Separate and overlapping functional roles for efference copies in the human thalamus.

How the perception of space is generated from the multiple maps in the brain is still an unsolved mystery in neuroscience. A neural pathway ascending from the superior colliculus through the medio-dorsal (MD) nucleus of thalamus to the frontal eye field has been identified in monkeys that conveys efference copy information about the metrics of upcoming eye movements. Information sent through this pathway stabilizes vision across saccades. We investigated whether this motor plan information might also shape spatial perception even when no saccades are performed. We studied patients with medial or lateral thalamic lesions (likely involving either the MD or the ventrolateral (VL) nuclei). Patients performed a double-step task testing motor updating, a trans-saccadic localization task testing visual updating, and a localization task during fixation testing a general role of motor signals for visual space in the absence of eye movements. Single patients with medial or lateral thalamic lesions showed deficits in the double-step task, reflecting insufficient transfer of efference copy. However, only a patient with a medial lesion showed impaired performance in the trans-saccadic localization task, suggesting that different types of efference copies contribute to motor and visual updating. During fixation, the MD patient localized stationary stimuli more accurately than healthy controls, suggesting that patients compensate the deficit in visual prediction of saccades - induced by the thalamic lesion - by relying on stationary visual references. We conclude that partially separable efference copy signals contribute to motor and visual stability in company of purely visual signals that are equally effective in supporting trans-saccadic perception.

The involvement of the thalamus in semantic retrieval: a clinical group study.

There is increasing attention about the role of the thalamus in high cognitive functions, including memory. Although the bulk of the evidence refers to episodic memory, it was recently proposed that the mediodorsal (MD) and the centromedian-parafascicular (CM-Pf) nuclei of the thalamus may process general operations supporting memory performance, not only episodic memory. This perspective agrees with other recent fMRI findings on semantic retrieval in healthy participants. It can therefore be hypothesized that lesions to the MD and the CM-Pf impair semantic retrieval. In this study, 10 patients with focal ischemic lesions in the medial thalamus and 10 healthy controls matched for age, education, and verbal IQ performed a verbal semantic retrieval task. Patients were assigned to a target clinical group and a control clinical group based on lesion localization. Patients did not suffer from aphasia and performed in the range of controls in a categorization and a semantic association task. However, target patients performed poorer than healthy controls on semantic retrieval. The deficit was not because of higher distractibility but of an increased rate of false recall and, in some patients, of a considerably increased rate of misses. The latter deficit yielded a striking difference between the target and the control clinical groups and is consistent with anomia. Follow-up high-resolution structural scanning session in a subsample of patients revealed that lesions in the CM-Pf and MD were primarily associated with semantic retrieval deficits. We conclude that integrity of the MD and the CM-Pf is required for semantic retrieval, possibly because of their role in the activation of phonological representations.

Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus.

The functional role of the mediodorsal thalamic nucleus (MD) and its cortical network in memory processes is discussed controversially. While Aggleton and Brown (1999) suggested a role for recognition and not recall, Van der Werf et al. (2003) suggested that this nucleus is functionally related to executive function and strategic retrieval, based on its connections to the prefrontal cortices (PFC). The present study used a lesion approach including patients with focal thalamic lesions to examine the functions of the MD, the intralaminar nuclei and the midline nuclei in memory processing. A newly designed pair association task was used, which allowed the assessment of recognition and cued recall performance. Volume loss in thalamic nuclei was estimated as a predictor for alterations in memory performance. Patients performed poorer than healthy controls on recognition accuracy and cued recall. Furthermore, patients responded slower than controls specifically on recognition trials followed by successful cued recall of the paired associate. Reduced recall of picture pairs and increased response times during recognition followed by cued recall covaried with the volume loss in the parvocellular MD. This pattern suggests a role of this thalamic region in recall and thus recollection, which does not fit the framework proposed by Aggleton and Brown (1999). The functional specialization of the parvocellular MD accords with its connectivity to the dorsolateral PFC, highlighting the role of this thalamocortical network in explicit memory (Van der Werf et al., 2003).

Altered error processing following vascular thalamic damage: evidence from an antisaccade task.

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response--the error-related negativity (ERN)--as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.

Differential impairment of remembering the past and imagining novel events after thalamic lesions.

Vividly remembering the past and imagining the future (mental time travel) seem to rely on common neural substrates and mental time travel impairments in patients with brain lesions seem to encompass both temporal domains. However, because future thinking-or more generally imagining novel events-involves the recombination of stored elements into a new event, it requires additional resources that are not shared by episodic memory. We aimed to demonstrate this asymmetry in an event generation task administered to two patients with lesions in the medial dorsal thalamus. Because of the dense connection with pFC, this nucleus of the thalamus is implicated in executive aspects of memory (strategic retrieval), which are presumably more important for future thinking than for episodic memory. Compared with groups of healthy matched control participants, both patients could only produce novel events with extensive help of the experimenter (prompting) in the absence of episodic memory problems. Impairments were most pronounced for imagining personal fictitious and impersonal events. More precisely, the patients' descriptions of novel events lacked content and spatio-temporal relations. The observed impairment is unlikely to trace back to disturbances in self-projection, scene construction, or time concept and could be explained by a recombination deficit. Thus, although memory and the imagination of novel events are tightly linked, they also partly rely on different processes.

Involvement of the human thalamus in relational and non-relational memory.

Damage to the human thalamus has been associated with selective anterograde recognition memory impairments. Recently, recognition memory has been subdivided into relational and non-relational memory. The aim of the present study was to assess the potentially differential involvement of the human thalamus in relational and non-relational memory. Ten patients with focal ischemic thalamic lesions were compared to individualized control groups of healthy subjects matched to each individual patient on age and IQ. Six patients showed poorer relational memory than their respective control samples. None of the 10 patients showed a significant deficit on the non-relational memory task. These observations suggest an involvement of the thalamus in relational memory, and are discussed in terms of disruption of mediotemporal-thalamic and thalamic-fronto-striatal circuits.

Domain-specific impairment of source memory following a right posterior medial temporal lobe lesion.

This single case analysis of memory performance in a patient with an ischemic lesion affecting posterior but not anterior right medial temporal lobe (MTL) indicates that source memory can be disrupted in a domain-specific manner. The patient showed normal recognition memory for gray-scale photos of objects (visual condition) and spoken words (auditory condition). While memory for visual source (texture/color of the background against which pictures appeared) was within the normal range, auditory source memory (male/female speaker voice) was at chance level, a performance pattern significantly different from the control group. This dissociation is consistent with recent fMRI evidence of anterior/posterior MTL dissociations depending upon the nature of source information (visual texture/color vs. auditory speaker voice). The findings are in good agreement with the view of dissociable memory processing by the perirhinal cortex (anterior MTL) and parahippocampal cortex (posterior MTL), depending upon the neocortical input that these regions receive.

Involvement of the mediodorsal thalamic nucleus in mediating recollection and familiarity.

The mediodorsal (MD) thalamic nucleus is thought to play an important role in memory processes. Distinct hippocampal-thalamic-prefrontal connections have been described as the potential neural substrate for both, recollection and familiarity. The aim of this study was to investigate whether the MD is part of the circuits underlying these two memory components. We assessed the effects of ischemic thalamic lesions with or without MD involvement on performance in a word list discrimination task and standard tests of memory and executive function. Estimates of recollection and familiarity were derived using the dual-process signal-detection model (DPSD). The results revealed impairments in both, recollection and familiarity, after unilateral thalamic damage, with recollection being more affected than familiarity. There were no significant differences in the memory performance of patients with MD lesions compared to patients with ventrolateral-thalamic lesions except for familiarity estimates, which were lower for the latter group. Lesions involving the MD led to recollection deficits, although inspection of individual cases suggested a decrease in both memory components after damage in the medial part of this nucleus. Executive dysfunction was associated with lateral MD lesions and also ventrolateral-thalamic damage. The findings suggest that MD contributes to recollection, with some preliminary evidence of a contribution of the medial MD to familiarity. The small sample size does, however, not yet allow any clear conclusions in this regard. Since damage in the ventrolateral thalamus leads to memory and executive dysfunction, further research is needed to elucidate the role of this thalamic region in cognition.