognition related to poor functional outcome.MethodsA total of 109 SSD and 70 matched healthy controls (HC) were recruited across three sites. Participants performed an fMRI task in which they observed or imitated emotional faces. For each participant, an individual pattern of activity (Imitate > Observe for emotional faces) was identified. Hierarchical clustering (Ward’s method) identified clusters of individuals with similar patterns of activity. We then examined whether new data-driven groups of participants (based on patterns of brain activity) demonstrated performance differences on a batter of social and neuro cognitive tests completed out of the scanner. As a validation of the importance of cluster membership, Euclidean distance was compared between participants to members of their own cluster, diagnosis, or site. The clustering analysis was repeated on a replication sample consisting of 32 SSD, 37 euthymic BPD, and 39 HC.ResultsThree clusters with distinct patterns of neural activity were found. Cluster one (24 HC and 44 SSD) represented ‘typical activators’ (lateral frontal and parietal activity). Cluster two (21 HC and 31 SSD) were identified as ‘hyper-activators’, showing more intense and extended activity. This was interpreted as a ‘compensatory’ response of over-activation related to impaired neural circuits, such as is seen in aging. Interestingly, cluster three (25 Controls and 35 SSD) showed a very atypical pattern, including suppression of activity during imitation in regions involved in the default mode network and/or higher order social cognition (e.g. theory of mind). This group also had improved social cognitive performance relative to the other clusters. Participants were found to have more similar patterns of brain activity to members of their cluster rather than to members of their diagnostic group or scanning site. Importantly, when clustering was applied to the replication sample, the same three patterns (typical activators, hyper activators, and deactivators) were identified.DiscussionIn independently collected samples, our findings demonstrate different patterns of neural activity among individuals during a socio-emotional task that were independent of DSM-diagnosis or scan site. Our findings may provide objective neuroimaging endpoints (or biomarkers) for subgroups of individuals in target engagement research aimed at enhancing cognitive performance independent of diagnostic category.

Transient and sustained ERP activity related to feedback processing in the probabilistic selection task

Feedback processing represents a fundamental component of adaptive decision-making. Extensive research using event-related brain potentials (ERPs) has explored the medial frontal feedback negativity (FN), P3a, and P3b components in the context of feedback processing. Additionally, recent studies examining the neural correlates of feedback processing in a gambling task revealed transient and sustained ERP activity over the lateral frontal and posterior regions of the scalp. Consistent with the neuroimaging literature, source analysis has localized this ERP activity to the lateral and medial frontal cortex, as well as the temporal-occipital and medial occipital cortices. The current experiments examine whether the pattern of transient medial frontal and sustained lateral frontal and posterior ERP activity extend to a reinforcement learning task, and may thereby represent a general property of feedback processing. Consistent with a large literature, the ERP data revealed the FN-P3a and P3b. In addition, these data revealed sustained ERP activity over the lateral frontal and posterior regions. These findings contribute to our understanding of the temporal dynamics of feedback processing across broadly distributed cortical and subcortical networks that are sensitive to the valence and probability of positive and negative outcomes.

Spatial Release From Informational Masking: Evidence From Functional Near Infrared Spectroscopy.

Informational masking (IM) can greatly reduce speech intelligibility, but the neural mechanisms underlying IM are not understood. Binaural differences between target and masker can improve speech perception. In general, improvement in masked speech intelligibility due to provision of spatial cues is called spatial release from masking. Here, we focused on an aspect of spatial release from masking, specifically, the role of spatial attention. We hypothesized that in a situation with IM background sound (a) attention to speech recruits lateral frontal cortex (LFCx) and (b) LFCx activity varies with direction of spatial attention. Using functional near infrared spectroscopy, we assessed LFCx activity bilaterally in normal-hearing listeners. In Experiment 1, two talkers were simultaneously presented. Listeners either attended to the target talker (speech task) or they listened passively to an unintelligible, scrambled version of the acoustic mixture (control task). Target and masker differed in pitch and interaural time difference (ITD). Relative to the passive control, LFCx activity increased during attentive listening. Experiment 2 measured how LFCx activity varied with ITD, by testing listeners on the speech task in Experiment 1, except that talkers either were spatially separated by ITD or colocated. Results show that directing of auditory attention activates LFCx bilaterally. Moreover, right LFCx is recruited more strongly in the spatially separated as compared with colocated configurations. Findings hint that LFCx function contributes to spatial release from masking in situations with IM.

Comorbid anxiety moderates the relationship between depression history and prefrontal EEG asymmetry.

The internalizing spectrum of psychiatric disorders-depression and anxiety-are common, highly comorbid, and challenging to treat. Individuals with childhood onset depression have a particularly poor prognosis. There is compelling evidence that individuals with depression display reduced resting-state EEG activity at sensors overlying the left prefrontal cortex, even during periods of remission, but it remains unknown whether this asymmetry is evident among individuals with a comorbid anxiety disorder. Here, we demonstrate that women with a history of childhood onset depression and no anxiety disorder (n = 37) show reduced left lateral frontal activity compared to psychiatrically healthy controls (n = 69). In contrast, women with a history of childhood onset depression and pathological levels of anxious apprehension (n = 18)-as indexed by a current generalized anxiety disorder, obsessive compulsive disorder, or separation anxiety disorder diagnosis-were statistically indistinguishable from healthy controls. Collectively, these observations suggest that anxious apprehension can mask the relationship between prefrontal EEG asymmetry and depression. These findings have implications for understanding (a) prefrontal EEG asymmetry as a neurophysiological marker of depression, (b) the comorbidity of depression and anxiety, and (c) failures to replicate the relationship between prefrontal EEG asymmetry and depression. More broadly, they set the stage for developing refined interventions for internalizing psychopathology.

Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism.

Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.

Deep brain stimulation of the subthalamic nucleus alters frontal activity during spatial working memory maintenance of patients with Parkinson’s disease

ABSTRACTDeep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson’s disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions, such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance.

Behavioral and autonomic reactivity to moral dilemmas in frontotemporal dementia versus Alzheimer’s disease

ABSTRACTThe personal/impersonal distinction of moral decision-making postulates intuitive emotional responses from medial frontal activity and rational evaluation from lateral frontal activity. This model can be analyzed in behavioral variant frontotemporal dementia (bvFTD), a disorder characterized by impaired emotional intuitions, ventromedial prefrontal cortex (vmPFC) involvement, and relative sparing of lateral frontal regions. Moral dilemmas were presented to 10 bvFTD, 11 Alzheimer’s disease (AD), and 9 healthy control (HC) participants while recording skin conductance responses, a measure of emotional arousal. We evaluated their personal versus impersonal conflict, subjective discomfort, and adherence to social norms. Replicating prior work, bvFTD participants were more willing to harm in the personal, but not the impersonal, dilemma compared to AD and HC groups. BvFTD participants had lower arousal and less of an increase in conflict on the personal versus the impersonal dilemma, in contrast to increased arousal and conflict for the AD and HC groups. Furthermore, bvFTD participants verbalized less discomfort, a correlate of low adherence to social norms. These findings support impaired emotional reactions to moral dilemmas in bvFTD and vmPFC lesions and the personal/impersonal model. It suggests a reversion to utilitarian-like considerations when emotional intuition is impaired in the brain.

Impact of cross-disorder polygenic risk on frontal brain activation with specific effect of schizophrenia risk

Evidence suggests that there is shared genetic aetiology across the major psychiatric disorders conferred by additive effects of many common variants. Measuring their joint effects on brain function may identify common neural risk mechanisms. We investigated the effects of a cross-disorder polygenic risk score (PGRS), based on additive effects of genetic susceptibility to the five major psychiatric disorders, on brain activation during performance of a language-based executive task. We examined this relationship in healthy individuals with (n=82) and without (n=57) a family history of bipolar disorder to determine whether this effect was additive or interactive dependent on the presence of family history. We demonstrate a significant interaction for polygenic loading×group in left lateral frontal cortex (BA9, BA6). Further examination indicated that this was driven by a significant positive correlation in those without a family history (i.e. healthy unrelated volunteers), with no significant relationships in the familial group. We then examined the effect of the individual diagnoses contributing to the PGRS to determine evidence of disorder-specificity. We found a significant association with the schizophrenia polygenic score only, with no other significant relationships. These findings indicate differences in left lateral frontal brain activation in association with increased cross-disorder PGRS in individuals without a family history of psychiatric illness. Lack of effects in the familial group may reflect epistatic effects, shared environmental influences or effects not captured by the PGRS. The specific relationship with loading for schizophrenia is notably consistent with frontal cortical inefficiency as a circumscribed phenotype of psychotic disorders.

Impaired working memory in geriatric depression: an FMRI study.

Older adults with major depressive disorder (MDD) experience poor cognitive and behavioral outcomes as MDD occurs in the context of other age-related brain changes. Patients with depression often have impairments on measures of frontal lobe functioning such as working memory. Understanding the effects of depression on cognitive functioning in older adults is important for the development of treatment strategies that focus on cognitive changes as well as mood. Eleven older adults with current MDD and 12 nondepressed comparison participants (all aged 60 years and older) performed the N-back test of working memory during fMRI. Depressed older adults performed worse than nondepressed participants on the N-back task. Depressed older adults had decreased lateral frontal and parietal activation during the most difficult working memory load condition on the N-back compared with nondepressed older adults. Cognitive dysfunction in geriatric depression may be related to reorganization of brain networks involved in working memory.

A Behavioral Manipulation Engages Right Frontal Cortex During Aphasia Therapy

Background. An aphasia treatment was designed to shift laterality from the left to right lateral frontal lobe during word production by initiating word-finding trials with complex left-hand movements. Previous findings indicated successful relateralization. Objective. The current study was designed to ascertain whether the shift was attributable to the left-hand movement. Methods. Using stratified random sampling, 14 subjects were equally divided between Intention (IT) and Control (CT) treatments. CT was identical to IT, except with no left-hand movements. Both treatments trained picture naming (phases 1 and 2) and category-member generation (phase 3), each phase lasting 10 sessions. Functional magnetic resonance imaging of category member generation occurred at pretreatment, posttreatment, and 3-month follow-up. Results. IT shifted lateral frontal activity rightward compared with pretreatment both at posttreatment (t = −2.602, df = 6, P < .05) and 3-month follow-up (t = −2.332, df = 5, P < .05), but CT did not. IT and CT yielded similar changes for all picture-naming and category probes. However, IT patients showed gains for untrained category (t = 3.33, df = 6, P < .01) and picture-naming probes (t = 3.77, df = 5, P < .01), but CT patients did not. Conclusions. The rightward shift in lateral frontal activity for IT was because of the left-hand movements. IT evoked greater generalization than CT.

The temporal dynamics of medial and lateral frontal neural activity related to proactive cognitive control

The neural correlates of proactive cognitive control were examined in two experiments using the counting Stroop task and a computerized Blackjack task in combination with event-related brain potentials (ERPs). The primary objective of the study was to determine whether slow wave activity related to proactive control would be observed in the two tasks. Consistent with the existing literature, transient components of the ERPs (i.e., medial frontal negativity and feedback related negativity) were observed over the medial frontal region in both tasks that were related to stimulus congruency and feedback processing, respectively. The medial frontal ERPs in both tasks were modeled with a pair of equivalent current dipoles placed along the anterior to posterior axis of the cingulate. Most importantly, slow wave activity was observed that differentiated incongruent trials from congruent trials after the response in the counting Stroop task, and losses from wins and ties in the Blackjack task. In the Blackjack task, a pair of dipoles in the left lateral frontal and posterior regions modeled the slow wave activity. These data reveal that updating goal representations that support proactive cognitive control may require several 100ms in contrast to conflict or outcome monitoring that is associated with transient medial frontal neural activity.

Frontal EEG asymmetry moderates the effects of stressful life events on internalizing symptoms in children at familial risk for depression

This study examined whether frontal alpha electroencephalographic (EEG) asymmetry moderates the association between stressful life events and depressive symptoms in children at familial risk for depression. Participants included 135 children ages 6 to 13, whose mothers had either a history of depression or no history of major psychiatric conditions. Frontal EEG was recorded while participants watched emotion-eliciting films. Symptoms and stressful life events were obtained via the Child Behavior Check List and a clinical interview, respectively. High-risk children displayed greater relative right lateral frontal activation (F7/F8) than their low-risk peers during the films. For high-risk children, greater relative left lateral frontal activation moderated the association between stressful life events and internalizing symptoms. Specifically, greater relative left lateral frontal activation mitigated the effects of stress in at-risk children.

Updating Beliefs for a Decision: Neural Correlates of Uncertainty and Underconfidence

Some decisions are made after obtaining several pieces of information, whereas others are reached quickly. Such differences may depend on the quality of information acquired, as well as individual variability in how cautiously evidence is evaluated. The current study examined neural activity while subjects accumulated sequential pieces of evidence and then made a decision. Uncertainty was updated with each piece of evidence, with individual ratings of subjective uncertainty characterizing underconfidence when observing evidence. Increased uncertainty during evidence accumulation was associated with activity in dorsal anterior cingulate cortex, whereas greater uncertainty when executing a decision uniquely elicited lateral frontal and parietal activity. Greater underconfidence when observing evidence correlated with activity in ventromedial prefrontal cortex. These results suggest that neural mechanisms of uncertainty depend on the stage of decision-making (belief updating vs decision) and that greater subjective uncertainty when evaluating evidence is associated with activity in ventromedial brain regions, even in the absence of overt risk.

Lateral Prefrontal Cortex Mediates the Cognitive Modification of Attentional Bias

BackgroundA tendency to orient attention toward threatening stimuli may be involved in the etiology of anxiety disorders. In keeping with this, both psychological and pharmacological treatments of anxiety reduce this negative attentional bias. It has been hypothesized, but not proved, that psychological interventions may alter the function of prefrontal regions supervising the allocation of attentional resources.MethodsThe current study examined the effects of a cognitive training regime on attention. Participants were randomly assigned to one of two training conditions: “attend-threat” training, which increases negative attentional bias, or “avoid-threat” training, which reduces it. The behavioral effects of training were assessed using a sample of 24 healthy participants. Functional magnetic resonance imaging data were collected in a further 29 healthy volunteers using a protocol that allowed the influence of both stimuli valence and attention to be discriminated.ResultsCognitive training induced the expected attentional biases in healthy volunteers. Further, the training altered lateral frontal activation to emotional stimuli, with these areas responding specifically to violations of the behavioral rules learned during training. Connectivity analysis confirmed that the identified lateral frontal regions were influencing attention as indexed by activity in visual association cortex.ConclusionsOur results indicate that frontal control over the processing of emotional stimuli may be tuned by psychological interventions in a manner predicted to regulate levels of anxiety. This directly supports the proposal that psychological interventions may influence attention via an effect on the prefrontal cortex.

Regional changes in word-production laterality after a naming treatment designed to produce a rightward shift in frontal activity

Five nonfluent aphasia patients participated in a picture-naming treatment that used an intention manipulation (opening a box and pressing a button on a device in the box with the left hand) to initiate naming trials and was designed to re-lateralize word production mechanisms from the left to the right frontal lobe. To test the underlying assumption regarding re-lateralization, patients participated in fMRI of category-member generation before and after treatment. Generally, the four patients who improved during treatment showed reduced frontal activity from pre- to post-treatment fMRI with increasing concentration of activity in the right posterior frontal lobe (motor/premotor cortex, pars opercularis), demonstrating a significant shift in lateraliity toward the right lateral frontal lobe, as predicted. Three of these four patients showed no left frontal activity by completion of treatment, indicating that right posterior lateral frontal activity supported category-member generation. Patients who improved in treatment showed no difference in lateralization of lateral frontal activity from normal controls pre-treatment, but post-treatment, their lateral frontal activity during category-member generation was significantly more right lateralized than that of controls. Patterns of activity pre- and post-treatment suggested increasing efficiency of cortical processing as a result of treatment in the four patients who improved. The one patient who did not improve during treatment showed a leftward shift in lateral frontal lateralization that was significantly different from the four patients who did improve. Neither medial frontal nor posterior perisylvian re-lateralization from immediately pre- to immediately post-treatment images was a necessary condition for significant treatment gains or shift in lateral frontal lateralization. Of the three patients who improved and in whom posterior perisylvian activity could be measured at post-treatment fMRI, all maintained equal or greater amounts of left-hemisphere perisylvian activity as compared to right. This finding is consistent with reviews suggesting both hemispheres are involved in recovery of language in aphasia patients.